Posology : מינונים

4.2   Posology and method of administration
Metoject should only be prescribed by physicians, who are familiar with the various characteristics of the medicinal product and its mode of action.
Metoject is injected once weekly.
The patient is to be explicitly informed about the fact of administration subcutaneously once weekly. It is advisable to determine a fixed, appropriate weekday as day of 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).

Dosage in adult patients with rheumatoid arthritis
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.

Dosage in children and adolescents below 16 years with polyarthritic forms of juvenile idiopathic arthritis
The recommended dose is 10–15 mg/m² body surface area (BSA) once weekly, administered subcutaneously. In therapy-refractory cases the weekly dosage may be increased up to 20 mg/m2 body surface area/once weekly. However, an increased monitoring frequency is indicated if the dose is increased.
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).

Dosage in patients with psoriasis vulgaris
It is recommended that a test dose of 5–10 mg should be administered subcutaneously, 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.
Dosage in patients with Crohn’s Disease
• 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 Metoject 50 mg/ml for the treatment of Crohn’s disease in this population.

Maximum weekly 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.

Patients with renal impairment
Metoject 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                           Metoject must not be used

See section 4.3.

Patients with 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. If bilirubin is  5 mg/dl (85.5 µmol/l), methotrexate is contraindicated.

For the full list of contraindications, see section 4.3.

Use in elderly patients
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.

Use in patients with a third distribution space (pleural effusions, ascites) 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).

Method of administration
The medicinal product is for single use only.
Metoject should be given subcutaneously. See section 6.6 for instructions for subcutaneous use.

The overall duration of the treatment is decided by the physician.
Note:
If changing the 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.