Methotrexate Ready-To-Use Syringe

Products

Prefilled methotrexate syringes have been approved in many countries since 2005 (Metoject, generic). They contain between 7.5 to 30 mg of active ingredient, in increments of 2.5 mg. The dose is much lower than for chemotherapy (“low-dose methotrexate“). The syringes are stored at room temperature between 15 to 25 °C and protected from light. Patients should therefore not remove them from their packaging for storage. For travel, a travel form is available for the health care provider to sign.

Structure and properties

Methotrexate (C20H22N8O5, Mr = 454.4 g/mol) exists as a yellow to orange, crystalline, hygroscopic powder that is practically insoluble in water. The more soluble sodium salt methotrexate disodium is contained in the syringes. Methotrexate is an antimetabolite and an analog of folic acid.

Effects

Methotrexate (ATC L01BA01) has anti-inflammatory, cytostatic, and immunosuppressive properties. It inhibits the synthesis of purines and pyrimidines by competitive inhibition of the enzyme dihydrofolate reductase. This results in decreased DNA and RNA synthesis. In deep-dose therapy, other pharmacological effects are important (see literature). The effect is not immediate but occurs after two to eight weeks, depending on the indication.

Indications

  • Active rheumatoid arthritis in adults.
  • Polyarthritic forms of severe, active juvenile idiopathic arthritis (2nd-line agents).
  • Severe, persistent and debilitating psoriasis vulgaris (2nd choice agent).
  • Severe psoriatic arthritis in adults (2nd choice agent).

The drugs are not suitable for chemotherapy for cancer.

Dosage

According to the SmPC. The drug is injected once a week and usually subcutaneously. Patients must be emphatically informed of this fact. Before treatment, a day of the week should be determined on which the injection will be administered. This is entered in a patient card. Daily use can lead to serious overdose and, in the worst case, death. Calcium folinate is available as an antidote.

Directions for use

  • Manufacturer’s checklists are available for clarification before starting therapy and for therapy monitoring.
  • Before administration, the skin should be cleaned and disinfected with an alcohol swab to prevent infection. Subsequently, at least one minute should be waited until the disinfectant has evaporated.
  • The injection site should be changed every week.
  • Methotrexate should not come into contact with the skin, mucous membrane or eyes. In case of accidental contact, rinse with plenty of water.
  • Prefilled syringes are intended for single use only. After use, they are placed in a disposal box, which can be delivered to a pharmacy.
  • During treatment, folic acid supplementation as prescribed by a doctor is usually recommended (tablets of 5 mg): 5 mg of folic acid once or twice a week, 24 to 48 hours after methotrexate administration.
  • Pregnant women should not handle the prefilled syringes because methotrexate has fertility-damaging properties.

Contraindications

Full details of precautions and interactions can be found in the drug label.

Interactions

Methotrexate has a high potential for drug-drug interactions with several drug groups. These include, for example (selection):

  • Liver-toxic and hematotoxic drugs.
  • Antibiotics
  • Organic anions, probenecid, NSAIDs
  • Proton pump inhibitors
  • Sulfonamides
  • Theophylline

Alcohol should be avoided as much as possible during treatment because of the risk for hepatotoxicity. Excessive consumption of caffeinated beverages is also not indicated.

Adverse effects

Methotrexate is a toxic substance with a narrow therapeutic range that can cause numerous adverse effects.The most common potential adverse effects include inflammation of the oral mucosa, dyspepsia, nausea, loss of appetite, and impaired liver function and hematopoietic system.