Introduction

Pazotab 200 mg (Pazopanib) is a potent multi-tyrosine kinase inhibitor developed by Eskayef Pharmaceuticals and distributed by Orio Pharma, representing a significant advancement in targeted cancer therapy. This once-daily oral medication specifically targets multiple receptors involved in tumor growth and angiogenesis, providing an effective treatment option for patients with advanced renal cell carcinoma (RCC) and soft tissue sarcoma (STS).

With its precise mechanism of action and established efficacy profile, Pazotab offers oncologists a valuable therapeutic tool for managing these challenging malignancies, potentially extending survival and improving quality of life for patients battling these aggressive forms of cancer.

Therapeutic Indications

Pazotab is specifically indicated for:

• Treatment of patients with advanced renal cell carcinoma (RCC)
• Treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy

It’s important to note that the efficacy of Pazotab has not been demonstrated for patients with adipocytic STS or gastrointestinal stromal tumors (GIST), highlighting the importance of accurate diagnosis and appropriate patient selection.

Mechanism of Action

Pazotab works by inhibiting multiple tyrosine kinases critical to tumor growth and progression, including:

• Vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3)
• Platelet-derived growth factor receptors (PDGFR-α and PDGFR-β)
• Fibroblast growth factor receptors (FGFR-1 and FGFR-3)
• Cytokine receptor (Kit)
• Interleukin-2 receptor-inducible T-cell kinase (Itk)
• Lymphocyte-specific protein tyrosine kinase (Lck)
• Transmembrane glycoprotein receptor tyrosine kinase (c-Fms)

By blocking these signaling pathways, Pazotab effectively interrupts tumor angiogenesis (formation of new blood vessels), cell proliferation, and survival mechanisms, ultimately inhibiting tumor growth and potentially inducing tumor cell death.

Pharmacokinetic Profile

Pazotab demonstrates favorable pharmacokinetic properties that support its convenient once-daily dosing regimen:

• Absorption: Orally absorbed with peak concentrations achieved within 2-4 hours
• Distribution: Greater than 99% bound to plasma proteins
• Metabolism: Primarily metabolized by CYP3A4 with minor contributions from CYP1A2 and CYP2C8
• Elimination: Mean half-life of approximately 31 hours with elimination primarily via feces (less than 4% excreted renally)

The medication exhibits linear pharmacokinetics with daily dosing at 800 mg resulting in appropriate therapeutic concentrations for effective cancer control.

Dosage and Administration

The recommended starting dose of Pazotab is 800 mg taken orally once daily without food (at least 1 hour before or 2 hours after a meal). This dosing regimen should not exceed 800 mg daily and requires specific administration guidelines:

• Tablets should not be crushed due to potential changes in absorption rate and systemic exposure
• If a dose is missed, it should not be taken if less than 12 hours remain until the next scheduled dose
• Always follow guidance from registered physicians for personalized dosing adjustments

The simple once-daily oral administration enhances treatment adherence and patient convenience compared to more complex cancer treatment regimens.

Clinical Considerations

Drug Interactions

Pazotab has several important drug interactions that require careful management:

CYP3A4 Inhibitors and Inducers:

• Strong CYP3A4 inhibitors (Ketoconazole, Ritonavir, Clarithromycin) increase Pazotab concentrations; if unavoidable, reduce Pazotab dose to 400 mg
• Grapefruit and grapefruit juice should be avoided due to CYP3A4 inhibition
• CYP3A4 inducers (Rifampin) may decrease Pazotab concentrations; chronic use of strong CYP3A4 inducers should be avoided

Transporter Inhibitors:

• Concomitant treatment with strong P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors should be avoided due to risk of increased Pazotab exposure

Effects on Other Medications:

• Pazotab may inhibit CYP3A4, CYP2C8, and CYP2D6 enzymes
• Concomitant use with agents with narrow therapeutic windows metabolized by these enzymes is not recommended
• Special caution with Simvastatin, which shows increased risk of ALT elevations when combined with Pazotab

Adverse Effects

Pazotab treatment may be associated with several significant adverse effects that require monitoring:

• Hepatic toxicity (potentially severe and fatal)
• QT prolongation and risk of Torsades de Pointes
• Cardiac dysfunction
• Hemorrhagic events
• Arterial and venous thromboembolic events
• Thrombotic microangiopathy
• Gastrointestinal perforation and fistula
• Interstitial lung disease/pneumonitis
• Reversible posterior leukoencephalopathy syndrome
• Hypertension
• Hypothyroidism
• Proteinuria
• Tumor lysis syndrome
• Infection risk
• Potential increased toxicity with other cancer therapies

Regular monitoring and appropriate management of these adverse effects are essential components of successful Pazotab therapy.

Special Populations

Pregnancy and Lactation:

• Pazotab can cause fetal harm; effective contraception is required during treatment and for 2 weeks after the final dose
• Breastfeeding is not recommended during treatment and for 2 weeks after the final dose

Males with Female Partners:

• Male patients should use condoms during treatment and for at least 2 weeks after the last dose

Special Age Groups:

• Elderly patients (>65 years) have greater risk for hepatotoxicity
• Safety and effectiveness in pediatric patients have not been established

Safety Monitoring

Due to potential hepatotoxicity, cardiac effects, and other serious adverse reactions, regular monitoring is essential during Pazotab therapy:

• Liver function tests should be performed before and during treatment
• ECG monitoring for QT prolongation
• Blood pressure monitoring for hypertension
• Thyroid function tests for potential hypothyroidism
• Monitoring for proteinuria
• Electrolyte monitoring and maintenance within normal ranges

Early detection of adverse reactions allows for appropriate dose modifications or supportive care to maintain treatment effectiveness while ensuring patient safety.

Storage Conditions

Pazotab should be stored below 30°C in a cool, dry place away from direct sunlight. As with all medications, it should be kept out of reach of children to prevent accidental ingestion.

Manufacturer & Supplier

Pazotab 200 mg is manufactured by Eskayef Pharmaceuticals Ltd., a leading pharmaceutical company in Bangladesh with over three decades of experience in producing world-class medicines. The product is distributed by Orio Pharma, a specialized supplier of anti-cancer and oncology medicines that began operations in June 2019.

Orio Pharma demonstrates its commitment to patient care through worldwide delivery within 3-7 working days, understanding the critical importance of timely access to life-saving cancer treatments.

Conclusion

Pazotab 200 mg (Pazopanib) represents an important advancement in targeted cancer therapy for patients with advanced renal cell carcinoma and soft tissue sarcoma. By simultaneously inhibiting multiple signaling pathways critical to tumor growth and angiogenesis, this medication offers a potent approach to managing these challenging malignancies.

The convenient once-daily oral dosing regimen, combined with Eskayef’s manufacturing excellence and Orio Pharma’s dedicated distribution network, provides patients and healthcare providers with a reliable treatment option that may help improve outcomes in these difficult-to-treat cancers.

As with all cancer therapies, treatment decisions should be made in consultation with qualified oncologists who can weigh the potential benefits against risks and monitor patients appropriately for optimal therapeutic outcomes.