Fluconazole with Fosphenytoin Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Fosphenytoin
- Cerebyx®
- Fosphenytoin Injection
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
An increased risk of phenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremors)
Interaction Summary
Careful monitoring of phenytoin concentrations in patients receiving fluconazole and phenytoin is recommended. Concomitant use of fluconazole with phenytoin increases the plasma concentrations of phenytoin. In 10 normal male volunteers, phenytoin AUC was determined after 4 days of phenytoin dosing (200 mg daily, orally for 3 days followed by 250 mg intravenously for one dose) both with and without the administration of fluconazole (oral fluconazole 200 mg daily for 16 days). There was a significant increase in phenytoin AUC. The mean +/- SD increase in phenytoin AUC was 88% (+/-68% range: 16% to 247%).Case reports and pharmacokinetic studies have shown that concurrent fluconazole and phenytoin administration may produce increased plasma levels of phenytoin resulting in toxicity .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Careful monitoring of phenytoin concentrations in patients receiving fluconazole and phenytoin is recommended. Concomitant use of fluconazole with phenytoin increases the plasma concentrations of phenytoin.
Mechanism Of Interaction
Inhibition of CYP2C9-mediated metabolism of phenytoin by fluconazole; inhibition of CYP2C19-mediated metabolism of phenytoin by fluconazole
Literature Reports
A) In 10 normal male volunteers, phenytoin AUC was determined after 4 days of phenytoin dosing (200 mg daily, orally for 3 days followed by 250 mg intravenously for one dose) both with and without the administration of fluconazole (oral fluconazole 200 mg daily for 16 days). There was a significant increase in phenytoin AUC. The mean +/- SD increase in phenytoin AUC was 88% (+/-68% range: 16% to 247%) .
B) Concomitant administration of oral fluconazole 200 mg at steady-state with phenytoin at steady-state resulted in an average increase in phenytoin AUC of 88% in normal volunteers .
C) Phenytoin administered with fluconazole caused an increase in phenytoin plasma levels. A 60-year-old patient with cryptococcal meningitis was administered phenytoin 300 mg daily for seizure prophylaxis and oral fluconazole 400 mg daily to treat the infection. The patient developed dizziness, ataxia, and nystagmus associated with a phenytoin plasma level of 35 mg/L. The dose of phenytoin was reduced and the plasma levels normalized as the patient's symptoms resolved .
D) A randomized, placebo-controlled study demonstrated fluconazole increased the plasma level of phenytoin during concurrent administration. Twenty healthy subjects received fluconazole 200 mg daily with phenytoin for two weeks. The 24-hour plasma level of intravenous phenytoin was elevated by 75% and the steady-state trough concentration increased by 128% .
E) Two cases of HIV-infected men suffered phenytoin toxicity, including dizziness, weakness, ataxia, vertigo, nausea, and vision problems, with coadministration of fluconazole. Their serum phenytoin levels were 202 mcmol/L in one patient (long-term concurrent use had occurred) and 95 mcmol/L in the other patient (normal 40 to 80 mcmol/L). After cessation of both drugs and resolution of symptoms, one patient resumed a reduced dose of phenytoin (from 300 mg daily to 200 mg daily) with substitution of clotrimazole for fluconazole. The second patient continued fluconazole 400 mg daily and successfully reinstated concurrent phenytoin reduced from 700 mg to 300 mg daily .
Fluconazole Overview
-
Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
Fosphenytoin Overview
-
Fosphenytoin injection is used to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Fosphenytoin injection may also be used to control certain type of seizures in people who cannot take oral phenytoin. Fosphenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.