Mobocertinib (Market withdrawal pending): Drug information

(For additional information see "Mobocertinib (Market withdrawal pending): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Special Alerts

Planned Withdrawal of Mobocertinib Indication November 2023

Takeda has announced that it is working with the FDA to voluntarily withdraw Exkivity (mobocertinib) in the United States. This decision is based on the outcome of the phase 3 EXCLAIM-2 confirmatory trial, which did not meet its primary end point; therefore, it did not meet the confirmatory data requirements of the accelerated approval granted by the FDA. Patients currently being treated with mobocertinib should consult their health care provider.

Further information, including contact information for ongoing access to mobocertinib, may be found at https://www.takeda.com/newsroom/newsreleases/2023/Takeda-Provides-Update-on-EXKIVITY-mobocertinib/.

ALERT: US Boxed Warning

QTc prolongation and torsades de pointes

Mobocertinib can cause life-threatening heart rate-corrected QT (QTc) prolongation, including torsades de pointes, which can be fatal, and requires monitoring of QTc and electrolytes at baseline and periodically during treatment. Increase monitoring frequency in patients with risk factors for QTc prolongation. Avoid use of concomitant drugs which are known to prolong the QTc interval and use of strong or moderate CYP3A inhibitors with mobocertinib, which may further prolong the QTc. Withhold, reduce the dose, or permanently discontinue mobocertinib based on the severity of QTc prolongation.

Brand Names: US

Exkivity

Pharmacologic Category

Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor

Dosing: Adult

Note: Assess QTc and correct electrolyte (sodium, potassium, calcium, and magnesium) abnormalities prior to initiating mobocertinib. Mobocertinib is associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

Non–small cell lung cancer, locally advanced or metastatic, EGFR exon 20 insertion-mutated

Non–small cell lung cancer, locally advanced or metastatic, EGFR exon 20 insertion-mutated:

Oral: 160 mg once daily until disease progression or unacceptable toxicity (Ref).

Missed doses: If a dose is missed by more than 6 hours, skip the dose and administer the next dose the following day at its regularly scheduled time. If a dose is vomited, do not administer an additional dose; administer the next dose the following day.

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

Dosing: Kidney Impairment: Adult

Kidney function estimated by Modification of Diet in Renal Disease (MDRD) equation.

eGFR ≥30 mL/minute/1.73 m²: No dosage adjustment necessary.

eGFR <30 mL/minute/1.73 m²: Reduce mobocertinib dose by ~50% (eg, from 160 to 80 mg, 120 to 40 mg, and 80 to 40 mg); monitor QTc interval more frequently.

Dosing: Hepatic Impairment: Adult

Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) to severe (total bilirubin >3 times ULN and any AST) impairment: No dosage adjustment necessary.

Dosing: Adjustment for Toxicity: Adult

**Mobocertinib Dosage Reduction Levels**
Usual initial dose	160 mg once daily
First dose reduction	120 mg once daily
Second dose reduction	80 mg once daily

