Methotrexate — Indian WHO-GMP supply across oncology high-dose and rheumatology low-dose lines.
Antifolate antimetabolite — the bridge molecule across ALL maintenance, CMF breast adjuvant, head-and-neck, osteosarcoma rescue, plus rheumatoid arthritis, psoriasis and IBD low-dose. Injection 50mg / 500mg / 1g vials (preservative-free intrathecal-grade available) + 2.5mg and 10mg tablets, from Indian WHO-GMP facilities.
Multiple WHO-GMP partner lines · injection 50mg / 500mg / 1g (preservative-free intrathecal-grade available) + tablets 2.5mg / 10mg · CTD dossier on file · WHO PQ pathway supported.
Active ingredient
Methotrexate, an antifolate antimetabolite. Mechanism: competitively inhibits dihydrofolate reductase, depleting tetrahydrofolate and blocking thymidylate and purine synthesis. Cytotoxic at high IV dose (oncology); immunomodulatory at low oral/SC dose (rheumatology) via adenosine accumulation and AICAR-transformylase inhibition. Dose response is non-linear: low-dose immunomodulation versus high-dose cytotoxic are mechanistically distinct.
Strengths stocked
Injection: 50mg/2ml (25 mg/ml), 500mg/20ml and 1000mg/40ml (25 mg/ml). Preservative-free intrathecal-grade formulations available for CNS prophylaxis in ALL — preservatives (benzyl alcohol) are neurotoxic intrathecally and contraindicated. Tablets: 2.5mg (rheumatology starting dose, fine titration) and 10mg (rheumatology maintenance). Both routes are tender-volume lines.
Indications
Oncology high-dose: ALL maintenance + intrathecal CNS prophylaxis, primary CNS lymphoma, CMF breast, head-and-neck, osteosarcoma rescue, choriocarcinoma, MVAC bladder. Rheumatology low-dose: RA (first-line DMARD), psoriatic arthritis, severe plaque psoriasis, Crohn's/UC maintenance, juvenile idiopathic arthritis, ectopic pregnancy management. WHO EML core. We supply both formulation routes.
Storage
Injection vials at 15-25°C, protected from light. Tablets at 15-25°C, in original blister to protect from moisture. Preservative-free intrathecal vials are single-use only — discard any unused volume after first puncture, do not store reconstituted product. Standard ambient-temperature dispatch lane; no cold-chain.
Shelf life
Injection: 24 months from manufacture; minimum 18 months at dispatch. Tablets: 36 months from manufacture; minimum 24 months at dispatch. Or we won't ship it.
Pack format
Injection: single vial per carton, hospital pack. Type-I clear glass vial, halobutyl rubber stopper, aluminium seal with flip-off cap. Preservative-free SKU clearly differentiated on outer carton with intrathecal-route warning. Tablets: aluminium-aluminium blister, 10 tablets per blister, 30 or 100 tablets per carton — destination-market dependent. Outer carton and leaflet in destination-regulator language. Folate antagonism warning prominently set.
Hospital pharmacies, oncology day-units, rheumatology clinics and tender desks across thirty markets.
India is our origin. We do not sell into the Indian market. Methotrexate is exported only.
United Kingdom
Methotrexate is core NHS oncology day-unit and rheumatology clinic stock — every adult oncology centre and specialist rheumatology unit holds it. Where the primary licensed supplier cannot fill against scheduled high-dose ALL or CMF demand, the MHRA Specials / named-patient import route is available. Preservative-free intrathecal-grade is a separate licensed-product line per MHRA — see MHRA Specials for the documentation pack we prepare manufacturer-side.
GCC (UAE, KSA, Kuwait, Oman, Qatar, Bahrain)
Through local licensed importers, against MoH tender awards (NUPCO and Saudi MoH for KSA; MoHAP, DHA and DOH Abu Dhabi for UAE; Kuwait MoH Central Drug Store; MoPH Qatar including Hamad Medical Corporation; MoH Oman; NHRA Bahrain) and hospital pharmacy purchase orders. SFDA, MoHAP and GCC central registration supported with a full CTD dossier covering both oncology and rheumatology indications.
