HeptalNAN

Ademetionine

Enteric-coated tablets

White or off-white, oval biconvex film-coated tablets.

Each tablet contains:
Active substance: ademetionine cation 500 mg (in the form of S-adenosyl-L-methionine 1.4-butandisulfonate).
Auxiliary substances: starch sodium glycolate (type A), anhydrous colloidal silicon dioxide, magnesium stearate, and microcrystalline cellulose.
Coating composition: methacrylic acid and ethylacrylate copolymer (1:1) type A, macrogol 6000, polysorbate 80, sodium hydroxide, and talc.

Other medications for treatment of gastrointestinal and metabolic diseases. Amino acids and their derivatives.

A16AA02

Ademetionine is an amino acid involved in various metabolic processes in the body.

The medication is indicated for use in adults with:

• intrahepatic cholestasis in precirrotic and cirrhotic conditions,
• intrahepatic cholestasis during pregnancy,
• symptoms of depression.

Ademetionine tablets should be taken orally, without chewing and with a sufficient amount of water. For better absorption of the active substance and to achieve maximum therapeutic effect, tablets should not be taken with food.
Ademethionine tablets should be taken out from the blister just prior to ingestion. If tablets are not white or off-white (due to leaky packaging), do not use HeptalNAN.

Intrahepatic cholestasis

Initial therapy:
The recommended dose is 10-15 mg/kg once daily. The usual initial dose is 1000 mg daily (2 tablets), the total daily dose should not exceed 1500 mg (3 tablets).

Supporting therapy:
The daily dose is 1000-1500 mg (2 or 3 tablets).
Treatment duration depends on the severity and course of the disease and is determined by the doctor individually.

Symptoms of depression

Initial therapy:
The recommended daily dose is 1000 mg (2 tablets).

Supporting therapy:
The recommended daily dose is 500 mg (1 tablet).
Treatment duration depends on the severity and course of the disease and is determined by the doctor individually.

Children and adolescents
The safety and efficacy of ademetionine in children (under 18 years of age) have not been established.

Elderly patients
Clinical studies of ademetionine did not include a sufficient number of patients aged 65 years and older to determine possible differences in effectiveness of HeptalNAN in this patient population and in younger patients.

Clinical experience has not revealed any differences in its effectiveness in elderly and younger patients. In general, considering high probability of existing renal, hepatic, or cardiac dysfunctions and other concomitant pathology or simultaneous therapy with other medications, the dose should be selected with caution in elderly patients. Start the treatment with the medication from the lower dose range limit.

Patients with renal insufficiency
No studies in patients with renal insufficiency have not been performed. Therefore, caution should be exercised when treating such patients with ademetionine.

Patients with hepatic insufficiency
Ademetionine pharmacokinetics parameters are similar in healthy volunteers and in patients with chronic liver diseases.

The most common concurrent reactions reported in the course of clinical trials were nausea, abdominal pain and diarrhea. Data on adverse reactions observed in the course of clinical trials with ademetionine and during the post-marketing period are shown below.

Infections and infestations: urinary tract infections.

Immune system disorders: hypersensitivity reactions, anaphylactoid or anaphylactic reactions (for example, hot flashes, dysponoea, bronchospasm, back pain, chest discomfort, changes in blood pressure (hypotension, hypertension) or heart rate (tachycardia, bradycardia)).

Psychiatric symptoms: anxiety, confusional state, insomnia.

Nervous system disorders: dizziness, headache, paraesthesia.

Cardiac disorders: cardiovascular accidents.

Vascular disorders: flashes, phlebitis of superficial veins

Respiratory, thoracic and mediastinal disorders: laryngeal edema.

Gastrointestinal disorders: bloating, abdominal pain, diarrhea, dry mouth, dyspepsia, esophagitis, flatulence, gastrointestinal pain, gastrointestinal disorders, gastrointestinal bleeding, nausea, vomiting.

Renal and urinary disorders: biliary colic, cirrhosis.

Skin and subcutaneous tissue disorders: hyperhidrosis, pruritus, allergic skin reactions (e.g., rash, itching, urticaria, erythema), Quincke oedema.

Musculoskeletal and connective tissue disorders: arthralgia, muscle spasms.

General disorders and administration site conditions: asthenia, chills, influenza-like syndrome, malaise, peripheral edema, fever.

If any of the undesirable effects listed in the instructions worsen, or you notice any other undesirable effects not listed in the instructions, inform your doctor about it.

• Hypersensitivity to ademetionine or to any other component of HeptalNAN.
• Genetic disorders affecting the methionine cycle and/or causing homocysteinuria and/or hyperhomocysteinemia (for example, deficiency of cystathionine beta-synthetase, vitamin B₁₂ metabolic imbalance).

If taking a larger dose than prescribed by your doctor, immediately contact specialists to provide timely medical care!
Overdose with ademetionine is unlikely. In the event of overdose, the patient should be observed and appropriate symptomatic treatment given.

