Metodect solution for subcutaneous injection 50mg/ml 0.2ml (10mg) syringe, 1pc

Composition

1 ml of the solution for subcutaneous use contains: Active ingredient: disodium methotrexate – 54.84 mg, which corresponds to 50 mg of methotrexate (prepared according to the prescription: methotrexate-50 mg, sodium hydroxide-9.6 mg); auxiliary components: sodium chloride, sodium hydroxide, water for injection.

Pharmacological action

Metodject is a cytotoxic drug, is a folic acid antagonist, an antimetabolite. It has antitumor and immunosuppressive effects. Antitumor activity is aimed at inhibiting the synthesis of deoxyribonucleic acid (DNA), which occurs due to the competitive inhibition of the enzyme dihydrofolate reductase, which is involved in the conversion of dihydrofolic acid to tetrahydrofolic acid. Tetrahydrofolic acid is a carrier of carbon fragments involved in the synthesis of purine nucleotides and their derivatives. It is not known whether the effectiveness of methotrexate in the treatment of rheumatoid arthritis (including juvenile chronic arthritis), psoriasis and psoriatic arthritis is due to either its immunosuppressive effect or its anti-inflammatory effect. The degree of influence of an increase in the extracellular concentration of adenosine caused by methotrexate at the sites of inflammation on 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 with ineffectiveness of standard therapy.

Contraindications

— severe hepatic impairment;

— alcoholism;

— renal failure severe (CC less than 20 ml/min);

— violation of hematopoiesis in history, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, severe anemia;

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

and ulcerative lesions of the oral cavity;

and ulcerative lesions of the gastrointestinal tract in the active phase;

pronounced immunodeficiency;

— pregnancy;

— lactation (breastfeeding);

— concurrent vaccination with live vaccines;

— hypersensitivity to the components of the drug.

With caution, the drug should be used in patients with ascites, dehydration, obstructive gastrointestinal diseases, pleural or peritoneal effusion, with chronic renal failure; with parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with the patient) – herpes simplex, herpes zoster in the viremic phase, chickenpox, measles, amoebiasis, strongyloidosis, or suspected (risk of developing severe generalized disease); gout (including a history) or urate nephrourolithiasis (including a history), infection and inflammation of the oral mucosa, vomiting and diarrhea (loss of fluid due to severe vomiting and diarrhea can lead to increased toxicity of methotrexate), gastric and duodenal ulcers, ulcerative colitis, with previous chemotherapy or radiation therapy, asthenia, in elderly patients.

Side effects

The most common side effects when using Metodject are reactions from the hematopoietic system and the digestive system.

Determining the frequency of side effects: very common (≥ 1/10), common (≥ 1/100, < 1/10), sometimes (≥ 1/1000, < 1/100), rare (≥ 1/10 000, < 1/1000), very rare (

From the digestive system:  very often – stomatitis, dyspepsia, nausea, loss of appetite, increased activity of transaminases; often – oral ulcers, diarrhea; sometimes – enteritis, vomiting, cirrhosis, fibrosis and fatty degeneration of the liver, hepatotoxicity (acute hepatitis, liver failure); rarely – erosive and ulcerative lesions of the gastrointestinal tract; very rarely-vomiting with blood admixture, bleeding from the gastrointestinal tract (including melena, hematemesis); possibly – pancreatitis.

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

Dermatological reactions:  often-exanthema, erythema, dermatitis, pruritus; sometimes-photosensitization, baldness, enlarged rheumatic nodes, vasculitis, infections caused by Herpes zoster, herpetiform skin rashes, urticaria; rarely-increased pigmentation; very rarely-changes in nail pigmentation, acute paronychia, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s 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 anaphylactic shock; allergic vasculitis, fever.

From the cardiovascular system:  pericarditis, pericardial effusion, pericardial tamponade, decreased blood pressure, thromboembolism (including arterial thrombosis, cerebral vascular thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, pulmonary embolism).

From the central nervous system and peripheral nervous system:  often-headache, fatigue, drowsiness; sometimes-dizziness, confusion, depression; very rarely-pain, muscle weakness or paresthesia of the extremities, impaired taste (metallic taste), convulsions, meningism, paralysis.

From the endocrine system:  possibly – diabetes mellitus.

