VIZIMPRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIZIMPRO (VIZIMPRO).
Dacomitinib is an irreversible inhibitor of the human epidermal growth factor receptor (EGFR/HER1), HER2, and HER4 tyrosine kinases. It inhibits autophosphorylation and downstream signaling pathways, leading to reduced cell proliferation and increased apoptosis in EGFR-mutant tumor cells.
| Metabolism | Primarily metabolized by CYP2D6 and CYP3A4. Dacomitinib is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatic metabolism (CYP3A4), with 77% of dose excreted in feces (primarily as metabolites) and 10% in urine (0.1% unchanged). |
| Half-life | 14-19 hours; at steady state, effective half-life supports once-daily dosing. |
| Protein binding | 91% bound, primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | 230 L (approximately 3.3 L/kg for a 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | 76% after oral administration; high-fat meal decreases Cmax and AUC by ~29% and 16%, respectively. |
| Onset of Action | Oral: Clinical effect (tumor response) observed within 2-4 weeks; maximal effect by 8-12 weeks. |
| Duration of Action | Continuous with daily dosing; treatment until disease progression or unacceptable toxicity. |
45 mg orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment is recommended for patients with mild, moderate, or severe renal impairment (creatinine clearance ≥15 mL/min). Insufficient data for patients with end-stage renal disease requiring hemodialysis. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 30 mg once daily. Severe hepatic impairment (Child-Pugh C): use is not recommended. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients. |
| Geriatric use | No specific dose adjustment is required for elderly patients. Clinical studies did not identify different responses in patients aged ≥65 years compared to younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIZIMPRO (VIZIMPRO).
| Breastfeeding | There are no data on the presence of dacomitinib in human milk, its effects on the breastfed infant, or its effects on milk production. Dacomitinib is present in rat milk. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with VIZIMPRO and for at least 17 days after the last dose. The M/P ratio is not available. |
| Teratogenic Risk | Based on its mechanism of action (EGFR inhibition) and animal studies, VIZIMPRO (dacomitinib) is expected to cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in embryolethality, reduced fetal body weight, and skeletal abnormalities at maternal exposures less than the human exposure at the recommended clinical dose. Avoid use during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for at least 17 days after the last dose. No data are available on the specific risks by trimester, but exposure should be avoided throughout pregnancy due to the potential for teratogenicity and embryotoxicity. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Interstitial lung disease (ILD)/pneumonitis","Diarrhea","Dermatologic adverse reactions","Ocular disorders","Embryo-fetal toxicity"] |
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| Fetal Monitoring | Monitor pregnant women for adverse effects such as interstitial lung disease, severe diarrhea, dermatologic toxicities, and hepatic impairment. Perform pregnancy testing in females of reproductive potential prior to initiating treatment. Monitor fetal growth and well-being by ultrasound if exposure occurs during pregnancy. Monitor for signs of fetal distress or oligohydramnios. Assess for congenital anomalies if exposure occurs. |
| Fertility Effects | Based on animal studies, VIZIMPRO may impair fertility in both males and females. In female rats, dacomitinib caused disruption of estrous cycles and reduced fertility at clinically relevant exposures. In male rats, adverse effects on reproductive organs (e.g., reduced testicular weight, degeneration of seminiferous tubules) were observed. The effect on human fertility is unknown; however, reversible impairment of spermatogenesis and ovulation may occur. |