Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Chloramphenicol belongs to the pharmacological class of Bacteriostatic antibiotics.
Chloramphenicol has been approved to relieve symptoms and also for the treatment and maintenance of Plague.
When administered orally, it is rapidly and completely absorbed from the gastrointestinal tract, with an oral bioavailability of approximately 80%. Intramuscular administration also results in good absorption, with a bioavailability of around 70%. The exact volume of distribution of chloramphenicol is not available. Protein binding in plasma ranges from 50-60% in adults and 32% in premature neonates. Chloramphenicol is eliminated from the body through various routes, but specific details regarding its route of elimination are not available.
The common side effects involved in using Chloramphenicol are Diarrhea, Nausea, Vomiting, Bone marrow suppression (including aplastic anemia), Anemia, Leukopenia (reduced white blood cell count), Thrombocytopenia (reduced platelet count)
Chloramphenicol is available in the form of Intravenous Solutions.
Chloramphenicol is approved in Germany, Japan, Malaysia, India, the U.K., the U.S, and China.
Chloramphenicol belongs to the pharmacological class of Bacteriostatic antibiotics.
Chloramphenicol possesses lipid solubility, enabling it to pass through the bacterial cell membrane via diffusion. Once inside, it binds reversibly to the L16 protein found in the 50S subunit of bacterial ribosomes. This binding action obstructs the transfer of amino acids to developing peptide chains, possibly by suppressing peptidyl transferase activity. Consequently, the formation of peptide bonds and the synthesis of proteins are inhibited.
Chloramphenicol has been approved to relieve symptoms and also for the treatment and maintenance of Plague.
When taken orally, chloramphenicol reaches its peak plasma concentration (Cmax) within 1 to 3 hours. Intravenous administration results in an immediate Cmax, as the medication is directly infused into the bloodstream.chloramphenicol is prescribed for a specified duration, usually 7 to 14 days, to ensure sufficient treatment of the infection.
Chloramphenicol is found to be available in the form of Intravenous solutions.
Chloramphenicol can be used in the following treatment:
- Plague
Chloramphenicol can help to relieve symptoms and also for the treatment and maintenance of plague.
Chloramphenicol is approved for use in the following clinical indications:
- Treatment of plague
- Treatment for Plague (Yersinia pestis):
Bubonic, Pharyngeal, Pneumonic, or Septicemic Plague (alternative agent):
Intravenous (IV) administration: Recommended dosage is 12.5 mg/kg (maximum: 1 g/dose) every 6 hours for a duration of 10 to 14 days, and continue for a few days after clinical resolution .
In severe infections, a higher dosage (25 mg/kg [maximum: 1 g/dose] every 6 hours) may be necessary. Once there is clinical improvement, the dose can be reduced to 12.5 mg/kg (maximum: 1 g/dose) every 6 hours as soon as possible .
- Plague Meningitis:
IV administration: Recommended dosage is 25 mg/kg (maximum: 1 g/dose) every 6 hours. After clinical improvement, the dose may be reduced to 12.5 mg/kg (maximum: 1 g/dose) every 6 hours. The recommended treatment duration is 10 to 14 days, and continue for a few days after clinical resolution when used for initial treatment (Ref). In the case of secondary plague meningitis when chloramphenicol is added to existing therapy, continue the entire regimen for an additional 10 days.
Injectable solution: 1000mg/vial
Injectable Solution.
Dosage Adjustments in Kidney Patients:
The manufacturer's labeling does not include specific dosage adjustments, so caution is advised along with a potential adjustment in dosage and/or time interval between doses.
Dosage Adjustments in Pediatric Patients:
- Meningitis and Pneumococcal Infections (Nonmeningeal)
Limited data available for infants, children, and adolescents:
Intravenous (IV) administration: Recommended dosage is 18.75 to 25 mg/kg/dose every 6 hours.
Maximum daily dose should not exceed 4,000 mg/day .
- Severe Infections
For infants, children, and adolescents with severe infections:
IV administration: Recommended dosage is 12.5 to 25 mg/kg/dose every 6 hours.
Maximum daily dose should not exceed 4,000 mg/day.
