Chloramphenicol Injection and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Chloramphenicol Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased phenytoin or fosphenytoin (prodrug of phenytoin) exposure and an increased risk of phenytoin or fosphenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor)
Interaction Deep Dive
Concurrent administration of phenytoin or fosphenytoin (prodrug of phenytoin) and chloramphenicol have resulted in increased exposure of phenytoin or fosphenytoin and lead to toxicity. Monitor patients for signs of phenytoin or fosphenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor) when receiving chloramphenicol concurrently. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when chloramphenicol is added to or withdrawn from a patient's regimen. Monitor phenytoin or fosphenytoin serum drug level during concurrent use of chloramphenicol and phenytoin or fosphenytoin567. Chloramphenicol has been shown to inhibit biotransformation of phenytoin in humans, and as much as a 2- or 3-fold increase in half-life may be seen 1.
Why it happens (mechanism)
Reduced phenytoin metabolism
Literature reports
1 report — tap to read
a) Chloramphenicol has been shown to inhibit biotransformation of phenytoin in humans, and as much as a 2- or 3-fold increase in half-life may be seen 1834. Phenytoin's effect on chloramphenicol is unpredictable; chloramphenicol concentrations have been increased 2 and decreased 9. An interaction between phenytoin, PHENobarbital, and chloramphenicol was reported in a child with hydrocephalus and a shunt infection. There was a lowered chloramphenicol serum concentration and an increased total body clearance of chloramphenicol, most likely because of increased metabolism. Other possible explanations include increased hepatic blood flow or chloramphenicol induction of its own metabolism 9.
Common questions
Can I take Chloramphenicol Injection and Phenytoin together?
Increased phenytoin or fosphenytoin (prodrug of phenytoin) exposure and an increased risk of phenytoin or fosphenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chloramphenicol Injection and Phenytoin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Chloramphenicol Injection or Phenytoin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (9)
- Christensen LK & Skovsted L: Inhibition of drug metabolism by chloramphenicol. Lancet 1969; 2:1397. DOI
- Krasinski K, Kusmiesz H, & Nelson JD: Pharmacologic interactions among chloramphenicol, phenytoin and phenobarbital. Pediatr Infect Dis 1982; 1:232-235. DOI
- Koup JR, Gibaldi M, McNamara P, et al: Interaction of chloramphenicol with phenytoin and phenobarbital: case report. Clin Pharmacol Ther 1978; 24:571-575. PubMed
- Perucca E: Pharmacokinetic interactions with antiepileptic drugs. Clin Pharmacokinet 1982; 7:57-84. DOI
- Product Information: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
- Ballek RE, Reidenberg MM, & Orr L: Inhibition of diphenylhydantoin metabolism by chloramphenicol. Lancet 1973; 1:150. PubMed
- Powell DA, Nahata MC, Durrell DC, et al: Interactions among chloramphenicol, phenytoin and phenobarbital in a pediatric patient. J Pediatr 1981; 98:1001-1003. DOI
Keep reading about Phenytoin
Keep reading about Chloramphenicol Injection
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist