Nilotinib: Drug information

For additional information see "Nilotinib: Patient drug information" and "Nilotinib: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

ALERT: US Boxed Warning

QT Prolongation and Sudden Deaths:

Nilotinib prolongs the QT interval. Prior to nilotinib administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. Obtain ECGs to monitor the QTc at baseline, 7 days after initiation, and periodically thereafter, and following any dose adjustments. Sudden deaths have been reported in patients receiving nilotinib. Do not administer nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome. Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors.

Tasigna: Avoid food 2 hours before and 1 hour after taking a nilotinib dose.

Brand Names: US

Danziten;
Tasigna

Brand Names: Canada

APO-Nilotinib;
Tasigna

Pharmacologic Category

Antineoplastic Agent, BCR-ABL Tyrosine Kinase Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

Dosage guidance:

Safety: Correct electrolyte abnormalities (eg, hypokalemia and/or hypomagnesemia) prior to nilotinib initiation. Do not administer nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome. Maintain adequate hydration and treat high uric acid levels prior to nilotinib initiation.

Dosing: When converting between nilotinib tablets (Danziten) and nilotinib capsules (Tasigna), utilize the provided dosage conversions.

Dosage form information: Nilotinib is available as different formulations, dosage forms, and strengths. Indications for use and dosing differ between formulations; do not substitute nilotinib capsules and tablets (or vice versa) on a mg-per-mg basis.

Clinical considerations: If clinically indicated, nilotinib may be administered in combination with hematopoietic growth factors (eg, erythropoietin, G-CSF) and with hydroxyurea or anagrelide.

Acute lymphoblastic leukemia, Philadelphia chromosome positive, newly diagnosed

Acute lymphoblastic leukemia, Philadelphia chromosome positive (Ph+), newly diagnosed (off-label use; Tasinga only): Oral: 400 mg twice daily starting on day 8 of induction chemotherapy (in combination with daunorubicin, vincristine, and prednisolone); continue up to the start of stem cell transplant conditioning or until the end of consolidation therapy. Patients who completed 5 cycles of consolidation treatment received 2 years of nilotinib maintenance. Patients who underwent allogeneic stem cell transplant did not receive nilotinib after transplant (Ref).

Acute lymphoblastic leukemia, Philadelphia chromosome positive, relapsed/refractory

Acute lymphoblastic leukemia, Philadelphia chromosome positive (Ph+), relapsed/refractory (off-label use; Tasigna only): Oral: 400 mg twice daily (Ref).

Chronic myeloid leukemia, Philadelphia chromosome positive, chronic phase, newly diagnosed

Chronic myeloid leukemia, Philadelphia chromosome positive (Ph+), chronic phase, newly diagnosed (Danziten, Tasigna) :

Capsule (Tasigna): Oral: 300 mg twice daily (Ref).

Tablet (Danziten): Oral: 142 mg twice daily (Ref).

Discontinuation of therapy (following a sustained molecular response [MR^4.5]) (Danziten, Tasigna): May consider nilotinib discontinuation in patients with newly diagnosed Ph+ chronic myeloid leukemia (in chronic phase) who have been treated with nilotinib for ≥3 years, maintained a molecular response of at least MR^4.0(corresponding to BCR-ABL/ABL ≤0.01% IS) for 1 year (prior to nilotinib discontinuation), achieved an MR^4.5(corresponding to BCR-ABL/ABL ≤0.0032% IS) for the last assessment taken immediately prior to discontinuation, been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), no history of accelerated phase or blast crisis, and no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.

Reinitiation of therapy: Patients with newly diagnosed Ph+ chronic myeloid leukemia (in chronic phase) who lose major molecular response after nilotinib discontinuation must reinitiate treatment within 4 weeks at the dose level used prior to nilotinib discontinuation. Monitor BCR-ABL transcript levels every 4 weeks until major molecular response is re-established and every 12 weeks thereafter. BCR-ABL kinase domain mutation testing should be performed if major molecular response is not achieved after 3 months of therapy reinitiation.

Chronic myeloid leukemia, Philadelphia chromosome positive, accelerated phase, previously treated

Chronic myeloid leukemia, Philadelphia chromosome positive (Ph+), accelerated phase, previously treated (resistant or intolerant to prior therapy; Danziten, Tasigna):

Capsule (Tasigna): Oral: 400 mg twice daily (Ref).

Tablet (Danziten): Oral: 190 mg twice daily (Ref).

Chronic myeloid leukemia, Philadelphia chromosome positive, chronic phase, previously treated

Chronic myeloid leukemia, Philadelphia chromosome positive (Ph+), chronic phase, previously treated (resistant or intolerant to prior therapy; Danziten, Tasigna) :

Capsule (Tasigna): Oral: 400 mg twice daily (Ref).

Tablet (Danziten): Oral: 190 mg twice daily (Ref).

Discontinuation of therapy (following a sustained molecular response [MR^4.5]) (Danziten, Tasigna): May consider nilotinib discontinuation in patients with previously treated (resistant or intolerant to prior imatinib therapy) Ph+ chronic myeloid leukemia (CML) in chronic phase who have been treated with nilotinib for ≥3 years, been treated with imatinib (only) prior to nilotinib treatment, achieved an MR^4.5(corresponding to BCR-ABL/ABL ≤0.0032% IS), achieved a sustained MR^4.5 for a minimum of 1 year immediately prior to nilotinib discontinuation, been confirmed to express the typical BCR-ABL transcripts (e13a2/b2a2 or e14a2/b3a2), no history of accelerated phase or blast crisis, and no history of prior attempts of treatment-free remission discontinuation that resulted in relapse.

Reinitiation of therapy (Danziten, Tasigna): Patients with previously treated (resistant or intolerant to prior imatinib therapy) Ph+ CML in chronic phase with confirmed loss of MR^4.0(2 consecutive readings separated by at least 4 weeks showing loss of MR^4.0 [corresponding to BCR-ABL/ABL ≤0.01% IS]) or loss of major molecular response after nilotinib discontinuation must reinitiate treatment within 4 weeks at the dose level used prior to nilotinib discontinuation. Monitor BCR-ABL transcript levels every 4 weeks until previous major molecular response or MR^4.0 is re-established and every 12 weeks thereafter. BCR-ABL kinase domain mutation testing should be performed if major molecular response is not achieved after 3 months of therapy reinitiation.

Gastrointestinal stromal tumor, refractory

Gastrointestinal stromal tumor, refractory (off-label use; Tasigna only): Oral: 400 mg twice daily until disease progression or unacceptable toxicity (Ref).

Missed doses: If a dose is missed, do not make up, resume with next scheduled dose; do not administer 2 doses at the same time.

Dose Conversions for Chronic Myeloid Leukemia:

**Dos** **e Conversions for Chronic Myeloid Leukemia**
Approved indication	Nilotinib tablet (Danziten) dosage	Nilotinib capsule (Tasigna) dosage
Chronic myeloid leukemia, Ph+, chronic phase, newly diagnosed	142 mg twice daily	300 mg twice daily
Chronic myeloid leukemia, Ph+, chronic or accelerated phase, previously treated	190 mg twice daily	400 mg twice daily

Dosage adjustment for total gastrectomy: Consider alternative therapy or a dosage increase (with more frequent monitoring) in patients with total gastrectomy (nilotinib exposure is reduced).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, nilotinib and its metabolites have minimal renal excretion; dosage adjustments for kidney dysfunction may not be necessary.