Serotonin syndrome has been reported in a patient taking ademetionine during treatment with clomipramine. Thus, although a possible interaction is hypothetical, caution should be taken when co-administering ademethionine with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), herbal remedies and medications that contain tryptophan.

Inform your doctor about all medications you are taking. Consult your doctor before you start taking any medication during treatment with HeptalNAN.

With simultaneous oral administration of ademethionine, blood nitrogen levels should be monitored in patients with cirrhosis and in precirrotic conditions with hyperazotemia. Since vitamin B12 and folic acid deficiency may result in decreasing ademethionine concentration, standard blood tests should be performed in patients at risk (with anemia, liver disease, pregnancy, probability of vitamin deficiency, other diseases or diet, for example, in vegetarians) to assess plasma concentrations of vitamins. If insufficiency is detected, it is recommended to take cyanocobalamin and folic acid before initiating treatment with ademethionine or co-administration with ademethionine.

Some patients may experience dizziness when using ademethionine. Patients should be advised to keep from driving vehicles or using mechanisms during treatment with the medication until reasonable confirmation that treatment with ademetionine does not cause impairment in ability to be engaged in this kind of activity (see Section Effects on ability to drive and use machines).

Suicidal ideation (in patients with symptoms of depression)
Depression is associated with an increased risk of suicidal thoughts and suicide. Such a risk persists until stable remission. Improvement may occur after several weeks of depression treatment. Patients should be closely monitored until improvement. Based on the available clinical experience, the risk of suicide may increase at early stages of treatment.

Patients with a history of suicidal behavior or those who have suicidal thoughts before treatment should be under close clinical observation during treatment. Meta-analysis of clinical studies on mental disorders treatment has shown that administration of antidepressants compared with placebo in patients under 25 years of age is accompanied by an increased risk of suicidal behavior. Patients should be carefully monitored when prescribing antidepressants, especially at initial stages of treatment and after dosage modification. Patients (as well as care-givers) should be aware of the need for constant monitoring and be ready to inform the attending physician immediately if their symptoms of depression do not decrease or worsen during treatment with ademetionine, as well as in case of behavioral changes or suicidal thoughts.
Ademethionine is not recommended for use in patients with bipolar disorder.

Cases of transition from depression to hypomania or mania have been reported in patients treated with ademethionine.
There is only one literary publication about serotonin syndrome in a patient who took ademethionine and clomipramine. Although a possible interaction is hypothetical, caution is recommended when prescribing ademethionine with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), herbs and medicinal products that contain tryptophan (see Section Interactions with other medicines).

Efficacy of ademethionine for treatment of depression has been demonstrated in short-term clinical trials (lasting 3-6 weeks). Efficacy of ademethionine for treatment of depression for a longer period of time is unknown. There are many medications available to treat depression, patients should consult with their physician and choose the optimal therapy. Patients should be aware of the need to inform their doctor if their symptoms of depression do not decrease or worsen during treatment with ademethionine.
Patients with depression have an increased risk of suicide and other serious adverse events, therefore, such patients should remain under close clinical observation by a psychiatrist for adequate assessment and treatment of symptoms of depression during treatment with ademethionine.

Cases of sudden emergence or increase of anxiety have been reported in patients treated with ademethionine. In most cases, interruption of therapy was not required. In isolated cases, anxiety passed after reducing the dose of the medication or discontinuation of therapy.

Effects on the results of homocysteine determination by immunological methods
During ademethionine administration, a false elevated plasma level of homocysteine may be observed, since ademethionine affects the results of homocysteine determination by immunological analysis. Thus, in patients treated with ademethionine, non-immunological methods to determine homocysteine plasma levels are recommended.

If you have one of the diseases or conditions listed above, be sure to consult your doctor before taking HeptalNAN.

Pregnancy
Therapeutic doses of ademethionine in women in the last trimester of pregnancy did not lead to any adverse effects. Ademethionine should not be used in the first trimester of pregnancy unless clearly necessary.

Breast-feeding
Administration of ademethionine during breast-feeding is allowed only when the expected benefits outweigh the potential risks to the infant.

Some patients may experience dizziness when using ademethionine. Patients should be advised to keep from driving vehicles or using mechanisms during treatment with the medication until reasonable confirmation that treatment with ademetionine does not cause impairment in ability to be engaged in this kind of activity (see Section Warnings and precautions).

Enteric-coated tablets 450 mg.
7 tablets in a blister made of OPA/Al/PVC (oriented polyamide / aluminum/PVC) blister foil and flexible packing based on aluminum foil. 3 blisters with a patient information leaflet, packed in a carton.

Protect from light and moisture, at a temperature not above 25°C. Keep away from children.

2 years. Do not use after the expiration date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus
Phone / Fax +375 17 268 63 64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en