Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Novartis South Africa (Pty) Ltd, Magwa Crescent West, Waterfall City, Jukskei View, Johannesburg, 2090
AFINITOR is indicated for
Treatment with AFINITOR should be initiated by a medical practitioner experienced in the use of anticancer therapies.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs.
General target population:
The recommended dose of AFINITOR is 10 mg, to be taken once daily.
Management of severe and/or intolerable suspected adverse reactions may require temporary dose reduction and/or interruption of AFINITOR therapy. If dose reduction is required, the suggested dose is 5 mg daily (see section 4.4).
Moderate CYP3A4 or PgP inhibitors: Use caution when administered in combination with moderate CYP3A4 inhibitors or PgP inhibitors. If patients require co-administration of a moderate CYP3A4 or PgP inhibitor, the dose should be reduced to 5 mg daily. Further dose reduction to 5 mg every other day may be required to manage adverse reactions (see sections 4.4 and 4.5).
If the moderate inhibitor is discontinued, consider a washout period of at least 2 to 3 days (average for most commonly used moderate inhibitors) should be allowed before the AFINITOR dose is increased. The AFINITOR dose should be returned to the dose used prior to initiation of the moderate CYP3A4/PgP inhibitor (see sections 4.4 and 4.5).
Strong CYP3A4 inducers: Avoid the use of concomitant strong CYP3A4 inducers. If patients require co- administration of a strong CYP3A4 inducer, consider doubling the daily dose of AFINITOR (based on pharmacokinetic data), using 5 mg increments. This dose of AFINITOR is predicted to adjust the AUC to the range observed without inducers. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued, consider a washout period of at least 3 to 5 days (reasonable time for significant enzyme de-induction), before AFINITOR dose is resumed to the dose used prior to initiation of the strong CYP3A4 inducer (see sections 4.4 and 4.5).
Table 1 summarises recommendations for dose reduction, interruption, or discontinuation of AFINITOR in the management of ADRs. General management recommendations are also provided as applicable. Clinical judgment of the treating medical practitioner should guide the management plan of each patient based on individual benefit/risk assessment.
Table 1. AFINITOR dose adjustment and management recommendations for adverse drug reactions:
| Adverse Drug Reaction | Severitya | AFINITOR Dose Adjustmentb and Management Recommendations |
|---|---|---|
| Non-infectious interstitial pneumonitis | Grade 1 Asymptomatic, clinical, or diagnostic observations only; intervention not indicated | No dose-adjustment required. Initiate appropriate monitoring. |
| Grade 2 Symptomatic, medical intervention indicated, limiting instrumental] ADLc | Consider interruption of therapy, rule out infection and consider treatment with corticosteroids until symptoms Improve to Grade <1 Re-initiate treatment at 5 mg daily. Discontinue treatment if failure to recover within 4 weeks. | |
| Grade 3: Severe symptoms; limiting self-care ADLc oxygen indicated | Interrupt treatment until symptoms resolve to Grade <1. Rule out infection and consider treatment with corticosteroids. Consider re-initiating treatment at 5 mg daily. If toxicity recurs at Grade 3, consider discontinuation. | |
| Grade 4 Life-threatening respiratory compromise; urgent intervention indicated (e.g. tracheotomy or intubation) | Discontinue treatment, rule out infection and consider treatment with corticosteroids. | |
| Stomatitis | Grade 1 Asymptomatic or mild symptoms; intervention not indicated | No dose adjustment required. Manage with non-alcoholic or salt water (0,9%) mouthwash several times a day. |
| Grade 2 Moderate pain; not interfering with oral intake; modified diet indicated | Temporary dose interruption until recovery to Grade <1. Re-initiate treatment at the same dose. If stomatitis recurs at Grade 2, interrupt dose until recovery to Grade <1. Re-initiate treatment at 5 mg daily. Manage with topical analgesic mouth treatments (e.g., benzocaine, butyl amino benzoate, tetracaine hydrochloride. menthol or phenol) with or without topical corticosteroids (i.e. triamcinolone oral paste).d | |
| Grade 3 Severe pain; interfering with oral intake | Temporary dose interruption until recovery to Grade <1. Re-initiate treatment at 5 mg daily. Manage with topical analgesic mouth treatments (e.g., benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol, or phenol) with or without topical corticosteroids (i.e. triamcinolone oral paste).d | |
| Grade 4 Life-threatening consequences; urgent intervention indicated | Discontinue treatment and treat with appropriate medical therapy | |