Dosing: Liver Impairment: Adult

Hepatic impairment prior to treatment initiation: Note: Consider alternative therapies first if possible; recommendations vary by indication. Monitor the QT interval closely in patients with hepatic impairment.

Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase: Mild, moderate, or severe impairment (Child-Pugh class A, B, or C):

Initial: 200 mg twice daily (Tasigna) or 95 mg twice daily (Danziten).

Dose adjustment (based on tolerability): May increase dose to 300 mg twice daily (Tasigna) or 142 mg twice daily (Danziten).

Previously treated (resistant or intolerant) Ph+ CML in chronic or accelerated phase:

Mild to moderate impairment (Child-Pugh class A or B):

Initial: 300 mg twice daily (Tasigna) or 142 mg twice daily (Danziten).

Dose adjustment (based on tolerability): May increase to 400 mg twice daily (Tasigna) or 190 mg twice daily (Danziten).

Severe impairment (Child-Pugh class C):

Initial: 200 mg twice daily (Tasigna) or 95 mg twice daily (Danziten).

Dose adjustment (based on tolerability): May increase to 300 mg twice daily (Tasigna) or 142 mg twice daily (Danziten), and then further increase to 400 mg twice daily (Tasigna) or 190 mg twice daily (Danziten).

Acute hepatotoxicity during treatment:

Elevated bilirubin ≥ grade 3: Withhold nilotinib and monitor bilirubin. If bilirubin returns to ≤ grade 1, resume nilotinib at:

Capsule (Tasigna): 400 mg once daily or
Tablet (Danziten): 190 mg once daily.

Elevated ALT or AST ≥ grade 3: Withhold nilotinib and monitor transaminases. If ALT or AST returns to ≤ grade 1, resume nilotinib at:

Capsule (Tasigna): 400 mg once daily or
Tablet (Danziten): 190 mg once daily.

Dosing: Adjustment for Toxicity: Adult

**Nilotinib Dosage Modifications for Adverse Reactions (Danziten, Tasigna)**
Adverse event	Severity	Dosage modification
^a CML = chronic myeloid leukemia.
Hematologic toxicity (unrelated to underlying leukemia): Newly diagnosed Ph+ CML^a in chronic phase and current dose: 300 mg twice daily (Tasigna) or 142 mg twice daily (Danziten). Previously treated (resistant or intolerant) Ph+ CML in chronic or accelerated phase and current dose: 400 mg twice daily (Tasigna) or 190 mg twice daily (Danziten).	ANC <1,000/mm³ and/or platelets <50,000/mm³	Withhold nilotinib and monitor blood counts. ANC >1,000/mm³ and platelets >50,000/mm³ within 2 weeks: Resume nilotinib at prior dose. Blood counts remain low for >2 weeks: Reduce nilotinib dose to: 400 mg once daily (Tasigna) or 190 mg once daily (Danziten).
QT prolongation	ECG with QTc prolongation >480 msec	Withhold nilotinib and monitor and correct potassium and magnesium levels; review concurrent medications. QTcF returns to <450 msec and to within 20 msec of baseline within 2 weeks: Resume nilotinib at prior dose. QTcF returns to 450 to 480 msec after 2 weeks: Reduce nilotinib dose to: 400 mg once daily (Tasigna) or 190 mg once daily (Danziten). QTcF returns to >480 msec after dosage reduction to 400 mg once daily (Tasigna) or 190 mg once daily (Danziten): Discontinue nilotinib. Repeat ECG ~7 days after any nilotinib dosage adjustment.
Amylase or lipase elevations	≥ Grade 3	Withhold nilotinib; monitor serum amylase or lipase. When lipase or amylase returns to ≤ grade 1, resume nilotinib at: 400 mg once daily (Tasigna) or 190 mg once daily (Danziten).
Lipase elevations in conjunction with abdominal symptoms	Any	Withhold nilotinib and consider diagnostics to exclude pancreatitis.
Bleeding or hemorrhage	Any	Manage as medically indicated.
Fluid retention	Any	Evaluate etiology and treat accordingly.
Hypertension	Any	If indicated, initiate appropriate antihypertensive therapy to reduce the risk for cardiovascular complications (ASCO [Armenian 2017], ESC [Lyon 2022]).
Lipid or glucose elevations	Any	Manage per standards of practice and treatment guidelines.
Other clinically significant nonhematologic toxicity (including medically severe fluid retention); Newly diagnosed Ph+ CML^a in chronic phase and current dose: 300 mg twice daily (Tasigna) or 142 mg twice daily (Danziten).	Moderate or severe	Withhold nilotinib until resolution of toxicity. Resume nilotinib at: 400 mg once daily (Tasigna) or 190 mg once daily (Danziten). If dose was previously reduced to 400 mg once daily (Tasigna) or 190 mg once daily (Danziten): Discontinue nilotinib. Consider re-escalation to 300 mg twice daily (Tasigna) or 142 mg twice daily (Danziten) if clinically appropriate.
Other clinically significant nonhematologic toxicity (including medically severe fluid retention); Previously treated (resistant or intolerant) Ph+ CML in chronic or accelerated phase and current dose: 400 mg twice daily (Tasigna) or 190 mg twice daily (Danziten).	Moderate or severe	Withhold nilotinib until resolution of toxicity. Resume nilotinib at: 400 mg once daily (Tasigna) or 190 mg once daily (Danziten). If dose was previously reduced to 400 mg once daily (Tasigna) or 190 mg once daily (Danziten): Discontinue nilotinib. Consider re-escalation to 400 mg twice daily (Tasigna) or 190 mg twice daily (Danziten) if clinically appropriate.
Acute lymphoblastic leukemia, Ph+, newly diagnosed (off-label use): Nonhematologic toxicity (Tasigna only)	≥ Grade 3	Temporarily reduce nilotinib dose to 400 mg once daily for ≥ grade 3 nonhematologic toxicity (resume when improved to grade 1); severe recurrent adverse events despite dose reduction may require permanent discontinuation (Ref).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Nilotinib: Pediatric drug information")

Dosage guidance :

Safety: Correct hypokalemia and/or hypomagnesemia prior to nilotinib initiation. Do not administer nilotinib to patients with long QT syndrome. Maintain adequate hydration and treat high uric acid levels prior to nilotinib initiation.

Dosing: Round capsule (Tasigna) dose to the nearest 50 mg increment; may combine different capsule strengths to achieve desired dose.

Dosage form information: Nilotinib is available as different salt formulations (hydrochloride [Tasigna]; tartrate [Danziten]) and dosage forms with unique strengths (capsules [Tasigna]; tablets [Danziten]). Indications for use and dosing differ between formulations; do not substitute nilotinib capsules and tablets (or vice versa) on a mg-per-mg basis; Tasigna capsules are approved for use in pediatric patients.

Chronic myeloid leukemia, Philadelphia chromosome positive, newly diagnosed in chronic phase

Chronic myeloid leukemia (CML), Philadelphia chromosome positive, newly diagnosed in chronic phase: Children and Adolescents: Capsules (Tasigna): Oral: 230 mg/m²/dose twice daily; maximum dose: 400 mg/dose. Continue therapy as long as observing clinical benefit or until unacceptable toxicity occurs.