Nigeria, Kenya, Ghana, South Africa, Ethiopia, Tanzania, Uganda
Public-sector tenders (NAFDAC-registered for Nigeria, KEMSA + MEDS for Kenya, FDA Ghana + Central Medical Stores, SAHPRA-registered for South Africa, EFDA + EPSS for Ethiopia, TMDA + MSD for Tanzania, NDA + NMS for Uganda). Methotrexate's dual oncology + autoimmune indication footprint makes it a cross-programme tender line. WHO Prequalification supported for Global Fund qualification.
Germany, France, Brazil, Mexico, Philippines
Supply via licensed importers under §72 AMG (Germany), ANSM equivalent (France), ANVISA (Brazil), COFEPRIS (Mexico), FDA Philippines, with Qualified Person (QP) certification on EU arrival. CTD dossier and CoPP prepared for BfArM, ANSM, ANVISA, COFEPRIS and FDA Philippines recognition. Preservative-free intrathecal grade requires the specific formulation dossier per destination.
Folic acid co-prescription, intrathecal-grade label discipline, weekly-NOT-daily dosing in rheumatology — methotrexate fails on small mistakes.
The single most common methotrexate fatality is daily-instead-of-weekly dosing in rheumatology. RA and psoriasis dosing is once weekly (typically 7.5-25 mg PO or SC); daily administration causes life-threatening pancytopenia and mucositis within days. UK NPSA alert NPSA/2006/13 and MHRA repeated safety communications mandate explicit weekly-day specification on every prescription, and dispensing in a weekly-pill organiser. Folic acid 5mg weekly (taken on a different day) is co-prescribed to reduce GI and mucositis toxicity without reducing therapeutic efficacy. Oncology high-dose: 1-12 g/m² IV with leucovorin (folinic acid) rescue starting 24 hours after infusion, dosed and continued until methotrexate plasma level drops below 0.1 µmol/L (typically 48-72 hours, longer if delayed clearance). Plasma methotrexate level monitoring is mandatory. Hydration (3 L/m²/day) and urinary alkalinisation (sodium bicarbonate to keep urine pH > 7.0) are required to prevent precipitation in renal tubules. Drug interactions are dangerous: NSAIDs, sulphonamides (Bactrim/Septrin/co-trimoxazole), penicillins, ciprofloxacin and PPIs all reduce methotrexate clearance and can trigger toxicity at standard doses. Folate-deficient patients are at elevated toxicity risk. Intrathecal route requires preservative-free formulation — benzyl alcohol preservatives are neurotoxic intrathecally; the wrong vial intrathecally is fatal. Vial discrimination on the SmPC is critical. Pregnancy is contraindicated (teratogenic, abortifacient — also licensed for medical management of ectopic pregnancy at 50 mg/m² IM).
The documentation pack a regulator actually asks for.
Methotrexate is a WHO EML core-list molecule and WHO PQ-listed. Our role is manufacturer-facing — we sit between the Indian WHO-GMP facility and your clinical, regulatory or procurement team and take the paperwork off both sides.
CTD Module 3
Full chemistry, manufacturing and controls section, prepared in eCTD-ready format where the importing authority accepts it. Module 2 quality overall summary included. Preservative-free intrathecal-grade has a separate dossier annex covering benzyl-alcohol-free excipient profile and stability of single-use sterile presentation.
CoA and MoA, per batch
HPLC assay of methotrexate (≥98%), related substances (4-aminofolate, deoxyfolate per Ph.Eur./USP), pH, sterility, bacterial endotoxin, particulate matter (preservative-free has tighter particulate spec for intrathecal route) — signed by the manufacturer's authorised QC head.
CoPP, WHO-GMP, MFG licence
Issued by CDSCO (Central Drugs Standard Control Organization, India) and apostilled where the destination requires it. Notarised copies included in the shipping pack. WHO-PQ certificate available for Global Fund qualification.
Pack insert, labels, artwork
Destination-language PIL, labelling to local regulator standards (MHRA SmPC style for the UK, MoH style for GCC, SAHPRA for South Africa, BfArM for Germany). Weekly-not-daily warning per UK NPSA/2006/13 and MHRA safety communication formatting prominently set. Intrathecal-route warning on preservative-free SKU. Folate-antagonism interaction warnings (NSAIDs, sulphonamides, PPIs) documented. Artwork QC before print, not after.
