METOJECT PEN Solution for injection in pre-filled pen Ref.[6980] Active ingredients: Methotrexate

Metoject PEN should only be prescribed by physicians who are familiar with the various characteristics of the medicinal product and its mode of action. Patients must be educated to use the proper injection technique. The first injection of Metoject PEN should be performed under direct medical supervision. Metoject PEN is injected once weekly.

The patient must be explicitly informed about the fact that Metoject PEN 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).

Posology

Posology 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. 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.

Paediatric population

Posology 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. 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.

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).

Posology in patients with psoriasis vulgaris and psoriatic arthritis

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.

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.

Posology 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 PEN for the treatment of Crohn’s disease in this population.

Patients with renal impairment

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

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 PEN solution for injection in pre-filled pen can only be given by subcutaneous route.

The overall duration of the treatment is decided by the physician.

Guidance on how to use Metoject PEN solution for injection in pre-filled pen can be found in section 6.6.

Please note that all of the contents have to be used.

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.

Symptoms of overdose

Toxicity of methotrexate mainly affects the haematopoietic system.

Treatment measures in the case of overdose

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.

Shelf life: 2 years.

Store below 25°C. Keep the pre-filled pens in the outer carton in order to protect from light.

Pre-filled pens containing a colourless pre-filled syringe (glass) with plunger stopper (chlorobutyl rubber) and embedded injection needle. The syringe is externally equipped with the device for self-administration (pen).

Pack sizes:

Pre-filled pens containing 0.15 ml (7.5 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.2 ml (10 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.25 ml (12.5 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.3 ml (15 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.35 ml (17.5 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.4 ml (20 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.45 ml (22.5 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.5 ml (25 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.55 ml (27.5 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Pre-filled pens containing 0.6 ml (30 mg) solution are available in packs of 1, 2, 4, 5, 6, 10, 11, 12, 14, 15, and 24 pre-filled pens.

Alcohol pads are included in the package.

Not all pack sizes may be marketed.

The manner of handling and disposal must be in accordance with local requirements. Pregnant healthcare personnel should not handle and/or administer Metoject PEN.

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.

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

Instructions for subcutaneous use

The most appropriate zones for the injection are:

• upper thighs,
• abdomen except around the navel.

1. Clean the area around the chosen injection site (e.g. by using the enclosed alcohol pad).
2. Pull the cap straight off.
3. Build a skin fold by gently squeezing the area at the injection site.
4. The fold must be held pinched until the Metoject PEN is removed from the skin after the injection.
5. Push the Metoject PEN firmly into the skin at a 90-degree angle in order to unlock the button. Then press the button (a click indicates the start of injection).
6. Do not remove the Metoject PEN from the skin before the end of the injection to avoid incomplete injection. This can take up to 5 seconds.
7. Remove the Metoject PEN from the skin at the same 90-degree angle.
8. The protective shield automatically moves into place over the needle and is then locked.