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. |
| Molecular Weight | 469.9 |
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 | Avoid. Based on its mechanism of action (EGFR inhibitor) and animal studies showing embryotoxicity and teratogenicity, VIZIMPRO (dacomitinib) should not be used during the first trimester. There are no adequate human studies. |
| 2nd trimester | Avoid. Dacomitinib may cause fetal harm when administered to pregnant women. The drug is an EGFR inhibitor and animal reproduction studies have demonstrated adverse effects including structural abnormalities and death. |
| 3rd trimester | Avoid. Use in the third trimester may cause oligohydramnios or fetal renal impairment due to EGFR inhibition. Dacomitinib should be discontinued prior to delivery if possible. |
Clinical note
Comprehensive clinical and safety monograph for VIZIMPRO (VIZIMPRO).
| Placental transfer | Based on its molecular weight (469.9 Da) and lipophilicity, dacomitinib is expected to cross the placenta. Animal studies confirm placental transfer and fetal exposure. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to dacomitinib or any excipientPregnancy
| Precautions | Interstitial lung disease (ILD)/pneumonitis, Diarrhea, Dermatologic adverse reactions, Ocular disorders, Embryo-fetal toxicity |
| Food/Dietary | Grapefruit and grapefruit juice may increase dacomitinib concentrations and should be avoided. No other significant food interactions are established. |
| Clinical Pearls | VIZIMPRO (dacomitinib) is an irreversible pan-HER tyrosine kinase inhibitor indicated for first-line treatment of EGFR exon 19 deletion or exon 21 L858R substitution mutations. Monitor for interstitial lung disease (ILD), diarrhea, and dermatologic adverse reactions. Dose reduction recommended for moderate hepatic impairment (Child-Pugh B). Avoid concomitant use with strong CYP2D6 inhibitors or inducers. |
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| It is not known whether dacomitinib or its metabolites are excreted in human milk. However, due to its molecular weight and potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during treatment and for at least 2 weeks after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| Patient Advice | Take VIZIMPRO exactly as prescribed, once daily with or without food. · If you miss a dose, skip it and take the next dose at the regular time; do not double the dose. · Contact your healthcare provider immediately if you experience new or worsening respiratory symptoms such as cough, fever, or trouble breathing. · You may experience severe diarrhea; stay hydrated and notify your doctor if diarrhea persists. · Use sunscreen and moisturizers to manage skin reactions like rash or dry skin. · Avoid grapefruit and grapefruit juice while taking VIZIMPRO. |