Anib 40 mg

Indication:

Anib 40 mg is indicated for the treatment of-

• First-Line Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC): Monotherapy for patients with metastatic non-small cell lung cancer whose tumors harbor non-resistant Epidermal Growth Factor Receptor (EGFR) mutations (specifically exon 19 deletions or exon 21 L858R substitution mutations), as detected by an FDA-approved test.
• Previously Treated Metastatic Squamous NSCLC: Monotherapy for the treatment of patients with metastatic squamous non-small cell lung cancer progressing on or after platinum-based chemotherapy.
• Off-Label/Emerging Indications (Under strict clinical supervision): Advanced or metastatic NSCLC harboring uncommon EGFR mutations (e.g., G719X, L861Q, S768I), excluding the primary T790M resistance mutation unless clinical context specifies combination regimens.

”রেজিস্ট্রার চিকিৎসকের পরামর্শ অনুযায়ী ঔষধ সেবন করুন”

Dogase & Adminstration:

Adult Dosage (Age 18 Years and Older):

• Recommended Starting Dose for EGFR Mutation-Positive NSCLC: 40 mg orally once daily.
• Recommended Starting Dose for Squamous NSCLC (Post-Platinum): 40 mg orally once daily.
• Dose Modifications for Adverse Reactions (e.g., Severe Diarrhea, Rash, Nephrotoxicity):
  • If a patient experiences severe adverse events (Grade ≥3 or persistent Grade 2), withhold afatinib until the reaction resolves to Grade ≤1 or baseline.
  • Resume treatment at a reduced dose: decrease the dose in 10 mg increments (e.g., from 40 mg to 30 mg daily, or 30 mg to 20 mg daily).
  • The minimum therapeutic dose is 20 mg daily. Permanently discontinue if the patient cannot tolerate 20 mg/day.

 Pediatric Dosage (Under 18 Years):

• Safety and Efficacy Not Established: The safety and effectiveness of afatinib in pediatric patients have not been established. Clinical trials are limited, and it is not recommended for routine use in children or adolescents.

Administration Instructions:

• Fasting Requirement: Afatinib must be taken on an empty stomach. Instruct patients not to eat for at least 2 hours before and at least 1 hour after taking the tablet.
• Missed Dose: If a dose is missed, it should be taken as soon as remembered. However, if the next scheduled dose is less than 12 hours away, skip the missed dose and resume the regular schedule. Do not take a double dose.
• Swallowing Difficulties: For patients unable to swallow whole tablets, the tablet can be dispersed in approximately 50 mL of non-carbonated water. No other liquids should be used. Stir until the tablet breaks up into minute particles (it will not dissolve completely) and drink immediately. Rinse the glass with an additional 100 mL of water and drink to ensure the full dose is consumed.

”রেজিস্ট্রার চিকিৎসকের পরামর্শ অনুযায়ী ঔষধ সেবন করুন”

Pharmacology:

• Mechanism of Action: Afatinib is a potent, selective, and irreversible ErbB family blocker. Unlike first-generation reversible EGFR inhibitors (such as gefitinib or erlotinib), afatinib covalently binds to and permanently disables the kinase domains of all homo- and heterodimers formed by the ErbB family receptors: EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4.
  • Downstream Inhibition: By covalently locking onto these receptors, afatinib irreversibly halts autophosphorylation and shuts down critical downstream signaling pathways, primarily the RAS/RAF/MEK/ERK pathway (regulating cell proliferation) and the PI3K/Akt/mTOR pathway (regulating cell survival).
  • Resistance Mitigation: Because it irreversibly blocks multiple ErbB receptors, it can delay or overcome resistance mechanisms that typically defeat narrower, reversible EGFR-TKI therapies, effectively suppressing tumor growth and inducing apoptosis in cells overexpressing these receptors.
• Pharmacokinetics:
  • Absorption: Following oral administration, peak plasma concentrations (Cmax​) are reached within 2 to 5 hours. A high-fat meal significantly decreases absorption, reducing the area under the curve (AUC) by approximately 50% and Cmax​ by 85%. Therefore, it must be taken on an empty stomach.
  • Distribution: Highly bound to human plasma proteins (~95%). It exhibits extensive tissue distribution with a high apparent volume of distribution (Vd​).
  • Metabolism & Elimination: Enzyme-catalyzed metabolic reactions are minimal. Afatinib undergoes non-enzymatic adduct formation with plasma proteins and nucleophiles. The primary route of excretion is fecal (~85%), with a minor fraction excreted via urine (~5%). The elimination half-life (t1/2​) is approximately 37 hours at steady-state, allowing for convenient once-daily dosing.

Side Effects:

• Very Common: Severe diarrhea (can lead to dehydration and hypokalemia), rash/acneiform dermatitis, stomatitis (mouth sores), paronychia (nail bed infection), dry skin, pruritus, and decreased appetite.
• Serious: Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis), severe hepatic impairment (elevated ALT/AST, bilirubin), keratitis (corneal inflammation/perforation), and left ventricular dysfunction.

Drug Interaction:

• P-glycoprotein (P-gp) Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, St. John’s Wort): Co-administration decreases afatinib plasma exposure. If a P-gp inducer is necessary, increase the afatinib daily dose by 10 mg as tolerated, and revert to the original dose 2–3 days after stopping the inducer.
• P-glycoprotein (P-gp) Inhibitors (e.g., Ritonavir, Cyclosporine, Ketoconazole, Erythromycin): Co-administration increases afatinib plasma exposure. If a P-gp inhibitor is necessary, monitor for adverse reactions and reduce the afatinib dose by 10 mg if not tolerated.
• Food Interactions: High-fat meals drastically reduce bio-availability. Strictly adhere to fasting protocols.

Pregnancy & Lactation:

• Pregnancy: Category D. Afatinib can cause fetal harm when administered to a pregnant woman based on its mechanism of action and animal data. Females of reproductive potential must use highly effective contraception during treatment and for at least 2 weeks after the final dose.
• Lactation: It is unknown whether afatinib is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding is strictly advised against during treatment and for 2 weeks after the final dose.

Over Dosage:

• Symptoms: Exaggerated pharmacological side effects including severe diarrhea, extensive skin rash, profound dehydration, electrolyte imbalances, and elevated liver enzymes.
• Treatment: There is no specific antidote for afatinib overdose. Treatment consists of immediate discontinuation of the drug and institution of general supportive care. Initiate aggressive intravenous hydration, manage diarrhea with anti-diarrheals (e.g., Loperamide), monitor electrolytes, and closely track pulmonary/hepatic functions.

Therapeutic Class:

 Antineoplastic Agent; Protein Kinase Inhibitor; Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor.

Storage Conditions:

Store below at 30°C  temperature in a dry place. Away from light and out of reach of children. Do not use the medication after its expiration date.