Chronic myeloid leukemia, Philadelphia chromosome positive, resistant or intolerant in chronic phase and accelerated phase

Chronic myeloid leukemia, Philadelphia chromosome positive, resistant or intolerant in chronic phase and accelerated phase: Children and Adolescents: Capsules (Tasigna): Oral: 230 mg/m²/dose twice daily; maximum dose: 400 mg/dose. Continue therapy as long as observing clinical benefit or until unacceptable toxicity occurs.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity:

Children and Adolescents: Capsules (Tasigna): Oral:

**Nilotinib Capsule (Tasigna) Dose Modifications for Adverse Reactions in Children and Adolescents**
Adverse event	Severity	Dosage modification
Hematologic toxicity (unrelated to underlying leukemia):	ANC <1,000/mm³ and/or platelets <50,000/mm³	Withhold nilotinib and monitor blood counts. • If ANC >1,500/mm³ and/or platelets >75,000/mm³ within 2 weeks: Resume nilotinib at prior dose. • If blood counts remain low for >2 weeks: Reduce nilotinib dose to 230 mg/m² once daily. • If an event occurs after dose reduction, consider discontinuation of treatment.
Nonhematologic toxicities
QT prolongation	ECG with QTc prolongation >480 msec	Withhold nilotinib and monitor and correct potassium and magnesium levels; review concurrent medications. • If QTcF returns to <450 msec and to within 20 msec of baseline within 2 weeks: Resume nilotinib at prior dose. • If QTcF returns to 450 to 480 msec after 2 weeks: Reduce nilotinib dose to 230 mg/m² once daily. • If QTcF returns to >480 msec after dosage reduction to 230 mg/m² once daily: Discontinue nilotinib. Repeat ECG ~7 days after any nilotinib dosage adjustment.
Amylase or lipase elevations	≥ Grade 3	Withhold nilotinib, monitor serum amylase and lipase until levels return to ≤ grade 1. • If prior dose 230 mg/m² once daily: Discontinue nilotinib. • If prior dose 230 mg/m² twice daily: Once ≤ grade 1, resume nilotinib at 230 mg/m² once daily.
Lipase increases in conjunction with abdominal symptoms	Any	Withhold nilotinib; consider diagnostics to exclude pancreatitis.
Other clinically significant moderate or severe nonhematologic toxicity (including medically severe fluid retention)		Withhold nilotinib until toxicity resolves. • If prior dose 230 mg/m²once daily: Discontinue nilotinib. • If prior dose 230 mg/m² twice daily: Resume nilotinib at 230 mg/m² once daily. May escalate back to 230 mg/m² twice daily if clinically appropriate.

Dosing: Kidney Impairment: Pediatric

Dosing: Liver Impairment: Pediatric

Children and Adolescents: Capsules (Tasigna): Oral:

Baseline: A reduced dosage and close monitoring of ECG (for QT prolongation) is recommended; based on experience in adult patients, it is recommended to consider alternative therapies if possible.

Hepatotoxicity occurring during treatment:

**Nilotinib Capsule (Tasigna) Dose Modifications for Hepatoxicity in Children and Adolescents**
Adverse event	Severity	Dosage modification
AST or ALT elevations	≥ Grade 3	Withhold treatment and monitor transaminases. • If ALT or AST elevation returns to ≤ grade 1, resume treatment at 230 mg/m² once daily (if previous dose was 230 mg/m² twice daily). • If previous dose was already 230 mg/m² once daily and recovery to ≤ grade 1 was longer than 28 days, discontinue treatment.
Elevated bilirubin	≥ Grade 2	Withhold treatment and monitor bilirubin. • If bilirubin elevation returns to ≤ grade 1, resume treatment at 230 mg/m²/dose once daily (if previous dose was 230 mg/m² twice daily). • If previous dose was already 230 mg/m² once daily and recovery to ≤ grade 1 was longer than 28 days, discontinue treatment.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise specified.

>10%:

Cardiovascular: Hypertension (10% to 11%), occlusive arterial disease (9% to 15%; including limb stenosis), peripheral edema (9% to 15%), prolonged QT interval on ECG (children, adolescents: >30 msec from baseline: 28%; adults: >60 msec from baseline: ≤4%; adults: >500 msec: <1%)

Dermatologic: Alopecia (11% to 13%), night sweats (12% to 27%), pruritus (20% to 32%), skin rash (children, adolescents: >20%; adults: 29% to 38%), xeroderma (12%)

Endocrine & metabolic: Hyperglycemia (50%), hypophosphatemia (grades 3/4: 8% to 17%), increased HDL cholesterol (≤28%), increased LDL cholesterol (≤28%), increased VLDL

Gastrointestinal: Abdominal pain (15% to 16%), constipation (19% to 26%), decreased appetite (15% to 17%; including anorexia), diarrhea (children, adolescents: >20%; adults: 19% to 28%; grades 3/4: 1% to 3%), increased serum lipase (28%), nausea (children, adolescents: >20%; adults: 22% to 37%; grades 3/4: ≤2%), upper abdominal pain (12% to 18%), vomiting (children, adolescents: >20%; adults: 13% to 29%; grades 3/4: <1%)

Hematologic & oncologic: Anemia (8%; grades 3/4: 4% to 27%; decreased hemoglobin: children, adolescents: 38%), decreased absolute lymphocyte count (children, adolescents: 36%), decreased white blood cell count (children, adolescents: 54%), neutropenia (children, adolescents: grades 3/4: >5%; adults: 15%; grades 3/4: 12% to 42%, grade 3: 16%, grade 4: 15% to 26%; decrease in absolute neutrophil count: children, adolescents: 44%), thrombocytopenia (adults: 18%; grades 3/4: 10% to 42%, grade 3: 11% to 12%, grade 4: 18% to 32%; decreased platelet count: children, adolescents: 44%)

Hepatic: Hyperbilirubinemia (children, adolescents: >20%; adults: ≥10%), increased serum alanine aminotransferase (children, adolescents: >20%; adults: 72%), increased serum aspartate aminotransferase (children, adolescents: >20%; adults: 47%)

Infection: Influenza (13%)

Nervous system: Asthenia (14% to 16%), dizziness (12%), fatigue (23% to 32%), headache (children, adolescents: >20%; adults: 20% to 35%), insomnia (7% to 12%)

Neuromuscular & skeletal: Arthralgia (16% to 26%), back pain (15% to 19%), limb pain (children, adolescents: >20%; adults: 15% to 20%), muscle spasm (12% to 15%), musculoskeletal pain (11% to 12%), myalgia (16% to 19%), ostealgia (14% to 15%)

Respiratory: Cough (17% to 27%), dyspnea (9% to 15%), nasopharyngitis (children, adolescents: >20%; adults: 15% to 27%), oropharyngeal pain (7% to 12%), upper respiratory tract infection (children, adolescents: >20%; adults: 10% to 17%)

Miscellaneous: Fever (children, adolescents: >20%; adults: 14% to 28%)

1% to 10%:

Cardiovascular: Angina pectoris, cardiac arrhythmia (including atrial fibrillation, atrioventricular block, bradycardia, cardiac flutter, extrasystoles, tachycardia), chest discomfort, chest pain, flushing, ischemic heart disease (5% to 9%), palpitations, pericardial effusion (≤2%), peripheral arterial disease (3% to 4%)

Dermatologic: Acne vulgaris, cutaneous papilloma, dermatitis (including acneiform eruption, allergic dermatitis, exfoliative dermatitis), eczema, erythema of skin, folliculitis, hyperhidrosis, urticaria

