Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Accord Healthcare Limited, Sage House, 319 Pinner Road, North Harrow, Middlesex, HA1 4HF, United Kingdom
Methotrexate is indicated for the treatment of:
Methotrexate should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risks of methotrexate therapy.
Methotrexate should only be prescribed by physicians, who are familiar with the various characteristics of the medicinal product and its mode of action. If considered appropriate, the treating physician can, in selected cases, delegate subcutaneous administration to the patient Patients must be educated and trained in the proper injection technique when self-administering methotrexate. The first injection of Methofill should be performed under direct medical supervision. Methotrexate is injected once weekly.
The patient must be explicitly informed about the fact that methotrexate is administered once a week only. It is advisable to determine an appropriate fixed day of the week for the injection.
Methotrexate elimination is reduced in patients with a third distribution space (ascites, pleural effusions). Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of methotrexate administration (see section 5.2 and 4.4).
Important warning about the dosage of Methofill (methotrexate):
Methofill (methotrexate) must only be used once a week for the treatment of Rheumatoid arthritis, Juvenile arthritis, Psoriatic arthritis, Psoriasis, Crohn’s disease. Dosage errors in the use of Methofill (methotrexate) can result in serious adverse reactions, including death. Please read this section of the summary of product characteristics very carefully.
The recommended initial dose is 7.5 mg of methotrexate once weekly, administered subcutaneously. Depending on the individual activity of the disease and tolerability by the patient, the initial dose may be increased gradually by 2.5 mg per week. A weekly dose of 25 mg should in general not be exceeded. However, doses exceeding 20 mg/week are associated with significant increase in toxicity, especially bone marrow suppression. Response to treatment can be expected after approximately 4-8 weeks. Upon achieving the therapeutically desired result, the dose should be reduced gradually to the lowest possible effective maintenance dose.
Children with body surface area below 0.75 m² could not be treated with this product. If lower doses than 7.5 mg are required, another medical product should be used.
The recommended dose is 10-15 mg/m² body surface area (BSA)/once weekly. In therapy-refractory cases the weekly dosage may be increased up to 20mg/m² body surface area/once weekly. However, an increased monitoring frequency is indicated if the dose is increased.
Due to limited data availability about intravenous use in children and adolescents, parenteral administration is limited to subcutaneous injection.
Patients with JIA should always be referred to a rheumatology specialist in the treatment of children/adolescents.
Use in children <3 years of age is not recommended as insufficient data on efficacy and safety is available for this population (see section 4.4).
It is recommended that a test dose of 5-10 mg should be administered parenterally, one week prior to therapy to detect idiosyncratic adverse reactions. The recommended initial dose is 7.5 mg of methotrexate once weekly, administered subcutaneously. The dose is to be increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. Doses exceeding 20 mg per week can be associated with significant increase in toxicity, especially bone marrow suppression. Response to treatment can generally be expected after approximately 2-6 weeks. Upon achieving the therapeutically desired result, the dose should be reduced gradually to the lowest possible effective maintenance dose.
The dose should be increased as necessary but should in general not exceed the maximum recommended weekly dose of 25 mg. In a few exceptional cases a higher dose might be clinically justified, but should not exceed a maximum weekly dose of 30 mg of methotrexate as toxicity will markedly increase.
Induction treatment: 25 mg/week administered subcutaneously.
Response to treatment can be expected after approximately 8 to 12 weeks.
Maintenance treatment: 15 mg/week administered subcutaneously.
There is not sufficient experience in the paediatric population to recommend methotrexate for the treatment of Crohn’s Disease in this population.
Methotrexate should be used with caution in patients with impaired renal function. The dose should be adjusted as follows:
| Creatinine clearance (ml/min) | Dose |
|---|---|
| >60 | 100% |
| 30-59 | 50% |
| <30 | Methotrexate must not be used |
See section 4.3.
Methotrexate should be administered with great caution, if at all, to patients with significant current or previous liver disease, especially if due to alcohol. If bilirubin is >5 mg/dl (85.5 µmol/l), methotrexate is contraindicated.
For a full list of contraindications, see section 4.3.
Dose reduction should be considered in elderly patients due to reduced liver and kidney function as well as lower folate reserves which occur with increased age.
As the half-life of Methotrexate can be prolonged to 4 times the normal length in patients who possess a third distribution space dose reduction or, in some cases, discontinuation of methotrexate administration may be required (see section 5.2 and 4.4).
The medicinal product is for single use only.
Methofill solution for injection can only be given by subcutaneous route
The overall duration of the treatment is decided by the physician.
Guidance on how to use Methofill solution for injection can be found in section 6.6.
Please note that all of the contents have to be used.
Note: If changing from oral application to parenteral administration a reduction of the dose may be required due to the variable bioavailability of methotrexate after oral administration.
Folic acid supplementation may be considered according to current treatment guidelines.
Toxicity of methotrexate mainly affects the haematopoietic system.
Calcium folinate is the specific antidote for neutralising the toxic undesirable effects of methotrexate.
In cases of accidental overdose, a dose of calcium folinate equal to or higher than the offending dose of methotrexate should be administered intravenously or intramuscularly within one hour and dosing continued until the serum levels of methotrexate are below 10-7 mol/l.
In cases of massive overdose, hydration and urinary alkalisation may be necessary to prevent precipitation of methotrexate and/or its metabolites in the renal tubules. Neither haemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. Effective clearance of methotrexate has been reported with acute, intermittent haemodialysis using a high flux dialyser.
24 months.
Store below 30°C. Keep the pre-filled injector in the outer carton in order to protect from light.
Pre-filled injector containing a colourless pre-filled glass syringe (type I) with plunger stopper (chlorobutyl rubber) and embedded injection needle. The syringe is externally equipped with the device for self-administration (pre-filled injector).
Pack sizes: For 0.15 mL: pack of 1, multipacks of 4 (4 packs of 1) or 8 (8 packs of 1) pre-filled injectors in a carton.
Not all pack sizes may be marketed.
The manner of handling and disposal must be consistent with that of other cytotoxic preparations in accordance with local requirements. Pregnant health care personnel should not handle and/or administer Methotrexate.
Methotrexate should not come into contact with the skin or mucosa. In the event of contamination, the affected area must be rinsed immediately with ample amount of water.
For single use only and please note that all of the contents should be used.
Any unused medicinal product or waste should be disposed of in accordance with local requirements.
The best places for the injection are:
Abdomen or thigh if a patient is injecting himself/herself, with the additional option of the back of the arm if a Healthcare Provider or caregiver is assisting them.
For illustrative instructions for subcutaneous use, see package leaflet.
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