1. Clinical Overview
Pazopanib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), fibroblast growth factor receptor (FGFR-1 and FGFR-3), cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). It is a cornerstone in the management of advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS) in the Indian oncology setting.
| Onset | Duration | Bioavailability |
|---|---|---|
| Peak plasma concentrations (Tmax) are achieved approximately 2 to 4 hours after oral administration. | The therapeutic effect is sustained over the dosing interval of 24 hours, necessitating once-daily dosing. | Bioavailability is variable and increased with food. The mean absolute bioavailability is approximately 21% under fasting conditions. |
2. Mechanism of Action
Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor that blocks the ATP-binding sites of specific receptors involved in tumor angiogenesis, tumor growth, and metastatic progression. Its primary anti-tumor effect is mediated through inhibition of VEGFR-2, which is critical for endothelial cell proliferation and new blood vessel formation (angiogenesis) required for tumor survival and growth.
3. Indications & Uses
- Advanced Renal Cell Carcinoma (RCC)
- Advanced Soft Tissue Sarcoma (STS) in patients who have received prior chemotherapy
4. Dosage & Administration
Adult Dosage: 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The recommended starting dose is 800 mg. For the 400mg tablet, this equates to two 400mg tablets taken together once daily.
Administration: Swallow tablet whole with water. Do not crush or break. Must be taken on an empty stomach, at least 1 hour before or 2 hours after a meal. If a dose is missed, it should not be taken if it is less than 12 hours until the next dose. Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole) should be avoided; if unavoidable, reduce pazopanib dose to 400 mg daily. Concomitant use of strong CYP3A4 inducers (e.g., rifampin) should be avoided as they may decrease pazopanib efficacy.
5. Side Effects
Common side effects may include:
- Hypertension
- Diarrhea
- Nausea
- Vomiting
- Fatigue
- Hair color changes (depigmentation)
- Anorexia
- Increased liver enzymes (ALT, AST)
- Dysgeusia (altered taste)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Significantly increase pazopanib plasma concentration, increasing risk of toxicity. | Major |
| Strong CYP3A4 Inducers (e.g., Rifampin, Carbamazepine, Phenytoin, St. John's Wort) | Significantly decrease pazopanib plasma concentration, reducing efficacy. | Major |
| CYP3A4/5/2C8 Substrates (e.g., Simvastatin) | Pazopanib may increase concentrations of these drugs. | Moderate |
| CYP2D6 Substrates (e.g., Debrisoquine) | Pazopanib is a weak inhibitor of CYP2D6; monitor for increased effects. | Moderate |
| P-gp Substrates (e.g., Digoxin) | Pazopanib may increase digoxin concentration; monitor serum levels. | Moderate |
| Antihypertensives | Pazopanib-induced hypertension may necessitate adjustment of antihypertensive therapy. | Moderate |
| Drugs that Prolong QT Interval (e.g., Class Ia/III antiarrhythmics, Moxifloxacin) | Additive risk of QT prolongation and cardiac arrhythmias. | Major |
7. Patient Counselling
- DO take the tablet on an empty stomach (1 hour before or 2 hours after food).
- DO swallow the tablet whole with water; do not crush or break.
- DO monitor your blood pressure regularly as advised by your doctor.
- DO report any signs of liver problems (yellowing of skin/eyes, dark urine, severe nausea, abdominal pain).
- DONT consume grapefruit or grapefruit juice while on this medication.
- DONT take over-the-counter medications, herbal supplements (especially St. John's Wort), or other prescriptions without consulting your doctor.
- DONT take the missed dose if it is less than 12 hours to your next scheduled dose.
8. Toxicology & Storage
Overdose: Symptoms may include severe hypertension, severe diarrhea, nausea, vomiting, fatigue, and exacerbation of adverse reactions such as hepatotoxicity. Single doses up to 2000 mg have been reported with increased frequency of adverse events.
Storage: Store at room temperature (15°C to 30°C). Protect from moisture. Keep in the original blister pack or container. Keep out of reach of children.