Drug Interaction Report

Ethotoin has a moderate potential interaction with Abnormal Glucose Tolerance.

Phenytoin, particularly in high dosages, may cause hyperglycemia by inhibiting insulin release. The drug may also raise serum glucose levels in diabetic patients. Therapy with phenytoin should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during phenytoin therapy, and their antidiabetic regimen adjusted accordingly. The same precautions should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Ethotoin has a moderate potential interaction with Anemia, Folate Deficiency.

Hydantoin anticonvulsants may interfere with folate metabolism and precipitate macrocytosis and megaloblastic anemia, which usually respond to folic acid therapy. These reactions have been fairly uncommon but may be of concern in patients with megaloblastic anemia or folate deficiency receiving hydantoin therapy.

Fluorouracil has a moderate potential interaction with Bleeding Disorder.

Fluorouracil (5- FU) induces myelosuppression, including thrombocytopenia. Therapy with 5- FU should be administered cautiously in patients with bleeding tendencies. Therapy with 5- FU should be promptly discontinued following bleeding from any sight. Patients should be instructed to immediately report any signs or symptoms suggesting bleeding such as petechiae, purpura, hematuria, or melena. Close clinical monitoring of hematopoietic function is recommended. Therapy with 5- FU should be withheld if platelet counts falls below 100,000/mm3.

Ethotoin has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Hematologic toxicities have been associated with the use of hydantoin anticonvulsants, particularly mephenytoin. Thrombocytopenia, leukopenia, neutropenia, agranulocytosis, pancytopenia and, rarely, hemolytic anemia, aplastic anemia and pure red cell aplasia have been reported. Therapy with hydantoin anticonvulsants should be administered cautiously in patients with preexisting blood dyscrasias and/or bone marrow depression. Complete blood counts, including platelets, should be performed prior to initiating therapy and regularly for several months thereafter. For mephenytoin, the manufacturer recommends performing counts after 2 weeks on a low dosage, after another 2 weeks when full dosage is reached, then monthly for a year, and every 3 months thereafter. Marked depression of blood counts may be indication for withdrawal of hydantoin therapy.

Fluorouracil has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

5- FU can cause severe and fatal myelosuppression. Therapy with 5- FU should be administered cautiously in patients who have had prior high-dose pelvic irradiation or alkylating agents or who have widespread metastatic tumor involvement of the bone marrow. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended and therapy should be withheld if platelet counts falls below 100,000/mm3 and/or white blood cell (WBC) counts falls below 3500/mm3 or a rapid fall in WBC is noted.

Fluorouracil has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Fluorouracil can cause cardiotoxicity, including angina, myocardial infarction, arrhythmia and heart failure based on post marketing reports. Reported risk factors for cardiotoxicity include administration by continuous infusion rather than intravenous bolus and presence of coronary artery disease. Caution and monitoring is advised in patients with coronary artery disease. Treatment should be discontinued for cardiotoxicity. The risks of treatment resumption after cardiotoxicity has been resolved have not been established.

Ethotoin has a moderate potential interaction with Depression.

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.

Ethotoin has a moderate potential interaction with Diabetes Mellitus.

Phenytoin, particularly in high dosages, may cause hyperglycemia by inhibiting insulin release. The drug may also raise serum glucose levels in diabetic patients. Therapy with phenytoin should be administered cautiously in patients with diabetes mellitus, glucose intolerance, or a predisposition to hyperglycemia. Patients with diabetes mellitus should be monitored more closely during phenytoin therapy, and their antidiabetic regimen adjusted accordingly. The same precautions should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Fluorouracil has a moderate potential interaction with Enzymopathy, Unspecified.

Capecitabine is metabolized to fluorouracil. Capecitabine and fluorouracil are not recommended for use in patients known to have certain variants in the DPYD gene known to result in complete (or near complete) DPD deficiency; enzymatic deficiency results in increased systemic drug exposure. Consider testing for genetic variants of DPYD prior to initiating therapy. No dose of capecitabine or fluorouracil has been proven safe for patients with complete DPD deficiency and there are insufficient data to recommend a dose in patients with partial DPD deficiency. Withhold or permanently discontinue therapy (based on clinical judgement) in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate complete DPD deficiency.

Ethotoin has a moderate potential interaction with Folic Acid/Cyanocobalamin Deficiency.

Hydantoin anticonvulsants may interfere with folate metabolism and precipitate macrocytosis and megaloblastic anemia, which usually respond to folic acid therapy. These reactions have been fairly uncommon but may be of concern in patients with megaloblastic anemia or folate deficiency receiving hydantoin therapy.

Fluorouracil has a major potential interaction with Infection.

Fluorouracil (5-FU) should not be used in patients with potentially serious infectious diseases. 5-FU induces myelosuppression. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during therapy with 5-FU. Close clinical monitoring of hematopoietic function is recommended.

Fluorouracil has a major potential interaction with Inflammatory Bowel Disease.

Fluorouracil (5-FU) induces stomatitis in the gastrointestinal tract. Therapy with 5-FU should be administered with extreme caution in patients with peptic ulcer disease and ulcerative colitis.

Ethotoin has a major potential interaction with Liver Disease.

Hydantoin anticonvulsants are primarily metabolized by the liver. Both metabolic activity and plasma protein binding may be significantly altered in patients with liver disease, resulting in elevated drug levels (total and unbound fraction) and increased risk of toxicity. Therapy with hydantoin anticonvulsants should be administered cautiously in patients with impaired hepatic function. Reduced dosages and slower titration may be necessary. In addition, periodic monitoring of liver function is recommended, since the use of anticonvulsants, including hydantoins, has been associated with hepatotoxicity related to drug hypersensitivity. Hepatic failure and death have occurred. Hydantoin therapy should be discontinued and not readministered if evidence of liver damage is observed and felt to be drug-related.

Fluorouracil has a major potential interaction with Peptic Ulcer.

Fluorouracil (5-FU) induces stomatitis in the gastrointestinal tract. Therapy with 5-FU should be administered with extreme caution in patients with peptic ulcer disease and ulcerative colitis.

Ethotoin has a major potential interaction with Porphyria.

The use of phenytoin has rarely been associated with exacerbation of porphyria. Therapy with phenytoin should be administered cautiously in patients with porphyria. The same precaution should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.

Ethotoin has a moderate potential interaction with Psychosis.

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.

Ethotoin has a moderate potential interaction with Vitamin D Deficiency.

Phenytoin may interfere with vitamin D metabolism. Hypocalcemia and osteomalacia have been reported. Therapy with phenytoin should be administered cautiously in patients with preexisting vitamin D deficiency. The same precaution should also be observed with other hydantoin anticonvulsants (i.e. ethotoin and mephenytoin) because of their structural and pharmacological similarities to phenytoin.