Dacomitinib


Generic Medicine Info
Indications and Dosage
Oral
EGFR positive locally advanced non-small cell lung cancer, EGFR positive metastatic non-small cell lung cancer
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).
Hepatic Impairment
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.
Administration
May be taken with or without food. Take at the same time each day.
Contraindications
Lactation.
Special Precautions
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.
Adverse Reactions
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.
Monitoring Parameters
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.
Overdosage
Symptoms: Gastrointestinal, dermatological, and constitutional reactions (e.g. malaise, fatigue, weight loss). Management: Symptomatic and supportive treatment.
Drug Interactions
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.
Action
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.
Chemical Structure

Chemical Structure Image
Dacomitinib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 11511120, Dacomitinib. https://pubchem.ncbi.nlm.nih.gov/compound/Dacomitinib. Accessed Apr. 26, 2021.

Storage
Store between 20-25°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01EB07 - dacomitinib ; Belongs to the class of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.
References
Anon. Dacomitinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/04/2021.

Anon. Dacomitinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/04/2021.

Buckingham R (ed). Dacomitinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/04/2021.

Joint Formulary Committee. Dacomitinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/04/2021.

Vizimpro 15 mg, 30 mg and 45 mg Film-Coated Tablets (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/04/2021.

Vizimpro 45 mg Film-Coated Tablets (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/04/2021.

Vizimpro Film Coated Tablet (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/04/2021.

Disclaimer: This information is independently developed by MIMS based on Dacomitinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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