Adult: As monotherapy for the 1st-line treatment of patients with EGFR activating mutations (exon 19 deletion or exon 21 L858R substitution mutations): 45 mg once daily, continued until disease progression or unacceptable toxicity occurs. Dose reduction and dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Severe (Child-Pugh class C): Initially, 30 mg once daily, may be increased to 45 mg once daily after at least 4 weeks of therapy based on individual safety and tolerability.
May be taken with or without food. Take at the same time each day.
Avoid concurrent use with PPIs; may use H2-receptor antagonists or locally-acting antacids as alternatives (give dacomitinib at least 2 or 6 hours before or 10 hours after the antacid or H2-receptor antagonist). Severe hepatic impairment (Child-Pugh class C). Pregnancy.
Significant: Diarrhoea, skin-related effects (e.g. erythematous and exfoliative skin reactions, rash), increased transaminases (e.g. AST, ALT). Blood and lymphatic system disorders: Anaemia, lymphopenia. Cardiac disorders: Chest pain. Eye disorders: Conjunctivitis, keratitis. Gastrointestinal disorders: Nausea, vomiting, stomatitis, constipation, mouth ulceration, dysgeusia. General disorders and administration site conditions: Fatigue, asthenia. Hepatobiliary disorders: Hyperbilirubinaemia. Investigations: Increased alkaline phosphatase and creatinine clearance, decreased weight. Metabolism and nutrition disorders: Hypokalaemia, decreased appetite, hypomagnesaemia, hyponatraemia, hypocalcaemia, hyperglycaemia, hypoalbuminaemia. Musculoskeletal and connective tissue disorders: Musculoskeletal pain, pain in the extremity. Psychiatric disorders: Insomnia. Respiratory, thoracic and mediastinal disorders: Cough, nasal mucosal disorder, dyspnoea, upper respiratory tract infection. Skin and subcutaneous tissue disorders: Palmar-plantar erythrodysaesthesia syndrome, pruritus, skin fissures, dry skin, alopecia, nail disorder (e.g. nail bed inflammation, discolouration), skin exfoliation, hypertrichosis, dermatitis. Potentially Fatal: Interstitial lung disease (ILD) or pneumonitis, severe diarrhoea leading to dehydration (with or without renal impairment). Rarely, hepatic failure.
Patient Counseling Information
This drug may cause ocular side effects and tiredness, if affected, do not drive or operate machinery. Routinely moisturise skin and avoid excessive exposure to sunlight. Use protective clothing and sunscreen when going outdoors. Females of childbearing potential must use effective contraceptive methods during and for at least 17 days after treatment completion.
Confirm EGFR mutation status (EGFR exon 19 deletion or exon 21 L858R substitution mutations) and pregnancy status (in females of childbearing potential) prior to treatment initiation. Monitor LFTs periodically; signs and symptoms of ILD or pneumonitis (e.g. cough, dyspnoea, fever), diarrhoea, and dermatologic reactions.
Symptoms: Gastrointestinal, dermatological, and constitutional reactions (e.g. malaise, fatigue, weight loss). Management: Symptomatic and supportive treatment.
May decrease serum concentrations and efficacy with PPIs (e.g. rabeprazole). May increase the exposure of CYP2D6 substrates (e.g. dextromethorphan) which may lead to increased incidence of drug toxicity or decreased exposure of active metabolites.
Description: Dacomitinib is a selective and irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. It has activity against EGFR/human epidermal growth factor receptor type 1 (HER1), HER2 and HER4, and against EGFR-activating mutations (exon 19 deletion and exon 21 L858R substitution mutations). Pharmacokinetics: Absorption: Bioavailability: 80%. Time to peak plasma concentration: Approx 6 hours (range: 2-24 hours). Distribution: Volume of distribution: 1,889 L. Plasma protein binding: Approx 98%, mainly to albumin and α1-acid glycoprotein. Metabolism: Metabolised in the liver via oxidation and glutathione conjugation primarily by CYP2D6 isoenzyme into O-desmethyl dacomitinib (active major metabolite) and by CYP3A4 isoenzyme into minor oxidative metabolites. Excretion: Mainly via faeces (79%; 20% as unchanged drug); urine (3%; <1% as unchanged drug). Elimination half-life: 70 hours.
Store between 20-25°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01EB07 - dacomitinib ; Belongs to the class of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.
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