METHOTREXATE Tablets Ref.[6981] Active ingredients: Methotrexate

Important warning about the dosage Methotrexate tablets (methotrexate):

In the treatment of rheumatic diseases or diseases of the skin requiring dosing once a week, Methotrexate tablets (methotrexate) must only be taken once a week. Dosage errors in the use of Methotrexate tablets (methotrexate) can result in serious adverse reactions, including death. Please read this section of the summary of product characteristics very carefully.

Methotrexate should only be prescribed by physicians with experience in the various properties of the medicinal product and its mode of action. Methotrexate is given once weekly.

It must be explicitly pointed out to the patient that methotrexate is applied only once a week.

The prescriber should specify the day of intake on the prescription.

Rheumatoid arthritis

The usual dose is 7.5-15 mg once weekly. The planned weekly dose may be administered in three divided doses over 36 hours. The schedule may be adjusted gradually to achieve an optimal response but should not exceed a total weekly dose of 20 mg. Thereafter the dose should be reduced to the lowest possible effective dose which in most cases is achieved within 6 weeks.

Psoriasis

Before starting treatment it is advisable to give the patient a test dose of 2.5–5.0 mg to exclude unexpected toxic effects. If, one week later, appropriate laboratory tests are normal, treatment may be initiated. The usual dose is 7.5–15 mg taken once weekly. The planned weekly dose administered as three divided doses over 24 hours. As necessary, the total weekly dose can be increased up to 25 mg. Thereafter the dose should be reduced to the lowest effective dose according to therapeutic response which in most cases is achieved within 4 to 8 weeks.

The patient should be fully informed of the risks involved and the clinician should pay particular attention to the appearance of liver toxicity by carrying out liver function tests before starting methotrexate treatment, and repeating these at 2 to 4 month intervals during therapy. The aim of therapy should be to reduce the dose to the lowest possible level with the longest possible rest period. The use of methotrexate may permit the return to conventional topical therapy which should be encouraged.

Elderly patients

Methotrexate should be used with extreme caution in elderly patients, a dose reduction should be considered due to reduced liver and kidney function as well as lower folate reserves which occur with increased age.

Renal impairment

Methotrexate should be used with caution in patients with impaired renal function. The dose should be adjusted as follows:

Hepatic impairment

Methotrexate should be administered with great caution, if at all, to patients with significant current or previous liver disease, especially if due to alcohol.

Cases of overdose have been reported, sometimes fatal, due to erroneous daily intake instead of weekly intake of oral methotrexate. In these cases, symptoms that have been commonly reported are haematological and gastrointestinal reactions.

The toxicity of methotrexate affects mainly the haematopoietic organs. Calcium folinate neutralises effectively the immediate haematopoietic toxic effects of methotrexate. Parenteral calcium folinate therapy should be started within one hour after the administration of methotrexate. The dose of calcium folinate should be at least as high as the dose of methotrexate received by the patient.

Massive overdose requires hydration and alkalinisation of the urine to prevent precipitation of methotrexate and/or its metabolites in the renal tubules. Haemodialysis or peritoneal dialysis has not been found to affect the elimination of methotrexate. Instead, effective clearance of methotrexate has been achieved by intermittent haemodialysis using a so-called “high-flux” dialysator.

Observation of serum methotrexate concentrations is relevant in determining the right dose of calcium folinate and the duration of the therapy.

Shelf life: 2 years.

This medicinal product does not require any special temperature storage conditions.

Blister: keep the blister in the outer carton in order to protect from light.

HDPE container: store in original container in order to protect from light.

2.5 mg tablets:

White high density polyethylene container with non CRC high density polyethylene cap with induction wad.

Pack size: 25 or 100 tablets.

Amber colour Polyvinylchloride (PVC)/Plain Aluminium blister foil.

Pack size: 10, 24, 25, 28 30, 50 or 100 tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.