Mobocertinib

Mobocertinib
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tejasvi Aryaputra

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Black Box Warning

TITLE See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Overview

Mobocertinib is a kinase inhibitor that is FDA approved for the treatment of locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include nausea, vomiting, fatigue, musculoskeletal pain, paronychia, diarrhea, dry skin, stomatitis, rash, and a decrease in appetite.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• 160 mg with or without food, once daily at the same time each day.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Mobocertinib in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Mobocertinib in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Mobocertinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Mobocertinib in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Mobocertinib in pediatric patients.

Contraindications

There are no contraindications associated with Mobocertinib

Warnings

TITLE See full prescribing information for complete Boxed Warning. Condition Name: (Content)

QTc Prolongation and Torsades de Pointes

• Torsades de Pointes and life-threatening heart rate-corrected QT can be caused when taking Mobocertinib.
• A QTc interval greater than 500 msec was found in 1.2% of patients in a study of a 250 patient subset who had scheduled and unscheduled ECGs. The patients in the subset were part of a pooled Mobocertinib safety population.
• A change-from-baseline QTc greater than 60 msec was found in 11% of patients in a study of a 250 patient subset who had scheduled and unscheduled ECGs. The patients in the subset were part of a pooled Mobocertinib safety population.
• 0.4% of patients experienced Grade 4 Torsades de Pointes in a study of a 250 patient subset who had scheduled and unscheduled ECGs. The patients in the subset were part of a pooled Mobocertinib safety population.
• Potassium, calcium, sodium, and magnesium abnormalities should be corrected prior to taking Mobocertinib.
• Both electrolytes at baseline and QTc at baseline should be assessed prior to taking Mobocertinib.
• Monitor electrolytes and QTc during treatment periodically.
• Increase monitoring of patients that have risk factors for QTc prolongation.
• Concomitant use of drugs known to prolong the QTc interval should be avoided.
• Concomitant use of Mobocertinib and moderate or strong CYP3A inhibitors should be avoided.
• Advise patients that QTc prolongation severity can cause Mobocertinib treatment to either be withheld, reduced, or permanently discontinued.

Interstitial Lung Disease (ILD)/Pneumonitis

• ILD/pneumonitis can be caused when taking Mobocertinib.
• 4.3% of patients of the pooled Mobocertinib safety population experienced ILD/pneumonitis. Of the 4.3% patients, 0.8% experienced Grade 3 events while 1.2% experienced events that were fatal.
• Monitor patients for any new pulmonary symptoms or worsening pulmonary symptoms that could potentially be indicative of ILD/pneumonitis.
• Advise patients that suspected ILD/pneumonitis in patients should withhold Mobocertinib treatment.
• Advise patients that confirmed ILD/pneumonitis in patients should permanently discontinue Mobocertinib treatment.

Cardiac Toxicity

• Cardiac toxicity that can lead to fatal heart failure can be caused when taking Mobocertinib.
• 2.7% of patients of the pooled Mobocertinib safety population experienced heart failure. Of the 2.7% patients, 1.2% of patients experienced Grade 3 reactions, 0.4% of patients experienced Grade 4 reactions, and 0.4% of patients experienced a fatal case of heart failure.
• Patients receiving Mobocertinib also experienced left bundle branch block (0.4%), ventricular extrasystoles (0.4%), ventricular tachycardia (0.4%), supraventricular extrasystoles (0.4%), Atrial fibrillation (1.6%), first degree atrioventricular block (0.4%), and second degree atrioventricular block (0.4%).
• Monitor patients cardiac function when taking Mobocertinib.
• Monitor patients left ventricular ejection fraction at baseline when taking Mobocertinib.
• Advise patients that cardiac function severity can cause Mobocertinib treatment to either be withheld, reduced, or permanently discontinued.