**Mobocertinib Dosage Modifications for Adverse Reactions**
Adverse reaction	Severity	Mobocertinib dosage modification
Cardiovascular toxicity: Decreased ejection fraction (LVEF) or heart failure	Grade 2 decreased LVEF	Withhold mobocertinib until ≤ grade 1 or baseline. If recovered to baseline within 2 weeks, resume mobocertinib at the same dose or at the next lower dose. If not recovered to baseline within 2 weeks, permanently discontinue mobocertinib.
	≥ Grade 2 heart failure or grade 3 or 4 decreased LVEF	Permanently discontinue mobocertinib.
Cardiovascular toxicity: QTc prolongation and torsades de pointes	QTc interval 481 to 500 msec (grade 2)	First occurrence: Withhold mobocertinib until ≤ grade 1 or baseline. Upon recovery, resume mobocertinib at the same dose. Recurrence: Withhold mobocertinib until ≤ grade 1 or baseline. Upon recovery, resume mobocertinib at the next lower dose or permanently discontinue mobocertinib.
	QTc interval ≥501 msec or QTc interval increase of >60 msec from baseline (grade 3)	First occurrence: Withhold mobocertinib until ≤ grade 1 or baseline. Upon recovery, resume mobocertinib at the next lower dose or permanently discontinue mobocertinib. Recurrence: Permanently discontinue mobocertinib.
	Torsades de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia (grade 4)	Permanently discontinue mobocertinib.
GI toxicity: Diarrhea	Any grade	Manage diarrhea promptly. Initiate an antidiarrheal agent (eg, loperamide) at first sign of diarrhea or increased bowel movement frequency and increase fluid and electrolyte intake.
	Intolerable or recurrent grade 2 or grade 3	Withhold mobocertinib until ≤ grade 1, then resume mobocertinib at the same dose or at the next lower dose.
	Grade 4	First occurrence: Withhold mobocertinib until ≤ grade 1, then resume mobocertinib at the next lower dose. Recurrence: Permanently discontinue mobocertinib.
Pancreatic effects: Lipase or amylase increase	Grade 3 without signs or symptoms	Withhold mobocertinib until ≤ grade 1, then resume mobocertinib at the same dose or at the next lower dose. If not recovered to ≤ grade 1 within 2 weeks, permanently discontinue mobocertinib.
	Grade 3 with signs or symptoms	Withhold mobocertinib until ≤ grade 1, then resume mobocertinib at the next lower dose. If not recovered to ≤ grade 1 within 2 weeks, permanently discontinue mobocertinib.
	Grade 4	First occurrence: Withhold mobocertinib until ≤ grade 1. If recovery occurs within 2 weeks, resume mobocertinib at the next lower dose. If recovery does not occur within 2 weeks, permanently discontinue mobocertinib. Recurrence: Permanently discontinue mobocertinib.
Pulmonary toxicity: Interstitial lung disease (ILD)/pneumonitis	Any grade	Withhold mobocertinib if ILD/pneumonitis is suspected. Permanently discontinue mobocertinib if ILD/pneumonitis is confirmed.
Other adverse reactions	Grade 3 or intolerable or recurrent grade 2	Withhold mobocertinib until ≤ grade 1, then resume mobocertinib at the same dose or at the next lower dose.
Other adverse reactions	Grade 4	First occurrence: Withhold mobocertinib until ≤ grade 1. If recovery occurs within 2 weeks, resume mobocertinib at the next lower dose. If recovery does not occur within 2 weeks, permanently discontinue mobocertinib. Recurrence: Permanently discontinue mobocertinib.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Rates of adverse reactions were defined during combination therapy with other antiretrovirals.

>10%:

Dermatologic: Alopecia (19%), paronychia (39%), pruritus (24%), skin rash (78%), xeroderma (32%)

Endocrine & metabolic: Decreased serum albumin (23%), decreased serum magnesium (23%), decreased serum potassium (29%), decreased serum sodium (20%), weight loss (21%)

Gastrointestinal: Abdominal pain (18%), decreased appetite (39%), diarrhea (92%; grade 3/4: 22%), dyspepsia (11%), gastroesophageal reflux disease (15%), increased serum amylase (40%), increased serum lipase (35%), nausea (37%; grade 3: 4%), stomatitis (46%; grade 3: 4%), vomiting (40%; grade 3: 3%)

Hematologic & oncologic: Decreased platelet count (26%; grade 3/4: <1%), decreased red blood cells (59%; grade 3/4: 4%), leukopenia (25%), lymphocytopenia (52%; grade 3/4: 15%)

Hepatic: Increased serum alanine aminotransferase (22%), increased serum alkaline phosphatase (25%), increased serum aspartate aminotransferase (21%)

Nervous system: Fatigue (≤29%)

Neuromuscular & skeletal: Asthenia (≤29%), musculoskeletal pain (34%)

Ophthalmic: Ocular toxicity (11%; including abnormal sensation in eyes, blepharitis, blurred vision, conjunctival hemorrhage, corneal edema, dry eye syndrome, eye pruritus, eye discharge, misdirected growth of eyelashes, vitreous floaters)

Renal: Increased serum creatinine (52%)

Respiratory: Cough (24%), dyspnea (15%), rhinorrhea (13%), upper respiratory tract infection (16%)

1% to 10%:

Cardiovascular: Atrial fibrillation (2%), cardiac failure (3%), edema (9%), hypertension (10%), prolonged QT interval on ECG (≤10%), ventricular arrhythmia (≤10%)

Dermatologic: Palmar-plantar erythrodysesthesia (4%)

Nervous system: Headache (10%), peripheral neuropathy (7%)

Renal: Acute kidney injury (8%)

Respiratory: Pleural effusion (serious: ≥2%), pneumonitis (3%)

Miscellaneous: Fever (serious: ≥2%)

<1%: Cardiovascular: First degree atrioventricular block, left bundle branch block, second degree atrioventricular block, supraventricular extrasystoles, ventricular premature contractions, ventricular tachycardia

