Metoject, 50 mg/ml suspension 0.2 ml

Metodect is a cytotoxic drug, is a folic acid antagonist, antimetabolite.

It has antitumor and immunosuppressive effects. Antitumor activity is aimed at inhibition of deoxyribonucleic acid (DNA) synthesis due to competitive inhibition of dihydrofolate reductase enzyme involved in conversion of dihydrofolic acid into tetrahydrofolic acid.

Tetrahydrofolic acid is a carrier of carbon fragments involved in the synthesis of purine nucleotides and their derivatives.

It is unknown what accounts for the effectiveness of methotrexate in the treatment of rheumatoid arthritis (including juvenile chronic arthritis), psoriasis and psoriatic arthritis: either its immunosuppressive effect or its anti-inflammatory effect.

The extent to which methotrexate-induced increases in extracellular adenosine concentrations at sites of inflammation affect the effectiveness of therapy has not been established.

Indications

– rheumatoid arthritis in adults;

– polyarthritis in patients with severe juvenile chronic arthritis in active form;

– severe generalized forms of psoriasis and psoriatic arthritis in adults when standard therapy has failed.

Active ingredient

Composition

How to take, the dosage

Metodect is administered p/k, i/m or i/v.

The injection needle included in the package is only intended for injection of Metodect by injection. For intravenous and intravenous administration, the appropriate needles for these routes of administration must be used.

The drug is used once a week. The total duration of treatment is determined by the doctor individually.

The medication must be prescribed by a physician who has experience using methotrexate and who has knowledge about its properties and effects.

In rheumatoid arthritis, the recommended starting dose for adults is 7.5 mg once weekly in m/v, iv or p/u. Depending on disease severity and tolerability of methotrexate, the dose can be gradually increased to 2.5 mg/week. Maximum dose is 25 mg/week. Therapeutic effect usually develops 4-8 weeks after the start of the drug administration. After achieving the optimal therapeutic effect, dose reduction should be started to the lowest effective maintenance dose. The duration of therapy with the drug may exceed 10 years.

In psoriasis and psoriatic arthritis, a week before the start of treatment, a test dose of 5-10 mg of methotrexate should be administered parenterally to detect intolerance reactions. The recommended initial dose is 7.5 mg once a week, i.m., i.v. or p/k. The dose should be gradually increased. In most cases, the dose should not exceed 25 mg/week, but in any case, the maximum dose is 30 mg/week. The therapeutic effect usually develops in 2-6 weeks after the start of the drug. After the desired response is achieved, the dose should be reduced to the lowest effective maintenance dose.

In patients with renal insufficiency, Metoject should be used with caution. The dose adjustment of the drug depending on the CK value is given in the table.

Patients with hepatic insufficiency: In patients with significant current or history of liver disease, especially caused by alcohol intake, Metoject should be used with great caution. Methotrexate is contraindicated in bilirubin concentrations > 5 mg/dL (85.5 µmol/L).

In elderly patients, Metodect should be used with caution, and downward dose adjustment is often necessary due to age-related decline in liver and renal function and decreased folate storage in the body.

In children under 16 years of age with polyarthritic form of juvenile chronic arthritis, the recommended dose of methotrexate is 10-15 mg/m2 body surface per week. If treatment is ineffective, the dose may be increased up to 20 mg/m2/week. Because of limited data on p/c and IV use in children, the drug in juvenile arthritis should be administered in m/m.

Transitioning from oral methotrexate to parenteral use may require dose reduction due to differences in bioavailability of the drug with different routes of administration.

The concomitant administration of folic acid medications should be considered during therapy with Metodect in accordance with current standards of care.

Contraindications

– significant impairment of liver function;

– alcoholism;

– severe renal failure (CK less than 20 ml/min);

– history of hematopoiesis disorders, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, severe anemia;

– severe acute or chronic infectious diseases, such as tuberculosis, HIV infection;

– oral ulcers;

– active gastrointestinal ulcers;

– severe immunodeficiency;

– pregnancy;

– period of lactation (breastfeeding);

– simultaneous vaccination with live vaccines;

– hypersensitivity to the components of the drug.

