Paramethadione Disease Interactions

Hematologic toxicities have been associated with the use of oxazolidinedione anticonvulsants. Fatal aplastic anemia, hypoplastic anemia, pancytopenia, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, eosinophilia, retinal and petechial hemorrhages, vaginal bleeding, epistaxis, and bleeding gums have been reported. Therapy with oxazolidinediones should be administered cautiously, if at all, in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts, including platelets, should be performed in all patients prior to initiating therapy and at monthly intervals, or as often as necessary, thereafter. A moderate degree of neutropenia, with or without a corresponding drop in the leukocyte count, is not uncommon and does not necessitate the discontinuation of therapy. However, more frequent monitoring is recommended if neutrophil count is less than 3000/mm3. Marked depression of blood counts (e.g., neutrophil count < 2500/mm3) is indication for withdrawal of oxazolidinedione therapy. Therapy with oxazolidinediones should ordinarily not be used in patients with severe blood dyscrasias.

Hemeralopia has occurred with the use of oxazolidinedione anticonvulsants, probably as a result of the drugs' effects on the neural layers of the retina. The condition may be reversed by a reduction in dosage. Therapy with oxazolidinediones should be administered cautiously in patients with diseases of the retina or optic nerve. The development of scotomata or other significant ocular abnormality is indication for withdrawal of oxazolidinedione therapy.

Hepatitis has been associated rarely with the use of oxazolidinedione anticonvulsants. In addition, these agents are primarily metabolized by the liver and may accumulate in the presence of liver disease. Therapy with oxazolidinediones should be administered cautiously, if at all, in patients with hepatic impairment. Liver function tests should be performed in all patients prior to initiating therapy and at monthly intervals, or as often as necessary, thereafter. The development of jaundice or other signs of liver dysfunction is indication for withdrawal of oxazolidinedione therapy.

Potentially serious reactions to oxazolidinedione anticonvulsants such as exfoliative dermatitis and severe forms of erythema multiforme have been reported. Therapy with oxazolidinediones should be administered cautiously in patients with preexisting drug-induced dermatitis, since it may delay the recognition of a potential reaction to oxazolidinediones. Oxazolidinedione therapy should be withdrawn promptly at the first sign of a dermatologic adverse effect. Even a minor acneiform or morbilliform rash should be allowed to clear completely before treatment with these agents is resumed.

Fatal nephrosis has been associated with the use of oxazolidinedione anticonvulsants. In addition, the active metabolites of these agents are excreted slowly by the kidney and may accumulate in the presence of renal disease. Therapy with oxazolidinediones should be administered cautiously, if at all, in patients with impaired renal function. Urinalyses should be performed in all patients prior to initiating therapy and at monthly intervals, or as often as necessary, thereafter. The development of persistent or increasing albuminuria or any other significant renal abnormality is indication for withdrawal of oxazolidinedione therapy.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

A myasthenia gravis-like syndrome has been associated with the chronic use of oxazolidinedione anticonvulsants. Therapy with oxazolidinediones should be administered cautiously in patients with myasthenia gravis. The development or exacerbation of myasthenic symptoms is indication for withdrawal of oxazolidinedione therapy.

Manifestations of systemic lupus erythematosus (SLE) have been associated with the use of oxazolidinedione anticonvulsants. Therapy with oxazolidinediones should be administered cautiously in patients with preexisting SLE. The development or exacerbation of SLE symptoms is indication for withdrawal of oxazolidinedione therapy.