Diarrhea

• Diarrhea can be caused when taking Mobocertinib.
• 93% of patients of the pooled Mobocertinib safety population experienced diarrhea. Of the 93% patients, 20% of patients experienced Grade 3 symptoms while 0.4% of patients experienced Grade 4 symptoms.
• 5 days is the median time to first onset of diarrhea in patients.
• 3 days is the median time to resolution of diarrhea in the 48% patients who had their diarrhea resolved.
• Advise patients with or without renal impairment that electrolyte imbalance or dehydration could be caused when experiencing diarrhea.
• Advise patients who start experiencing first signs of diarrhea to start using an antidiarrheal agent.
• Advise patients that electrolyte imbalances can cause Mobocertinib treatment to either be withheld, reduced, or permanently discontinued.

Embryo-Fetal Toxicity

• Based on animal data, Mobocertinib potentially can cause harm to females fetus during pregnancy.
• Studies done on rats showed embryolethality at maternal exposures 1.7 times the human exposure based on AUC at one 160 mg dose daily during the period of organogenesis.
• Advise pregnant females about fetal risks when treated with Mobocertinib.
• Advise females of reproductive potential to use effective non hormonal contraception during treatment with Mobocertinib and for at least 1 months after the last dose.
• Advise males with female partners of reproductive potential to use effective contraception during treatment with Mobocertinib and for at least 1 week after the last dose.

Adverse Reactions

Clinical Trials Experience

Clinical Trials Experience

• Because clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pooled Safety Population Study

• The adverse reactions of Mobocertinib were looked at in 256 patients receiving one daily dosage of 160 mg Mobocertinib. Of the 256 patients, 114 of the patients had EGFR exon 20 insertion mutation-positive locally advanced, metastatic NSCLC from Study AP32788-15-101, and patients with other solid tumors. Nausea, paronychia, musculoskeletal pain, rash, decreased appetite, dry skin, diarrhea, stomatitis, and vomiting were the most common adverse reactions reported (>20%). Increased amylase, decreased potassium, decreased magnesium, increased lipase, decreased lymphocytes, increased creatinine, and decreased hemoglobin were the most common Grade 3 or 4 laboratory abnormalities reported (≥2%).

Study AP32788-15-101

• A subset of patients that have metastatic NSCLC who received prior platinum-based chemotherapy or EGFR exon 20 insertion mutation-positive locally advanced were used in a study to test the safety of Mobocertinib. The total amount of patients were 114 that received 160 mg once daily dosage of Mobocertinib in this study.
• Patients that were excluded from the study included patients with significant, uncontrolled, active cardiovascular disease, prolonged QTc interval, radiation pneumonitis that required steroid treatment, a history of interstitial lung disease, or drug-related pneumonitis.
• 46% of patients experienced severe reactions when treated with Mobocertinib. Pyrexia, nausea, dyspnea, cardiac failure, acute kidney injury, diarrhea, and pleural effusion were the severe adverse reactions reported in the patient subset.
• 1.8% of patients reported fatal adverse reactions when taking Mobocertinib. Pneumonitis and cardiac failure were some of the fatal adverse reactions experienced by patients.
• 17% of patients had to permanently discontinue treatment with Mobocertinib with diarrhea and nausea being some of the adverse reactions reported leading to permanent discontinuation.
• 51% of patients had interruptions in Mobocertinib dosage with diarrhea, nausea and vomiting being some of the adverse reactions reported leading to dosage interruptions.
• 25% of patients had reductions in Mobocertinib dosage with diarrhea being one of the many adverse reactions reported leading to dosage reductions.

Table 3 shows the Adverse Reactions in patients part of Study AP32788-15-101 who are treated with Mobocertinib.

Insert Table 3

• Peripheral neuropathy, cardiac failure, acute kidney injury, palmar-plantar erythrodysaesthesia, edema, and pneumonitis are clinically relevant adverse reactions reported by patients treated with Mobocertinib.

Table 4 shows the Laboratory Abnormalities in patients part of Study AP32788-15-101 who are treated with Mobocertinib.

Insert Table 4

Postmarketing Experience

There is limited information about "Postmarketing Experiance" in the drug label.

