Chemotherapy / Immunosuppressant — Head and Neck / Granulomatosis
Pregnancy: ABSOLUTE CONTRAINDICATION — teratogenic and embryotoxic; 3-month contraception required before and 6 months after treatment
Methotrexate
Brand names: Methofar, Zlatal, Methofar
Adult dose
Dose: Head and neck cancer: 40 mg/m² IV weekly. Granulomatosis with polyangiitis (GPA/Wegener's — ENT manifestation): 15–25 mg once weekly oral/SC
Route: IV (oncology) / Oral or SC (rheumatological ENT conditions)
Frequency: Weekly
Max: 40 mg/m² per week (oncology); 25 mg/week (rheumatological)
Used in ENT for: relapsed/refractory HNSCC (weekly IV), and ENT manifestations of granulomatosis with polyangiitis (Wegener's — saddle-nose deformity, subglottic stenosis, otitis media, orbital disease). Folic acid 5 mg weekly (taken on a different day) must be co-prescribed.
Paediatric dose
Dose: Seek specialist opinion mg/m²/kg
Route: IV / Oral
Frequency: Weekly
Max: Per specialist oncology/rheumatology protocol
Specialist paediatric use only — dose and monitoring per specialist centre
Dose adjustments
Renal
Avoid if eGFR <30 mL/min/1.73m² — methotrexate is renally excreted; accumulation causes severe toxicity
Hepatic
Avoid in significant hepatic impairment — hepatotoxic; contraindicated with pre-existing hepatic fibrosis
Paediatric weight-based calculator
Specialist paediatric use only — dose and monitoring per specialist centre
Clinical pearls
- ABSOLUTE CONTRAINDICATION in pregnancy — potent folate antagonist; causes miscarriage, fetal malformations; 3-month washout required before conception
- Trimethoprim interaction: AVOID concurrent use — both are antifolates; additive bone marrow suppression can be fatal
- NSAIDs: reduce methotrexate renal excretion → toxicity; avoid concurrent use or use with caution and reduce methotrexate dose
- Pulmonary toxicity (methotrexate lung): acute onset dyspnoea, dry cough, fever — CXR may show diffuse infiltrates; stop immediately and seek respiratory review
- Folic acid 5 mg once weekly (on a different day from methotrexate) is mandatory — reduces mucositis and hepatotoxicity without reducing efficacy
- GPA (Wegener's): saddle-nose deformity, nasal crusting, subglottic stenosis, otitis media with effusion, orbital pseudotumour — methotrexate used for remission maintenance after cyclophosphamide induction
Contraindications
- Pregnancy — ABSOLUTE CONTRAINDICATION
- Significant renal impairment (eGFR <30)
- Significant hepatic impairment
- Active infection
- Immunodeficiency syndromes
- Alcohol excess (additive hepatotoxicity)
Side effects
- Myelosuppression (dose-dependent)
- Mucositis/stomatitis
- Hepatotoxicity (fibrosis with long-term use)
- Pulmonary toxicity (methotrexate pneumonitis)
- Nephrotoxicity (high dose)
- Teratogenicity
- Nausea
Interactions
- NSAIDs — increase methotrexate toxicity significantly (reduce renal excretion)
- Penicillins — similar mechanism; avoid concurrent use
- Trimethoprim — additive folate antagonism (severe — avoid)
- Proton pump inhibitors — increase methotrexate levels
Monitoring
- FBC (weekly initially, then every 2–4 weeks)
- LFTs (every 6–12 weeks)
- Renal function
- Chest X-ray if respiratory symptoms
- Pregnancy test before initiating
Reference: BNFc; BNF 90; BNFc; MHRA Methotrexate guidance; BSR GPA Guidelines 2014; NICE NG100. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.
Calculators