Trepmac 90mg Tablet

✔️ Uses of Trepmac 90mg Tablet

Non-Small Cell Lung Cancer

✔️ How does Trepmac 90mg Tablet work?

• Tyrosine kinase inhibitor with in vitro activity against multiple kinases, including ALK, ROS1, IGF-1R, FLT-3, EGFR, and more.
• Inhibits autophosphorylation of ALK and downstream signaling proteins.
• Exhibits in vivo antitumor activity against various mutant forms of EML4-ALK.

✔️ Side Effects of Trepmac 90mg Tablet

Increased AST, hyperglycemia, increased ALT, nausea, fatigue, headache, increased CPK, increased amylase, dyspnea, vomiting, anemia, decreased appetite, prolonged aPTT, increased lipase, diarrhea, constipation, lymphopenia, cough, abdominal pain, increased alkaline phosphatase, decreased phosphorus, rash, pyrexia, arthralgia, peripheral neuropathy, muscle spasms, hypertension, pain in extremity, insomnia.

✔️ Quick Suggestions:

• Administer until disease progression or unacceptable toxicity.
• If interrupted for 14 days or longer for reasons other than adverse reactions, resume at 90 mg once daily for 7 days before increasing to the tolerated dose.
• May be taken with or without food.
• Tablets should be swallowed whole, not crushed or chewed.
• If a dose is missed or vomiting occurs after taking a dose, do not administer an additional dose.

✔️ Indication of Trepmac 90mg Tablet

Non-small cell Lung Cancer (NSCLC) is indicated for anaplastic lymphoma kinase (ALK)-positive metastatic NSCLC in patients who have progressed on or are intolerant to crizotinib.

✔️ Pharmacology

• Brigatinib is a tyrosine kinase inhibitor with in vitro activity against multiple kinases, including ALK, ROS1, IGF-1R, FLT-3, EGFR deletion, and point mutations.
• Inhibits autophosphorylation of ALK and downstream signaling proteins.
• Demonstrated antitumor activity against EML4-ALK-positive NSCLC xenografts in mice.

Absorption:

• Median time to peak concentration (Tmax) ranged from 1 to 4 hours after single oral doses of Brigatinib (30 to 240 mg).

Distribution:

• Brigatinib is 66% bound to human plasma proteins.
• The mean apparent volume of distribution (Vz/F) at steady-state is 153 L.

Elimination:

• The mean apparent oral clearance (CL/F) at steady-state is 12.7 L/h.
• The mean plasma elimination half-life is 25 hours.

Metabolism:

• Primarily metabolized by CYP2C8 and CYP3A4.
• N-demethylation and cysteine conjugation are major metabolic pathways.

Excretion:

• 65% of the administered dose is excreted in feces, and 25% in urine.
• Unchanged Brigatinib represented a significant portion of total radioactivity in feces and urine.

✔️ Dosage & Administration of Trepmac 90mg Tablet

Adult Dose:

• Initial dose: 90 mg orally once daily for the first 7 days.
• If tolerated, increase the dose to 180 mg orally once daily.
• Continue until disease progression or unacceptable toxicity.

Hepatic Impairment:

• Mild or moderate (Child-Pugh A or B): No dose adjustment required.
• Severe (Child-Pugh C): Reduce once daily dose by ~40%.

Renal Dose:

• Mild or moderate renal impairment (CrCl 30-89 mL/min): No dose adjustment required.
• Severe renal impairment (CrCl 15-29 mL/min): Reduce brigatinib dose by ~50%.

✔️ Interaction

• Increased plasma concentration and adverse reactions with strong CYP3A inhibitors (e.g., certain antivirals, macrolide antibiotics, antifungals, conivaptan).
• Decreased plasma concentration and efficacy with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort).
• Decreased concentration and loss of efficacy of CYP3A substrates (e.g., hormonal contraceptives).

✔️ Contraindications

Hypersensitivity to Brigatinib or any other components.

✔️ Pregnancy & Lactation

• Pregnancy: Contraindicated. Potential risk to a fetus.
• Lactation: Advised not to breastfeed during treatment and for 1 week following the final dose.

✔️ Precautions & Warnings

• Risk of interstitial lung disease (ILD)/pneumonitis, hypertension, bradycardia, visual disturbances, creatine phosphokinase (CPK), pancreatic enzyme elevation, and hyperglycemia.
• Withhold treatment in case of Grade 3 or 4 CPK elevation, Grade 3 or 4 pancreatic enzyme elevation, inadequate hyperglycemic control.
• Discontinue in case of Grade 3 or 4 ILD/pneumonitis, Grade 4 hypertension, life-threatening bradycardia, or Grade 4 visual disturbances.
• Use with caution in combination with antihypertensive agents causing bradycardia.
• Females of reproductive potential should use effective non-hormonal contraception during treatment and for at least 4 months following the final dose.
• Males with female partners of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose.
• Pregnancy and lactation are contraindications.

✔️ Storage Conditions

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.