Drug Interactions

Effect of Other Drugs on Mobocertinib

Insert Table

Effect of Mobocertinib on Other Drugs

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Drugs that Prolong the QTc Interval

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Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Studies done on animals show that fetal harm may occur to pregnant women treated with Mobocertinib. Pregnant rat studies show administration of Mobocertinib leads to maternal toxicity at plasma exposures approximately 1.7 times (10 mg/kg) the human exposure based on AUC, and embryolethality during the period of organogenesis. Decreased fetal weight was recorded in pregnant rats, but there were no clear signs at high doses (10 mg/kg) of Mobocertinib that show fetal malformations occurred. Female patients should be advised if pregnant about the potential risks that may occur to the fetus when treated with Mobocertinib.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Mobocertinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Mobocertinib during labor and delivery.

Nursing Mothers

Data on Mobocertinib for its effects on milk production or the effects on the breastfed child have not been found. Advise female patients to not nurse during Mobocertinib treatment, and or 1 week after their last dose of Mobocertinib.

Pediatric Use

Safety and effectiveness in pediatric populations have not been established.

Geriatic Use

Of the total number of subjects (114) in the clinical studies treated with Mobocertinib, around 37% of the patients were 65 years or older in age, and 7% were 75 years or older in age. No differences among young patients compared to patients 65 years or older in age were found when looking at safety and efficacy of Mobocertinib. Higher percentages of Grade 3 and 4 adverse reactions occurred in patients 65 years and older when compared to patients younger than 65 years of age (69% vs 47%) based on exploratory analysis. Higher percentages of serious adverse reactions occurred in patients 65 years and older when compared to patients younger than 65 years of age (64% vs 35%) based on exploratory analysis.

Gender

There is no FDA guidance on the use of Mobocertinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Mobocertinib with respect to specific racial populations.

Renal Impairment

Mild to moderate renal impairment in patients do not require a dosage adjustment of Mobocertinib. Dosage recommendations of Mobocertinib in patients with severe renal impairment have not been established.

Hepatic Impairment

Mild to moderate hepatic impairment in patients do not require a dosage adjustment of Mobocertinib. Dosage recommendations of Mobocertinib in patients with severe hepatic impairment have not been established.

Females of Reproductive Potential and Males

Advise females of reproductive potential to use effective non hormonal contraception during treatment with Mobocertinib and for at least 1 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Mobocertinib and for at least 1 week after the last dose. Fertility may be impaired in both females and males when treated with Mobocertinib.

Immunocompromised Patients

There is no FDA guidance on the use of Mobocertinib with respect to immunocompromised populations.

Administration and Monitoring

Administration

• Recommended dosage of Mobocertinib as prescribed by the doctor can be taken with or without food.
• Swallow Mobocertinib tablets whole.
• Mobocertinib should be taken at the same time each day.
• Instruct patients to not chew, open, or dissolve contents of the tablets.
• If a dosage of Mobocertinib is missed by more than 6 hours, then skip dosage and take next dosage at scheduled time the next day.
• Do not take extra dosage of Mobocertinib if dosage taken is vomited, just take next dosage at scheduled time the next day.

Monitoring

Dosage Modifications for Moderate CYP3A Inhibitors

• Advise patients to avoid concomitant use of Mobocertinib with a moderate CYP3A inhibitor.
• Reduce Mobocertinib dosage by 50% if concomitant use of a moderate CYP3A inhibitor is unavoidable. Mobocertinib dosage can return to normal amount after the inhibitor is discontinued for 3 to 5 elimination half-lives.
• Monitor patients for QTc interval when concomitant use of a moderate CYP3A inhibitor is unavoidable during Mobocertinib treatment.

Dosage Modifications for Adverse Reactions

Table 1 and 2 show the Reduction in Dosage to Mobocertinib for Patients with Adverse Reactions.

Insert Table 1 and 2

IV Compatibility

There is limited information regarding the compatibility of Mobocertinib and IV administrations.

Overdosage

There is limited information regarding Mobocertinib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Mobocertinib Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Mobocertinib Mechanism of Action in the drug label.

Structure

There is limited information regarding Mobocertinib Structure in the drug label.

Pharmacodynamics

There is limited information regarding Mobocertinib Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Mobocertinib Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Mobocertinib Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Mobocertinib Clinical Studies in the drug label.

How Supplied

There is limited information regarding Mobocertinib How Supplied in the drug label.

Storage

There is limited information regarding Mobocertinib Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Mobocertinib Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Mobocertinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Mobocertinib Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Mobocertinib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.