Version July 2025
Hutchinson-Gilford progeria syndrome: Oral: Initial: 115 mg/m2/dose twice daily for 4 months, then increase to 150 mg/m2/dose twice daily. Note: Round the total daily dose to the nearest 25 mg increment.
Processing-deficient progeroid laminopathies, treatment: Note: Indicated for use in patients with heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations: Oral: Initial: 115 mg/m2/dose twice daily for 4 months, then increase to 150 mg/m2/dose twice daily. Note: Round the total daily dose to the nearest 25 mg increment.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Missed doses: A missed dose may be taken with food up to 8 hours prior to the next scheduled dose. If it is <8 hours prior to the next scheduled dose, resume with the next scheduled dose.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
GI: Repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss following a dose increase to 150 mg/m2/dose: Reduce dose to 115 mg/m2/dose twice daily.
QTc interval prolongation: Hold lonafarnib if the QTc interval is ≥500 msec. It may be restarted at the same dose when the QTC interval is <470 msec.
Refer to adult dosing.
(For additional information see "Lonafarnib: Pediatric drug information")
Hutchinson-Gilford progeria syndrome (HGPS):
Children and Adolescents:
BSA <0.39 m2: Use not recommended; an appropriate dosage strength is not available.
BSA ≥0.39 m2:
BSA-directed dosing: Initial: Oral: 115 mg/m2/dose twice daily for 4 months then increase to 150 mg/m2/dose twice daily. Note: Round the total daily dose to the nearest 25 mg increment.
BSA-band fixed dose: Dosing based on an initial dose of 115 mg/m2/dose twice daily for 4 months then increase to 150 mg/m2/dose twice daily.
Initial dose (115 mg/m2/dose twice daily): Continue for 4 months.
0.39 to 0.48 m2: Oral: 50 mg twice daily.
0.49 to 0.59 m2: Oral: 75 mg in the morning and 50 mg in the evening.
0.6 to 0.7 m2: Oral: 75 mg twice daily.
0.71 to 0.81 m2: Oral: 100 mg in the morning and 75 mg in the evening.
0.82 to 0.92 m2: Oral: 100 mg twice daily.
0.93 to 1 m2: Oral: 125 mg in the morning and 100 mg in the evening.
Increased dose (150 mg/m2/dose twice daily):
0.39 to 0.45 m2: Oral: 75 mg in the morning and 50 mg in the evening.
0.46 to 0.54 m2: Oral: 75 mg twice daily.
0.55 to 0.62 m2: Oral: 100 mg in the morning and 75 mg in the evening.
0.63 to 0.7 m2: Oral: 100 mg twice daily.
0.71 to 0.79 m2: Oral: 125 mg in the morning and 100 mg in the evening.
0.8 to 0.87 m2: Oral: 125 mg twice daily.
0.88 to 0.95 m2: Oral: 150 mg in the morning and 125 mg in the evening.
0.96 to 1 m2: Oral: 150 mg twice daily.
Processing-deficient progeroid laminopathies, treatment:
Note: Indicated for use in patients with heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations:
Children and Adolescents:
BSA <0.39 m2: Use not recommended; an appropriate dosage strength is not available.
BSA ≥0.39 m2:
BSA-directed dosing: Oral: Initial: 115 mg/m2/dose twice daily for 4 months then increase to 150 mg/m2/dose twice daily. Note: Round the total daily dose to the nearest 25 mg increment.
BSA-band fixed dose: Note: Dosing based on initial dose of 115 mg/m2/dose twice daily for 4 months then increase to 150 mg/m2/dose twice daily:
Initial dose (115 mg/m2/dose twice daily): Continue for 4 months.
0.39 to 0.48 m2: Oral: 50 mg twice daily.
0.49 to 0.59 m2: Oral: 75 mg in the morning and 50 mg in the evening.
0.6 to 0.7 m2: Oral: 75 mg twice daily.
0.71 to 0.81 m2: Oral: 100 mg in the morning and 75 mg in the evening.
0.82 to 0.92 m2: Oral: 100 mg twice daily.
0.93 to 1 m2: Oral: 125 mg in the morning and 100 mg in the evening.
Increased dose (150 mg/m2/dose twice daily):
0.39 to 0.45 m2: Oral: 75 mg in the morning and 50 mg in the evening.
0.46 to 0.54 m2: Oral: 75 mg twice daily.
0.55 to 0.62 m2: Oral: 100 mg in the morning and 75 mg in the evening.
0.63 to 0.7 m2: Oral: 100 mg twice daily.
0.71 to 0.79 m2: Oral: 125 mg in the morning and 100 mg in the evening.
0.8 to 0.87 m2: Oral: 125 mg twice daily.
0.88 to 0.95 m2: Oral: 150 mg in the morning and 125 mg in the evening.
