Lucius Version of Afatinib: Dosage and Administration, Indications, Precautions

Lucius Version of Afatinib: Dosage and Administration, Indications, Precautions

Indications

Afatinib is a kinase inhibitor indicated for:

First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.

Usage Limitation: The safety and efficacy of afatinib in patients with tumors harboring resistant EGFR mutations have not been established.

Treatment of patients with metastatic squamous NSCLC who have progressed after platinum-based chemotherapy.

Dosage and Administration

Recommended Dose: 40 mg orally, once daily.

Renal Impairment: For patients with severe renal impairment, the dose is 30 mg orally once daily.

Instruct patients to take afatinib at least 1 hour before or 2 hours after meals.

Drug Interactions

P-glycoprotein (P-gp) Interactions

Based on in vitro data, afatinib is a substrate of P-gp. Clinical data indicate that concomitant use with P-gp inhibitors or inducers may alter afatinib exposure.

Results from drug interaction studies confirm that P-gp inhibitors (e.g., ritonavir) can be safely co-administered with this product either concomitantly or after administration of this product.

If administered prior to this product, strong P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) may increase afatinib exposure and should be used with caution (see [Dosage and Administration], [Precautions], and [Pharmacokinetics]).

Strong P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, or St. John’s Wort) may decrease afatinib exposure (see [Precautions] and [Pharmacokinetics]).

Effect of Food on Afatinib

Co-administration of this product with a high-fat meal results in a significant reduction in afatinib exposure, with a approximately 50% decrease in Cmax and a approximately 39% decrease in AUC0-∞. This product should not be taken with food (see [Dosage and Administration] and [Pharmacokinetics]).

Overdosage

1. Symptoms

In phase I clinical trials, the highest doses of this product studied in a limited number of patients were 160 mg once daily for 3 consecutive days and 100 mg once daily for 2 consecutive weeks. Adverse reactions at these doses were mainly dermatological (rash/acne) and gastrointestinal events (especially diarrhea).

Two healthy adolescents who each ingested 360 mg of afatinib (as part of a mixed medication intake) experienced overdose-related adverse reactions including nausea, vomiting, fatigue, dizziness, headache, abdominal pain, and elevated amylase (<1.5 times the upper limit of normal [ULN]). Both subjects recovered from these adverse events.

2. Treatment

There is no specific antidote for afatinib overdosage. When overdose is suspected, administration of this product should be discontinued and supportive care initiated. If indicated, unabsorbed afatinib may be removed by emesis or gastric lavage.

Warnings and Precautions

Diarrhea: Diarrhea may lead to dehydration and renal failure. For severe and prolonged diarrhea unresponsive to antidiarrheal medications, hold afatinib.

Bullous and Exfoliative Dermatological Disorders: Severe bullous, blistering, and exfoliative lesions occurred in 0.2% of patients. Discontinue afatinib for life-threatening skin reactions. Withhold afatinib for severe and prolonged skin reactions.

Interstitial Lung Disease (ILD): Occurred in 1.6% of patients. Withhold afatinib in patients with acute onset or worsening of pulmonary symptoms. Discontinue afatinib if ILD is diagnosed.

Hepatotoxicity: Fatal hepatic injury occurred in 0.2% of patients. Perform regular liver function tests. Hold or discontinue afatinib if worsening liver disease is detected.

Gastrointestinal Perforation: Occurred in 0.2% of patients. Permanently discontinue afatinib in patients who develop gastrointestinal perforation.

Keratitis: Occurred in 0.7% of patients. Hold afatinib for evaluation of keratitis. Withhold or discontinue afatinib for confirmed ulcerative keratitis.

Embryo-Fetal Toxicity: May cause fetal harm when administered to pregnant women. Advise pregnant women and females of reproductive potential of the potential risk to the fetus and to use effective contraception.

Adverse Reactions

The most common adverse reactions (≥20%) are diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, and pruritus.

Contraindications

None identified.

Dosage Form

Tablets

Storage

Store at 20°C to 25°C (68°F to 77°F); short-term storage is permitted at 15°C to 30°C (59°F to 86°F) for transportation.