Endocrine & metabolic: Decreased serum albumin (grades 3/4: 3% to 4%), diabetes mellitus, fluid retention (grades 3/4: 3% to 4%), hypercalcemia, hyperkalemia (grades 3/4: 2% to 6%), hyperphosphatemia, hypertriglyceridemia, hypocalcemia (grades 3/4: ≤5%), hypokalemia (grades 3/4: ≤9%), hypomagnesemia, hyponatremia (grades 3/4: 1% to 7%), weight gain, weight loss

Gastrointestinal: Abdominal distention, abdominal distress, dysgeusia, dyspepsia (4% to 10%), flatulence, gastroenteritis (7%), gastrointestinal hemorrhage (3% to 5%), increased serum amylase, pancreatitis

Genitourinary: Pollakiuria

Hematologic & oncologic: Bruise, change in serum protein (decreased globulins), eosinophilia, febrile neutropenia, hemophthalmos, hemorrhage (grades 3/4: 1% to 2%), leukopenia, lymphocytopenia, pancytopenia

Hepatic: Abnormal liver function, ascites (≤2%), increased gamma-glutamyl transferase, increased serum alkaline phosphatase (grades 3/4: ≤1%)

Nervous system: Anxiety, cerebral ischemia (1% to 3%), depression, hypoesthesia, malaise, myasthenia, noncardiac chest pain, pain, paresthesia, peripheral neuropathy, vertigo, voice disorder

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, linear skeletal growth rate below expectation (children, adolescents: 5%; including decreased plasma growth hormone level, growth suppression), musculoskeletal chest pain, neck pain

Ophthalmic: Conjunctivitis, dry eye syndrome, eye pruritus, eyelid edema (1%)

Renal: Flank pain

Respiratory: Dyspnea on exertion, epistaxis, pleural effusion (≤2%)

<1%:

Cardiovascular: Acute myocardial infarction, arteriosclerosis, coronary artery disease, dependent edema, heart failure, heart murmur, hypertensive crisis, intermittent claudication, syncope

Dermatologic: Ecchymoses, fixed drug eruption, skin pain

Endocrine & metabolic: Dehydration, gynecomastia, hyperthyroidism, hypothyroidism, increased lactate dehydrogenase

Gastrointestinal: Esophageal pain, gastritis, gastroesophageal reflux disease, increased appetite, melena, oral candidiasis, oral mucosa ulcer, stomatitis, toothache (sensitivity), xerostomia

Genitourinary: Dysuria, erectile dysfunction, mastalgia, nocturia, urinary tract infection, urinary urgency

Hematologic & oncologic: Hematoma

Hepatic: Hepatotoxicity, jaundice, toxic hepatitis

Hypersensitivity: Facial edema

Infection: Candidiasis

Local: Local alterations in temperature sensations

Nervous system: Cerebral infarction, chills, disturbance in attention, facial nerve paralysis, hyperesthesia, intracranial hemorrhage, ischemic stroke, loss of consciousness, migraine, transient ischemic attacks, tremor

Neuromuscular & skeletal: Gout, joint swelling, muscle rigidity

Ophthalmic: Blurred vision, conjunctival hemorrhage, conjunctival hyperemia, decreased visual acuity, eye irritation, injected sclera, ocular hyperemia, periorbital edema, photopsia, visual impairment

Renal: Increased blood urea nitrogen, increased serum creatinine (grades 3/4)

Respiratory: Bronchitis, cyanosis, flu-like symptoms, interstitial lung disease, pharyngolaryngeal pain, pleurisy, pleuritic chest pain, pneumonia, pulmonary edema, throat irritation

Frequency not defined:

Cardiovascular: Hypotension, pericarditis, reduced ejection fraction, shock (hemorrhagic), thrombosis, troponin increased in blood specimen, ventricular dysfunction

Dermatologic: Cutaneous nodule (sebaceous hyperplasia), dermal ulcer, epidermal cyst of skin, erythema multiforme, erythema nodosum, exfoliation of skin, furuncle, hyperkeratosis, palmar-plantar erythrodysesthesia, psoriasis, skin atrophy, skin blister, skin discoloration, skin hyperpigmentation, skin hypertrophy, skin photosensitivity, tinea pedis

Endocrine & metabolic: Altered hormone level (insulin C-peptide decreased), heavy menstrual bleeding, hyperparathyroidism (secondary), hyperuricemia, hypoglycemia, thyroiditis

Gastrointestinal: Cholestasis, enterocolitis, gastric ulcer (perforation possible), gingivitis, hematemesis, hemorrhoids, hiatal hernia, intestinal obstruction, oral lesion (papilloma), rectal hemorrhage, ulcerative esophagitis

Genitourinary: Breast induration, hematuria, urinary incontinence, urine discoloration

Hematologic & oncologic: Leukocytosis, paraproteinemia, petechia, retroperitoneal hemorrhage, thrombocythemia

Hepatic: Hepatomegaly

Hypersensitivity: Hypersensitivity reaction

Infection: Anal abscess, reactivation of HBV, sepsis, subcutaneous abscess

Local: Local swelling (nipple), localized edema

Nervous system: Amnesia, brain edema, confusion, disorientation, dysesthesia, dysphoria, lethargy, restless leg syndrome

Neuromuscular & skeletal: Arthritis

Ophthalmic: Allergic conjunctivitis, blepharitis, diplopia, eye pain, optic neuritis, papilledema, photophobia, retinopathy (chorioretinopathy), swelling of eye

Otic: Auditory impairment, otalgia, tinnitus

Renal: Kidney failure

Respiratory: Pulmonary hypertension, wheezing

Postmarketing:

Endocrine & metabolic: Ascorbic acid deficiency (Oak 2016)

Hematologic & oncologic: Thrombotic microangiopathy, tumor lysis syndrome

Neuromuscular & skeletal: Osteonecrosis

Contraindications

Danziten, Tasigna: Hypokalemia, hypomagnesemia, or long QT syndrome.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to nilotinib or any component of the formulation; persistent QTc >480 msec.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Nilotinib may cause myelosuppression, including grades 3 and 4 thrombocytopenia, neutropenia, and anemia; myelosuppression is generally reversible.

• Cardiovascular toxicity: Cardiovascular events such as ischemic heart disease-related events, arterial vascular occlusive events, peripheral arterial occlusive disease, and ischemic cerebrovascular accident have been reported. Assess patients for cardiovascular risk factors. Patients with uncontrolled or significant cardiovascular disease (including recent MI, heart failure, unstable angina, or clinically significant bradycardia) were excluded from studies.

• Electrolyte imbalance: Electrolyte abnormalities may occur during treatment, including hypophosphatemia, hyper-/hypokalemia, hypocalcemia, and hyponatremia.

• Fluid retention: Fluid retention, including pleural and pericardial effusions, ascites, and pulmonary edema, were reported; may be severe. Signs/symptoms of fluid retention include unexpected rapid weight gain or swelling; symptoms of respiratory or cardiac distress include shortness of breath.

• Hemorrhage: Serious hemorrhagic events (including fatal events) have occurred in chronic myeloid leukemia (CML) patients treated with nilotinib. In a clinical study comparing nilotinib and imatinib in the treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase CML, hemorrhagic events (eg, GI hemorrhage, including grade 3 or 4 events) occurred more frequently in the nilotinib arm.

• Hepatotoxicity: Nilotinib may cause hepatotoxicity, including elevations in bilirubin, transaminases, and alkaline phosphatase; grade 3 or 4 bilirubin, AST, and ALT elevations were observed more frequently in pediatric versus adult patients.