| Other non-hematologic toxicities (excluding metabolic events) | Grade 1 | If toxicity is tolerable, no dose adjustment required. Initiate appropriate medical therapy and monitor. |
| Grade 2 | If toxicity is tolerable, no dose adjustment required. Initiate appropriate medical therapy and monitor. If toxicity becomes intolerable, temporary dose interruption until recovery to Grade ≤1. Re-initiate treatment at the same dose. If toxicity recurs at Grade 2, interrupt treatment until recovery to Grade ≤1. Re-initiate treatment at 5 mg daily. | |
| Grade 3 | Temporary dose interruption until recovery to Grade ≤1. Initiate appropriate medical therapy and monitor. Consider re-initiating treatment at 5 mg daily. If toxicity recurs at Grade 3, consider discontinuation. | |
| Grade 4 | Discontinue treatment and treat with appropriate medical therapy. | |
| Metabolic events (e.g. hyper-glycaemia, dys-lipidemia) | Grade 1 | No dose adjustment required. Initiate appropriate medical therapy and monitor. |
| Grade 2 | No dose adjustment required. Manage with appropriate medical therapy and monitor. | |
| Grade 3 | Temporary dose interruption. Re-initiate treatment at 5 mg daily. Manage with appropriate medical therapy and monitor. | |
| Grade 4 | Discontinue treatment and treat with appropriate medical therapy. | |
| Thrombocytopenia (Platelet count decreased) | Grade 1 (<LLNe - 75,000/mm³; <LLNe - 75.0 × 109/L) | No dose adjustment required. |
| Grade 2 (<75,000 – 50,000/mm³; <75.0 – 50.0 × 109/L) | Temporary dose interruption until recovery to Grade ≤1. Re-initiate treatment at same dose. | |
| Grade 3 (<50,000 – 25,000/mm³; <50.0 – 25.0 × 109/L) OR Grade 4 (<25,000/mm³; <25.0 × 109/L) | Temporary dose interruption until recovery to Grade ≤1. Re-initiate treatment at 5 mg daily. | |
| Neutropenia (Neutrophil count decreased) | Grade 1 (<LLNe - 1,500/mm³; <LLNe - 1.5 × 109/L) ORGrade 2 (<1,500 – 1,000/mm³; <1.5 – 1.0 × 109/L) | No dose adjustment required. |
| Grade 3 (<1,000 – 500/mm³; <1.0 – 0.5 × 109/L) | Temporary dose interruption until recovery to Grade ≤2. Re-initiate treatment at same dose. | |
| Grade 4 (<500/mm³; <0.5 × 109/L) | Temporary dose interruption until recovery to Grade ≤2. Re-initiate treatment at 5 mg daily. | |
| Febrile neutropenia | Grade 3 ANCf <1,000/mm³ with a single temperature of >38.3°C (101°F) or a sustained temperature of ≥38°C (100.4°F) for more than one hour. | Temporary dose interruption until recovery to Grade ≤2 and no fever. Re-initiate treatment at 5 mg daily. |
| Grade 4 Life-threatening consequences; urgent intervention indicated | Discontinue treatment. |
a Severity Grade description: 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = life-threatening symptoms. Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
b If dose reduction is required, the suggested dose is approximately 50% lower than the dose previously administered.
c Activities of daily living (ADL)
d Avoid using agents containing alcohol, hydrogen peroxide, iodine, and thyme derivatives in management of stomatitis as they may worsen mouth ulcers.
e Lower limit of normal (LLN)
f Absolute Neutrophil Count (ANC)
AFINITOR is not recommended for use in paediatric cancer patients with advanced renal cell carcinoma.
No dosage adjustment is required (see section 5).
No dosage adjustment is required (see section 5).
Hormone receptor-positive advance breast cancer, advanced neuroendocrine tumours of gastrointestinal, lung, or pancreatic origin, advanced renal cell carcinoma and TSC with renal angiomyolipoma
AFINITOR should be administered orally once daily at the same time every day, either consistently with or consistently without food (see section 5).
AFINITOR tablets should be swallowed whole with a glass of water. The tablets should not be chewed or crushed.
For patients unable to swallow tablets, AFINITOR tablet(s) should be dispersed completely in a glass of water (containing approximately 30 ml) by gently stirring, immediately prior to drinking. The glass should be rinsed with the same volume of water and the rinse completely swallowed to ensure the entire dose is administered (see section 5).
General symptomatic and supportive measures should be initiated in case of overdose.
Pack size 30: 3 years.
Pack size 60 and 90: 2 years.
Store at or below 30°C.
Protect from light and moisture.
Store in original package.
Clear colourless thermoformed PA/Al/PVC (polyamide/aluminium/polyvinylchloride) blisters with silver aluminium foil backing.
Pack size of 30, 60, and 90.
Not all pack sizes may be marketed.
The blister foil is imprinted with the proprietary name, company name, batch number and expiry date.
The blisters are packed into a white cardboard carton.
Any unused product or waste material should be disposed of in accordance with local requirements.
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