0.96 to 1 m2: Oral: 150 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity:
Children and Adolescents: Oral:
|
Adverse reaction |
Severity |
Lonafarnib dose modification |
|---|---|---|
|
Gastrointestinal |
Repeated episodes of vomiting and/or diarrhea resulting in dehydration or weight loss following dose increase |
Reduce dose to 115 mg/m2/dose twice daily. |
|
QTc prolongation |
QTc ≥500 msec |
Hold lonafarnib. Restart at same dose when QTc <470 msec. Correct serum electrolyte abnormalities. |
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Electrolyte abnormalities commonly occurred with lonafarnib during clinical trials; reported abnormalities include hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hypocalcemia, hypokalemia, and hyponatremia. In one trial, the majority of electrolyte abnormalities were grades 1 or 2 (Ref); cases of grades 3 and 4 hypokalemia have also been described (Ref). According to the manufacturer, electrolyte abnormalities often improve despite continued administration of lonafarnib (Ref).
Onset: Varied; presence of electrolyte abnormalities has been reported throughout the course of therapy during clinical trials (Ref)
GI effects, including nausea, vomiting, and diarrhea, are the most commonly reported adverse events associated with lonafarnib. While the majority of reported cases were mild or moderate, severe (grades 3/4) vomiting and diarrhea have occurred (Ref). Patients may also experience subsequent dehydration, decreased appetite, and weight loss. May result in treatment interruption, dosage adjustment, or discontinuation (Ref); patients may require the addition of symptomatic or prophylactic treatment of diarrhea and nausea (Ref).
Onset: Varied; presence of GI effects has been reported throughout the course of therapy during clinical trials (Ref)
Elevations in liver enzymes, including increased serum alanine aminotransferase and increased serum aspartate aminotransferase, commonly occurred during clinical trials. The majority of cases were grades 1 or 2; however, grade 3 elevations may also occur (Ref). According to the manufacturer, liver enzyme elevations often improve despite continued administration of lonafarnib (Ref).
Onset: Varied; presence of elevated liver enzymes has been reported throughout the course of therapy during clinical trials (Ref).
Lonafarnib use may result in mild bone marrow depression including a decrease in absolute neutrophil count, decreased hematocrit, decreased hemoglobin, decreased white blood cell count, and lymphopenia. According to the manufacturer, hematologic parameters often improve despite continued administration of lonafarnib (Ref).
Onset: Varied; evidence of bone marrow suppression has been reported throughout the course of therapy during clinical trials (Ref).
Hypertension, including new-onset hypertension, was reported in clinical trials. According to the manufacturer, 35% of patients at baseline had either a systolic or diastolic blood pressure or both above the 95th percentile while 29% exhibited hypertension on ≥3 occasions during treatment with lonafarnib; 8% of patients who were normotensive at baseline had either a systolic or diastolic blood pressure or both above the 95th percentile at the end of treatment.
Mechanism: Exact mechanism is unknown; impact of disease process must be considered.
Ocular changes (ophthalmic signs and symptoms), including conjunctivitis, corneal opacity, decreased visual acuity, keratitis, and watery eyes, commonly occurred during clinical trials. In addition, retinal toxicity has been reported in monkeys at plasma drug exposures similar to that achieved with the human dose.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Cerebral ischemia (11%), hypertension (29%)
Dermatologic: Skin rash (11%)
Endocrine & metabolic: Decreased serum bicarbonate (33%), electrolyte disorder (43%; including hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hypokalemia, hyponatremia), weight loss (37%)
Gastrointestinal: Abdominal pain (48%), anorexia (≤53%), constipation (22%), decreased appetite (≤53%), diarrhea (81%; including severe diarrhea), nausea (56%), vomiting (90%; including severe vomiting)
Hematologic & oncologic: Bone marrow depression (35%; including decrease in absolute neutrophil count, decreased hematocrit, decreased hemoglobin, decreased white blood cell count, lymphocytopenia)
Hepatic: Increased serum alanine aminotransferase (27%), increased serum aspartate aminotransferase (35%)
Infection: Infection (78%)
Nervous system: Fatigue (51%), headache (37%)
Neuromuscular & skeletal: Musculoskeletal pain (48%)
Ophthalmic: Ophthalmic signs and symptoms (ocular changes: 24%; including conjunctivitis, corneal opacity, decreased visual acuity, keratitis, watery eyes)
Respiratory: Cough (33%), epistaxis (21%), rhinitis (19%), upper respiratory tract infection (51%)
Miscellaneous: Fever (14%)
1% to 10%:
Dermatologic: Pruritus (8%)
Endocrine & metabolic: Dehydration (5%)
Gastrointestinal: Flatulence (6%), stomatitis (8%)
Nervous system: Depressed mood (5%)
Concomitant use with strong CYP3A inhibitors, strong or moderate CYP3A inducers, midazolam, lovastatin, simvastatin, or atorvastatin.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• QTc interval prolongation: Lonafarnib can increase the risk of Torsades de pointes, serious arrhythmias, or sudden death. Avoid use in patients with a history of cardiac arrhythmias, combination with other drugs known or suspected to prolong QTc interval, and situations that may increase risks of Torsades de pointes or sudden death including symptomatic bradycardia, hypokalemia, or hypomagnesemia.