• Pancreatitis: Nilotinib may cause increases in serum lipase. Patients with a history of pancreatitis may be at increased risk for lipase increases.

• QT prolongation/sudden death: Nilotinib prolongs the QT interval in a concentration-dependent manner; sudden deaths have been reported. Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors; also avoid concurrent use with antiarrhythmics; may increase the risk of potentially fatal arrhythmias. The sudden deaths reported appear to be related to dose-dependent ventricular repolarization abnormalities. Prolonged QT interval may result in torsade de pointes, which may cause syncope, seizure, and/or death.

• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been reported in patients with resistant or intolerant CML; the majority of cases had malignant disease progression, high WBC counts, and/or dehydration.

Disease-related concerns:

• Gastrectomy: Consider alternative therapy or a dosage increase (with more frequent monitoring) in patients with total gastrectomy (nilotinib exposure is reduced).

Special populations:

• Pediatrics: Growth retardation has been reported in pediatric patients with Ph+ CML in chronic phase. Patients <12 years of age at baseline experienced more pronounced growth deceleration.

• Polymorphisms: Patients with the (TA)7/(TA)7 genotype (UGT1A1*28) of UGT1A1 are at a statistically significant increase in the risk of hyperbilirubinemia compared to the (TA)6/(TA)6 and (TA)6/(TA)7 genotypes.

Dosage form specific issues:

• Lactose (Tasigna only): Capsules contain lactose; do not use with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption syndromes.

• Do not substitute: Nilotinib is available as different formulations, dosage forms, and strengths. Indications for use, dosing, and treatment populations differ between formulations; do not substitute nilotinib products on a mg-per-mg basis. A substitution of nilotinib tablets for nilotinib capsules (and vice-versa) on a mg per mg basis may result in clinically significant increase or decrease in nilotinib exposure, which may increase the risk of adverse reactions, or a decrease nilotinib effectiveness, respectively. When converting between nilotinib tablets (Danziten) and nilotinib capsules (Tasigna), utilize the manufacturer-provided dosage conversion in appropriate treatment populations.

Other warnings/precautions:

• BCR-ABL transcript monitoring: Monitor BCR-ABL transcript levels in patients eligible for treatment discontinuation using an authorized test validated to measure molecular response levels with a sensitivity of at least MR^4.5 (BCR-ABL/ABL ≤0.0032% IS). Information on authorized tests for detection and quantitation of BCR-ABL transcripts is available at http://www.fda.gov/CompanionDiagnostics.

Warnings: Additional Pediatric Considerations

With tyrosine-kinase inhibitor therapy, hyper- and hypothyroidism has been reported; pediatric-specific reports are lacking; however, thyroid function should be monitored in pediatric patients regularly during therapy since it is essential for normal growth and development (Hamnvik 2011; Kim 2010; Samis 2016)

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Tasigna: 50 mg, 150 mg, 200 mg

Tablet, Oral, as tartrate [strength expressed as base]:

Danziten: 71 mg, 95 mg

Generic Equivalent Available: US

Pricing: US

Capsules (Tasigna Oral)

50 mg (per): $231.91

150 mg (per each): $231.91

200 mg (per each): $231.91

Tablets (Danziten Oral)

71 mg (per each): $193.13

95 mg (per each): $193.13

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

Tasigna: 50 mg [DSC], 150 mg, 200 mg

Generic: 150 mg, 200 mg

Administration: Adult

Note: Nilotinib is available as different formulations, dosage forms, and strengths. Indications for use and dosing differ between formulations; do not substitute nilotinib capsules and tablets (or vice versa) on a mg-per-mg basis.

Oral: Administer twice daily with doses ~12 hours apart.

Capsules (Tasigna): Administer on an empty stomach, at least 1 hour before or 2 hours after food. Swallow whole with water. If unable to swallow whole, may empty contents into 5 mL applesauce (pureed apple) and administer within 15 minutes (do not save for later use).

Tablets (Danziten): Administer with or without food. Swallow whole with water; do not cut, crush, or chew.

Administration: Pediatric

Oral: Capsule (Tasigna): Administer twice daily with doses ~12 hours apart; swallow capsule whole with water. Administer on an empty stomach; no food should be consumed for at least 2 hours before and for at least 1 hour after a dose.

Oral administration in applesauce: If unable to swallow whole capsule, may empty contents into 5 mL applesauce (puréed apple) and administer within 15 minutes (do not save for later use).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 2]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Nilotinib: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218922s000lbl.pdf#page=37

Tasigna: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022068s035s036lbl.pdf

Use: Labeled Indications

Chronic myeloid leukemia, Philadelphia chromosome positive, chronic phase, newly diagnosed (Danziten, Tasigna):

Treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase in adults and pediatric patients ≥1 year of age. Note: Danziten is approved for the treatment of newly diagnosed Ph+ CML in chronic phase in adults only.

Chronic myeloid leukemia, Philadelphia chromosome positive, chronic or accelerated phase, previously treated (Danziten, Tasigna):

Treatment of chronic and accelerated phase Ph+ CML in adults with resistance or intolerance to prior tyrosine kinase therapy that included imatinib.

Treatment of chronic and accelerated phase Ph+ CML in pediatric patients ≥1 year of age with resistance or intolerance to prior tyrosine kinase therapy. Note: Danziten is approved for the treatment of previously treated (prior therapy including imatinib) Ph+ chronic or accelerated phase CML in adults only.

Use: Off-Label: Adult

Acute lymphoblastic leukemia, Philadelphia chromosome-positive; Gastrointestinal stromal tumor, refractory

Medication Safety Issues

Sound-alike/look-alike issues:

Nilotinib may be confused with bosutinib, cabozantinib, dasatinib, enasidenib, imatinib, momelotinib, neratinib, nilutamide, nintedanib, niraparib, PONATinib, regorafenib, SUNItinib, tepotinib, vandetanib.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

Substrate of CYP3A4 (Major), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Moderate);

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abemaciclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider Therapy Modification

Acrivastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acrivastine. Risk C: Monitor

ALfentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider Therapy Modification

Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alfuzosin. Risk C: Monitor

Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alitretinoin (Systemic). Risk C: Monitor

ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider Therapy Modification

Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor

AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of AmLODIPine. Risk C: Monitor

Antacids: May decrease serum concentration of Nilotinib. Management: Separate the administration of nilotinib and any antacid by at least 2 hours whenever possible in order to minimize the risk of a significant interaction. Risk D: Consider Therapy Modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

Apixaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Apixaban. Risk C: Monitor

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Aprepitant. Risk X: Avoid

ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor

ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor

Atogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atogepant. Risk C: Monitor

Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atorvastatin. Risk C: Monitor

Avacopan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avacopan. Risk C: Monitor

Avanafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider Therapy Modification

Avapritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider Therapy Modification

Axitinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Axitinib. Risk C: Monitor

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

Barnidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Barnidipine. Risk C: Monitor

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Benidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benidipine. Risk C: Monitor

Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor

Blonanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Blonanserin. Risk C: Monitor

Bortezomib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bortezomib. Risk C: Monitor

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bosutinib. Risk X: Avoid

Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor

Brigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider Therapy Modification

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider Therapy Modification

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor

Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider Therapy Modification

Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Topical). Risk X: Avoid

Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Buprenorphine. Risk C: Monitor

BusPIRone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of BusPIRone. Risk C: Monitor

Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cabozantinib. Risk C: Monitor

