Pazopanib

BRAND NAMES

Pazopanib is commonly sold under the brand name Votrient and comes in oral tablets, usually in 200 mg or 400 mg strengths. Generic formulations may be available in certain areas. The drug is primarily prescribed for the treatment of advanced renal cell carcinoma (RCC) and soft tissue sarcomas (STS). Choice of brand often depends on local regulatory approvals and availability.

MECHANISM OF ACTION

Pazopanib is a tyrosine kinase inhibitor (TKI) that targets multiple receptors. It blocks VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α/β, and c-Kit, which are involved in tumor growth and angiogenesis. By inhibiting these pathways, it prevents tumor blood vessel formation, slowing cancer progression. It also indirectly reduces tumor cell proliferation. The drug’s effects are dose-dependent and require continuous administration for maximal benefit.

PHARMACOKINETICS

Absorption: Pazopanib is orally absorbed, with peak plasma concentrations reached in 3–5 hours.

Distribution: It is highly protein-bound (~99%) and distributes extensively in body tissues.

Metabolism: Metabolized mainly in the liver via CYP3A4, with minor contributions from CYP1A2 and CYP2C8.

Excretion: Eliminated primarily in feces, with a half-life of approximately 30 hours.

PHARMACODYNAMICS

Pazopanib inhibits angiogenesis, reducing tumor vascular supply and oxygen delivery. This action slows tumor growth and metastasis. Its therapeutic effect is concentration-dependent and correlates with plasma drug levels. It also affects tumor signaling pathways, decreasing cell proliferation. Continuous monitoring of blood pressure and liver function helps optimize therapy.

ADMINISTRATION

Pazopanib is administered orally as a tablet, usually once daily. It should be taken on an empty stomach, at least one hour before or two hours after food. Swallow tablets whole without crushing or chewing. Dose modifications may be required for liver impairment or severe side effects. Patients should follow strict adherence to maintain efficacy.

DOSAGE AND STRENGTH

For the treatment of renal cell carcinoma or soft tissue sarcoma, the typical dose is 800 mg once daily. Tablets come in 200 mg and 400 mg strengths, enabling dose adjustments as needed. Dose reductions may be required in cases of liver toxicity or significant side effects. Therapy usually continues until the disease progresses or adverse effects become unacceptable. Regular monitoring helps maintain safe and effective dosing.

DRUG INTERACTIONS

Pazopanib is metabolized by CYP3A4, so strong inhibitors or inducers can alter its levels. Concomitant use with CYP3A4 inhibitors (like ketoconazole) increases risk of toxicity. CYP3A4 inducers (like rifampin) can reduce efficacy. Co-administration with QT-prolonging drugs may increase cardiac risk. Careful review of all concurrent medications is essential before starting therapy.

FOOD INTERACTIONS

Pazopanib should be taken on an empty stomach as food increases absorption variability. High-fat meals may increase drug exposure, potentially worsening side effects. Patients should avoid grapefruit juice, which can interfere with metabolism.

CONTRAINDICATIONS

Pazopanib should not be used in individuals who are hypersensitive to the drug or have severe liver impairment. Caution is advised in patients with heart disease or uncontrolled high blood pressure. Its use during pregnancy or breastfeeding is generally not recommended unless the potential benefits outweigh the risks. Patients with bleeding disorders or a history of vascular events require careful monitoring.

SIDE EFFECTS

• hypertension

• diarrhea

• hair color changes

• nausea

• Fatigue.

OVER DOSE

An overdose of pazopanib may result in severe hypertension, liver toxicity, or cardiac arrhythmias. Signs and symptoms can include nausea, vomiting, fatigue, and hypotension. Treatment is primarily supportive, involving careful monitoring of vital signs, liver function, and heart status. There is no specific antidote for a pazopanib overdose, so early recognition and immediate medical care are essential for patient safety.

TOXICITY

Pazopanib toxicity primarily affects the liver, cardiovascular system, and gastrointestinal tract. Hepatotoxicity is the most concerning, requiring dose adjustment or discontinuation. It may also cause bleeding, proteinuria, and cardiac arrhythmias. Toxicity risk increases with high doses, drug interactions, or pre-existing organ impairment. With proper monitoring, most toxic effects are reversible after dose modification or discontinuation.