Frequency not defined:

Cardiovascular: Torsades de pointes

Respiratory: Interstitial pulmonary disease

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiotoxicity: Mobocertinib may cause cardiotoxicity (including decreased ejection fraction, cardiomyopathy, and congestive heart failure) resulting in heart failure, which can be fatal. Grade 3 or higher events have occurred (rarely). Mobocertinib may cause QT prolongation (heart-rate corrected; QTc) resulting in torsades de pointes; atrial fibrillation, ventricular tachycardia, first- or second-degree atrioventricular block, left bundle branch block, and supraventricular and ventricular extrasystoles have been observed in a small number of patients. QTc interval >500 msec and QTc change >60 msec from baseline have been reported. Patients with QTc >470 msec were excluded from clinical trials.

• GI toxicity: Mobocertinib can cause diarrhea, which may be severe. Diarrhea occurred in most patients; grade 3 diarrhea occurred in one-fifth of patients and grade 4 diarrhea occurred in a small percentage of patients. The median time to first onset of diarrhea was 5 days, although diarrhea has occurred within 24 hours after initiating mobocertinib. Diarrhea resolved in almost half of patients, with a median time to resolution of 3 days. Diarrhea may lead to dehydration or electrolyte imbalance, with or without kidney impairment.

• Pulmonary toxicity: Mobocertinib can cause interstitial lung disease/pneumonitis, which may be fatal; grade 3 and 4 events have occurred (rarely).

Special populations:

• Older age: Patients ≥65 years of age may experience a higher incidence of grade 3 and 4 and/or serious adverse reactions when compared to patients <65 year of age.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Select patients for mobocertinib treatment based on the presence of epidermal growth factor receptor exon 20 insertion mutation. Information on approved tests is available at http://www.FDA.gov/CompanionDiagnostics.

Dosage Forms: US

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

Capsule, Oral, as succinate:

Exkivity: 40 mg

Generic Equivalent Available: US

Pricing: US

Capsules (Exkivity Oral)

40 mg (per each): $267.50

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

Prescribing and Access Restrictions

Exkivity is available through specialty pharmacies and distributors. Information regarding access is available from the manufacturer at https://www.exkivityhcp.com/files/EXKIVITY-Distribution-Flashcard-Digital-Print.pdf.

Administration: Adult

Oral: Administer at approximately the same time each day, with or without food. Swallow capsules whole; do not open, chew, or dissolve capsule contents.

Mobocertinib is associated with a moderate or high emetic potential. Administering with food may reduce nausea; standard antiemetics (eg, prochlorperazine) may be used to manage vomiting or may utilize prophylactic antiemetics if needed (Ref).

Use: Labeled Indications

Non-small cell lung cancer, locally advanced or metastatic, EGFR exon 20 insertion-mutated: Treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an approved test, and whose disease has progressed on or after platinum-based chemotherapy.

Medication Safety Issues

Sound-alike/look-alike issues:

Mobocertinib may be confused with ceritinib, momelotinib, osimertinib.

Exkivity may be confused with Zontivity.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak)

Drug Interactions

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

Amiodarone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. 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

Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). 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 greater risk. Risk D: Consider therapy modification

Atogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification

Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Carbetocin: May enhance the QTc-prolonging effect 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

Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. 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

Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination

Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. 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

ClomiPRAMINE: May enhance the QTc-prolonging effect 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

CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mobocertinib. Management: Avoid use of moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mobocertinib. Risk X: Avoid combination

Dabrafenib: May enhance the QTc-prolonging effect of Mobocertinib. Dabrafenib may decrease serum concentrations of the active metabolite(s) of Mobocertinib. Dabrafenib may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination

Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Dronedarone: May enhance the QTc-prolonging effect of Mobocertinib. Dronedarone may increase serum concentrations of the active metabolite(s) of Mobocertinib. Dronedarone may increase the serum concentration of Mobocertinib. Management: Avoid use of dronedarone and mobocertinib whenever possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification

DroPERidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Encorafenib: May enhance the QTc-prolonging effect of Mobocertinib. Encorafenib may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Etelcalcetide: May enhance the QTc-prolonging effect 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

Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. 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

Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. 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

Gemifloxacin: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Gemifloxacin. 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

Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification

Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect 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: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. 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

Hormonal Contraceptives: Mobocertinib may decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination

HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy

Imipramine: May enhance the QTc-prolonging effect 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

Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. 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

Lefamulin: May enhance the QTc-prolonging effect 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 combination

