• Severe hepatotoxicity (including fatal liver failure) → check LFTs before treatment and regularly during therapy
• Severe bleeding risk (GI, pulmonary, intracranial, genitourinary) → discontinue if severe
• GI perforation or fistula can occur → stop treatment immediately if suspected
• Severe hypertension → control BP before starting and monitor regularly
• Hand–foot skin reaction (HFSR) is common and dose-limiting
• Impaired wound healing → interrupt before major surgery
• Serious infections may occur
• Reversible posterior leukoencephalopathy syndrome (RPLS) reported
• Pregnancy and breastfeeding contraindicated
Generic name: Regorafenib
Brand name: STIVARGA®
Drug class: Oral multikinase inhibitor (anti-angiogenic and anti-proliferative)
Formulation: Film-coated tablets
Strength: 40 mg
Mechanism of Action:
Regorafenib inhibits multiple protein kinases involved in tumour angiogenesis, oncogenesis and the tumour microenvironment, leading to reduced tumour growth and spread.
STIVARGA is indicated for the treatment of the following malignancies in adult patients:
• Colon or rectal cancer that has metastasised, in patients who have:
– Received prior fluoropyrimidine-based chemotherapy, and
– Received anti-VEGF therapy, and
– If RAS wild-type, received anti-EGFR therapy, or
– Are not candidates for these treatments
• Unresectable or metastatic gastrointestinal stromal tumours,
• In patients who have been previously treated with two tyrosine kinase inhibitors
• Liver cancer in patients who have been previously treated with another anticancer medicine
Recommended dose (adults):
• 160 mg once daily (4 × 40 mg tablets)
Schedule:
• Take once daily for 3 weeks on, followed by 1 week off
• One cycle = 4 weeks
Administration:
• Take at the same time each day
• Swallow tablets whole with water
• Take after a light, low-fat meal
• Avoid grapefruit juice
Continue treatment as long as clinical benefit is observed and toxicity is acceptable.
• Dose reductions, interruptions or permanent discontinuation may be required for toxicity
• Reduce dose stepwise based on tolerability
• Permanently discontinue for:
– Severe liver injury
– GI perforation or fistula
– Life-threatening bleeding
• Hypersensitivity to regorafenib or excipients
• Pregnancy
• Breastfeeding
• Severe gastrointestinal disorders
• Liver function tests: Baseline and regularly during treatment
• Blood pressure: Baseline and during therapy
• Full blood count: Periodically
• Electrolytes: As clinically indicated
• Clinical monitoring for bleeding, infection, skin toxicity and GI symptoms
• Hand–foot skin reaction
• Fatigue / asthenia
• Diarrhoea
• Decreased appetite and weight loss
• Hypertension
• Infections
• Stomatitis / mucosal inflammation
• Nausea and vomiting
• Alopecia
• Rash
• Fever
• Severe liver injury
• Severe bleeding
• Gastrointestinal perforation or fistula
• Myocardial ischaemia or infarction
• Hypertensive crisis
• Pancreatitis
• RPLS
• Stevens–Johnson syndrome / toxic epidermal necrolysis
• Secondary skin malignancies
• CYP3A4 inhibitors (e.g. ketoconazole) → ↑ regorafenib levels
• CYP3A4 inducers (e.g. rifampicin) → ↓ effectiveness
• Warfarin → ↑ bleeding risk
• Avoid grapefruit juice
• Hepatic impairment:
– Mild–moderate: use with close monitoring
– Severe: contraindicated
• Renal impairment: No dose adjustment required
• Elderly: No dose adjustment required
• Pregnancy: Contraindicated
• Breastfeeding: Contraindicated
Continue until:
• Disease progression, or
• Unacceptable toxicity
Permanently discontinue if:
• Severe hepatotoxicity
• GI perforation or fistula
• Life-threatening bleeding
• Severe skin or neurological toxicity
https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2022/11/STIVARGA-ENG-PIL-01.06.2020.pdf
| Trade Name | |
|---|---|
| Drug Class | 1 |
| Cost | |
| Company | |
|---|---|
| Drug Rep | Admin |
| Indications | Hepatocellular Carcinoma (HCC), Colon Cancer, Gastric (stomach) Cancer |
| Dosage |