• Renal effects: Although not reported in humans, nephrotoxicity has occurred in animals; therefore, the manufacturer recommends regular monitoring of renal function.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zokinvy: 50 mg, 75 mg
No
Capsules (Zokinvy Oral)
50 mg (per each): $1,033.76
75 mg (per each): $1,550.64
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Oral: Administer with the morning and evening meals. Swallow capsules whole with water; do not chew. For patients unable to swallow capsules whole, the entire contents of each capsule may be emptied and mixed with 5 to 10 mL of Ora Blend SF, Ora-Plus, or orange juice (avoid juice containing grapefruit or Seville oranges), or 1 to 2 teaspoonfuls of applesauce; mix well and administer entire mixture within ~10 minutes of preparing. A fresh mixture must be prepared for each dose.
Oral: Capsules: Administer with the morning and evening meals. Swallow capsules whole with plenty of water; do not chew capsules.
Oral administration in applesauce: For patients who are unable to swallow whole capsules, capsules may be opened and the entire contents mixed with 1 to 2 teaspoonfuls of applesauce; mix well. Administer the entire mixture within 10 minutes of preparing. A fresh mixture must be prepared for each dose.
Oral administration in liquid: For patients who are unable to swallow whole capsules, capsules may be opened and the entire contents mixed with 5 to 10 mL of Ora Blend SF, Ora-Plus, or orange juice (avoid juice containing grapefruit or Seville oranges); mix well. Administer the entire mixture within 10 minutes of preparing. A fresh mixture must be prepared for each dose.
Missed dose: Administer missed dose as soon as possible with food. If the next scheduled dose is due in <8 hours, skip the missed dose and resume the regular dosing schedule.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Lonafarnib may cause reproductive toxicity and teratogenicity.
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.
Hutchinson-Gilford progeria syndrome: To reduce the risk of mortality in Hutchinson-Gilford progeria syndrome in patients ≥12 months of age with a BSA ≥0.39 m2.
Processing-deficient progeroid laminopathies: Treatment of processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations in patients ≥12 months of age with a BSA ≥0.39 m2.
Limitations of use: Not indicated for other progeroid syndromes or processing-proficient progeroid laminopathies.
Lonafarnib may be confused with lapatinib, larotrectinib, lenvatinib, lorlatinib.
Substrate of CYP1A2 (Minor), CYP2A6 (Minor), CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP2E1 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (Weak), CYP3A4 (Strong);
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.
Abemaciclib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. Risk D: Consider Therapy Modification
Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Acalabrutinib. Risk X: Avoid
Acrivastine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Acrivastine. Risk C: Monitor
Adagrasib: Lonafarnib may increase QTc-prolonging effects of Adagrasib. Adagrasib may increase serum concentration of Lonafarnib. Lonafarnib may increase serum concentration of Adagrasib. Risk X: Avoid
Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider Therapy Modification
ALfentanil: CYP3A4 Inhibitors (Strong) may increase serum concentration of ALfentanil. Management: If use of alfentanil and strong 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 (Strong) may increase serum concentration of Alfuzosin. Risk X: Avoid
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Almotriptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Almotriptan. Management: Limit initial almotriptan dose to 6.25 mg and maximum dose to 12.5 mg in any 24-period when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. Risk D: Consider Therapy Modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase serum concentration of Alosetron. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of ALPRAZolam. Risk X: Avoid
Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase serum concentration of AmLODIPine. Risk C: Monitor
Apixaban: CYP3A4 Inhibitors (Strong) may increase serum concentration of Apixaban. Risk C: Monitor
Aprepitant: Lonafarnib may increase serum concentration of Aprepitant. Aprepitant may increase serum concentration of Lonafarnib. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, initial starting dose, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Artemether and Lumefantrine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. Risk C: Monitor
Asciminib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Asciminib. Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended atogepant dose is 10 mg once daily with a concurrent strong CYP3A4 inhibitor. If used for treatment of chronic migraine, concurrent use of atogepant with strong CYP3A4 inhibitors should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: Lonafarnib may increase serum concentration of Atorvastatin. Risk X: Avoid
Avacopan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk D: Consider Therapy Modification
Barnidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Barnidipine. Risk X: Avoid
Beclomethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Beclomethasone (Systemic). Risk C: Monitor
Bedaquiline: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Bedaquiline. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Bedaquiline. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Benidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Benidipine. Risk C: Monitor
Benperidol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Benperidol. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Betamethasone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Nasal). Risk C: Monitor
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Ophthalmic). Risk C: Monitor
Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Systemic). Risk C: Monitor
Betamethasone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Betamethasone (Topical). Risk C: Monitor
Bitter Orange: May increase serum concentration of Lonafarnib. Risk X: Avoid
Blonanserin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Blonanserin. Risk X: Avoid
Bortezomib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bosutinib. Risk X: Avoid
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider Therapy Modification
Brigatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider Therapy Modification
Bromocriptine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bromocriptine. Management: Consider alternatives to the use of bromocriptine with strong CYP3A4 inhibitors. If combined, monitor closely for increased bromocriptine toxicities and consider bromocriptine dose reductions. Risk D: Consider Therapy Modification
Bromperidol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Bromperidol. Risk C: Monitor
Brotizolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Brotizolam. Risk C: Monitor
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Nasal). Risk C: Monitor
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider Therapy Modification
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Strong) may increase serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. Dose adjustments of buspirone or a strong CYP3A4 inhibitor should be based on clinical assessment. Risk D: Consider Therapy Modification