Levofloxacin-Containing Products (Systemic): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Levofloxacin-Containing Products (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

Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. 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

Meglumine Antimoniate: May enhance the QTc-prolonging effect 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

Methadone: QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of Methadone. 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

Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. 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

Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination

Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy

OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. 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

Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Oxytocin: May enhance the QTc-prolonging effect 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

Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. 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 therapy

PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination

Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). 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

Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. 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

Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination

Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination

Posaconazole: May increase the 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 combination

Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination

Propafenone: May enhance the QTc-prolonging effect 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

Propofol: May enhance the QTc-prolonging effect 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 Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest 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 therapy

QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest 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 therapy

QT-prolonging Class IA Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IA 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 Class III Antiarrhythmics (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect 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): May enhance the QTc-prolonging effect 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 Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Highest Risk). Risk X: Avoid combination

QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Kinase Inhibitors (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous 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 Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentrations of the active metabolite(s) of Mobocertinib. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Mobocertinib. Management: Avoid use of QT prolonging moderate CYP3A4 inhibitors with mobocertinib when possible. If combined, the mobocertinib dose should be reduced by approximately 50% (ie, from 160 mg to 80 mg, 120 mg to 40 mg, or 80 mg to 40 mg). Monitor QTc interval closely. Risk D: Consider therapy modification

QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Mobocertinib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of Mobocertinib. Risk X: Avoid combination

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Mobocertinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentrations of the active metabolite(s) of Mobocertinib. QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Mobocertinib. Risk X: Avoid combination

QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

Quizartinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination

RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. 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

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination

Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy

Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination

SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Terbutaline: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification

Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification

Reproductive Considerations

Verify pregnancy status prior to use in patients who could become pregnant.

Patients who could become pregnant should use effective nonhormonal contraception during therapy and for 1 month after the last mobocertinib dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 1 week after the last mobocertinib dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to mobocertinib may cause fetal harm.

Breastfeeding Considerations

It is not known if mobocertinib is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last mobocertinib dose.

Monitoring Parameters

EGFR exon 20 insertion mutation status (prior to treatment). Monitor cardiac function, including assessment of left ventricular ejection fraction at baseline and during treatment. Assess QTc and electrolytes (sodium, potassium, calcium, and magnesium) at baseline and periodically during treatment; increase monitoring frequency in patients with risk factors for QTc prolongation (eg, patients with congenital long QT syndrome, heart disease, kidney impairment, electrolyte abnormalities). Monitor electrolytes closely in patients with diarrhea. Evaluate pregnancy status prior to treatment (in patients who could become pregnant). Monitor for new or worsening signs/symptoms (eg, dyspnea, cough, fever) indicative of interstitial lung disease/pneumonitis. Monitor adherence.

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

Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Mechanism of Action

Mobocertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (Riely 2021). It binds to and inhibits EGFR exon 20 insertion mutations (at lower concentrations than wild type [WT] EGFR). The active metabolites, AP32960 and AP32914, have inhibitor profiles similar to mobocertinib. Mobocertinib also inhibits HER2 and HER4 (EGFR family members) and B-lymphocyte kinase (BLK) activity at clinically relevant concentrations. In cell models, mobocertinib inhibited the proliferation of cells driven by different EGFR exon 20 insertion mutation variants at lower concentrations than WT-EGFR signaling inhibition.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_dss; 3,509 L.

Protein binding: Mobocertinib: ~99%; AP32960: >99%; AP32914: ~99%.

Metabolism: Primarily via CYP3A; forms 2 active metabolites (AP32960 and AP32914).

Bioavailability: 37%.

Half-life elimination: Mobocertinib: 18 hours; AP32960: 24 hours; AP32914: 18 hours.

Time to peak: 4 hours.

Excretion: Feces: ~76% (~6% as unchanged drug; ~12% as AP32960); Urine: ~4% (~1% as unchanged drug; ~1% as AP32960).

Clearance (at steady state): Mobocertinib: 138 L/hour; AP32960: 149 L/hour; AP32914: 159 L/hour.

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Riely GJ, Neal JW, Camidge DR, et al. Activity and safety of mobocertinib (TAK-788) in previously treated non-small cell lung cancer with EGFR exon 20 insertion mutations from a phase I/II trial. Cancer Discov. 2021;11(7):1688-1699. doi:10.1158/2159-8290.CD-20-1598 [PubMed 33632775]
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Topic 132715 Version 48.0

خرید پکیج

Mobocertinib (Market withdrawal pending): Drug information