Ademetionin-Vial - instructions for use, dose, side effects, contraindications

Excipients: microcrystalline cellulose - 96.00 mg; sodium carboxymethyl starch - 17.10 mg; magnesium stearate - 4.28 mg; silicon dioxide colloidal - 8.60 mg.

Auxiliary shell: Macrogol-6000 - 8.864 mg; titanium dioxide - 6.870 mg, talc - 3.990 mg, hypromellose - 2.4360 mg.

Enteric coating: Macrogol-6000 - 17,720 mg; titanium dioxide - 13.730 mg, talc - 7.980 mg, methacrylic acid and methyl methacrylate copolymer [1: 1] - 4.870 mg.

Description:

Biconvex tablets of oval form, covered with a film shell of white or almost white color; on the cross-section there is a nucleuswhite or almost white.

Pharmacotherapeutic group:Hepatoprotective agent

ATX: & nbsp

A.16.A.A.02 Ademethionine

Pharmacodynamics:

Ademetionine belongs to the group of hepatoprotectors with antidepressant activity. Has choleretic and cholekinetic effect, has detoxification, regenerating, antioxidant, antifibrozing and neuroprotective properties.

Replenishes the deficit of ademetionine and stimulates its production in the body primarily in the liver and brain. Participates in biological reactions of transmethylation (a methyl group donor) - a molecule S-adenosyl-Lmethionine (ademethionine) donates a methyl group in the reactions of methylation of phospholipids of cell membranes of proteins, hormones, neurotransmitters, etc .; transsulfation - the precursor of cysteine, taurine, glutathione (provides redox mechanism of cellular detoxification), coenzyme acetylation. Increases the glutamine content in the liver, cysteine and taurine in plasma; reduces the content of methionine in the serum, normalizing metabolic reactions in the liver.After decarboxylation it participates in aminopropylation processes as a precursor of polyamines-putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the ribosome structure.

Has a choleretic effect due to increased mobility and polarization of hepatocyte membranes, due to stimulation of the synthesis of phosphatidylcholine in them. This improves the function of hepatocyte-associated transport systems of bile acids and promotes the passage of bile acids into the biliary system. Effective with intraloble variant of cholestasis (a violation of synthesis and current of bile).

It contributes to the detoxification of bile acids, increases the content of conjugated and sulfated bile acids in hepatocytes. Conjugation with taurine increases the solubility of bile acids and their removal from the hepatocyte. The process of sulphation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates the passage through the membrane of the hepatocyte and excretion with bile. In addition, sulfated bile acids protect the liver cell membranes from the toxic effect of non-sulphated bile acids (in highconcentrations of those present in hepatocytes with intrahepatic cholestasis).

In patients with diffuse liver disease (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome reduces the severity of skin itching and changes in biochemical parameters, incl. concentration of direct bilirubin, activity of alkaline phosphatase, aminotransferases, etc.

Choleretic and hepatoprotective effects persist up to 3 months after discontinuation of treatment.

Efficacy is shown for hepatopathies due to hepatotoxic drugs.

The appointment of patients with opioid addiction, accompanied by liver damage, leads to regression of clinical manifestations of abstinence, improvement of the functional state of the liver and the processes of microsomal oxidation.

Antidepressant activity manifests itself gradually, starting from the end of the first week treatment and stabilized within 2 weeks of treatment. Effective for recurrent endogenous and neurotic depressions resistant to amitriptyline. Has the ability to interrupt recurrence of depression.

The appointment in osteoarthritis reduces the severity of the pain syndrome, increases the synthesis of proteoglycans and leads to partial regeneration of the cartilaginous tissue.

Pharmacokinetics:

With a single intake of 400 mg the maximum concentration in the plasma (C_mOh) - 0.7 mg / l. Time to reach the maximum concentration (TC_mOh) - 2-6 hours Bioavailability of the drug for oral administration is 5%, increases with fasting. The connection with plasma proteins is insignificant, it penetrates the blood-brain barrier. When ademetionine is taken, there is a significant increase in its concentration in the cerebrospinal fluid. Metabolised in the liver. The half-life (T_1/₂) - 1.5 hours. It is excreted by the kidneys.

The tablets of the preparation are covered with a special coating that dissolves only in the intestine, ademethionine is released in the duodenum.

Indications:

Intrahepatic cholestasis with precirrotic and cirrhotic conditions, which can be observed in the following diseases:

- fatty degeneration of the liver;

- chronic hepatitis;

- toxic liver damage of various etiologies, including alcoholic, viral, medicinal (antibiotics, antitumor, antituberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives);

- chronic non-calculous cholecystitis;

- cholangitis;

- encephalopathy, incl. associated with hepatic insufficiency (alcoholic, etc.).

Intrahepatic cholestasis in pregnant women.

Alcoholic liver disease.

Symptoms of depression.

Contraindications:

Hypersensitivity to ademetionin and / or other components of the drug.

Age to 18 years.

Genetic disorders affecting the methionine cycle and / or causing homocystinuria and / or hyperhomocysteinemia (cystathione deficiency of beta-synthase, a disturbance in the metabolism of vitamin B₁₂ (cyanocobalamin)).

Carefully:

Should carefully use ademethionine together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), herbal preparations and preparations containing tryptophan.

In elderly patients, patients with bipolar disorders; with renal failure.

Pregnancy and lactation:

The use of ademetionine in the II and III trimesters of pregnancy did not cause undesirable effects.

Admission in the first trimester of pregnancy and during breastfeeding is possible if the potential benefit to the mother exceeds the possible risk to the fetus or child.

Dosing and Administration:

Inside.

Tablets should be taken whole, not liquid, preferably in the morning between meals.