Temperature control
Pre-shipment validation on each shipper configuration. Methotrexate ships at 15-25°C ambient; the failure mode is light exposure (degradation to 4-aminofolate) — opaque shipper outer protects the consignment. Tablets pair temperature with humidity logging.
Pharmacovigilance
Local PV partner or a named PV contact organised in the destination market against registration. Periodic Safety Update Reports compiled to ICH E2C. Daily-instead-of-weekly dosing errors (rheumatology), high-dose plasma-level monitoring failures, intrathecal preservative-misadministration, and drug-interaction toxicities (NSAID, sulphonamide, PPI) remain the PSUR priority signals for this molecule.
CMF, ALL maintenance and the rheumatology cross-supply.
Methotrexate's dual oncology + autoimmune footprint means it sits at the crossover between the cytotoxic backbone and the rheumatology DMARD line.
Cyclophosphamide
Alkylating agent, the 'C' in CMF. 200mg / 500mg / 1g vials.
5-Fluorouracil
Fluoropyrimidine, the 'F' in CMF/FAC/FEC. 250mg / 500mg / 1g / 5g vials.
Doxorubicin
Anthracycline, the 'A' in AC and FAC. 10mg / 50mg / 200mg + PEGylated liposomal 20mg.
Cisplatin
Platinum cytotoxic, MVAC bladder regimen. 10mg / 25mg / 50mg / 100mg vials.
Anti-allergy / Immunology →
Rheumatology DMARD cluster — sulfasalazine, hydroxychloroquine, leflunomide, biologic biosimilars.
All oncology →
120+ oncology SKUs: cytotoxics, targeted therapy, supportive care.
Molecule · strength · volume · destination. One working day to a quote.
- Send us the specifics. Strength, vial count or tablet count, formulation (standard injection / preservative-free intrathecal / oral tablet), destination, NHS / GCC tender / African public-sector / Global Fund / NGO, target delivery. Flag if the receiving formulary needs the weekly-not-daily warning compliance set documented.
- We route to the right line. Multiple WHO-GMP methotrexate lines on the M Care roster — separate facilities for preservative-free intrathecal-grade given the tighter particulate spec. WHO PQ-listed lines available for Global Fund and Africa CDC tender qualification.
- Commercial and regulatory offer. FOB / CIF price, lead time, dossier status per destination, weekly-not-daily warning compliance documentation per destination labelling, and the documentation pack you'll receive. Inside one working day.
- Order, produce, release, ship. QC release on the Indian side. Ambient-temperature dispatch lane, light-protected shipper outer, in-transit temperature logging, on-arrival inspection. Photo evidence of seal integrity on request. Preservative-free SKUs ship in clearly-differentiated outer cartons to prevent vial-confusion at the receiving pharmacy.
- After delivery. Batch records, CoA and thermal logs archived for the full shelf life of the consignment. Pharmacovigilance contact opened on registration; daily-instead-of-weekly dosing errors, high-dose plasma-level failures, intrathecal preservative misadministration and drug-interaction toxicities remain the PSUR priority signals.
Methotrexate supply — the specific questions.
What strengths and formulations of methotrexate do you supply?
Injection: 50mg/2ml, 500mg/20ml and 1000mg/40ml at 25 mg/ml. Preservative-free intrathecal-grade formulations available — preservatives (benzyl alcohol) are neurotoxic intrathecally and the preservative-free SKU is a separate licensed product line. Tablets: 2.5mg (rheumatology starting dose, fine titration) and 10mg (rheumatology maintenance). The 50mg vial is the highest-volume rheumatology subcutaneous tender line; 500mg and 1g cover oncology high-dose ALL and osteosarcoma protocols. Tablet pack is aluminium-aluminium blister, 10 per blister, 30 or 100 per carton.
Is preservative-free intrathecal-grade methotrexate a separate product?
Yes — preservative-free intrathecal-grade is a regulatorily distinct product, not interchangeable with the standard preservative-containing injection. Standard methotrexate vials contain benzyl alcohol as a preservative; benzyl alcohol is neurotoxic intrathecally and the wrong vial intrathecally is fatal (well-documented inadvertent-substitution deaths internationally). The preservative-free formulation has its own MAH/CTD dossier annex, tighter particulate spec, single-use vial format, and clearly-differentiated outer carton with intrathecal-route warning. We supply both formulations from WHO-GMP facilities; the SKU code differs and the pre-dispatch pack flags the formulation explicitly.
