Dacomitinib is used as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) who have specific epidermal growth factor receptor (EGFR) mutations, including exon 19 deletion or exon 21 L858R substitution mutation. These mutations must be confirmed by an FDA-approved diagnostic test before starting treatment.

Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR receptor family, including EGFR/HER1, HER2, and HER4. It also targets certain activating EGFR mutations such as exon 19 deletion and exon 21 L858R substitution mutation. In laboratory studies, dacomitinib has shown the ability to inhibit other kinases such as DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations. Preclinical studies demonstrated that dacomitinib causes dose-dependent inhibition of EGFR and HER2 autophosphorylation and suppresses tumor growth in mice implanted with human tumor xenografts driven by HER family targets, including mutated EGFR. Additionally, oral administration of dacomitinib showed antitumor activity in mice with intracranial human tumor xenografts associated with EGFR amplification.

The recommended dosage of Dacomitinib is 45 mg taken orally once daily, until disease progression or unacceptable toxicity occurs. Dacomitinib can be taken with or without food. Take Dacomitinib the same time each day. If the patient vomits or misses a dose, do not take an additional dose or make up a missed dose but continue with the next scheduled dose. First dose reduction Dose Level-30 mg Dose (Once Daily) Second dose reduction Dose Level-15 mg Dose.

Proton Pump Inhibitors (PPIs): Concomitant use of PPIs with Dacomitinib should be avoided because they may reduce its effectiveness. If needed, use locally acting antacids or an H2-receptor antagonist. Dacomitinib should be taken at least 6 hours before or 10 hours after taking an H2-receptor antagonist.

CYP2D6 Substrates: Avoid using Dacomitinib together with medicines that are CYP2D6 substrates, especially when even small increases in their concentration could cause serious or life-threatening toxicity.

The most common side effects (occurring in more than 20% of patients) include diarrhea, skin rash, paronychia (nail infection), stomatitis, decreased appetite, dry skin, weight loss, hair loss, cough, and itching.

Dacomitinib may cause harm to an unborn baby if used during pregnancy. There is no available data on whether Dacomitinib or its metabolites pass into human breast milk or their effect on a breastfed infant. Because of the possibility of serious adverse reactions in nursing infants, women should avoid breastfeeding during treatment and for at least 17 days after the last dose.

Interstitial Lung Disease (ILD): If ILD is confirmed, Dacomitinib treatment should be permanently discontinued.

Diarrhea: Treatment may need to be temporarily stopped or the dose reduced depending on the severity.

Dermatologic Reactions: Severe skin reactions may require interruption of therapy or dose reduction.

Embryo-Fetal Toxicity: Dacomitinib can harm the fetus; therefore, women of reproductive potential should use effective contraception during treatment.

Pediatric Use: The safety and effectiveness of Dacomitinib in children have not yet been established.

Renal Impairment: No dose adjustment is required for patients with mild to moderate kidney impairment (Creatinine Clearance 30–89 mL/min). However, the appropriate dose has not been determined for patients with severe renal impairment (Creatinine Clearance <30 mL/min).

Cytotoxic Chemotherapy

Store below 30°C, protected from light, and keep out of the reach of children.