Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Therakind (Europe) Limited, Paramount Court, Corrig Road, Sandyford Business Park, Dublin 18, D18 R9C7, Ιreland
Jylamvo is for use in the following indications:
Methotrexate should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risks of methotrexate therapy.
Important warning about the dosage of Jylamvo (methotrexate)
In the treatment of rheumatological or dermatological diseases, Jylamvo (methotrexate) must only be taken once a week. Dosage errors in the use of Jylamvo (methotrexate) can result in serious adverse reactions, including death. Please read this section of the summary of product characteristics very carefully.
The prescriber should ensure that patients or their carers will be able to comply with the once weekly regimen.
The prescriber should specify the day of intake on the prescription.
The dose and duration of treatment are determined individually on the basis of the patient’s clinical picture and the tolerability of methotrexate. Treatment of active rheumatoid arthritis, severe JIA, severe psoriasis and severe psoriatic arthritis represents a long-term treatment.
A weekly dose of 25 mg (12.5 ml) should not be exceeded. Doses exceeding 20 mg (10 ml)/week can be associated with a substantial increase in toxicity, especially bone marrow depression.
Concurrent folic acid supplementation of 5 mg twice weekly (except on the day of administration) is indicated additionally.
The recommended initial dose is 7.5 mg (3.75 ml) methotrexate once weekly. Depending on the individual activity of the disease and tolerability by the patient, the dose may be increased gradually by 2.5 mg (1.25 ml) per week.
Response to treatment can be expected after approximately 4-8 weeks.
After the desired treatment outcome is achieved, the dose should be reduced gradually to the lowest possible effective maintenance dose.
Symptoms may return after treatment discontinuation.
Patients with JIA should always be referred to a rheumatology unit specialising in the treatment of children/adolescents.
The recommended dose is 10-15 mg (5-7.5 ml)/m² body surface area (BSA)/week. In therapy-refractory cases the weekly dosage may be increased to 20 mg (10 ml)/m² BSA/week. However, an increased monitoring frequency is indicated if the dosage is increased.
It is recommended that a test dose of 2.5-5 mg (1.25-2.5 ml) be administered one week prior to initiation of therapy, in order to detect early occurring adverse reactions. If, one week later, appropriate laboratory tests are normal, treatment may be initiated. The recommended initial dose is 7.5 mg (3.75 ml) methotrexate once weekly. The dose should be increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. The usual dose is 10 mg-25 mg (5 ml-12.5 ml) taken once weekly. Doses exceeding 20 mg (10 ml) per week can be associated with significant increase in toxicity, especially bone marrow suppression.
Response to treatment can generally be expected after approximately 4-8 weeks. After the desired treatment outcome is achieved, the dose should be reduced gradually to the lowest possible effective maintenance dose.
Low-dose methotrexate is used in the maintenance treatment of ALL in children aged 3 years and over, adolescents and adults within complex protocols in combination with other cytostatic medicinal products. Treatment should follow current therapy protocols.
Common accepted single doses lie in the range of 20-40 mg (10-20 ml)/m² body surface area.
If methotrexate is administered in combination with chemotherapy regimens, the dosage should take into consideration any overlapping toxicity of the other medicinal product components.
Higher dosages should be given parenterally.
Methotrexate should be used with caution in paediatric patients. Treatment should follow currently published therapy protocols for children (see section 4.4).
Doses are usually based on the patient’s BSA and maintenance treatment represents a long-term treatment.
Methotrexate should be used with caution in patients with impaired renal function (see section 4.4).
The dose should be adjusted as follows for patients with rheumatoid arthritis, juvenile arthritis, psoriasis and psoriatic arthritis. For the oncology indication recommendations in published protocols should also apply.
| Creatinine clearance (ml/min) | % of dose to be administered |
|---|---|
| >60 | 100 |
| 30-59 | 50 |
| <30 | Jylamvo must not be administered |
Methotrexate should be administered only with the greatest caution, if at all, in patients with significant existing or previous liver disease, especially if due to alcohol. If bilirubin levels are >5 mg/dl (85.5 µmol/l), methotrexate is contraindicated (see sections 4.3 and 4.4).
Use in children under 3 years of age is not recommended as insufficient data on efficacy and safety are available for this patient group
Dose reduction should be considered in elderly patients (65 years and over) due to reduced liver and kidney function as well as low folic acid reserves which occur with increased age. In addition, close monitoring of patients for possible early signs of toxicity is recommended (see sections 4.4, 4.5, 4.8 and 5.2).
As the half-life of methotrexate can be prolonged four-fold in patients with pathological fluid accumulations, it may be necessary to reduce the dose and in some cases even to discontinue methotrexate (see sections 4.4 and 5.2). The amount of dose reduction should be decided on a case by case basis.
Jylamvo is for oral use only.
The medicinal product can be taken with or without food. The solution is provided ready for use, and it must be swallowed with some water to remove any methotrexate residue from the oral cavity. A 10 ml oral dosing syringe is provided for accurate measurement of the prescribed dose (see Package Leaflet).
If the oral route is ineffective, a change to a parenteral dosage form is indicated. This can be done with methotrexate as an intramuscular or subcutaneous administration and is recommended for patients who exhibit inadequate absorption of the oral form of methotrexate or who do not tolerate oral administration well.
The symptoms following oral overdose predominantly affect the haematopoietic and gastrointestinal systems.
Symptoms include leucocytopenia, thrombocytopenia, anaemia, pancytopenia, neutropenia, myelosuppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration and bleeding.
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 hematological and gastrointestinal reactions.
There are reports of deaths from sepsis, septic shock, renal failure and aplastic anaemia.
Calcium folinate is the specific antidote for neutralising the adverse toxic effects of methotrexate. In the event 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 1 hour, and dosing continued until serum level of methotrexate are below 10-7 mol/L.
In the event of a massive overdose, hydration and alkalinisation of the urine may be required to prevent precipitation of methotrexate and/or its metabolites in the renal tubules. Neither haemodialysis nor peritoneal dialysis has been shown to improve the elimination of methotrexate. Effective clearance of methotrexate is reported to be achieved with acute intermittent haemodialysis using a high-flux dialyser.
Unopened bottle: 18 months.
After first opening: 3 months.
Do not store above 25°C.
Keep the bottle tightly closed (see section 6.6).
75 ml amber type III glass bottle with tamper evident child-resistant closure (polypropylene with expanded polyethylene liner) containing 60 ml of oral solution.
Each pack contains one bottle, an LDPE bottle adaptor and a 10 ml white polypropylene dosing syringe (with major graduations at every 1 ml and minor graduations at every 0.25 ml).
Anyone handling methotrexate should wash their hands before and after administering a dose. To decrease the risk of exposure, parents and care givers should wear disposable gloves when handling methotrexate.
Contact with the skin or mucous membrane must be avoided. If methotrexate comes into contact with skin or mucosa, it should be washed immediately and thoroughly with soap and water.
Spillages must be wiped immediately.
Women who are pregnant, planning to be or breast-feeding should not handle methotrexate.
Parents, care givers and patients should be advised to keep methotrexate out of the reach of children, preferably in a locked cupboard.
Accidental ingestion can be lethal for children.
Keep the bottle tightly closed to protect the integrity of the product and minimise the risk of accidental spillage.
The usual caution should be exercised in handling cytostatics.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic products.
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