DACOMITINIB Drug Interactions: What You Need to Know

INTERACTIONS

• Proton Pump Inhibitors (PPIs): Avoid use with VIZIMPRO; use locally-acting antacids or H2-receptor antagonist; administer VIZIMPRO at least 6 hours before or 10 hours after H2-receptor antagonist. ( 2.4 , 7.1 )
• CYP2D6 Substrates: Avoid concomitant use with VIZIMPRO where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities. ( 7.2 )

7.1 Effect of Other Drugs on VIZIMPRO Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce VIZIMPRO efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours after taking an H2-receptor antagonist <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ]</span> .

7.2 Effect of VIZIMPRO on CYP2D6 Substrates Concomitant use of VIZIMPRO increases the concentration of drugs that are CYP2D6 substrates <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> which may increase the risk of toxicities of these drugs. Avoid concomitant use of VIZIMPRO with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

None. None. ( 4 )

AND PRECAUTIONS

• Interstitial Lung Disease (ILD): Permanently discontinue VIZIMPRO if ILD is confirmed. ( 5.1 )
• Diarrhea: Withhold and reduce the dose of VIZIMPRO based on the severity. ( 2.3 , 5.2 )
• Dermatologic Adverse Reactions: Withhold and reduce the dose of VIZIMPRO based on the severity. ( 2.3 , 5.3 )
• Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm. Advise females of reproductive potential to use effective contraception. ( 5.4 , 8.1 , 8.3 )

5.1 Interstitial Lung Disease (ILD) Severe and fatal ILD/pneumonitis occurred in patients treated with VIZIMPRO and occurred in 0.5% of the 394 VIZIMPRO-treated patients; 0.3% of cases were fatal. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold VIZIMPRO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue VIZIMPRO if ILD is confirmed <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .

5.2 Diarrhea Severe and fatal diarrhea occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated patients; Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal. Withhold VIZIMPRO for Grade 2 or greater diarrhea until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of diarrhea <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) and Adverse Reactions (6.1) ]</span>. Promptly initiate anti-diarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea.

5.3 Dermatologic Adverse Reactions Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Rash occurred in 78% of the 394 VIZIMPRO-treated patients; Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients.

Grade

3 or 4 exfoliative skin reactions were reported in 1.8% of patients. Withhold VIZIMPRO for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of the dermatologic adverse reaction [see Dosage and Administration (2.3) and Adverse Reactions (6.1) ]. The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of VIZIMPRO, initiate use of moisturizers and appropriate measures to limit sun exposure. Upon development of Grade 1 rash, initiate treatment with topical antibiotics and topical steroids. Initiate oral antibiotics for Grade 2 or more severe dermatologic adverse reactions.

5.4 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, VIZIMPRO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration of dacomitinib to pregnant rats during the period of organogenesis resulted in an increased incidence of post-implantation loss and reduced fetal body weight at doses resulting in exposures near the exposure at the 45 mg human dose. The absence of EGFR signaling has been shown to result in embryolethality as well as post-natal death in animals. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 and 8.3) ]</span> .