Heptral lyophilized powder for preparation of solution for injection 500 mg in vials of 5 pcs. complete with solvent in ampoules of 5 ml 5 pcs.

• intrahepatic cholestasis in adults, including patients with chronic hepatitis of various etiologies and liver cirrhosis;
• Intrahepatic cholestasis in pregnant women.

• active ingredient: ademetionine;
• 1 vial of lyophilized powder contains 949 mg of ademethionine 1,4-butanedisulfonate, which corresponds to 500 mg of ademethionine cation;
• excipients: none.
• 1 ampoule with solvent contains L-lysine, sodium hydroxide, water for injection.

Hypersensitivity to the active substance or to any of the excipients of the drug (see section “Composition”).

Genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g. cystathionine beta synthase deficiency, vitamin B12 metabolism defect).

The most commonly reported side effects during treatment with ademetionine were headache, diarrhea, and nausea.

From the gastrointestinal tract: often – abdominal pain, diarrhea, nausea; infrequently – dry mouth, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, gastrointestinal disorders, vomiting, esophagitis; rarely – abdominal bloating.

General disorders and administration site conditions: common: asthenia; uncommon: edema, hyperthermia, chills*, injection site reactions*, injection site necrosis*; rare: malaise.

Nervous system disorders: often – headache; infrequently – dizziness, paresthesia, dysgeusia*.

Mental disorders: often – anxiety, insomnia; infrequently – agitation, confusion.

Respiratory, thoracic and mediastinal disorders: uncommon – laryngeal edema*.

Skin and subcutaneous tissue disorders: common: pruritus; uncommon: hyperhidrosis, angioedema*, allergic skin reactions (e.g. rash, pruritus, urticaria, erythema)*.

Treatment can be initiated with parenteral administration of the drug followed by the use of the drug in tablet form or immediately with the use of tablets.

For intramuscular or intravenous administration, the lyophilized powder must be dissolved in the special solvent provided immediately before use. For intravenous administration, the required dose of dissolved ademetionine must be further diluted in 250 ml of physiological saline or 5% dextrose (glucose) solution and infused slowly over 1–2 hours. Any unused portion of the solution must be discarded.

Ademetionine should not be mixed with alkaline solutions or solutions containing calcium ions. If the lyophilized powder has a color other than white to yellowish (due to cracks in the vial or exposure to elevated temperature), it should be avoided.

Initial therapy

Intravenous or intramuscular: The recommended dose is 5–12 mg/kg body weight per day for 2 weeks. The usual starting dose is 500 mg/day, the total daily dose should not exceed 1000 mg.

Supportive therapy

Administer orally (inside) according to the instructions for medical use of the drug Heptral® in the form of enteric-coated tablets.

The duration of therapy depends on the severity and course of the disease and is determined by the doctor individually.

Use during pregnancy or breastfeeding

In clinical studies, no adverse reactions were observed in women treated with ademetionine during the third trimester of pregnancy. Ademetionine should be used only if clearly needed during the first two trimesters of pregnancy.

During breastfeeding, ademetionine can be used only if the potential benefit from its use outweighs the potential risk to the infant.

Children

The safety and effectiveness of ademetionine in children have not been established.

Ability to influence reaction speed when driving vehicles or other mechanisms

Some patients may experience dizziness when taking ademetionine. Patients should refrain from driving or operating machinery until they are certain that ademetionine therapy does not affect their ability to perform these activities.

Cases of overdose with ademetionine have been observed rarely. In case of overdose, physicians should contact local poison control centers. In general, patient monitoring and supportive treatment are recommended.

Serotonin syndrome has been reported in a patient taking ademetionine while taking clomipramine. Therefore, although the possibility of an interaction is theoretically possible, caution should be exercised when ademetionine is used concomitantly with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), and drugs and herbal remedies containing tryptophan.

Store at a temperature not exceeding 25C in a place inaccessible to children.