From the side of the senses:  conjunctivitis; very rarely-visual impairment (including temporary blindness); possibly-tinnitus.

Respiratory system disorders:  often-interstitial alveolitis / pneumonia, symptoms of potentially serious interstitial pneumonia (dry, unproductive cough, shortness of breath, and fever); sometimes – pharyngitis; rarely – pulmonary fibrosis, pulmonary pneumocystis, pulmonary insufficiency, and bronchial asthma; possibly – pleural effusion, nosebleeds.

From the urinary system:  sometimes-inflammation and ulcerative lesions of the bladder, painful urination, hematuria, hyperuricemia, renal failure; rarely-severe renal failure, oliguria, anuria, azotemia.

From the side of the reproductive system:  less often-inflammation and ulcerative lesions of the vagina; very rarely-vaginal discharge, loss of sexual desire, impotence, oligospermia, menstrual disorders, infertility.

Musculoskeletal disorders:  rarely-arthralgia, myalgia, osteoporosis, osteonecrosis, increased risk of fractures; possibly-soft tissue necrosis.

From the side of metabolism:  excessive sweating, hypogammaglobulinemia; rarely – electrolyte disturbances.

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

Neoplasms:  in some cases, the occurrence of lymphomas. In a recent study, methotrexate therapy was not found to increase the incidence of lymphomas.

Local reactions:  when used in / m use – a burning sensation at the injection site, the formation of an aseptic abscess, the destruction of adipose tissue.

The frequency and severity of side effects of methotrexate treatment depends on the dose and frequency of use. However, severe side effects can also occur when using methotrexate in low doses, so it is necessary that patients receiving methotrexate regularly undergo medical examinations at short intervals.

How to take, course of use and dosage

Metodject is prescribed by subcutaneous injection, intravenous injection, or intravenous injection.

The injection needle included in the package is intended only for subcutaneous injection of Metodject. For intravenous and intravenous use of the drug, it is necessary to use needles suitable for these methods of use.

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

The drug should be prescribed by a doctor who has experience with the use of methotrexate and knowledge of the properties of the drug and the features of its action.

For adults with rheumatoid arthritis, the recommended starting dose is 7.5 mg once a week in / m, iv or subcutaneous injection. Depending on the severity of the disease and tolerability of methotrexate, the dose can be gradually increased – 2.5 mg/week. The maximum dose is 25 mg / week. The therapeutic effect usually develops 4-8 weeks after the start of the drug. Once the optimal therapeutic effect is achieved, the dose should be reduced to the lowest effective maintenance dose. The duration of therapy with the drug may exceed 10 years.

For psoriasis and psoriatic arthritis, a week before the start of treatment, it is recommended to enter a parenteral test dose of 5-10 mg of methotrexate to detect intolerance reactions. The recommended starting dose is 7.5 mg 1 time / week in / m, iv or subcutaneous. 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 2-6 weeks after the start of the drug. Once the desired response is achieved, the dose should be reduced to the lowest effective maintenance dose.

In patients with renal insufficiency, Metodject should be used with caution. Correction of the dose of the drug depending on the creatinine clearance value is shown in the table.

Patients with hepatic insufficiency: in patients with severe liver diseases currently or in the anamnesis, especially caused by alcohol intake, Metodject should be used with great caution. Methotrexate is contraindicated in patients with bilirubin concentrations > 5 mg/dl (85.5 mmol/L).

In elderly patients Metodject should be used with caution, as it is often necessary to adjust the dose downward due to age-related decline in liver and kidney function, as well as a decrease in the body’s folate supply.

In children under 16 years of age with polyarthritic juvenile chronic arthritis, the recommended dose of methotrexate is 10-15 mg/m2 of body surface area per week. If treatment is not effective enough, the dose can be increased up to 20 mg / m2 / week. Due to limited data on subcutaneous and intravenous use in children, the drug should be used intravenously for juvenile arthritis.

When switching from oral methotrexate to parenteral use, a dose reduction may be required due to differences in the bioavailability of the drug with different methods of use.

During therapy with Metodject, consideration should be given to concomitant use of folic acid preparations in accordance with existing treatment standards.

Form of production

The solution for injection is yellow, transparent.

Active ingredient

Methotrexate

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults as directed by your doctor

Indications

Rheumatoid Arthritis