Heptral Special Precautions

To be used under the supervision of a physician.
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 (see Pharmacology: Pharmacokinetics under Actions).
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 (SSRIs), tricyclic antidepressants (eg, clomipramine) and over-the-counter and herbal supplements containing tryptophan (see Interactions).
Renal Impairment: Studies have not been conducted in patients with renal impairment. Therefore, caution is recommended when administering ademetionine to these patients.
Hepatic Impairment: Pharmacokinetic parameters are similar in healthy volunteers and patients with chronic liver disease.
Effects on the Ability to Drive or Operate Machinery: 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 reasonabty certain that ademetionine therapy does not affect their ability to engage in such activities.
Use in pregnancy: The use of high doses of ademetionine in women in the last 3 months of pregnancy did not lead to any adverse effect. It is advisable to administer ademetionine in the first 3 months of pregnancy only if it is absolutely necessary.
Use in lactation: Ademetionine should be used while breastfeeding only if the potential benefit justifies the potential risk to the infant.
Use in children: The safety and efficacy of ademetionine for the use in children has not been established.
Use in the elderly: Clinical studies of ademetionine did not include sufficient numbers of subjects ≥65 years to determine whether they respond differently from younger subjects. Reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.