METHOFILL (METHOTREXATE) 25MG 0.5ML INJ 1`S

Methotrexate (MTX) is a folic acid antagonist that competitively inhibits dihydrofolate reductase (DHFR), depleting active folate cofactors essential for DNA synthesis, nucleotide production, and cell proliferation. At low weekly doses (used for rheumatological and dermatological conditions), its anti-inflammatory and immunomodulatory effects predominate, likely through inhibition of the purine synthesis pathway and increased adenosine signalling.

The 25 mg/0.5 mL pre-filled syringe formulation is for subcutaneous (SC) injection — used primarily for:

•       Rheumatoid arthritis (RA) — the gold-standard DMARD; used as first-line monotherapy or in combination with biologic agents.

•       Psoriasis and psoriatic arthritis — moderate-to-severe disease.

•       Other inflammatory conditions: Crohn's disease, adult-onset Still's disease, vasculitis, uveitis.

Note: High-dose intravenous or intrathecal methotrexate for oncology is a separate formulation. The 25 mg SC pre-filled syringe is specifically for DMARD use.

The dose is given ONCE WEEKLY by SC injection — always on the same day of the week. NEVER take daily — daily methotrexate is a life-threatening medication error. Administer SC into the abdomen or thigh. Rotate injection sites. Take folic acid 5 mg once weekly (on a different day from methotrexate) to reduce side effects.

Methotrexate is contraindicated in: pregnancy (highly teratogenic — strict contraception during treatment and for 3 months after in women, 6 months after in men); breastfeeding; severe hepatic impairment; severe renal impairment (eGFR < 20); active infections; significant immunodeficiency; blood dyscrasias; excessive alcohol consumption.

•       NSAIDs (ibuprofen, naproxen, diclofenac): reduce renal methotrexate clearance — increased toxicity risk; avoid high-dose NSAIDs or monitor very closely.

•       Trimethoprim / co-trimoxazole: additive antifolate effect — significant myelosuppression risk; avoid.

•       Proton pump inhibitors (omeprazole, pantoprazole): may increase MTX levels — monitor.

•       Ciclosporin: additive nephrotoxicity; complex pharmacokinetic interaction.

•       Alcohol: additive hepatotoxicity — AVOID completely.

•       Live vaccines: contraindicated.

Store at 2–8°C (refrigerate). Protect from light. Do not freeze. Single use — discard any unused portion. Cytotoxic — handle with gloves; dispose via pharmaceutical waste.

The single most important thing to remember about methotrexate is: ONE injection ONCE A WEEK — never more. Taking it more frequently than once a week is extremely dangerous and has caused deaths.

Take folic acid 5 mg on a different day each week (e.g. methotrexate on Monday, folic acid on Thursday) — it significantly reduces nausea, mouth sores, and hair loss without reducing methotrexate's therapeutic effect.

Avoid alcohol completely — even small amounts of alcohol combined with regular methotrexate significantly increase liver scarring risk. Regular blood tests are essential and protect you from serious toxicity.

Report immediately to your rheumatology nurse: new dry cough or breathlessness (possible lung inflammation), fever with chills, mouth ulcers that are unusually severe or painful, or unusually pale or bruising.

SC methotrexate has ~30% higher bioavailability than oral at equivalent doses, with better GI tolerability — preferred at doses > 15 mg/week. The pre-filled syringe (25 mg/0.5 mL) is single-dose. NHSE/BSR shared care protocols for RA require specific monitoring and communication. Folic acid 5 mg once weekly (or daily 1 mg except on MTX day) should always be co-prescribed.

The MHRA patient safety alert mandates: all prescriptions must state dose in mg AND state 'Once weekly'; dispensing labels must repeat 'Take once weekly on [day]'; patients must carry a methotrexate monitoring booklet.

Drug interactions: trimethoprim must never be used in MTX patients — switch to nitrofurantoin or cefalexin for UTI. NSAIDs: if essential, monitor FBC and renal function closely.

Can I drink alcohol at all?

No — even small amounts of alcohol increase the risk of liver scarring (fibrosis) when you are on regular methotrexate. This is one of the firm lifestyle restrictions that is medically important, not just a general caution.

Why do I feel tired and unwell the day after my injection?

This is the well-known 'methotrexate hangover' — systemic effects in the 24–48 hours after injection. Taking your injection in the evening can help you 'sleep through' the worst of it. Folic acid and good hydration help. Some patients find the SC route causes fewer systemic effects than oral.

What are the signs I need to go to hospital straight away?

Fever above 38°C (possible serious infection due to low white cells); new dry cough or breathlessness (possible lung inflammation — methotrexate pneumonitis); very severe mouth ulcers; or unusual bruising/bleeding (low platelets).

How long will I be on methotrexate?

For RA and psoriasis, methotrexate is often taken long-term — years or even indefinitely — as it continues to suppress disease activity. The dose may be adjusted over time. Regular monitoring continues throughout.

Can I have vaccinations on methotrexate?

Inactivated vaccines (flu, pneumococcal, COVID-19 booster) are safe and strongly recommended. Live vaccines (yellow fever, MMR) should be avoided. Discuss your vaccination schedule with your rheumatologist.