How is the weekly-not-daily dosing safety communication built into your labelling?
The most common methotrexate fatality is daily-instead-of-weekly dosing in rheumatology. UK NPSA alert NPSA/2006/13 (2006) and subsequent MHRA Drug Safety Updates (2020, 2022) mandate explicit weekly-day specification on UK prescriptions, and dispensing in weekly-pill organisers. Our destination-language pack inserts and SmPCs carry the weekly-not-daily warning prominently, in regulator-mandated formatting (UK MHRA SmPC, EU EMA template, ANSM French-language version, AsdfAR Brazilian Portuguese, etc.). Tablets ship in weekly-pack-compatible blister formats for the rheumatology channel. The dispensing-side responsibility (clear weekly instruction at point of dispensing) sits with the dispensing pharmacy; the manufacturer-side responsibility (clear labelling) is ours.
Which markets can you ship methotrexate into?
The UK (NHS hospital pharmacy supply or named-patient / MHRA Specials route during shortage), the GCC (UAE, Saudi Arabia, Kuwait, Oman, Qatar, Bahrain) through licensed local importers, sub-Saharan Africa (Nigeria, Kenya, Ghana, South Africa, Ethiopia, Tanzania, Uganda, Rwanda) for tender and teaching-hospital supply with WHO PQ pathway support, Egypt, Jordan, Iraq on the Levant side, Germany under §72 AMG, France under ANSM-equivalent route, Brazil (ANVISA), Mexico (COFEPRIS) and the Philippines (FDA Philippines). We do not supply into India. Preservative-free intrathecal-grade requires the formulation-specific dossier per destination. Full market coverage is at markets.
What documentation is included with a methotrexate consignment?
Every consignment ships with a batch-specific Certificate of Analysis (HPLC assay, related substances per Ph.Eur./USP, pH, sterility, bacterial endotoxin, particulate matter — preservative-free SKU has tighter particulate spec for intrathecal route), Method of Analysis, Certificate of Pharmaceutical Product (CoPP), WHO-GMP certificate, manufacturing licence, WHO Prequalification certificate where applicable, Certificate of Origin (chamber-attested), destination-language pack insert with weekly-not-daily warning and folate-antagonism interaction warnings, intrathecal-route warning on preservative-free SKU, and temperature/light logs from pre-dispatch through on-arrival. PV contact nominated in the destination market on registration.
Do you provide CTD dossiers for methotrexate registration?
Yes. Full CTD Module 3 dossiers are available against a non-disclosure agreement, for registration with MHRA, GCC central registration, SFDA, MoHAP, NAFDAC, PPB, SAHPRA, EFDA, TMDA, NDA, BfArM, ANSM, ANVISA, COFEPRIS, FDA Philippines and comparable bodies. Module 2 summaries and Module 1 administrative sections are prepared in destination-specific format. Standard preservative-containing injection has a well-established CMC template; preservative-free intrathecal-grade has a separate dossier annex with tighter particulate spec and benzyl-alcohol-free excipient profile. Tablet dossier (oncology and rheumatology indications) is filed separately. Lead time on a dossier against a new registration is typically 4-6 weeks for any single formulation. WHO PQ dossier prepared separately for Global Fund qualification. See dossier preparation.
What are typical lead times for methotrexate orders, and does methotrexate need cold-chain transit?
For registered markets with stock on hand, dispatch is typically 5-10 working days from confirmed order. For tender awards (Global Fund, NUPCO, KEMSA, CMS Ghana), the lead time is set in the tender award document. For UK NHS hospital pharmacy ad-hoc supply with urgency flagged, air-freight out of Mumbai can be on a flight within 72 hours. Made-to-order batches run 6-10 weeks inclusive of QC release and destination artwork. Methotrexate does not require cold-chain — it ships at 15-25°C ambient with light protection. Transit temperature is logged with light-exposure protocol on every consignment.
Send the specifics. You'll have a price inside one working day.
Strength, formulation (standard / preservative-free intrathecal / tablet), volume, destination, oncology / rheumatology / Global Fund / NGO, target delivery, weekly-not-daily warning compliance documentation if needed. That's the enquiry. Everything else is on us.