Cannabis: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor

Capivasertib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider Therapy Modification

Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Cariprazine. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a moderate CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cilostazol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Citalopram: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Citalopram. Risk C: Monitor

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

CloZAPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of CloZAPine. Risk C: Monitor

Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider Therapy Modification

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

Codeine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Codeine. Risk C: Monitor

Colchicine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider Therapy Modification

Conivaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Conivaptan. Risk C: Monitor

Copanlisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Copanlisib. Risk C: Monitor

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

Crizotinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Crizotinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Crizotinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor

CYP3A4 Inducers (Moderate): May decrease serum concentration of Nilotinib. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Nilotinib. Risk X: Avoid

CYP3A4 Inhibitors (Strong): May increase serum concentration of Nilotinib. Management: Avoid if possible. If coadministration cannot be avoided, nilotinib dose adjustments are recommended and depend on the dosage form of nilotinib used and indication treated. See full monograph for details. Risk D: Consider Therapy Modification

Dabrafenib: May increase QTc-prolonging effects of Nilotinib. Nilotinib may increase serum concentration of Dabrafenib. Dabrafenib may decrease serum concentration of Nilotinib. Nilotinib may increase active metabolite exposure of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Also monitor for decreased nilotinib efficacy and increased dabrafenib adverse effects. Risk C: Monitor

Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider Therapy Modification

Daridorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Darifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Darifenacin. Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Deflazacort: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

DiazePAM: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor

Diazoxide Choline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor

Dienogest: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dienogest. Risk C: Monitor

DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DilTIAZem. Risk C: Monitor

DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOCEtaxel. Risk C: Monitor

Domperidone: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Domperidone. Risk X: Avoid

DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DroNABinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor

Ebastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ebastine. Risk C: Monitor

Elacestrant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elacestrant. Risk X: Avoid

Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor

Eletriptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eletriptan. Risk X: Avoid

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with moderate CYP3A4 inhibitors, elexacaftor/tezacaftor/ivacaftor should be given in the morning, every other day. Ivacaftor alone should be given in the morning, every other day on alternate days. Risk D: Consider Therapy Modification

Eliglustat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider Therapy Modification

Encorafenib: May increase QTc-prolonging effects of Nilotinib. Nilotinib may increase serum concentration of Encorafenib. Encorafenib may decrease serum concentration of Nilotinib. Risk X: Avoid

Ensartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ensartinib. Risk X: Avoid

Entrectinib: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Entrectinib. Risk X: Avoid

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider Therapy Modification

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor

Erlotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erlotinib. Risk C: Monitor

Erythromycin (Systemic): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Erythromycin (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Escitalopram: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor

Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eszopiclone. Risk C: Monitor

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Etravirine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Etravirine. Risk C: Monitor

Everolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Everolimus. Risk C: Monitor

Fedratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fedratinib. Risk C: Monitor

Felodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Felodipine. Risk C: Monitor

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider Therapy Modification

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Finerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Finerenone. Risk C: Monitor

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid

Fluconazole: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Fluorouracil Products: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Nasal). Risk C: Monitor

Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor

Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosamprenavir. Risk C: Monitor

Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosaprepitant. Risk X: Avoid

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Gepirone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider Therapy Modification

Gepotidacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepotidacin. Risk C: Monitor

Gilteritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gilteritinib. Risk C: Monitor

Glasdegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Glasdegib. Risk C: Monitor

Grapefruit Juice: May increase serum concentration of Nilotinib. Risk X: Avoid

GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider Therapy Modification

Haloperidol: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Histamine H2 Receptor Antagonists: May decrease serum concentration of Nilotinib. Management: The nilotinib dose should be given 10 hours after or 2 hours before the H2 receptor antagonist in order to minimize the risk of a significant interaction. Risk D: Consider Therapy Modification

HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of HYDROcodone. Risk C: Monitor

Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider Therapy Modification

Ifosfamide: CYP3A4 Inhibitors (Moderate) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor

Iloperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Iloperidone. Risk C: Monitor

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease serum concentration of Nilotinib. Management: Avoid this combination. Histamine H2 receptor antagonists (H2RAs) given 10 hours before or 2 hours after nilotinib, or antacids given 2 hours before or 2 hours after nilotinib are acceptable alternatives. Risk X: Avoid

Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor

Isavuconazonium Sulfate: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Moderate) may increase isavuconazole serum concentrations. Risk C: Monitor

Isradipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Isradipine. Risk C: Monitor

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivabradine. Risk X: Avoid

Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions may be required; consult full drug interaction monograph content for age- and weight-specific dosage recommendations. Risk D: Consider Therapy Modification

Ivosidenib: Nilotinib may increase QTc-prolonging effects of Ivosidenib. Nilotinib may increase serum concentration of Ivosidenib. Risk X: Avoid

Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ixabepilone. Risk C: Monitor

Lapatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lapatinib. Risk C: Monitor

Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Larotrectinib. Risk C: Monitor

Lefamulin: May increase QTc-prolonging effects of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification

Lemborexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lemborexant. Risk X: Avoid

Leniolisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Leniolisib. Risk C: Monitor

Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lercanidipine. Risk C: Monitor

Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levamlodipine. Risk C: Monitor

Levoketoconazole: QT-prolonging CYP3A4 Substrates may increase QTc-prolonging effects of Levoketoconazole. Levoketoconazole may increase serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid

Levomethadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomethadone. Risk C: Monitor

Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomilnacipran. Risk C: Monitor

Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lidocaine (Systemic). CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. Risk C: Monitor

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Lomitapide: Nilotinib may increase serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent nilotinib; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk X: Avoid

Lovastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lovastatin. Risk C: Monitor

Lumateperone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification

Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification

Macitentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Macitentan. Risk C: Monitor

Manidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Manidipine. Risk C: Monitor

Maraviroc: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Maraviroc. Risk C: Monitor

Mavacamten: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor, and reduce the mavacamten dose by one dose level if initiating a moderate CYP3A4 inhibitor. Avoid initiating moderate CYP3A4 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification

Mavorixafor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavorixafor. Risk C: Monitor

Meperidine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Meperidine. Risk C: Monitor

MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor

Methysergide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methysergide. Risk X: Avoid

Midazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider Therapy Modification

Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mirodenafil. Risk C: Monitor

Mitapivat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider Therapy Modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Naldemedine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naldemedine. Risk C: Monitor

Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nalfurafine. Risk C: Monitor

Naloxegol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider Therapy Modification

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Neratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Neratinib. Risk C: Monitor

NIFEdipine (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine (Topical). Risk C: Monitor

NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine. Risk C: Monitor

NiMODipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NiMODipine. Risk C: Monitor

Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nirogacestat. Risk X: Avoid

Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nisoldipine. Risk X: Avoid

Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nitrendipine. Risk C: Monitor

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

Olaparib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider Therapy Modification

Oliceridine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Oliceridine. Risk C: Monitor

Olmutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor

Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider Therapy Modification

Ondansetron: May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor

PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor

PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor

Pacritinib: Nilotinib may increase serum concentration of Pacritinib. Pacritinib may decrease serum concentration of Nilotinib. Risk C: Monitor

Palbociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palbociclib. Risk C: Monitor

Palovarotene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider Therapy Modification

Panobinostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Panobinostat. Risk C: Monitor

PAZOPanib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of PAZOPanib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider Therapy Modification

Pentamidine (Systemic): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider Therapy Modification

