Drug Interaction Report

GENERALLY AVOID: Coadministration of deferiprone and other drugs that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity. Serious infection and death have been reported. The mechanism by which deferiprone leads to neutropenia or agranulocytosis is unknown. In pooled clinical trials of 642 patients with thalassemia syndromes, neutropenia occurred in 6.2% and agranulocytosis in 1.7% of deferiprone-treated patients. Similarly, agranulocytosis occurred in 1.5% of deferiprone-treated patients in pooled clinical trials of 196 patients with sickle cell disease or other anemias. Pediatric patients experienced a higher rate of decreases in neutrophil count when compared to adults being treated with deferiprone for the same condition. Neutropenia and agranulocytosis generally resolve upon discontinuation of deferiprone.

MANAGEMENT: Concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis should generally be avoided. Some authorities consider this combination to be contraindicated. If coadministration is unavoidable, the patient's baseline absolute neutrophil count (ANC) should be measured and then closely monitored during deferiprone therapy according to the manufacturer's product labeling. If neutropenia or infection develops, deferiprone and any other concomitant therapy associated with neutropenia or agranulocytosis should be discontinued. A complete blood cell (CBC) count, including a white blood cell (WBC) count corrected for the presence of nucleated red blood cells, an ANC, and a platelet count should be obtained daily until recovery. Patients should be advised to seek immediate medical assistance if they develop symptoms of infection (e.g., fever, sore throat, flu-like symptoms). For patients who develop agranulocytosis (ANC less than 0.5 x 10^9/L), hospitalization should be considered, and deferiprone should not be resumed following recovery unless potential benefits outweigh the risks. Likewise, patients who develop neutropenia with deferiprone should not be rechallenged unless potential benefits outweigh the risks.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.