Ademetionine (S-Adenosyl methionine)
Indications
Ademetionine (S-Adenosyl methionine) is used for:
Treatment of adults with intrahepatic cholestasis in precirrhotic and cirrhotic states, and intrahepatic cholestasis in pregnancy.
Adult Dose
Treatment can be initiated with parenteral administration and continued or initiated orally.
Adults: Intrahepatic Cholestasis: 10-25 mg/kg/day orally. Usual Starting Dose: 800 mg/day. Total Daily Dose: Not to exceed 1600 mg.
Maintenance Therapy: 800-1600 mg/day.
Child Dose
Renal Dose
Administration
Should not be taken with meals.
Contra Indications
Known hypersensitivity to ademetionine
Precautions
Ammonia levels should be monitored in patients with precirrhotic and cirrhotic states of hyperammonemia taking oral ademetionine.
Because vitamin B12 and folate deficiencies may decrease ademetionine levels, at risk patients (anemia, liver disease, pregnancy or potential for vitamin deficiencies due to other illnesses or eating habits eg, vegans) should have routine blood tests to check the plasma levels. If a deficiency is found, treatment with vitamin B12 and/or folate is recommended prior to or concurrently with administration of ademetionine.
Pregnancy-Lactation
Interactions
Serotonin syndrome has been reported in patients taking ademetionine and clomipramine. Therefore, although a potential interaction is postulated, caution is recommended when administering ademetionine concomitantly with SSRIs, tricyclic antidepressants (eg, clomipramine), and over-the-counter and herbal supplements-containing tryptophan
Adverse Effects
Side effects of Ademetionine (S-Adenosyl methionine) :
Nausea, abdominal pain and diarrhea were the most frequently reported adverse reactions.
Infections and Infestations: Urinary tract infection.
Psychiatric Disorders: Confusion, insomnia.
Nervous System Disorders: Dizziness, headache, paresthesia.
Cardiac Disorders: Cardiovascular disorders.
Vascular Disorders: Hot flushes, superficial phlebitis.
Gastrointestinal Disorders: Abdominal distension and pain, diarrhea, dry mouth, dyspepsia, esophagitis, flatulence, gastrointestinal pain and hemorrhage, nausea, vomiting.
Hepatobiliary Disorders: Biliary colic, hepatic cirrhosis.
Skin and Subcutaneous Tissue Disorders: Hypehydrosis, pruritus, skin reactions.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, muscle spasms.
General Disorders and Administration Site Conditions: Asthenia, chills, injection site reactions, influenza-like illness, malaise, peripheral edema, pyrexia.
Post-Marketing Experience: Immune System Disorders: Anaphylactic reaction.
Respiratory, Thoracic and Mediastinal Disorders: Laryngeal edema.
Skin and Subcutaneous Tissue Disorders: Injection site reactions (very rarely with skin necrosis), rash, angioedema.
Mechanism of Action
S-adenosyl-L-methionine (ademetionine) is a naturally occurring amino acid present in virtually all body tissues and fluids. Ademetionine functions primarily as a coenzyme and donor transfer of the methyl group (transmethylation) is an essential metabolic process in humans and animals. Methyl transfer is also essential to the development of the phospholipid bilayer of cell membranes and contributes to membrane fluidity.
Ademetionine can penetrate the blood-brain barrier and ademetionine-mediated transmethylation is critical in the formation of neurotransmitters in the central nervous system including catecholamines (dopamine, noradrenalin, adrenaline), serotonin, melatonin and histamine.
Ademetionine is also a precursor in the formation of physiological sulfurated compounds (cysteine, taurine, glutathione, CoA, etc) via transsulfuration. Glutathione, the most potent antioxidant in the liver, is important in hepatic detoxificatlon. Ademetionine increases hepatic glutathione levels in alcoholic and non-alcoholic liver disease patients. Both folate and vitamin B12 are essential co-nutrients in the metabolism and replenishment of ademetionine.