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimavanserin. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid

Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid

Pirtobrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pirtobrutinib. Risk C: Monitor

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

PONATinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PONATinib. Risk C: Monitor

Posaconazole: May increase serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid

Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification

Prazepam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Prazepam. Risk C: Monitor

Praziquantel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Praziquantel. Risk C: Monitor

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

QT-prolonging Agents (Highest Risk): May increase QTc-prolonging effects of Nilotinib. Risk X: Avoid

QT-prolonging Antidepressants (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor

QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May increase QTc-prolonging effects of Nilotinib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase serum concentration of Nilotinib. Risk X: Avoid

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Nilotinib may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Nilotinib. Management: Avoid concomitant use of nilotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, nilotinib dose reductions are required. Monitor patients for nilotinib toxicities including QTc prolongation and arrhythmias. Risk D: Consider Therapy Modification

Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

Ranolazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider Therapy Modification

Red Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Red Yeast Rice. Risk C: Monitor

Regorafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Regorafenib. Risk C: Monitor

Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Repotrectinib. Risk X: Avoid

Ribociclib: Nilotinib may increase QTc-prolonging effects of Ribociclib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider Therapy Modification

Rifabutin: May decrease serum concentration of Nilotinib. Nilotinib may increase serum concentration of Rifabutin. Risk C: Monitor

Rimegepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider Therapy Modification

RisperiDONE: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor

Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Rupatadine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rupatadine. Risk C: Monitor

Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Salmeterol. Risk C: Monitor

SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SAXagliptin. Risk C: Monitor

Selumetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider Therapy Modification

Sertindole: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Sertindole. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Sertindole. Risk X: Avoid

Sildenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sildenafil. Risk C: Monitor

Silodosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Silodosin. Risk C: Monitor

Simeprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simeprevir. Risk X: Avoid

Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Simvastatin. Risk C: Monitor

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider Therapy Modification

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m² when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification

Solifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Solifenacin. Risk C: Monitor

Sonidegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider Therapy Modification

Sparsentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sparsentan. Risk C: Monitor

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor

SUFentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUFentanil. Risk C: Monitor

SUNItinib: QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of SUNItinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of SUNItinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor

Suvorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider Therapy Modification

Suzetrigine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suzetrigine. Management: Reduce suzetrigine dose as follows: initiate with 100 mg for 1 dose; then 12 hours after first dose, give 50 mg every 12 hours for doses 2, 3, and 4; then 50 mg every 24 hours for dose 5 and thereafter. Risk D: Consider Therapy Modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Tadalafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tadalafil. Risk C: Monitor

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor

Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider Therapy Modification

Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor

Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor

Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with moderate CYP3A4 inhibitors, give tezacaftor/ivacaftor in the morning, every other day; give ivacaftor in the morning, every other day on alternate days. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph Risk D: Consider Therapy Modification

Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid

Thiotepa: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor

Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ticagrelor. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor

Tilidine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tilidine. Risk C: Monitor

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Tolterodine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolterodine. Risk C: Monitor

Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider Therapy Modification

Trabectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Trabectedin. Risk C: Monitor

TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of TraMADol. Risk C: Monitor

TraZODone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraZODone. Risk C: Monitor

Tretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tretinoin (Systemic). Risk C: Monitor

Triamcinolone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor

Triazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Udenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Udenafil. Risk C: Monitor

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor

Vamorolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vamorolone. Risk C: Monitor

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification

Vardenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification

Venetoclax: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Verapamil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Verapamil. Risk C: Monitor

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vilazodone. Risk C: Monitor

VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinBLAStine. Risk C: Monitor

VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinCRIStine. Risk C: Monitor

Vindesine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vindesine. Risk C: Monitor

Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Vinflunine. Risk C: Monitor

Voclosporin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vorapaxar. Risk C: Monitor

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification

Zopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zopiclone. Risk C: Monitor

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Zuranolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zuranolone. Risk C: Monitor

Food Interactions

Capsule (Tasigna): Compared to the fasted state, AUC is increased 82% when administered 30 minutes after a high-fat meal (800 to 1,000 calories, with 500 to 600 calories from fat, 150 calories from protein, and 250 calories from carbohydrates). Management: Administer at least 1 hour before or 2 hours after food.

Tablet (Danziten): Compared to a fasted state in healthy subjects, there were no clinically significant differences in nilotinib exposure observed following administration (142 mg or 190 mg) with a high-fat meal (800 to 1,000 calories, with 50% fat) or a low-fat meal (400 to 500 kcal, with 25% fat).

Grapefruit and grapefruit juice may result in increased concentrations of nilotinib and potentiate QT prolongation. Management: Avoid concomitant administration with grapefruit products; monitor for increased effects/toxicity with concomitant use.

Reproductive Considerations

Verify pregnancy status prior to initiating therapy in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 14 days after the last nilotinib dose.

Changes in menstrual patterns have been reported with tyrosine kinase inhibitor (TKI) therapy (Yu 2019).

Based on the mechanism of action, TKIs have the potential to adversely affect fertility by acting on receptors in the ovaries or testes; primarily when administered prior to puberty in males. Although there are cases showing difficulty conceiving, successful pregnancies have also been reported. Fertility data related to long-term TKI use are limited. Recommendations are available for fertility preservation prior to TKI treatment (ASCO [Oktay 2018]; Madabhavi 2019; Rambhatla 2021).

Patients planning to become pregnant but currently receiving a TKI should minimize the risk of first trimester exposure (Rambhatla 2021). Discontinuing TKI for chronic myelogenous leukemia can be considered if the patient is eligible for a tumor-free remission, allowing a washout period before attempting to conceive (Baccarani 2019; ELN [Hochhaus 2020]; Madabhavi 2019). Because the time to conception can be highly variable, treatment may also be discontinued at the first positive pregnancy test, prior to organogenesis in select patients (Abruzzese 2020).

Outcome data following male use of nilotinib prior to conception are available (Assi 2021; Carlier 2017; Szakács 2020). Based on available data, nilotinib does not need to be stopped prior to conception in patients planning to father a child (Abruzzese 2020; Baccarani 2019; ELN [Hochhaus 2020]).

Pregnancy Considerations

Nilotinib crosses the placenta (Chelysheva 2018b).

Limited outcome data following use of nilotinib for the treatment of chronic myeloid leukemia (CML) during pregnancy are available (Assi 2021; Barkoulas 2018; Dou 2019; Lasica 2019; Madabhavi 2019). Based on data from animal reproduction studies and the mechanism of action, nilotinib may cause fetal harm if administered during pregnancy.

Treatment of CML in pregnant patients should be individualized based on gestational age, hematologic parameters, and clinical condition at presentation. If pregnancy is detected in the first trimester in patients already receiving a tyrosine kinase inhibitor (TKI), treatment should be discontinued as soon as pregnancy is confirmed. Treatments other than a TKI are recommended in pregnant patients not eligible for a tumor-free remission. If a TKI is needed, nilotinib may be considered after the first trimester; however, second generation TKIs such as nilotinib have less pregnancy outcome information and should be avoided until after delivery when possible. Close maternal and fetal monitoring is recommended (Abruzzese 2020; BSH [Smith 2020]; ELN [Hochhaus 2020]; Madabhavi 2019).

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).

Breastfeeding Considerations

Nilotinib is present in breast milk (Chelysheva 2018a).

