Afatinib


Thông tin thuốc gốc
Chỉ định và Liều dùng
Oral
Locally advanced non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma
Adult: In patients with non-resistant or activating EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, and locally advanced or metastatic squamous non-small cell lung carcinoma (NSCLC) progressing on or after platinum-based chemotherapy: 40 mg once daily; if tolerated, may increase up to 50 mg daily. Dose increase may be considered after 21 days for EGFR mutation-positive NSCLC; 28 days for squamous NSCLC. Continue until disease progression or unacceptable toxicity occurs. Dose reduction, interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Special Patient Group
Patients taking P-gp inhibitors: Reduce daily dose by 10 mg, preferably given 6 hours apart (for P-gp inhibitors dosed bid) or 12 hours apart (for P-gp inhibitors dosed once daily). Resume to usual afatinib dose upon discontinuation of P-gp inhibitors.

Patients taking P-gp inducer: Increase daily dose by 10 mg as tolerated. Resume to usual afatinib dose 2-3 days after discontinuation of P-gp inducer.
Renal Impairment
Severe (eGFR 15-29 mL/min/1.73m2): Reduce starting dose to 30 mg once daily. Patients with eGFR <15 mL/min/1.73m2 or on haemodialysis: Not recommended.
Hepatic Impairment
Severe (Child-Pugh class C): Not recommended.
Cách dùng
Should be taken on an empty stomach. Take at least 1 hr before or 3 hr after meals. Swallow whole. For patients w/ difficulty swallowing, tab may be dispersed in approx 100 mL of plain, non-carbonated water. No other liqd should be used. Drop the tab in water & stir w/o crushing until it disperses (approx 15 min). Drink immediately. Rinse glass w/ another 100 mL of water & drink. Dispersed liqd may also be administered via nasogastric tube.
Hướng dẫn pha thuốc
May disperse in approx 100 mL of non-carbonated drinking water.
Chống chỉ định
Pregnancy and lactation.
Thận trọng
Patients with cardiac risk factors or decreased LVEF; lower body weight, history of keratitis, ulcerative keratitis or severe dry eyes; history of gastrointestinal ulceration, diverticular disease or bowel metastases. Renal and hepatic impairment. Concomitant use with P-glycoprotein (P-gp) inhibitors and inducers.
Phản ứng phụ
Significant: Decreased baseline LVEF, cutaneous reactions (e.g. acneiform rash, erythema, rash or acne), palmar-plantar erythrodysaesthesia syndrome, gastrointestinal effects (e.g. diarrhoea, stomatitis), paronychia. Rarely, keratitis.
Eye disorders: Dry eyes, conjunctivitis.
Gastrointestinal disorders: Nausea, vomiting, dyspepsia, dysgeusia, cheilitis, pancreatitis.
General disorders and admin site conditions: Pyrexia.
Investigations: Increased ALT/AST, weight decreased.
Metabolism and nutrition disorders: Decreased appetite, hypokalaemia.
Musculoskeletal and connective tissue disorders: Muscle spasms.
Renal and urinary disorders: Cystitis.
Respiratory, thoracic and mediastinal disorders: Rhinorrhoea.
Skin and subcutaneous tissue disorders: Pruritus, dry skin, nail disorders.
Vascular disorders: Epistaxis.
Potentially Fatal: Interstitial lung disease (ILD) or ILD-like reactions (e.g. lung infiltration, pneumonitis, acute respiratory distress syndrome, allergic alveolitis), gastrointestinal perforation, abnormal LFTs and hepatic failure, dehydration with or without renal impairment; bullous, blistering, or exfoliative skin lesions including cases suggestive of Stevens-Johnson syndrome or toxic epidermal necrolysis.
Thông tin tư vấn bệnh nhân
This drug may cause ocular adverse reactions e.g. conjunctivitis, dry eyes, or keratitis, if affected, do not drive or operate machinery. Avoid direct sun exposure and utilise adequate sun protection (e.g. wear protective clothing, use of sunscreen) as it may worsen possible skin reactions. Avoid use of contact lenses.
Monitoring Parameters
Establish EGFR mutation status prior to treatment initiation. Obtain LVEF assessment prior to and during treatment in patients with cardiac risk factors. Monitor LFTs and renal function tests periodically; signs and symptoms of keratitis, ILD, skin toxicity, diarrhoea, and dehydration.
Quá liều
Symptoms: Rash, acne, diarrhoea, nausea, vomiting, asthenia, dizziness, headache, abdominal pain, and elevated amylase. Management: Supportive treatment. May consider emesis or gastric lavage if indicated.
Tương tác
Increased plasma concentration with strong P-gp inhibitors (e.g. ritonavir, ciclosporin A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, amiodarone). Decreased plasma concentration with strong P-gp inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital). May increase bioavailability of oral breast cancer resistance protein (BCRP) substrates (e.g. rosuvastatin, sulfasalazine).
Food Interaction
Significantly decreased absorption and exposure with high-fat meals. Decreased plasma exposure with St. John’s wort.
Tác dụng
Description: Afatinib is a potent and highly selective tyrosine kinase inhibitor of ErbB family. It covalently binds to epidermal growth factor receptor (EGFR or ErbB1), human epidermal growth factor receptor types 2 (HER2 or ErbB2), and 4 (HER4 or ErbB4) in order to irreversibly block the tyrosine kinase autophosphorylation and to downregulate ErbB signalling.
Pharmacokinetics:
Absorption: Reduced absorption with high-fat meals. Bioavailability: 92%. Time to peak plasma concentration: 2-5 hours.
Distribution: Plasma protein binding: Approx 95%.
Metabolism: Covalently adducted to proteins and nucleophilic small molecules. Undergoes minimal enzymatic metabolism.
Excretion: Via faeces (85%) and urine (4%), mainly as unchanged drug. Elimination half-life: 37 hours.
Đặc tính

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Afatinib, CID=10184653, https://pubchem.ncbi.nlm.nih.gov/compound/Afatinib (accessed on Jan. 20, 2020)

Bảo quản
Store at 25°C. Protect from high humidity or moisture, and light.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
Phân loại MIMS
Phân loại ATC
L01EB03 - afatinib ; Belongs to the class of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.
References
Anon. Afatinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/11/2019.

Buckingham R (ed). Afatinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/11/2019.

Gilotrif Tablet, Film Coated (Boehringer Ingelheim Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 21/11/2019.

Joint Formulary Committee. Afatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/11/2019.

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