Introduction

Bigatab 90 mg (Brigatinib) represents a significant advancement in precision oncology, specifically developed for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to Crizotinib. This powerful tyrosine kinase inhibitor, manufactured by Eskayef Pharmaceuticals Ltd. and supplied by Orio Pharma, offers new hope for patients with this specific genetic alteration through its targeted mechanism of action and established clinical efficacy.

Mechanism of Action

Brigatinib is a multi-targeted tyrosine kinase inhibitor with activity against several critical cancer-driving proteins. At clinically achievable concentrations, Brigatinib demonstrates inhibitory effects against multiple kinases including:

• ALK (anaplastic lymphoma kinase)
• ROS1 (c-ros oncogene 1)
• IGF-1R (insulin-like growth factor-1 receptor)
• FLT-3 (FMS-like tyrosine kinase 3)
• EGFR deletion and point mutations (epidermal growth factor receptor)

In both laboratory and living systems, Brigatinib effectively blocks ALK autophosphorylation and inhibits ALK-mediated phosphorylation of downstream signaling proteins STAT3, AKT, ERK1/2, and S6. This comprehensive inhibition of cellular signaling pathways disrupts cancer cell growth and survival mechanisms, leading to tumor regression.

The compound demonstrates particular effectiveness against cells expressing EML4-ALK and NPM-ALK fusion proteins—genetic alterations commonly found in ALK-positive NSCLC—and has shown dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in preclinical mouse models.

Clinical Applications

Bigatab is specifically indicated for patients with ALK-positive metastatic non-small cell lung cancer who have:

• Experienced disease progression while on Crizotinib therapy
• Developed intolerance to Crizotinib treatment

This targeted therapy represents an important treatment option for patients whose cancer continues to advance despite first-generation ALK inhibitor treatment.

Dosage and Administration

Bigatab follows a unique two-step dosing regimen designed to minimize adverse events while maintaining efficacy:

1. Initial Phase: 90 mg orally once daily for the first 7 days
2. Maintenance Phase: If 90 mg is well-tolerated during the first week, increase to 180 mg orally once daily

Additional administration guidelines include:

• 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, wait until the next scheduled time for the next dose
• For treatment interruptions lasting 14 days or longer (for reasons other than adverse reactions), resume at 90 mg once daily for 7 days before increasing to the previously tolerated dose
• Continue treatment until disease progression or unacceptable toxicity occurs

Pharmacokinetic Profile

Understanding Bigatab’s pharmacokinetics helps optimize treatment outcomes:

• Absorption: Following single oral doses of 30-240 mg, median time to peak concentration ranges from 1-4 hours
• Distribution: 66% bound to human plasma proteins; blood-to-plasma concentration ratio of 0.69; mean apparent volume of distribution at steady-state is 153 L
• Metabolism: Primarily metabolized by CYP2C8 and CYP3A4 enzymes; N-demethylation and cysteine conjugation are the two major metabolic pathways
• Elimination: Mean apparent oral clearance at steady-state is 12.7 L/h with a plasma elimination half-life of 25 hours
• Excretion: Following administration of radiolabeled Brigatinib, 65% of the dose was recovered in feces and 25% in urine

Important Safety Information

Warnings and Precautions

1. Interstitial Lung Disease (ILD)/Pneumonitis

Severe, life-threatening, and fatal pulmonary adverse reactions can occur. Monitor for new or worsening respiratory symptoms and promptly evaluate for ILD/pneumonitis. Discontinue permanently for Grade 3-4 ILD/pneumonitis or recurrence of Grade 1-2 ILD/pneumonitis.

2. Hypertension

Hypertension occurs in 11-21% of patients receiving Bigatab. Control blood pressure prior to treatment initiation, monitor after 2 weeks and at least monthly thereafter. Withhold for Grade 3 hypertension despite optimal antihypertensive therapy.

3. Bradycardia

Monitor heart rate and blood pressure regularly, especially when used with medications known to cause bradycardia.

4. Visual Disturbances

Adverse reactions such as blurred vision, diplopia, and reduced visual acuity occur in 7-10% of patients. Obtain ophthalmologic evaluation for new or worsening visual symptoms of Grade 2 or greater severity.

5. Creatine Phosphokinase (CPK) Elevation

CPK elevation occurred in 27-48% of patients. Monitor CPK levels and withhold treatment for Grade 3-4 elevation.

6. Pancreatic Enzyme Elevation

Amylase and lipase elevations occur in 21-45% of patients. Monitor regularly and withhold for Grade 3-4 elevation.

7. Hyperglycemia

New or worsening hyperglycemia affects 43% of patients. Monitor fasting serum glucose prior to treatment initiation and periodically thereafter.

Drug Interactions

CYP3A Inhibitors

• Strong CYP3A Inhibitors: Avoid concomitant use with ketoconazole, certain antivirals, macrolide antibiotics, and antifungals
• Avoid grapefruit and grapefruit juice
• If strong CYP3A inhibitor use cannot be avoided, reduce Bigatab dose by approximately 50%

CYP3A Inducers

• Avoid concomitant use with strong CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John’s Wort

CYP3A Substrates

• May decrease concentrations of CYP3A substrates, including hormonal contraceptives

Use in Special Populations

Pregnancy and Lactation

• May cause fetal harm; advise pregnant women of potential risks
• Advise lactating women not to breastfeed during treatment and for 1 week after final dose

Reproductive Potential

• Females should use effective non-hormonal contraception during treatment and for 4 months afterward
• Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months afterward
• May cause reduced fertility in males based on animal studies

Quality Assurance

Each Bigatab 90 mg tablet is manufactured under stringent quality control standards by Eskayef Pharmaceuticals Ltd., a leading pharmaceutical company with over three decades of experience in producing world-class medications. The manufacturing process adheres to international standards, ensuring consistent potency and purity in every dose.

Global Availability

Orio Pharma, established in 2019 as a specialized oncology medication supplier, ensures that Bigatab 90 mg reaches patients worldwide within 3-7 working days. Our commitment to patient care is reflected in our core values:

1. Compassion: We empathize with cancer patients and their families
2. Integrity: We maintain transparent and ethical business practices
3. Innovation: We continuously seek advanced cancer treatment solutions
4. Collaboration: We partner with healthcare professionals to improve cancer care

Storage Recommendations

For optimal potency, store Bigatab 90 mg tablets below 30°C, protected from light and moisture. Always keep out of reach of children.

Conclusion

Bigatab 90 mg (Brigatinib) represents a significant advancement in targeted therapy for ALK-positive metastatic NSCLC patients who have progressed on or developed intolerance to Crizotinib. Through its multitargeted tyrosine kinase inhibition and unique step-up dosing regimen, Bigatab provides an important treatment option with demonstrated efficacy in this specific patient population.

While offering substantial clinical benefits, Bigatab therapy requires vigilant monitoring for potential adverse reactions, particularly pulmonary, cardiovascular, visual, and metabolic effects. With appropriate patient selection, close monitoring, and management of side effects, Bigatab can contribute meaningfully to improved outcomes for patients with ALK-positive metastatic NSCLC.

For healthcare providers seeking this targeted therapy for appropriate patients, Orio Pharma offers convenient worldwide delivery of authentic Bigatab 90 mg tablets manufactured by Eskayef Pharmaceuticals Ltd., ensuring patients receive this important medication when needed most.