Bigatab 90mg Tablet

Uses of Bigatab 90mg Tablet

Non-Small Cell Lung Cancer

How does Bigatab 90mg Tablet work?

It acts by inhibiting ALK phosphorylation and the activation of downstream signaling proteins.7

Side Effects of Bigatab 90mg Tablet

• Interstitial Lung Disease (ILD)/Pneumonitis
• Hypertension
• Bradycardia
• Visual Disturbance
• Creatine Phosphokinase (CPK) Elevation
• Pancreatic Enzyme Elevation
• Hyperglycemia

Quick Suggestions:

• Avoid grapefruit and grapefruit juice while taking brigatinib.
• Skip the missed dose and continue the regular schedule.
• If brigatinib is not taken for 14 days or longer, consult with your doctor before restarting.

Indication of Bigatab 90mg Tablet

Bigatab is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic Non-Small Cell Lung Cancer (NSCLC) 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 Bigatab 90mg Tablet

• Recommended dosing regimen:
  • 90 mg orally once daily for the first 7 days.
  • If tolerated, increase to 180 mg orally once daily.
• 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.

Interaction

Drugs that may Increase Bigatab Plasma Concentrations:

• Strong CYP3A inhibitors: Avoid concomitant use; if unavoidable, reduce Bigatab dose by approximately 50%.

Drugs that may Decrease Bigatab Plasma Concentrations:

• Strong CYP3A inducers: Avoid concomitant use.

Drugs that may have their Plasma Concentrations altered by Bigatab:

• CYP3A substrates: Bigatab induces CYP3A in vitro, may decrease concentrations of CYP3A substrates.

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.

Precaution & Warnings:

Interstitial Lung Disease (ILD)/Pneumonitis:

• Promptly evaluate for ILD/pneumonitis with new or worsening respiratory symptoms.
• Discontinue permanently for Grade 3 or 4 ILD/pneumonitis.

Hypertension:

• Control blood pressure before treatment.
• Monitor regularly; withhold for Grade 3 hypertension; consider discontinuation for Grade 4 or recurrent Grade 3.

Bradycardia:

• Monitor heart rate and blood pressure; consider more frequent monitoring with concomitant use of bradycardia-inducing drugs.

Visual Disturbance:

• Withhold and obtain an ophthalmologic evaluation for Grade 2 or greater severity; resume at a reduced dose upon recovery.

CPK Elevation:

• Monitor for unexplained muscle pain, tenderness, or weakness.
• Withhold for Grade 3 or 4 CPK elevation.

Pancreatic Enzyme Elevation:

• Monitor lipase and amylase during treatment.
• Withhold for Grade 3 or 4 pancreatic enzyme elevation.

Hyperglycemia:

• Monitor fasting serum glucose; initiate or optimize antihyperglycemic medications.
• Withhold for inadequate hyperglycemic control; consider dose reduction.

Storage Conditions

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