Phenytoin (Eptoin) Effects on Gastrointestinal and Hematological Systems
Gastrointestinal Effects
Phenytoin commonly causes nausea, vomiting, and constipation as dose-related adverse effects, with these symptoms being among the most frequently reported gastrointestinal manifestations. 1
Common GI Manifestations
- Nausea and vomiting occur frequently and are typically dose-related 1, 2
- Constipation is a common complaint during phenytoin therapy 1
- These symptoms often manifest early in treatment and may require symptomatic management 2
Serious GI Complications
- Toxic hepatitis and liver damage can occur, though less commonly than the above symptoms 1
- Hepatic complications may present with elevated liver enzymes and require immediate discontinuation of the drug 1
- Gastrointestinal absorption of phenytoin can be affected by nutritional formulas and activated charcoal, which may decrease drug bioavailability 3
Clinical Pitfall
The gastrointestinal side effects are often overlooked as minor complaints, but persistent nausea and vomiting can lead to medication non-adherence and subtherapeutic drug levels. Monitor patients closely during dose adjustments when GI symptoms are most likely to emerge 2.
Hematological Effects
Phenytoin can cause serious and potentially fatal hematologic complications including thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia, requiring vigilant monitoring of complete blood counts. 1
Common Hematological Changes
- Macrocytosis and megaloblastic anemia occur with chronic use and typically respond to folic acid supplementation 1
- These changes result from phenytoin's interference with folate metabolism 1
Serious Hematological Complications
Thrombocytopenia can develop, with cases reported as early as 15 days after initiation 4
Leukopenia, granulocytopenia, and agranulocytosis have been reported, some with fatal outcomes 1
Pancytopenia with or without bone marrow suppression represents the most severe hematologic complication 1
Lymphoproliferative Disorders
- Lymphadenopathy including benign lymph node hyperplasia and pseudolymphoma can occur 1
- Rare cases of malignant lymphoma, Hodgkin's disease, and mycosis fungoides-like lesions have been reported with chronic phenytoin use 1, 5
Monitoring Requirements
Complete blood counts should be monitored regularly, particularly during the first few months of therapy and when patients present with unexplained fever, sore throat, or bleeding. 1, 4
Drug Interactions Affecting Hematology
- Cotrimoxazole (trimethoprim/sulfamethoxazole) increases the risk of hematological adverse reactions when combined with phenytoin, as cotrimoxazole reduces phenytoin metabolism 6
- Monitor serum phenytoin levels when these drugs are co-administered 6
Critical Warning
Thrombocytopenia in neurosurgical patients is particularly dangerous as it can cause confusion that mimics postoperative neurological complications and may lead to cerebral hemorrhage with permanent deficits 4. Any unexplained drop in platelet count warrants immediate phenytoin discontinuation and consideration of alternative antieconvulsants such as levetiracetam 7.