Butorphanol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Butorphanol. Risk C: Monitor
Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Risk D: Consider Therapy Modification
Cabozantinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider Therapy Modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Calcitriol (Systemic). Risk C: Monitor
Cannabidiol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cannabidiol. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Capivasertib. Management: Avoid concomitant use of capivasertib with strong CYP3A4 inhibitors when possible. If combined, 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
Capmatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Capmatinib. Risk C: Monitor
Cariprazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a strong 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
ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase serum concentration of ChlordiazePOXIDE. Risk C: Monitor
Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ciclesonide (Oral Inhalation). Risk C: Monitor
Cilnidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cilnidipine. Risk C: Monitor
Cilostazol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cinacalcet. Risk C: Monitor
Cisapride: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Cisapride. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Cisapride. Risk X: Avoid
Citalopram: May increase QTc-prolonging effects of QT-prolonging Strong 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
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentration of CloBAZam. CYP2C19 Inhibitors (Weak) may increase active metabolite exposure of CloBAZam. Risk C: Monitor
ClonazePAM: CYP3A4 Inhibitors (Strong) may increase serum concentration of ClonazePAM. Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Colchicine. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of P-gp inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Conivaptan. Risk X: Avoid
Copanlisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider Therapy Modification
Cortisone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cortisone. Risk C: Monitor
Crizotinib: 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 Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, crizotinib dose adjustments are required, which vary according to indication. See full interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of CycloSPORINE (Systemic). Management: Monitor cyclosporine serum concentrations and clinical cyclosporine closely with concurrent use of any strong CYP3A4 inhibitor. Cyclosporine dose reductions and/or prolongation of the dosing interval will likely be required. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Lonafarnib. Risk X: Avoid
CYP3A4 Inducers (Strong): May decrease serum concentration of Lonafarnib. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Lonafarnib. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Lonafarnib. Risk X: Avoid
Cyproterone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Cyproterone. Risk C: Monitor
Dabrafenib: Lonafarnib may increase QTc-prolonging effects of Dabrafenib. Dabrafenib may decrease serum concentration of Lonafarnib. Risk X: Avoid
Daclatasvir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Dapoxetine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk X: Avoid
Daridorexant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Daridorexant. Risk X: Avoid
Darifenacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Darifenacin. Management: Limit the darifenacin dose to no more than 7.5 mg daily if combined with strong CYP3A4 inhibitors. Monitor patients for increased darifenacin toxicities (eg, dry mouth, constipation, headache, CNS effects) when these agents are combined. Risk D: Consider Therapy Modification
Dasatinib: 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 Dasatinib. Management: Avoid this combination if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. If taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Monitor for prolonged QT interval Risk D: Consider Therapy Modification
Deflazacort: CYP3A4 Inhibitors (Strong) 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
Delamanid: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Delamanid. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Delamanid. Management: If coadministration of delamanid with any strong CYP3A4 inhibitor is considered necessary, very frequent monitoring of ECGs is recommended throughout the full delamanid treatment period. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
DiazePAM: CYP3A4 Inhibitors (Strong) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dienogest. Risk C: Monitor
Digitoxin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Digitoxin. Risk C: Monitor
DilTIAZem: CYP3A4 Inhibitors (Strong) may increase serum concentration of DilTIAZem. Risk C: Monitor
DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. Risk D: Consider Therapy Modification
Domperidone: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Domperidone. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Domperidone. Risk X: Avoid
Doxazosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Doxazosin. Risk C: Monitor
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): CYP3A4 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
DroNABinol: CYP3A4 Inhibitors (Strong) may increase serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: Lonafarnib may increase QTc-prolonging effects of Dronedarone. Dronedarone may increase serum concentration of Lonafarnib. Lonafarnib may increase serum concentration of Dronedarone. Risk X: Avoid
Dutasteride: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dutasteride. Risk C: Monitor
Duvelisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Monitor closely for evidence of altered response to treatment. Risk D: Consider Therapy Modification
Dydrogesterone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Dydrogesterone. Risk C: Monitor
Ebastine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ebastine. CYP3A4 Inhibitors (Strong) may increase serum concentration of Ebastine. Risk C: Monitor
Efonidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Efonidipine. Risk C: Monitor
Elacestrant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elacestrant. Risk X: Avoid
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid
Elagolix: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Risk D: Consider Therapy Modification
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elbasvir and Grazoprevir. Management: Consider alternatives to this combination when possible. If combined, monitor for increased elbasvir/grazoprevir toxicities, including ALT elevations. Risk D: Consider Therapy Modification
Eletriptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Administer elexacaftor/tezacaftor/ivacaftor in the morning, twice a week, 3 to 4 days apart, with no evening doses of ivacaftor alone. Specific dosing varies by age and weight. See full monograph for details. Risk D: Consider Therapy Modification
Eliglustat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Encorafenib: Lonafarnib may increase QTc-prolonging effects of Encorafenib. Encorafenib may decrease serum concentration of Lonafarnib. Risk X: Avoid
Ensartinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: 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 Entrectinib. Risk X: Avoid
Eplerenone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eplerenone. Risk X: Avoid
Erdafitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider Therapy Modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid
Erlotinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider Therapy Modification
Erythromycin (Systemic): 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 Erythromycin (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Escitalopram: May increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
Esketamine (Injection): CYP3A4 Inhibitors (Strong) may increase serum concentration of Esketamine (Injection). Risk C: Monitor
Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase serum concentration of Estrogen Derivatives. Risk C: Monitor
Eszopiclone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Risk D: Consider Therapy Modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Etizolam. Risk C: Monitor
Everolimus: CYP3A4 Inhibitors (Strong) may increase serum concentration of Everolimus. Management: Consider avoiding use of strong CYP3A4 inhibitors with everolimus. If combined, closely monitor for increased everolimus serum concentrations and toxicities. Everolimus dose reductions will likely be required. Risk D: Consider Therapy Modification
Evogliptin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Evogliptin. Risk C: Monitor
Fedratinib: Lonafarnib may increase serum concentration of Fedratinib. Management: Avoid this combination if possible. If required, reduce fedratinib to 200 mg/day. Increase to 300 mg/day for 2 weeks after lonafarnib is discontinued, and 400 mg/day thereafter as tolerated. Monitor for lonafarnib toxicities. Risk D: Consider Therapy Modification
Felodipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Felodipine. Management: Consider using lower felodipine doses when combined with strong CYP3A4 inhibitors. Monitor patients for increased felodipine effects and toxicities (eg, hypotension, edema) when combined. Risk D: Consider Therapy Modification
FentaNYL: CYP3A4 Inhibitors (Strong) may increase serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a strong 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
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily in patients who are also receiving strong CYP3A4 inhibitors. This combination is not recommended in pediatric patients weighing 25 kg up to 35 kg. Risk D: Consider Therapy Modification
Fexinidazole: Lonafarnib may increase QTc-prolonging effects of Fexinidazole. Fexinidazole may decrease serum concentration of Lonafarnib. Lonafarnib may decrease active metabolite exposure of Fexinidazole. Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Finerenone. Risk X: Avoid
Flibanserin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Flibanserin. Management: Use of flibanserin with strong 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
Flunitrazepam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Flunitrazepam. Risk C: Monitor
Fluorouracil Products: QT-prolonging Strong 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 (Strong) may increase serum concentration of Fluticasone (Nasal). Risk X: Avoid
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentration of Fluticasone (Oral Inhalation). Management: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider Therapy Modification
Fluticasone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Fluticasone (Topical). Risk C: Monitor
Fosamprenavir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Fosaprepitant. Risk X: Avoid
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Fostamatinib. Risk C: Monitor
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
Gefitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Gepirone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gepirone. Risk X: Avoid
Gepotidacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Gepotidacin. Management: Avoid coadministration of gepotidacin and strong CYP3A4 inhibitors if possible. If coadministration cannot be avoided, conduct a baseline ECG, monitor closely for altered electrolytes, and correct electrolyte abnormalities as needed. Risk D: Consider Therapy Modification
Gilteritinib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Gilteritinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Gilteritinib. Management: Consider alternatives to the use of gilteritinib with strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. Risk D: Consider Therapy Modification
Glasdegib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Lonafarnib. Risk X: Avoid
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider Therapy Modification
Halofantrine: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Halofantrine. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Haloperidol: 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 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
Hormonal Contraceptives: CYP3A4 Inhibitors (Strong) may increase serum concentration of Hormonal Contraceptives. Risk C: Monitor
HYDROcodone: CYP3A4 Inhibitors (Strong) may increase serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Ibrutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Risk X: Avoid
Ifosfamide: CYP3A4 Inhibitors (Strong) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Iloperidone. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Imatinib: May increase serum concentration of Lonafarnib. Lonafarnib may increase serum concentration of Imatinib. Risk C: Monitor
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Imidafenacin. Risk C: Monitor
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider Therapy Modification
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid
Isradipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inhibitors (Strong) may increase serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Risk D: Consider Therapy Modification
Ivabradine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full drug interaction monograph content for age- and weight-specific recommendations. Risk D: Consider Therapy Modification
Ivosidenib: 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 Ivosidenib. Management: Avoid using strong CYP3A4 inhibitors together with ivosidenib if possible. If the combination must be used, reduce the ivosidenib dose to 250 mg once daily and monitor for increased ivosidenib toxicities, including QTc interval prolongation. Risk D: Consider Therapy Modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Ketamine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ketamine. Risk C: Monitor
Lacidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lacidipine. Risk C: Monitor
Lapatinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Larotrectinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor's half-life. Risk D: Consider Therapy Modification
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
Lemborexant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lercanidipine. Risk X: Avoid
Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levobupivacaine. Risk C: Monitor
Levoketoconazole: Lonafarnib may increase QTc-prolonging effects of Levoketoconazole. Levoketoconazole may increase serum concentration of Lonafarnib. Lonafarnib may increase serum concentration of Levoketoconazole. Risk X: Avoid
