PAZOPANIB HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Pazopanib is a multi-targeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptors (VEGFR-1, -2, -3), platelet-derived growth factor receptors (PDGFR-α, -β), and stem cell factor receptor (c-Kit). It also inhibits other kinases such as fibroblast growth factor receptors (FGFR-1, -3), cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor (c-Fms).
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP1A2 and CYP2C8. Pazopanib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). |
| Excretion | Primarily fecal (83%), with renal elimination accounting for <4% of the administered dose. |
| Half-life | Terminal half-life is approximately 31 hours, supporting once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 34.4 L (0.49 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 21–30% following a 800 mg dose; can be increased by food (high-fat meal) but is not recommended. |
| Onset of Action | Peak plasma concentrations attained 2–5 hours after oral administration; clinical effect (e.g., tumor response) typically observed within weeks. |
| Duration of Action | Duration of therapeutic effect is maintained with continuous daily dosing; steady-state reached within 2–3 weeks. |
| Molecular Weight | 473.36 |
800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). Do not crush tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe impairment (CrCl <30 mL/min). |
| Liver impairment | Mild impairment (Child-Pugh A): no dose adjustment. Moderate impairment (Child-Pugh B): reduce dose to 200 mg orally once daily, titrate as tolerated. Severe impairment (Child-Pugh C): contraindicated. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended. Monitor for greater sensitivity to adverse effects (e.g., hypertension, hepatotoxicity) due to potential age-related renal and hepatic function decline. |
| 1st trimester | Avoid due to risk of teratogenicity; animal studies show fetal harm. |
| 2nd trimester | Avoid; may cause fetal growth restriction and oligohydramnios. |
| 3rd trimester | Avoid; risk of neonatal hypotension, renal impairment, and other adverse effects. |
Clinical note
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause hepatotoxicity and QT prolongation.
| Placental transfer | Pazopanib is highly bound to plasma proteins (99.9%), likely crosses placenta based on animal studies; human data lacking but expected due to low molecular weight. |
| Breastfeeding | No human data; high protein binding suggests limited excretion, but potential for infant harm exists. Discontinue breastfeeding or drug. |
| Lactation Rating |
■ FDA Black Box Warning
Severe and fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function before and during treatment. Pazopanib should not be used in patients with severe hepatic impairment (Child-Pugh class C).
| Common Effects | soft tissue sarcoma |
| Serious Effects |
Hypersensitivity to pazopanib or any excipientsSevere hepatic impairment (Child-Pugh Class C)Uncontrolled hypertensionQTc interval >500 msRecent hemoptysis (≥2.5 mL red blood) within 4 weeks
| Precautions | Hepatotoxicity (monitor LFTs), hypertension (monitor blood pressure), QT prolongation (monitor ECG), cardiac dysfunction (including left ventricular ejection fraction decline), hemorrhage (especially in STS patients), thrombotic microangiopathy, gastrointestinal perforation or fistula, hypothyroidism, proteinuria, wound healing complications, increased risk of infection, and reversible posterior leukoencephalopathy syndrome (RPLS). |
Loading safety data…
| L5 |
| Teratogenic Risk | Based on animal studies and its mechanism of action (VEGF receptor inhibitor), pazopanib is associated with teratogenicity and embryofetal toxicity. In pregnant women, use is contraindicated. First trimester exposure carries risk of structural anomalies including cardiovascular and skeletal malformations. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and potential fetal renal impairment due to anti-angiogenic effects. |
| Fetal Monitoring | Monitor blood pressure every 2 weeks during pregnancy (if inadvertent exposure). Perform fetal ultrasound for growth and anatomy at 18-22 weeks and serial growth scans every 4 weeks from 28 weeks. Monitor amniotic fluid index. Assess renal function (creatinine) in mother and fetus. Evaluate urine protein for proteinuria. |
| Fertility Effects | Pazopanib may impair fertility in females based on animal studies showing decreased ovarian weight, follicular atresia, and reduced corpora lutea. In males, testicular degeneration and reduced sperm count have been observed. Reversibility is unknown. Preclinical data suggest potential for ovarian failure and male infertility. |
| Food/Dietary |
| Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition increasing pazopanib levels. Avoid St. John's wort as it may reduce drug efficacy. Administer on an empty stomach; high-fat meals decrease absorption and increase variability. |
| Clinical Pearls | Monitor liver function tests at baseline and monthly; pazopanib has boxed warning for hepatotoxicity. Dose reduction required for moderate hepatic impairment; avoid in severe impairment. Check blood pressure weekly for first 8 weeks due to hypertension risk. Monitor thyroid function; hypothyroidism is common. Pazopanib is a strong CYP3A4 inhibitor; avoid concurrent use with sensitive CYP3A4 substrates. Administer on empty stomach at least 1 hour before or 2 hours after meals to maximize absorption. |
| Patient Advice | Take pazopanib on an empty stomach, at least 1 hour before or 2 hours after a meal. · Do not crush or split tablets; swallow whole. · Avoid grapefruit, grapefruit juice, and St. John's wort during treatment. · Report yellowing of skin or eyes, dark urine, or abdominal pain immediately. · Monitor blood pressure regularly; report severe headaches or vision changes. · Use effective contraception during treatment and for 2 weeks after last dose. · Avoid prolonged sun exposure; use sunscreen and protective clothing. |