EXKIVITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EXKIVITY (EXKIVITY).
Irreversible tyrosine kinase inhibitor that selectively targets epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations, and specifically inhibits EGFR T790M and C797S resistance mutations, with less activity against wild-type EGFR.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP2C8 and CYP2D6. |
| Excretion | Primarily hepatic metabolism with biliary excretion; 91% of total recovered in feces (30% as unchanged drug), <1% in urine. |
| Half-life | Terminal elimination half-life is approximately 48 hours, supporting once-daily dosing for systemic exposure. |
| Protein binding | 99.8% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent Vd is 14.6 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 58-60% under fasted conditions; absorption increased with high-fat meal. |
| Onset of Action | Oral: Time to peak plasma concentration (Tmax) occurs at 4-6 hours post-dose; clinical effect onset not defined. |
| Duration of Action | Duration corresponds to dosing interval (24h) due to half-life; sustained plasma levels achieved with daily dosing. |
| Molecular Weight | 607.77 |
150 mg orally once daily with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not studied in severe renal impairment (eGFR <30 mL/min) or dialysis. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): reduce to 100 mg once daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age; monitor renal function due to age-related decline. |
| 1st trimester | Contraindicated: category X. Risk based on animal data showing teratogenicity and embryofetal toxicity. Avoid pregnancy. |
| 2nd trimester | Contraindicated: category X. No human data; animal studies show fetal harm. Use only if benefit outweighs risk and patient is aware. |
| 3rd trimester | Contraindicated: category X. May cause fetal harm; use only if maternal condition requires and no alternatives. |
Clinical note
Comprehensive clinical and safety monograph for EXKIVITY (EXKIVITY).
| Placental transfer | Placental transfer is expected due to molecular weight; no specific human data but animal studies indicate crossing. |
| Breastfeeding | Exkivity is excreted in human milk; due to potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 1 week after the last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to mobocertinib or any excipientsPregnancy
| Precautions | Interstitial lung disease (ILD)/pneumonitis, QTc interval prolongation, Embryo-fetal toxicity, Cutaneous adverse reactions, Diarrhea |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment as they may increase drug levels. No other dietary restrictions are known. |
| Clinical Pearls | EXKIVITY (mobocertinib) is a tyrosine kinase inhibitor indicated for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. Monitor for QTc prolongation, diarrhea, and hepatotoxicity. Baseline and periodic monitoring of left ventricular ejection fraction is recommended. Avoid use with strong or moderate CYP3A4 inhibitors or inducers. Dose reduction may be needed for adverse reactions. |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on the mechanism of action (EGFR tyrosine kinase inhibitor) and animal studies, EXKIVITY is predicted to cause fetal harm when administered to a pregnant woman. There are no adequate human data. In animal reproduction studies, embryo-fetal toxicity and teratogenicity (including skeletal abnormalities and reduced fetal weight) occurred at maternal exposures below the human exposure at the recommended dose. Therefore, EXKIVITY is contraindicated in pregnancy. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus. The risk applies throughout all trimesters. |
| Fetal Monitoring | If EXKIVITY is inadvertently used during pregnancy, close monitoring of fetal development is recommended, including serial fetal ultrasounds to assess for growth restriction, skeletal anomalies, and amniotic fluid volume. Maternal monitoring should include liver function tests, serum electrolytes, and assessment for adverse events such as diarrhea, rash, and interstitial lung disease. Consider regular pregnancy surveillance by maternal-fetal medicine. |
| Fertility Effects | Based on animal studies and its mechanism of action, EXKIVITY may impair fertility in females. In animal studies, ovarian effects including follicular atresia and reduced corpora lutea were observed, suggesting potential impairment of female fertility. Effects on male fertility have not been adequately studied, but testicular toxicity cannot be excluded. The clinical relevance in humans is unknown. Advise patients of potential impact on reproductive capacity. |
| Patient Advice | Take EXKIVITY exactly as prescribed, with or without food. · Do not take grapefruit or grapefruit juice while on this medication. · Report any new or worsening shortness of breath, chest pain, or palpitations immediately. · Contact your doctor if you experience severe diarrhea, nausea, vomiting, or loss of appetite. · Avoid becoming pregnant and use effective contraception during treatment and for 1 month after last dose. · Tell your doctor if you have a history of heart problems or liver disease. |