There are no specific dietary restrictions associated with the use of chloramphenicol. However, it is always important to maintain a healthy and balanced diet to support overall health and well-being during antibiotic treatment. Here are some general dietary recommendations that can be followed while taking chloramphenicol or any other antibiotic:
Take with or without food: Chloramphenicol can generally be taken with or without food, as directed by your healthcare professional or the specific instructions provided with the medication. If there are specific instructions regarding food intake, follow them accordingly.
Stay hydrated: It is important to stay adequately hydrated while taking any medication, including chloramphenicol. Drink plenty of water throughout the day to support proper hydration.
Avoid alcohol: While there is no specific dietary restriction related to chloramphenicol, it is advisable to avoid consuming alcohol during treatment with antibiotics. Alcohol can interact with certain antibiotics and may cause adverse reactions or reduce the effectiveness of the medication.
Chloramphenicol may be contraindicated under the following conditions:
- Patients who have a known hypersensitivity to any component of Chloramphenicol or to other drugs in the same class.
The physician should closely monitor the patients and keep pharmacovigilance as follows:
- Serious and Fatal Blood Dyscrasias
Aplastic anemia, bone marrow hypoplasia, thrombocytopenia, and granulocytopenia have been reported with the use of chloramphenicol.
Adequate blood studies are essential to monitor for these potential adverse effects.
- Appropriate Use of Chloramphenicol
Chloramphenicol should not be used for minor infections or conditions where it is not indicated, such as colds, influenza, or upper respiratory tract infections.
- Types of Bone Marrow Depression
Chloramphenicol can cause two types of bone marrow depression: a common, reversible dose-related depression, and a rare, sudden, delayed, and potentially fatal bone marrow hypoplasia.
Precautions
- Regular blood studies are necessary during chloramphenicol treatment. However, these studies may not always detect the rare and irreversible bone marrow depression before the development of aplastic anemia.
- Baseline blood studies should be followed by periodic blood studies during therapy, and the drug may need to be discontinued if certain blood alterations occur.
- Repeated courses of chloramphenicol should be avoided if possible, and treatment should not be continued longer than necessary to achieve a cure with minimal risk of relapse.
- Concurrent use of other drugs that may cause bone marrow depression should be avoided.
- Patients with impaired liver or kidney function, including infants with immature metabolic processes, may experience excessive blood levels of chloramphenicol. Dosage adjustments and monitoring of blood concentration are necessary.
- Caution is needed when using chloramphenicol in premature and full-term infants to prevent "gray syndrome" toxicity. Serum drug levels should be closely monitored in neonatal therapy.
- The safety of chloramphenicol during pregnancy has not been established. The potential benefits to the mother must be weighed against the possible risks to the fetus. Use during labor may pose additional risks as chloramphenicol crosses the placental barrier.
- Like other antibiotics, chloramphenicol may lead to the overgrowth of nonsusceptible organisms, including fungi.
Alcohol Warning
There is no specific alcohol warning associated with the use of Chloramphenicol. However, it is generally recommended to avoid excessive alcohol consumption while taking antibiotics as it can interfere with the effectiveness of the medication and may also increase the risk of certain side effects such as nausea, vomiting, and dizziness.
Breast Feeding Warning
Chloramphenicol should generally be avoided during pregnancy and lactation, unless the potential benefits outweigh the risks. The drug crosses the placenta and is excreted in breast milk, posing potential risks to the developing fetus or nursing infant.
Pregnancy Warning
Pregnancy Category C:
Chloramphenicol is classified as a pregnancy category C medication by the U.S. Food and Drug Administration (FDA). Pregnancy category C indicates that studies in animals have shown adverse effects on the fetus, but there are limited or no adequate and well-controlled studies in pregnant women.
While chloramphenicol crosses the placenta and reaches the fetal circulation, there is limited clinical data available regarding its safety in pregnancy. Studies in animals have demonstrated potential reproductive toxicity, including embryotoxicity and teratogenic effects. In humans, chloramphenicol has been associated with a rare but serious condition called gray syndrome in newborns, especially premature infants, characterized by abdominal distension, cyanosis, cardiovascular collapse, and metabolic acidosis.
Due to these potential risks, chloramphenicol is generally avoided during pregnancy unless the benefits outweigh the potential harms. It is typically reserved for the treatment of life-threatening infections caused by susceptible organisms when safer alternatives are not available or suitable.
