Severe hepatotoxicity (including fatal hepatic failure):
Common and potentially fatal.
Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin at baseline, weeks 3, 5, 7, 9, months 3–4, then periodically.
Permanently discontinue if ALT >3 × upper limit of normal (ULN) with bilirubin >2 × ULN.
Hypertension and hypertensive crisis:
Occurs early (often within first 1–2 weeks).
Control blood pressure before starting; monitor frequently.
Interrupt or discontinue if severe or persistent.
Cardiac toxicity:
Risk of heart failure, reduced left ventricular ejection fraction (LVEF), QT prolongation, and Torsade de Pointes.
Baseline and periodic ECG and LVEF assessment in at-risk patients.
Thrombotic events:
Arterial thrombosis (myocardial infarction, ischaemic stroke, transient ischaemic attack).
Venous thromboembolism including pulmonary embolism.
Thrombotic microangiopathy (TMA):
Includes thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome.
Permanently discontinue if TMA develops.
Tumour lysis syndrome (TLS):
Including fatal cases, especially in patients with high tumour burden or renal impairment.
Ensure hydration and close biochemical monitoring.
Posterior reversible encephalopathy syndrome (PRES):
Presents with headache, seizures, confusion, visual disturbance.
Permanently discontinue if suspected.
Interstitial lung disease / pneumonitis:
Can be fatal.
Stop treatment if respiratory symptoms develop.
Gastrointestinal perforation or fistula:
Rare but life-threatening; permanently discontinue if occurs.
Wound-healing complications:
Stop at least 7 days before surgery; restart only after adequate wound healing.
Pregnancy and breastfeeding:
Contraindicated — foetal harm expected.
Generic name: Pazopanib
Brand name: VOTRIENT®
Drug class: Multi-target tyrosine kinase inhibitor (VEGF inhibitor)
Formulation: Film-coated tablets
Strengths: 200 mg, 400 mg
Mechanism of Action:
Pazopanib inhibits vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), platelet-derived growth factor receptors (PDGFR-α, PDGFR-β), and c-KIT, leading to inhibition of tumour angiogenesis and tumour growth.
Treatment of advanced and/or metastatic renal cell carcinoma in adults.
May be used as first-line therapy or after cytokine-based therapy.
Treatment of adult patients with selective subtypes of advanced soft tissue sarcoma:
Who have received prior chemotherapy for metastatic disease, or
Who have progressed within 12 months after neoadjuvant or adjuvant therapy.
⚠️ Important limitation:
Efficacy is established only in specific STS histological subtypes, including:
Leiomyosarcoma
Synovial sarcoma
Fibroblastic and fibrohistiocytic sarcomas
Malignant peripheral nerve sheath tumours
Vascular sarcomas (e.g. angiosarcoma)
Undifferentiated soft tissue sarcoma (NOS)
❌ Not indicated for:
Gastrointestinal stromal tumours (GIST)
Adipocytic sarcomas
Osteosarcoma, chondrosarcoma, Ewing sarcoma
Standard dose (RCC and STS):
800 mg orally once daily
Administration instructions:
Take without food (≥1 hour before or ≥2 hours after meals).
Swallow tablets whole — do not crush or break.
Missed dose:
Do not take if <12 hours to next scheduled dose.
General:
Dose adjustments in 200 mg increments based on tolerability.
Maximum dose: 800 mg daily.
Hepatic impairment:
Mild impairment: No adjustment.
Moderate impairment: 200 mg once daily.
Severe impairment: Contraindicated.
Hypertension, hepatotoxicity, cardiac toxicity, proteinuria:
Interrupt, reduce dose, or permanently discontinue depending on severity.
Avoid with:
Strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, ritonavir) — ↑ toxicity.
Strong CYP3A4 inducers (e.g. rifampicin) — ↓ efficacy.
Grapefruit or grapefruit juice.
Proton pump inhibitors (↓ absorption).
Caution with:
Simvastatin (↑ risk of liver enzyme elevation).
QT-prolonging drugs.
Antihypertensives (monitor BP closely).
Hypersensitivity to pazopanib or excipients
Pregnancy and breastfeeding
Severe hepatic impairment
Baseline and ongoing:
Liver function tests (ALT, AST, bilirubin)
Blood pressure
ECG ± electrolytes (potassium, magnesium, calcium)
Urinalysis (proteinuria)
Thyroid function tests
LVEF in patients with cardiac risk
| Frequency | Adverse Effect | Management |
|---|---|---|
| Very common | Hypertension, diarrhoea, fatigue, nausea, hair depigmentation | Symptomatic treatment |
| Common | Hepatotoxicity, hypothyroidism, proteinuria, palmar-plantar erythrodysaesthesia | Dose interruption/reduction |
| Serious | Heart failure, QT prolongation, thromboembolism, TMA, PRES, TLS | Stop drug permanently |
| Rare/fatal | Hepatic failure, GI perforation, pneumonitis | Emergency management |
Elderly: No dose adjustment required.
Renal impairment: No adjustment if creatinine clearance ≥30 mL/min.
Hepatic impairment: Dose reduction required; avoid if severe.
Pregnancy/Lactation: Contraindicated.
Paediatrics: Not recommended.
Continue until:
Disease progression, or
Unacceptable toxicity.
Permanently discontinue if:
Severe hepatotoxicity
Thrombotic microangiopathy
Posterior reversible encephalopathy syndrome
Gastrointestinal perforation
Reference: https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2025/04/votrient-pi-31032025.pdf
| Generic Name | Pazopanib |
|---|---|
| Drug Class | 1 |
| Cost | |
| Company | |
|---|---|
| Drug Rep | Admin |
| Indications | Kidney Cancer (Renal Cell Carcinoma) - RCC, Sarcomas |
| Dosage |