Nilotinib breast milk concentrations were evaluated in a lactating patient diagnosed with chronic myeloid leukemia (CML) prior to pregnancy. Treatment was discontinued after the fourth week of pregnancy and during the postpartum period while breastfeeding. A single dose of nilotinib 400 mg/day was administered at 28 months postpartum. Breast milk was sampled at specified intervals from 1 to 24 hours after the maternal dose. The maximum concentration of nilotinib in breast milk (129 ng/mL) occurred 4 hours after the maternal dose (Chelysheva 2018a).

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 14 days after the last nilotinib dose. Patients diagnosed with CML requiring a tyrosine kinase inhibitor may consider short-term breastfeeding for the first 2 to 5 days postpartum to provide the benefits of colostrum to the newborn prior to starting or restarting therapy (Abruzzese 2020; Madabhavi 2019).

Dietary Considerations

Avoid concomitant administration with grapefruit products.

Monitoring Parameters

Philadelphia chromosome status (prior to treatment); CBC with differential (every 2 weeks for the first 2 months, then monthly, or as clinically indicated); electrolytes (including potassium, calcium, and magnesium; at baseline and periodically during treatment); lipid profile and glucose (at baseline and periodically during the first year, then at least yearly), hepatic function (ALT/AST, bilirubin, alkaline phosphatase; baseline and monthly or as clinically indicated); serum lipase/amylase (baseline and monthly or as clinically indicated), uric acid (baseline); bone marrow assessments (as indicated). Evaluate pregnancy status prior to initiating therapy in patients who could become pregnant. Monitor ECG and QTc (at baseline, 7 days after treatment initiation or dosage adjustments, and periodically thereafter). Assess patients for cardiovascular risk factors prior to treatment initiation and monitor cardiovascular status of patients during treatment. Monitor for signs/symptoms of cardiovascular events, bleeding/hemorrhage, and/or fluid retention (including symptoms of respiratory or cardiac compromise). Monitor bone growth and development in pediatric patients. Monitor adherence.

Chronic myeloid leukemia: In patients who discontinue nilotinib after a sustained molecular response (MR^4.5), monitor BCR-ABL transcript levels and CBC with differential monthly for 1 year, then every 6 weeks for the second year, and every 12 weeks thereafter. Upon the loss of MR^4.0(corresponding to BCR-ABL/ABL ≤0.01% IS) during the treatment-free phase, monitor BCR-ABL transcript levels every 2 weeks until the BCR-ABL levels remain lower than major molecular response (MMR, corresponding to MR^3.0 or BCR-ABL/ABL ≤0.1% IS) for 4 consecutive measurements; patients can then proceed to the original monitoring schedule. In patients who have reinitiated nilotinib after loss of molecular response, monitor CBC and BCR-ABL transcript levels every 4 weeks until a major molecular response (MR^4.0) is re-established, and then every 12 weeks thereafter. BCR-ABL kinase domain mutation testing should be performed if major molecular response is not achieved after 3 months of therapy reinitiation.

Thyroid function testing (Hamnvik 2011):

Preexisting levothyroxine therapy: Obtain baseline thyroid-stimulating hormone (TSH) levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months.

Without preexisting thyroid hormone replacement: TSH at baseline, then monthly for 4 months, then every 2 to 3 months.

Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; repeat assessment every 3 months for the first year and then every 6 to 12 months thereafter (ASCO [Armenian 2017]; ESC [Lyon 2022]). Assess QTc at baseline, then at 2 to 4 weeks, as well as 2 weeks after any dose increase; check ECG at baseline, every 3 months for the first year and every 6 to 12 months thereafter. Consider baseline echocardiography in all patients; repeat every 3 months for high- and very high-risk patients (ESC [Lyon 2022]).

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Nilotinib is a selective tyrosine kinase inhibitor that targets BCR-ABL kinase, c-KIT and platelet derived growth factor receptor (PDGFR); it does not have activity against the SRC family. Nilotinib inhibits BCR-ABL mediated proliferation of leukemic cell lines by binding to the ATP-binding site of BCR-ABL and inhibiting tyrosine kinase activity. Nilotinib has activity in imatinib-resistant BCR-ABL kinase mutations.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Capsule: Compared to the fasted state, AUC is increased 82% when administered 30 minutes after a high-fat meal (800 to 1,000 calories, with 500 to 600 calories from fat, 150 calories from protein, and 250 calories from carbohydrates).

Protein binding: ~98%.

Metabolism: Hepatic; oxidation and hydroxylation, primarily via CYP3A4 (minor extent via CYP2C8) to inactive metabolites.

Bioavailability: Capsule: ~50% (when compared to oral solution with pH of 1.2 to 1.3); two 200 mg capsules sprinkled on applesauce was determined to be bioequivalent to two 200 mg intact capsules.

Half-life elimination: Capsule: ~17 hours; Tablet: ~14 hours.

Time to peak: Capsule: 3 hours; Tablet (following a single 190 mg dose in a fasted state): 2.7 hours (range: 1 to 4.7 hours).

Excretion: Feces (93%; 69% as parent drug).

Clearance: Capsule: ~29 L/hour.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Following a single 200 mg nilotinib capsule dose (95 mg equivalent nilotinib tablet dose), the mean AUC increased 1.4-fold in patients with Child-Pugh classes A and B impairment and 1.6-fold in patients with Child-Pugh class C impairment compared to subjects with normal hepatic function.

Total gastrectomy: Median steady-state trough concentrations are decreased by 53% (compared to patients who had not undergone gastric surgeries).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Tasigna;
(AR) Argentina: Henilot | Tasigna;
(AT) Austria: Tasigna;
(AU) Australia: Nilotinib;
(BG) Bulgaria: Tasigna;
(BR) Brazil: Tasigna;
(CI) Côte d'Ivoire: Tasigna;
(CL) Chile: Tasigna;
(CO) Colombia: Tasigna;
(DE) Germany: Tasigna;
(DO) Dominican Republic: Tasigna;
(EC) Ecuador: Nilotinib | Niloxel | Tasigna;
(EE) Estonia: Tasigna;
(EG) Egypt: Tasigna;
(ET) Ethiopia: Tasigna;
(GR) Greece: Tasigna;
(HK) Hong Kong: Tasigna;
(HR) Croatia: Tasigna;
(IN) India: Tasigna;
(JO) Jordan: Tasigna;
(JP) Japan: Tasigna;
(KE) Kenya: Tasigna;
(KR) Korea, Republic of: Tasigna;
(KW) Kuwait: Tasigna;
(LB) Lebanon: Tasigna;
(LT) Lithuania: Tasigna;
(MA) Morocco: Tasigna;
(MX) Mexico: Tasigna;
(NL) Netherlands: Tasigna;
(NZ) New Zealand: Tasigna;
(PE) Peru: Tasigna;
(PK) Pakistan: Nitonib;
(PR) Puerto Rico: Tasigna;
(PT) Portugal: Tasigna;
(PY) Paraguay: Tasigna;
(QA) Qatar: Tasigna;
(RU) Russian Federation: Nilotinib | Nilotinib nativ | Tasigna;
(SA) Saudi Arabia: Tasigna;
(SE) Sweden: Tasigna;
(TN) Tunisia: Tasigna;
(TR) Turkey: Tasigna;
(TW) Taiwan: Tasigna;
(UG) Uganda: Tasigna;
(ZA) South Africa: Tasigna;
(ZW) Zimbabwe: Tasigna

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Topic 9448 Version 430.0

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Nilotinib: Drug information