Pazorest 200 mg (Pazopanib Hydrochloride) Tablet

Introduction

Pazorest 200 mg (Pazopanib Hydrochloride) is a potent multi-targeted tyrosine kinase inhibitor (TKI) used in the treatment of various advanced cancers, notably renal cell carcinoma (RCC) and soft tissue sarcoma (STS). As a first-line targeted therapy option, Pazorest offers a critical therapeutic intervention where other chemotherapeutic regimens have failed or become intolerable. Supplied by Saif Pharma, a globally recognized oncology medicine supplier, and manufactured under stringent standards by Everest Pharmaceuticals Ltd, Pazorest ensures accessibility to advanced cancer care across international markets.

Key Indications

1. Advanced Renal Cell Carcinoma (RCC):
   Pazorest is indicated for the treatment of adult patients with advanced RCC, offering a targeted approach to slow disease progression by inhibiting angiogenesis.
2. Advanced Soft Tissue Sarcoma (STS):
   Indicated for patients who have received prior chemotherapy. Pazorest improves progression-free survival in eligible STS subtypes, except for adipocytic STS and gastrointestinal stromal tumors (GIST), where efficacy has not been demonstrated.

Mechanism of Action

Pazopanib works by inhibiting multiple receptor tyrosine kinases (RTKs) responsible for tumor angiogenesis and cell proliferation. These include:

• VEGFR-1, VEGFR-2, VEGFR-3 (Vascular Endothelial Growth Factor Receptors)
• PDGFR-α and PDGFR-β (Platelet-Derived Growth Factor Receptors)
• FGFR-1 and FGFR-3 (Fibroblast Growth Factor Receptors)
• KIT, Itk, Lck, and c-Fms (Cytokine and immune cell receptors)

By blocking these pathways, Pazorest effectively reduces tumor vascularization and slows the growth of malignant cells.

Pharmacokinetics

Absorption:
Following oral administration, Pazorest achieves peak plasma concentration (Cmax) within 2 to 4 hours. Systemic exposure increases up to the 800 mg dose, beyond which absorption plateaus.

Distribution:
Over 99% plasma protein binding with no significant concentration dependency. Pazopanib is a substrate for P-gp and BCRP, affecting its cellular transport.

Metabolism:
Primarily metabolized by CYP3A4, with minor contributions from CYP1A2 and CYP2C8.

Elimination:
Mean terminal half-life is approximately 30.9 hours. The majority of the dose is excreted via feces, with less than 4% excreted renally.

Dosage & Administration

• Standard Dose: 800 mg orally once daily
• Administration: Take without food (at least 1 hour before or 2 hours after meals). Do not crush tablets to avoid increased absorption.
• Missed Dose: If a dose is missed, it should not be taken if it is less than 12 hours until the next scheduled dose.
• Always follow the prescribing physician’s instructions for dosing adjustments based on tolerability and drug interactions.

Drug Interactions

CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin):
Increase Pazorest levels. Reduce Pazorest to 400 mg if co-administered.

CYP3A4 Inducers (e.g., Rifampin):
May lower Pazorest efficacy. Avoid if possible.

P-gp/BCRP Inhibitors:
May elevate Pazorest concentrations; monitor closely and consider alternatives.

Simvastatin:
Increased ALT levels reported with co-administration. Monitor liver enzymes and consider switching statins.

CYP Substrate Drugs:
Pazorest is a weak CYP3A4, CYP2D6, and CYP2C8 inhibitor. Caution is advised when used with drugs having a narrow therapeutic index.

Contraindications

• Known hypersensitivity to Pazopanib or any of its excipients
• Severe hepatic impairment
• Pregnancy and lactation (due to risk of fetal harm and unknown effects in infants)

Adverse Reactions

Common Side Effects (>10% incidence):

• Hypertension
• Diarrhea
• Hair color changes
• Nausea and vomiting
• Fatigue
• Anorexia
• Weight loss
• Headache
• Proteinuria

Serious Side Effects:

• Hepatotoxicity: Elevated liver enzymes, sometimes fatal
• QT Prolongation & Torsades de Pointes
• Cardiac Dysfunction & Thromboembolic Events
• Hemorrhagic Events & Gastrointestinal Perforation
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
• Interstitial Lung Disease

Pregnancy & Lactation

• Pregnancy: Pazorest is teratogenic and can cause fetal harm. Women of reproductive potential should use effective contraception during treatment and for at least 2 weeks after the final dose.
• Lactation: Unknown if excreted in human milk. Breastfeeding is contraindicated during therapy and for at least 2 weeks after the last dose.

Precautions & Warnings

1. Hepatic Monitoring: Liver function tests should be performed before and during treatment.
2. Cardiac Risk: Use cautiously in patients with prior QT prolongation or on QT-prolonging agents.
3. Blood Pressure: Monitor for hypertension and manage appropriately.
4. Proteinuria: Monitor urinalysis during treatment.
5. Infections & GI Events: Patients should report signs of infection or abdominal symptoms immediately.
6. Use in Elderly: Caution advised due to increased risk of hepatotoxicity.

Use in Special Populations

• Geriatric: No dose adjustment required, but monitor liver function more frequently.
• Pediatric: Safety and efficacy have not been established.
• Renal Impairment: No dose adjustment necessary for mild to moderate impairment.
• Hepatic Impairment: Not recommended for patients with severe hepatic dysfunction.

Overdose Management

In clinical trials, doses up to 2000 mg daily have been tested. Dose-limiting toxicity includes Grade 3 fatigue and hypertension. There is no specific antidote. Management involves general supportive care. Due to high protein binding and low renal excretion, hemodialysis is unlikely to be beneficial.

Storage Information

• Store below 30°C
• Protect from light, moisture, and heat
• Keep out of the reach of children

Conclusion

Pazorest 200 mg (Pazopanib Hydrochloride) is a clinically proven, targeted cancer therapy offering a survival benefit in patients with advanced renal cell carcinoma and soft tissue sarcoma. With its broad kinase inhibition profile, Pazorest effectively blocks tumor growth and angiogenesis. Saif Pharma, as a trusted global supplier of oncology medications, ensures reliable access to this essential therapy. Manufactured by Everest Pharmaceuticals Ltd, Pazorest upholds the highest quality standards in pharmaceutical production.

Patients must use Pazorest strictly under the supervision of a registered oncologist or specialist. Regular monitoring and awareness of side effects and interactions are critical for effective and safe therapy. This product represents a vital solution in the modern management of difficult-to-treat solid tumors.