Levomethadone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Strong) may increase serum concentration of Levomilnacipran. Management: The dose of levomilnacipran should not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Lidocaine (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Lidocaine (Systemic). Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lomitapide. Risk X: Avoid
Loperamide: Lonafarnib may increase serum concentration of Loperamide. Management: When first using loperamide with lonafarnib, do not exceed loperamide 1 mg/day. If needed, the loperamide dose can then be slowly increased according to the loperamide labeling. This combination is contraindicated in patients under 2 years of age. Risk D: Consider Therapy Modification
Lovastatin: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Lovastatin. CYP3A4 Inhibitors (Strong) may increase serum concentration of Lovastatin. Risk X: Avoid
Lumateperone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Lurasidone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lurasidone. Risk X: Avoid
Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and strong CYP3A4 inhibitors. If coadministration with a strong CYP3A4 inhibitor cannot be avoided, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Macitentan. Risk X: Avoid
Manidipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Risk D: Consider Therapy Modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider Therapy Modification
Mavacamten: CYP2C19 Inhibitors (Weak) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor, and reduce the mavacamten dose by one dose level if initiating a weak CYP2C19 inhibitor. Avoid initiating weak CYP2C19 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification
Mavacamten: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mavacamten. Management: For patients on stable therapy with a strong CYP3A4 inhibitor initiate mavacamten at 2.5 mg daily. For patients initiating a strong CYP3A4 inhibitor during mavacamten therapy, dose reductions are recommended. See full mono for details. Risk D: Consider Therapy Modification
Mavorixafor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mavorixafor. Management: Decrease the mavorixafor dose to 200 mg daily if combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Mefloquine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mefloquine. Risk C: Monitor
Meperidine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Meperidine. Risk C: Monitor
Methadone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Methadone. Management: If coadministration with strong CYP3A4 inhibitors is necessary, consider methadone dose reductions until stable effects are achieved. Monitor patients closely for respiratory depression and sedation. Risk D: Consider Therapy Modification
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Midazolam: Lonafarnib may increase serum concentration of Midazolam. Management: Combined use is contraindicated. For patients who must receive midazolam, discontinue lonafarnib for 10 to 14 days before and for 2 days after midazolam administration. Risk X: Avoid
Midostaurin: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Midostaurin. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Midostaurin. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Risk D: Consider Therapy Modification
Mirtazapine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mirtazapine. Risk C: Monitor
Mirvetuximab Soravtansine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Mirvetuximab Soravtansine. Risk C: Monitor
Mobocertinib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Mobocertinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Mobocertinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase active metabolite exposure of Mobocertinib. Risk X: Avoid
Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Mometasone (Nasal). Risk C: Monitor
Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor
Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Mometasone (Topical). Risk C: Monitor
Naldemedine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Naloxegol. Risk X: Avoid
Neratinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Neratinib. Risk X: Avoid
NiCARdipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of NiCARdipine. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of NIFEdipine (Topical). Risk X: Avoid
NIFEdipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider Therapy Modification
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
Nilvadipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of NiMODipine. Risk X: Avoid
Nirogacestat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Nitrendipine. Risk C: Monitor
Olaparib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100 mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily. Risk D: Consider Therapy Modification
Oliceridine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 50 mg daily and monitor closely for adverse reactions. Discontinue coadministration if adverse reactions occur. Risk D: Consider Therapy Modification
Ondansetron: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Ondansetron. 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
Osilodrostat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Osimertinib: May increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Ospemifene: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ospemifene. Risk C: Monitor
OxyBUTYnin: CYP3A4 Inhibitors (Strong) may increase serum concentration of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CYP3A4 Inhibitors (Strong) may increase adverse/toxic effects of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor
P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors): Lonafarnib may increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pacritinib. Risk X: Avoid
Palbociclib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider Therapy Modification
Palovarotene: CYP3A4 Inhibitors (Strong) may increase serum concentration of Palovarotene. Risk X: Avoid
Panobinostat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider Therapy Modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Paricalcitol. Risk C: Monitor
PAZOPanib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of PAZOPanib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of PAZOPanib. Risk X: Avoid
Pemigatinib: CYP3A4 Inhibitors (Strong) 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 strong 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 Strong 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
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease metabolism of Pimecrolimus. Risk C: Monitor
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Piperaquine: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Piperaquine. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Pirtobrutinib. Management: Avoid concomitant use when possible. If combined, reduce the pirtobrutinib dose by 50 mg. If current dose is 50 mg, interrupt pirtobrutinib treatment during strong CYP3A4 inhibitor use. Risk D: Consider Therapy Modification
Polatuzumab Vedotin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. Risk C: Monitor
PONATinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
