TRANSMETIL Tablet / Powder for solution for injection Ref.[27974] Active ingredients: Ademetionine

Intravenous ademetionine should be administered slow IV (see DOSAGE AND ADMINISTRATION).

Ammonia levels should be monitored in patients with pre-cirrhotic 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 such as vegans) should have routine blood tests to check the plasma levels. If a deficiency is found, treatment with B₁₂ and/or folate is recommended prior to or concurrently with administration of ademetionine. (see PHARMACOLOGIC PROPERTIES – Metabolism).

Some patients may experience dizziness with the use of ademetionine. Patients should be advised not to drive or operate machinery during treatment until they are reasonably certain that ademetionine therapy does not affect their ability to engage in such activities. (see EFFECTS ON ABILITY TO DRIVE OR USE MACHINES).

Ademetionine is not recommended for use in patients with bipolar disease. There have been reports of patients switching from depression to hypomania or mania when treated with ademetionine.

There has been a single literature report of serotonin syndrome in a patient taking ademetionine and clomipramine. Although a potential interaction is postulated, caution is recommended when administering ademetionine concomitantly with selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (such as clomipramine), and over-the-counter and herbal supplements containing tryptophan. (see DRUG INTERACTIONS).

The efficacy of ademetionine in the treatment of depression was studied in short-term clinical trials (3-6 weeks in duration). The effectiveness of ademetionine in the treatment of depression over longer periods is unknown. There are many medications to treat depression, and patients should consult with their physicians to determine optimal therapy. Patients should be encouraged to inform their physicians if their symptoms do not abate or worsen during ademetionine therapy.

Patients with depression are at risk for suicide and other serious events and therefore should receive continuous psychiatric support during therapy with ademetionine to ensure that the symptoms of depression are adequately addressed and treated.

There have been reports of transient or worsening anxiety in patients treated with ademetionine. In most cases, interruption of therapy was not required. In a few cases, the anxiety resolved after a reduction in dosage or discontinuation of therapy.

Interference with homocysteine immunoassays

Ademetionine interferes with homocysteine immunoassays, which may show falsely elevated levels of plasma homocysteine in patients treated with ademetionine. In patients treated with ademetionine, it is therefore recommended to use non-immunological methods to measure plasma homocysteine.

Serotonin syndrome has been reported in a patient taking ademetionine and clomipramine. Therefore, although a potential interaction is postulated, caution is recommended when administering ademetionine concomitantly with selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (such as clomipramine), and over-the-counter and herbal supplements containing tryptophan. (see WARNINGS AND PRECAUTIONS).

Pregnancy

The use of high doses of ademetionine in women in the last three months of pregnancy did not lead to any adverse effect. It is advisable to administer ademetionine in the first three months of pregnancy only if it is absolutely necessary.

Lactation

Ademetionine should be used while breast-feeding only if the potential benefit justifies the potential risk to the infant.

Some patients may experience dizziness with the use of ademetionine. Patients should be advised not to drive or operate machinery during treatment until they are reasonably certain that ademetionine therapy does not affect their ability to engage in such activities (see WARNINGS AND PRECAUTIONS).

Clinical Trials

Ademetionine was studied in 2434 patients of whom 1983 were exposed to ademetionine with liver disease and 817 patients with depression, in controlled and open trials for up to 2 years.

The table is based on 1667 patients in 22 clinical trials treated with ademetionine, of whom 121 (7.2%) experienced a total of 188 adverse reactions. Nausea, abdominal pain, and diarrhea were the most frequently reported adverse reactions. A causal relationship of the adverse event with the drug was not always assessable.

Post Marketing Experience

Immune system disorders: Hypersensitivity, Anaphylactoid reactions or anaphylactic reactions (e.g. flushing, dyspnea, bronchospasm, back pain, chest discomfort, alterations in blood pressure [hypotension, hypertension] or pulse rate [tachycardia, bradycardia]).

Psychiatric disorders: Anxiety

Respiratory, thoracic and mediastinal disorders: Laryngeal edema

Skin and subcutaneous tissue disorders: Injection site reaction (very rarely with skin necrosis), angioedema, allergic skin reactions (e.g. rash, pruritus, urticaria, erythema).