Chloramphenicol Injection and Penicillin G: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Chloramphenicol Injection
Penicillin G
No brand names on record
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
Decreased antibacterial effectiveness
Interaction Deep Dive
Both in-vitro and in-vivo data suggest the combination of chloramphenicol and penicillin G has a lower bactericidal effect than either drug alone789. However, this interaction is not clinically significant in most cases, and these drugs may be used together effectively 6.
Why it happens (mechanism)
Decreased bactericidal activity
Literature reports
3 reports — tap to read
a) Chloramphenicol is a bacteriostatic antibiotic which acts by inhibiting the function of messenger RNA. Penicillin is a bactericidal antibiotic which acts by inhibiting a specific step in cell wall synthesis; penicillin exerts its greatest activity during the early phase of bacterial growth. When bacterial growth is inhibited, the activity of penicillin may be considerably reduced 1. Although there is in vivo and in vitro evidence that chloramphenicol may antagonize the bactericidal action of penicillin, this is only clinically significant in a few situations. Clinical evidence of this interaction has not been adequately evaluated. In fact, there are several studies using chloramphenicol with ampicillin indicating that a combination of chloramphenicol and ampicillin is superior to chloramphenicol alone 234.
b) In addition, it has been recommended that in bacterial meningitis in children older than 2 months, that chloramphenicol be given concomitantly with ampicillin until results of cultures and sensitivity tests are known 5.
c) The significance of the interaction of penicillin and chloramphenicol is questionable. Therapy in patients where chloramphenicol and a penicillin is warranted may be initiated. However, studies have suggested that in certain cases of Listeria meningitis, the opsonization of the CSF became inefficient 6.
Common questions
Can I take Chloramphenicol Injection and Penicillin G together?
Decreased antibacterial effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chloramphenicol Injection and Penicillin G interaction?
It is rated minor. Usually limited clinical impact.
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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Chloramphenicol Injection or Penicillin G 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 anything you'd monitor while I'm on both?
References (9)
- Anon: American Academy of Pediatrics: Committee on Infectious Disease. Current status of ampicillin-resistent Haemophilus influenzae type b. Pediatrics 1976; 57:417.
- Robertson RP, Wahab MFA, & Raasch FO: Evaluation of chloramphenicol and ampicillin in salmonella enteric fever. N Engl J Med 1968; 278:171-176. DOI
- DeRitis F, Giammanco G, & Manzillo G: Chloramphenicol combined with ampicillin in treatment of typhoid. Br Med J 1972; 4:17-18. PubMed
- Gjessing HC & Odegaard K: Oral chloramphenicol alone and with intramuscular procaine penicillin in the treatment of gonorrhea. Br J Vener Dis 1967; 43:133-136.
- Anon: The choice of antimicrobial drugs. Med Lett Drugs Ther 1978; 20:1.
- Winslow DL, Damme J, & Dieckman E: Delayed bactericidal activity of beta-lactam antibiotics against Listeria monocytogenes; antagonism of chloramphenicol and rifampin. Antimicrob Agents Chemother 1983; 23:555-558. PubMed
- Shann F, Barker J, & Poore P: Chloramphenicol alone versus chloramphenicol plus penicillin for bacterial meningitis in children. Lancet 1985; 2:681-684. DOI
- Shann F, Barker J, & Poore P: Chloramphenicol alone versus chloramphenicol plus penicillin for severe pneumonia in children. Lancet 1985a; 2:684-686. DOI
- Wallace JF, Smith RH, Garcia M, et al: Studies on the pathogenesis of meningitis. VI. Antagonism between penicillin and chloramphenicol in experimental pneumococcal meningitis. J Lab Clin Med 1967; 70:408-418.
Keep reading about Chloramphenicol Injection
Keep reading about Penicillin G
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