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 (Strong) 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 (Strong) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Strong) may increase serum concentration of Praziquantel. Risk C: Monitor
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inhibitors (Strong) may increase serum concentration of PredniSONE. Risk C: Monitor
Propafenone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Propafenone. Risk C: Monitor
Propofol: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Propofol. 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 Agents (Highest Risk): Lonafarnib may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Risk C: Monitor
QT-prolonging Antipsychotics (Moderate Risk): Lonafarnib 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 Strong 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 Class III Antiarrhythmics (Highest Risk): 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 QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-Prolonging Inhalational Anesthetics (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 (Highest Risk): 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 QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Risk X: Avoid
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects 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 Moderate CYP3A4 Inhibitors (Moderate Risk): Lonafarnib 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 Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Strong 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 (Moderate Risk): Lonafarnib 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 Lonafarnib. Risk X: Avoid
QUEtiapine: 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 QUEtiapine. Management: Reduce the quetiapine dose to one-sixth of the regular dose when initiating these strong CYP3A4 inhibitors. In patients already receiving these strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and titrate cautiously as needed. Risk D: Consider Therapy Modification
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor
Quizartinib: 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 Quizartinib. Management: If combination is necessary, reduce quizartinib dose as follows: from 53 mg daily to 26.5 mg daily; from 35.4 mg daily to 17.7 mg daily; from 26.5 mg daily to 17.7 mg daily. If taking 17.7 mg daily avoid quizartinib while on the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Radotinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Radotinib. Risk X: Avoid
Ramelteon: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ramelteon. Risk C: Monitor
Ranolazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ranolazine. Risk X: Avoid
Reboxetine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Reboxetine. Risk C: Monitor
Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Risk X: Avoid
Regorafenib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Regorafenib. Risk X: Avoid
Repaglinide: CYP3A4 Inhibitors (Strong) may increase serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Repotrectinib. Risk X: Avoid
Retapamulin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended in patients less than 2 years old. No action is required in other populations. Risk C: Monitor
Revumenib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Revumenib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Revumenib. Management: Avoid combination is possible. If required, for patients weighing 40 kg or more decrease the revumenib dose to 160 mg orally twice/day, and for patients weighing less than 40 kg decrease to 95 mg/m2 orally twice/day. Monitor ECG more closely. Risk D: Consider Therapy Modification
Ribociclib: 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 Ribociclib. Management: Avoid use of ribociclib and strong CYP3A4 inhibitors that prolong the QTc interval when possible. If combined, decrease ribociclib to 400 mg daily in advanced or metastatic breast cancer; reduce ribociclib to 200 mg daily in early breast cancer. Risk D: Consider Therapy Modification
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rilpivirine. Risk C: Monitor
Rimegepant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rimegepant. Risk X: Avoid
Riociguat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Riociguat. Risk C: Monitor
Ripretinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ripretinib. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Ripretinib. Risk C: Monitor
RisperiDONE: CYP3A4 Inhibitors (Strong) may increase serum concentration of RisperiDONE. Risk C: Monitor
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rivaroxaban. For clarithromycin, refer to more specific clarithromycin-rivaroxaban monograph recommendations. Risk C: Monitor
Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase serum concentration of RomiDEPsin. Risk C: Monitor
Rupatadine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Rupatadine. Risk X: Avoid
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Ruxolitinib (Topical). Risk X: Avoid
Salmeterol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Salmeterol. Risk X: Avoid
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Selpercatinib: Lonafarnib may increase QTc-prolonging effects of Selpercatinib. Lonafarnib may increase serum concentration of Selpercatinib. Management: Avoid this combination if possible. If coadministration is required, reduce selpercatinib from 120 mg twice daily to 40 mg twice daily, or from 160 mg to 80 mg twice daily. Monitor for QT prolongation. Risk D: Consider Therapy Modification
Selumetinib: CYP3A4 Inhibitors (Strong) 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 Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Sertindole. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider Therapy Modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Silodosin. Risk X: Avoid
Simeprevir: CYP3A4 Inhibitors (Strong) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: Lonafarnib may increase serum concentration of Simvastatin. Risk X: Avoid
Sirolimus (Conventional): CYP3A4 Inhibitors (Strong) may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with strong CYP3A4 inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sirolimus (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Sirolimus (Topical). Risk C: Monitor
Solifenacin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Solifenacin. Management: Limit adult solifenacin doses to 5 mg daily and limit doses in pediatric patients to the recommended weight-based starting dose (and do not increase the dose) when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sonidegib. Risk X: Avoid
Sparsentan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Sparsentan. Risk X: Avoid
SUFentanil: CYP3A4 Inhibitors (Strong) may increase serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). Risk D: Consider Therapy Modification
SUNItinib: QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase QTc-prolonging effects of SUNItinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of SUNItinib. Management: Avoid when possible. If combined, decrease sunitinib dose to a minimum of 37.5 mg daily when treating GIST or RCC. Decrease sunitinib dose to a minimum of 25 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider Therapy Modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Suvorexant. Risk X: Avoid
Suzetrigine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tacrolimus (Systemic). Management: Reduce tacrolimus dose to one-third of the original dose if starting posaconazole or voriconazole. Coadministration with nelfinavir is not generally recommended. Tacrolimus dose reductions or prolongation of dosing interval will likely be required. Risk D: Consider Therapy Modification
Tacrolimus (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
Tadalafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tadalafil. Management: Avoid this combination in patients taking tadalafil for pulmonary arterial hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if taking daily or 10 mg no more frequently than every 72 hours if used as needed. Risk D: Consider Therapy Modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk X: Avoid
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tasimelteon. Risk C: Monitor
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tazemetostat. Risk X: Avoid
Temsirolimus: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph for details. Risk D: Consider Therapy Modification
Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Thiotepa: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Thiotepa. CYP3A4 Inhibitors (Strong) may increase serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider Therapy Modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase serum concentration of Ticagrelor. Risk X: Avoid
Tilidine: CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Strong) may increase serum concentration of Tilidine. Risk C: Monitor
Tisotumab Vedotin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tisotumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider Therapy Modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase serum concentration of Tolvaptan. Risk X: Avoid
Toremifene: 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 Toremifene. Management: Avoid concomitant use of toremifene and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined, monitor patients for toremifene toxicities including QTc prolongation and TdP. Risk D: Consider Therapy Modification
Trabectedin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Trabectedin. Risk X: Avoid
TraMADol: CYP3A4 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Strong) may increase serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Tretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inhibitors when possible. If combined, monitor for increased tretinoin concentrations and toxicities (eg, pseudotumor cerebri, hypercalcemia). Risk D: Consider Therapy Modification
Triamcinolone (Nasal): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Nasal). Risk C: Monitor
Triamcinolone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Ophthalmic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Triamcinolone (Topical): CYP3A4 Inhibitors (Strong) may increase serum concentration of Triamcinolone (Topical). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Strong) may increase serum concentration of Triazolam. Risk X: Avoid
Ubrogepant: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ubrogepant. Risk X: Avoid
Udenafil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Udenafil. Risk X: Avoid
Ulipristal: CYP3A4 Inhibitors (Strong) may increase serum concentration of Ulipristal. Risk C: Monitor
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Upadacitinib. Management: Upadacitinib dose adjustments are often needed when combined with strong CYP3A4 inhibitors. Specific adjustments vary based on upadacitinib indication. See full interact monograph for details. Risk D: Consider Therapy Modification
Valbenazine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vamorolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vamorolone. Management: Reduce the vamorolone dose to 4 mg/kg daily, with a maximum dose of 200 mg daily for patients weighing over 50 kg, when combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Strong) 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 (Strong) may increase serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification
Vemurafenib: 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 Vemurafenib. Management: Avoid concomitant use of vemurafenib and strong CYP3A4 inhibitors that prolong the QTc interval whenever possible. If combined monitor patients for vemurafenib toxicities including QTc prolongation and TdP, and consider a vemurafenib dose reduction. Risk D: Consider Therapy Modification
Venetoclax: CYP3A4 Inhibitors (Strong) may increase serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider Therapy Modification
Verapamil: CYP3A4 Inhibitors (Strong) may increase serum concentration of Verapamil. Risk C: Monitor
Vilanterol: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vilanterol. Risk C: Monitor
Vilazodone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vilazodone. Management: Limit the maximum vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
VinBLAStine: CYP3A4 Inhibitors (Strong) may increase serum concentration of VinBLAStine. Risk C: Monitor
VinCRIStine: CYP3A4 Inhibitors (Strong) may increase serum concentration of VinCRIStine. Risk X: Avoid
Vindesine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of Vinflunine. Risk X: Avoid
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vinorelbine. Risk C: Monitor
Voclosporin: CYP3A4 Inhibitors (Strong) may increase serum concentration of Voclosporin. Risk X: Avoid
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase serum concentration of Vorapaxar. Risk X: Avoid
Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification
Zolpidem: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zolpidem. Risk C: Monitor
Zopiclone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Risk D: Consider Therapy Modification
Zuranolone: CYP3A4 Inhibitors (Strong) may increase serum concentration of Zuranolone. Management: Reduce the zuranolone dose to 30 mg once daily when used concomitantly with a strong CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Coadministration with grapefruit, grapefruit juice, Seville oranges, or Seville orange juice may increase lonafarnib plasma concentrations. Management: Avoid concomitant administration with grapefruit, grapefruit juice, Seville oranges, or Seville orange juice.
Based on data from animal reproduction studies, the manufacturer recommends effective contraception during therapy in patients who may become pregnant.
Based on data from animal reproduction studies, in utero exposure to lonafarnib may cause fetal harm.
It is not known if lonafarnib is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Avoid grapefruit, grapefruit juice, Seville oranges, or Seville orange juice.
Obtain an ECG and electrolytes before starting therapy and as clinically appropriate during therapy. Monitor CBC and LFTs periodically; renal function tests regularly. Perform ophthalmologic exams regularly (or with new onset or worsening of existing visual changes). Monitor for GI symptoms (eg nausea, vomiting, and/or diarrhea).
Lonafarnib is a farnesyltransferase inhibitor that prevents farnesylation and subsequent accumulation of progerin and progerin-like proteins.
Distribution: Vd: 87.8 to 97.4 L.
Protein binding: ≥99%.
Metabolism: Hepatic via CYP3A (major pathway) and CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1.
Half-life elimination: ~4 to 6 hours.
Time to peak: Median: 2 to 4 hours (range: 0 to 12 hours).
Excretion: Urine (<1%); feces (~62%).