The drug should be used with caution in patients with ascites, dehydration, obstructive gastrointestinal diseases, pleural or peritoneal effusion, with chronic renal failure; parasitic and infectious diseases of viral, fungal or bacterial nature (current or recent, including recent contact with a patient) – herpes simplex, herpes zoster in viremic phase, varicella, measles, amebiasis, strongyloidosis established or suspected (risk of severe generalized disease); in gout (including a history of gout); in the case of gout (including a history of gout).or urate nephrolithiasis (including anamnesis), oral infection and inflammation, vomiting and diarrhea (fluid loss due to severe vomiting and diarrhea may lead to increased toxicity of methotrexate), peptic ulcer, ulcerative colitis, prior chemo- or radiation therapy, asthenia, in elderly patients.

Side effects

The most frequent side effects when using Metodect are reactions from the hematopoietic system and digestive system.

Frequency determination of side effects: very frequently (≥ 1/10), frequently (≥ 1/100, < 1/10), sometimes (≥ 1/1000, < 1/100), rarely (≥ 1/10 000, < 1/1000), very rarely (< 1/10 000).

Digestive system disorders: very common – stomatitis, dyspepsia, nausea, loss of appetite, increased transaminase activity; common – oral ulcers, diarrhea; sometimes – enteritis, vomiting, cirrhosis, liver fibrosis and fatty degeneration, hepatotoxicity (acute hepatitis, liver failure); rare – erosive-ulcerative lesions of the GI; very rare – vomiting with blood admixture, GI bleeding (incl.melena, hematemesis); pancreatitis is possible.

Hematopoietic system: often – leukopenia, anemia (including aplastic), neutropenia, thrombocytopenia; sometimes – pancytopenia; very rarely – agranulocytosis, severe suppression of bone marrow function.

Dermatological reactions: frequent – exanthema, erythema, dermatitis, skin itching; sometimes – photosensitization, alopecia, enlargement of rheumatic nodes, vasculitis, infections caused by Herpes zoster, herpetiform skin rash, urticaria; rare – increased pigmentation; very rare – changes in nail pigmentation, acute paronychia, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome). In the treatment of psoriasis – a burning sensation of the skin, rarely – painful erosive plaques on the skin.

Allergic reactions: various manifestations up to and including anaphylactic shock; allergic vasculitis, fever.

Cardiovascular system disorders: pericarditis, pericardial effusion, pericardial tamponade, decreased BP, thromboembolism (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, pulmonary embolism).

CNS and peripheral nervous system disorders: frequently – headache, fatigue, somnolence; sometimes – dizziness, confusion, depression; very rarely – pain, muscle weakness or paresthesia of extremities, taste disorders (metallic taste), seizures, meningismus, paralysis.

Endocrine system: possibly – diabetes mellitus.

Sensory organs: conjunctivitis; very rare – visual impairment, (including transient blindness); possible – tinnitus.

Respiratory organs: often – interstitial alveolitis/pneumonia, symptoms of potentially serious interstitial pneumonia (dry non-productive cough, dyspnea and fever); sometimes – pharyngitis; rarely – pulmonary fibrosis, pulmonary pneumocystis, lung failure and bronchial asthma; possible – pleural effusion, nasal bleeding.

Urinary system: sometimes – inflammation and ulceration of the bladder, painful urination, hematuria, hyperuricemia, renal failure; rarely – severe renal failure, oliguria, anuria, azotemia.

Perior genital system disorders: less frequently – vaginal inflammation and ulceration; very rarely – vaginal discharge, loss of libido, impotence, oligospermia, menstrual disorders, infertility.

Muscular system disorders: rare – arthralgia, myalgia, osteoporosis, osteonecrosis, increased risk of fractures; soft tissue necrosis is possible.

Mechanical disorders: increased sweating, hypogammaglobulinemia; rarely – electrolyte balance disorders.

Infections: possibly – life-threatening opportunistic infections (including pneumocystis pneumonia), cytomegalovirus infections (CMV) (including CMV pneumonia), sepsis (including fatal), nocardiasis, histoplasmosis, cryptococcosis, infections caused by Herpes zoster and Herpes simplex (including disseminated), impaired wound healing.

New growths: in isolated cases, the occurrence of lymphoma. In a recent study, methotrexate therapy was not found to increase the incidence of lymphoma.

Local reactions: when administered by injection, burning sensation at the injection site, aseptic abscess formation, destruction of fatty tissue.

The frequency and severity of side effects of treatment with methotrexate depend on the dose and frequency of use. However, severe side effects can also occur with methotrexate at low doses, so it is important that patients receiving methotrexate be monitored regularly at short intervals.

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