Tablets of the drug Ademethionine should be removed from the blister immediately before ingestion. In case the tablets have a color different from white or almost white (due to leaks in the aluminum foil), the preparation Ademethionine use is not recommended.

Initial therapy

The recommended dose is 10-25 mg / kg / day.

Intrahepatic cholestasis

The dose is from 800 mg / day to 1600 mg / day.

Depression

The dose is from 800 mg / day to 1600 mg / day.

The duration of therapy is determined by the doctor. Ademetionine therapy can be started with intravenous or intramuscular injection followed by the use of the drug Ademethionine in the form of tablets.

Elderly patients

Clinical experience with ademethionine has not revealed any difference in its efficacy in elderly patients and younger patients. However, given the high likelihood of existing violations of the liver, kidney or heart, other concomitant pathologies or simultaneous therapy with other drugs, the dose of the drug Ademethionine Elderly patients should be selected with caution, starting the use of the drug from the lower limit of the dose range.

Renal insufficiency

There are limited clinical data on the use of ademetionine in patients with renal insufficiency, in this regard, it is recommended to use caution when using the drug Ademethionine in such patients.

Liver failure

The pharmacokinetics of ademetionin are similar in healthy volunteers and in patients with chronic liver disease.

Children

Application of the drug Ademethionine in children is contraindicated (efficacy and safety not established).

Side effects:

Among the most common adverse reactions identified in clinical trials involving more than 2,100 patients were: headache, nausea and diarrhea.

The following are data on adverse reactions observed during clinical trials (n= 2115) and in the post-marketing application of ademetionine ("spontaneous reports"). All reactions are distributed according to organ systems and the frequency of development: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000).

Infectious and parasitic diseases: infrequently - urinary tract infections.

From the immune system: infrequently - hypersensitivity reactions, anaphylactoid or anaphylactic reactions (including hyperemia of the skin, dyspnea, bronchospasm, back pain, a feeling of discomfort in the chest, changes in blood pressure (arterial hypotension, arterial hypertension) or pulse rate (tachycardia, bradycardia)) *.

Mental disturbance: often - anxiety, insomnia; rarely - agitation, confusion.

From the nervous system: often - headache; infrequently - dizziness, paresthesia.

From the side of the vessels: infrequently - "hot flashes", arterial hypotension, phlebitis.

From the respiratory system, chest and mediastinum: infrequently - swelling of the larynx *.

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

From the skin and subcutaneous tissues: often - itchy skin; infrequently - increased sweating, angioedema, * skin-allergic reactions (including rash, itching, urticaria, erythema) *.

From the musculoskeletal and connective tissue: infrequently - arthralgia, muscle spasms.

General disorders and disorders at the site of administration: infrequently - asthenia, edema, fever, chills *, reactions at the injection site *, necrosis of the skin at the injection site *; rarely - malaise.

* - the undesirable effects revealed in the postmarketing use of ademetionine ("spontaneous" reports), not observed in clinical trials, were classified as undesirable effects with a frequency of "infrequent" on the grounds that the upper limit of the 95% exceeds 3 / X, where X = 2115 (the total number of subjects observed in clinical trials).

Overdose:

There were no clinical cases of overdose.

Interaction:

No known interactions with other drugs have been observed.

There is a report on the syndrome of excess serotonin in the patient who took ademethionine and clomipramine. It is believed that such interaction is possible, and should be cautiously appointed ademethionine together with selective inhibitors of the inverse seizure of serotonin, tricyclic antidepressants (such as clomipramine), a also with herbal preparations and preparations containing tryptophan.

Special instructions:

Given the tonic effect of the drug, its use is not recommended before bedtime.

In the treatment of patients with cirrhosis associated with hyperosotemia, systematic monitoring of the nitrogen content of the blood is necessary.

During prolonged therapy, it is necessary to determine the content of urea and creatinine in the blood serum.

It is not recommended to apply ademethionine patients with bipolar disorders. There are reports of the transition of depression to hypomania or mania in patients taking ademethionine.

There are reports of sudden onset or worsening of anxiety in patients taking ademethionine. In most cases, withdrawal of therapy is not required, in several cases, anxiety disappeared after dose reduction.

Because vitamin B deficiency₁₂ and folic acid can reduce the concentration of ademetionine in patients at risk (with anemia, liver disease, pregnancy or the likelihood of vitamin deficiency, due to other diseases or diet, for example, in vegetarians), you should monitor the content of these vitamins. If insufficiency is detected, simultaneous administration of ademetionine with vitamin B is recommended₁₂ and folic acid.

Ademetionin influences the result of immunological analysis of homocysteine, which can be the cause of a falsely high concentration of homocysteine in the plasma. For patients receiving ademethionine, it is recommended to use non-immunological assays to determine the concentration of homocysteine.

Care should be taken in patients with renal insufficiency, since no studies have been conducted in this category of patients.

Effect on the ability to drive transp. cf. and fur:

Some patients may experience dizziness when taking ademetionine. It is not recommended to drive the car and work with the machines during the drug until the patients are sure that the therapy does not affect the ability to engage in this type of activity.

Form release / dosage:

Intestinal-coated tablets, 400 mg.

Packaging:

10 tablets per blister of aluminum foil and combined material (polyamide / aluminum / PVC);

1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blisters are placed in a cardboard box together with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004002

Date of registration:06.12.2016

Expiration Date:06.12.2021

The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia

Manufacturer: & nbsp

Beijing Kawin Technology Share-Holding Co., Ltd China

Representation: & nbspVIAL, LLCVIAL, LLC

Information update date: & nbsp04.02.2017

Illustrated instructions

Instructions

Ademethionine-Vial (Ademetionine-Vial)