Food Warning
Chloramphenicol interacts with certain foods and beverages, leading to a potential interaction known as a disulfiram-like reaction. A disulfiram-like reaction is characterized by symptoms such as flushing, nausea, vomiting, headache, and increased heart rate. These symptoms occur when chloramphenicol is taken along with alcohol or certain foods that contain alcohol or have undergone fermentation.
Certain foods that undergo fermentation, such as sauerkraut, soy sauce, vinegar, and some cheeses, may contain trace amounts of alcohol. It is advisable to limit or avoid these foods to prevent a potential interaction.
The adverse reactions related to Chloramphenicol can be categorized as follows:
Common
- Bone marrow suppression (including aplastic anemia)
- Anemia
- Leukopenia (reduced white blood cell count)
- Thrombocytopenia (reduced platelet count)
- Nausea
- Vomiting
- Diarrhea
- Skin rash
- Itching
- Headache
Less Common
- Hypersensitivity reactions (e.g., allergic reactions, angioedema)
- Peripheral neuropathy (nerve damage in the extremities)
- Optic neuritis (inflammation of the optic nerve)
- Confusion
- Delirium
- Glossitis (inflammation of the tongue)
- Stomatitis (inflammation of the mouth)
Rare
- Gray syndrome (primarily observed in newborns and premature infants)
- Anaphylaxis (severe allergic reaction)
- Seizures
- Hypotension (low blood pressure)
- Disulfiram-like reaction (when alcohol is consumed concurrently)
- Skin discoloration (grayish appearance)
- Fever
The clinically relevant drug interactions of Chloramphenicol are briefly summarized here:
Effect of Other Drugs on Chloramphenicol:
- Oral Retinoids: Chloramphenicol should not be taken with oral retinoids, as both may cause increased intracranial pressure.
- Antacids and Iron Preparations: Taking Chloramphenicol with antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, or iron-containing preparations may impair its absorption and decrease its efficacy. To avoid this, separate dosing of Chloramphenicol from antacids and iron preparations.
- Penicillin: Chloramphenicol may interfere with the bactericidal action of penicillin. Avoid coadministration of Chloramphenicol with penicillin.
- Anticoagulants: Chloramphenicol may depress plasma prothrombin activity, which may increase the risk of bleeding in patients who are on anticoagulant therapy. Decrease anticoagulant dosage when coadministered with Chloramphenicol as appropriate.
- P-Glycoprotein (P-gp) Substrates: Concomitant use of Chloramphenicol may increase concentrations of concomitantly administered P-gp substrates (e.g. digoxin). Monitor for toxicities of drugs that are P-gp substrates and may require dosage reduction when given concurrently with Chloramphenicol.
Effect of Chloramphenicol on Other Drugs:
- Oral Hormonal Contraceptives: Chloramphenicol does not significantly affect the efficacy of oral contraceptives containing ethinyl estradiol and norethindrone acetate.
The following are the side effects involving Chloramphenicol:
- Bone marrow suppression (including aplastic anemia)
- Anemia
- Leukopenia (reduced white blood cell count)
- Thrombocytopenia (reduced platelet count)
- Nausea
- Vomiting
- Diarrhea
- Skin rash
- Itching
- Headache
- Yeast infections
Pregnancy:
Pregnancy Category C:
Chloramphenicol is classified as a pregnancy category C medication by the U.S. Food and Drug Administration (FDA). Pregnancy category C indicates that studies in animals have shown adverse effects on the fetus, but there are limited or no adequate and well-controlled studies in pregnant women.
While chloramphenicol crosses the placenta and reaches the fetal circulation, there is limited clinical data available regarding its safety in pregnancy. Studies in animals have demonstrated potential reproductive toxicity, including embryotoxicity and teratogenic effects. In humans, chloramphenicol has been associated with a rare but serious condition called gray syndrome in newborns, especially premature infants, characterized by abdominal distension, cyanosis, cardiovascular collapse, and metabolic acidosis.
Due to these potential risks, chloramphenicol is generally avoided during pregnancy unless the benefits outweigh the potential harms. It is typically reserved for the treatment of life-threatening infections caused by susceptible organisms when safer alternatives are not available or suitable.
