Oral Anticancer Medicine Safety

Oral anticancer medicines are taken at home without nursing supervision, so safety depends on clear instructions, adherence, interaction checks and monitoring. Errors in weekly versus daily dosing, cycle length and missed monitoring cause serious harm. Prescribing is by an oncology team and follows a regimen sheet.

Types. Cytotoxics (capecitabine, temozolomide, hydroxycarbamide, mercaptopurine, methotrexate), targeted agents (imatinib, erlotinib, sunitinib, lapatinib), and hormonal agents (tamoxifen, letrozole, anastrozole, abiraterone).

Core safety elements.

• Name of drug, strength, dose, schedule (days on and days off) and cycle length written on the prescription and on a patient calendar.
• Limit supply to one cycle at a time; no automatic repeats.
• Pharmacist check for interactions at every cycle.
• Documented teach-back with the patient and carer, a 24 hour contact number and a written plan for missed doses, vomiting and side effects.

Common regimens (adult).

• Capecitabine 1000 to 1250 mg/m2 orally twice daily within 30 minutes of food, on days 1 to 14 every 21 days (850 to 1000 mg/m2 twice daily in combination regimens).
• Imatinib 400 mg orally daily with food (600 to 800 mg in advanced gastrointestinal stromal tumour or blast phase).
• Temozolomide 150 to 200 mg/m2 orally daily on days 1 to 5 every 28 days (75 mg/m2 daily during radiotherapy, with pneumocystis prophylaxis).
• Hydroxycarbamide 15 to 30 mg/kg orally daily, adjusted to counts.
• Mercaptopurine 50 to 75 mg/m2 orally daily in maintenance (reduce with allopurinol; check thiopurine methyltransferase).
• Tamoxifen 20 mg daily, letrozole 2.5 mg daily, anastrozole 1 mg daily.
• Abiraterone 1000 mg orally daily on an empty stomach with prednisolone 5 mg twice daily.

Handling.

• Swallow tablets whole; do not crush, split or open (capecitabine, imatinib, temozolomide capsules).
• Wear gloves when handling cytotoxics and wash hands; carers should not handle broken tablets.
• Store in the original container away from children and heat; return unused tablets to the pharmacy.
• Body fluids may contain drug for 48 hours after temozolomide or capecitabine: flush toilets twice and wash soiled linen separately.

Missed or vomited doses. Do not double the next dose. If a dose is missed by less than half the dosing interval, take it; otherwise skip it. If vomiting occurs within 30 minutes of a dose, do not repeat unless the oncologist advises.

Kidney impairment. Capecitabine: reduce to 75% when eGFR is 30 to 50 mL/min; contraindicated under 30 mL/min. Imatinib: reduce the starting dose to 400 mg if eGFR is 20 to 39 mL/min, with caution under 20 mL/min. Methotrexate and hydroxycarbamide: reduce dose.

Liver impairment. Imatinib: reduce to 300 mg in severe impairment. Capecitabine, abiraterone, erlotinib and sunitinib: reduce or avoid in moderate to severe impairment.

Interactions.

• Capecitabine and warfarin: marked rise in INR; monitor INR weekly or use a direct oral anticoagulant or low molecular weight heparin.
• Imatinib: CYP3A4 inhibitors (clarithromycin, azoles, ritonavir) raise levels; inducers (rifampicin, carbamazepine, phenytoin, St John’s wort) lower levels and should be avoided.
• Proton pump inhibitors and H2 blockers lower absorption of erlotinib, lapatinib and some other targeted agents.
• Tamoxifen: paroxetine and fluoxetine (CYP2D6 inhibitors) reduce activity; avoid.
• Allopurinol with mercaptopurine: reduce mercaptopurine to a quarter or a third.
• Grapefruit raises imatinib and other levels; avoid.

Pharmacogenetics. DPYD deficiency: severe or fatal toxicity from capecitabine; reduce or avoid where testing is available.

Pregnancy and breastfeeding. Contraindicated or not advised. Use highly effective contraception during treatment and for 6 months after most agents (longer for some); partners of men on treatment also use condoms. Do not breastfeed.

Adherence. Ask at every visit; use pill counts, calendars, text reminders and caregiver support. Cost, distance and drug stock-outs are the main reasons for poor adherence.

Regional. Access to oral agents is limited in East Africa; imatinib is more available through patient access programmes, and generic capecitabine through some cancer centres. Do not substitute with herbal products. Confirm the supply for the full cycle before starting.

Monitoring. Full blood count, creatinine, liver tests and electrolytes before each cycle (capecitabine, temozolomide), every 1 to 2 weeks in the first month of imatinib, then every 3 months. Weight and blood pressure at each visit. INR weekly for warfarin users on capecitabine.

Patient instructions. Report diarrhoea of 4 or more stools more than usual in a day, mouth ulcers, hand and foot pain or blisters, fever, bleeding, jaundice or persistent vomiting the same day; stop the medicine until reviewed for grade 3 diarrhoea, hand-foot syndrome or fever.

Escalation. Withhold for neutrophils under 1.0 x 10⁹/L, platelets under 75 x 10⁹/L, ALT over 5 times the upper limit, or serious infection; refer to the oncology team for dose adjustment.

Stopping. Stop for progression, severe unresolved toxicity, cardiotoxicity, pregnancy or patient choice. Hormonal therapy continues for 5 to 10 years in breast cancer; do not stop early without advice.