Nursing Mothers
Chloramphenicol should generally be avoided during pregnancy and lactation, unless the potential benefits outweigh the risks. The drug crosses the placenta and is excreted in breast milk, posing potential risks to the developing fetus or nursing infant.
Pediatric Use
Chloramphenicol can be used in neonates and infants for the treatment of serious bacterial infections, particularly when caused by susceptible organisms. However, due to the risk of gray syndrome and hematological toxicity, careful monitoring of blood cell counts is necessary, especially in premature infants.
Geriatric Use
There were not enough participants aged 65 and above in clinical trials of Chloramphenicol to establish whether they have a different response to the medication compared to younger individuals.
Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Chloramphenicol.
Hematological Effects: One of the most significant concerns with chloramphenicol overdose is its potential to cause bone marrow suppression, leading to a decrease in blood cell production. This can result in anemia, leukopenia (reduced white blood cell count), and thrombocytopenia (reduced platelet count).
Neurological Effects: High levels of chloramphenicol in the body may lead to neurological symptoms such as confusion, delirium, headache, and seizures.
Gastrointestinal Effects: Overdose can cause gastrointestinal symptoms such as nausea, vomiting, and abdominal pain.
Cardiovascular Effects: In some cases, chloramphenicol overdose has been associated with cardiovascular effects like hypotension (low blood pressure) and cardiovascular collapse.
Other Effects: Overdose of chloramphenicol may also result in gray syndrome, a potentially life-threatening condition characterized by abdominal distension, cyanosis, cardiovascular collapse, and metabolic acidosis. This condition is more commonly seen in neonates.
Pharmacodynamics
Chloramphenicol is a synthetic antibiotic with broad-spectrum activity that was originally derived from the bacterium Streptomyces venezuelae. It is effective against a wide range of microorganisms. However, due to its potential for serious side effects, such as bone marrow damage including aplastic anemia, its use in humans is typically limited to the treatment of severe and life-threatening infections, such as typhoid fever.
Chloramphenicol exhibits bacteriostatic properties, but it can also have bactericidal effects at high concentrations or when used against highly susceptible organisms. Its mechanism of action involves binding to the bacterial ribosome, specifically blocking the peptidyl transferase enzyme and thus inhibiting protein synthesis. This disruption of protein synthesis leads to the inhibition of bacterial growth.
Pharmacokinetics
- Absorption:
Oral administration: Chloramphenicol is rapidly and completely absorbed from the gastrointestinal tract, with a bioavailability of 80%.
Intramuscular administration: Well absorbed, with a bioavailability of 70%.
Topical application: Chloramphenicol can be absorbed intraocularly and systemically after topical application to the eye.
- Volume of distribution:
The information regarding the volume of distribution is not available.
- Protein binding:
In adults, chloramphenicol exhibits a plasma protein binding of 50-60%. Premature neonates, on the other hand, have a protein binding of 32%.
- Metabolism:
Chloramphenicol undergoes hepatic metabolism, with approximately 90% of the drug being conjugated to inactive glucuronide.
- Route of elimination:
The information regarding the specific route of elimination is not available.
- "Comparative Evaluation of Intracameral Cefuroxime and Chloramphenicol in Preventing Postoperative Endophthalmitis after Cataract Surgery: A Randomized Controlled Trial."Sharma N, et al. Indian Journal of Ophthalmology. 2018 Feb;66(2):230-235.
- https://pdf.hres.ca/dpd_pm/00001590.PDF
- https://www.sandoz.ca/sites/www.sandoz.ca/files/Pentamycetin-Product-Monograph.pdf
- https://go.drugbank.com/drugs/DB00446
- https://www.merckmanuals.com/en-ca/professional/infectious-diseases/bacteria-and-antibacterial-drugs/chloramphenicol
- https://www.sciencedirect.com/topics/medicine-and-dentistry/chloramphenicol
- https://medlineplus.gov/druginfo/meds/a608008.html
- https://www.drugs.com/cdi/chloramphenicol.html
- https://reference.medscape.com/drug/chloramphenicol-iv-chloromycetin-342554
- https://www.webmd.com/drugs/2/drug-19138-880/chloramphenicol-ophthalmic-eye/chloramphenicol-ointment-ophthalmic/details
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/050155s039lbl.pdf
