1. Clinical Overview
Chloramphenicol is a broad-spectrum bacteriostatic antibiotic originally derived from *Streptomyces venezuelae*. It is a potent inhibitor of bacterial protein synthesis. Due to its association with serious and potentially fatal adverse effects, most notably dose-independent irreversible bone marrow aplasia (aplastic anemia) and the 'Gray Baby Syndrome' in neonates, its use in clinical practice is now highly restricted. In India, it is reserved for the treatment of severe, life-threatening infections where safer alternatives are ineffective, contraindicated, or unavailable, particularly those caused by multidrug-resistant organisms like *Salmonella typhi* (typhoid fever) and *Haemophilus influenzae* (meningitis).
| Onset | Duration | Bioavailability |
|---|---|---|
| Oral: Peak plasma concentrations reached in 1-3 hours. Intravenous: Immediate onset of systemic effect. | Approximately 4-8 hours, necessitating multiple daily doses. | Oral: 75-90% (well absorbed). |
2. Mechanism of Action
Chloramphenicol binds reversibly to the 50S subunit of the bacterial 70S ribosome. This binding inhibits the peptidyl transferase activity, thereby preventing the transfer of the growing peptide chain to the newly attached aminoacyl-tRNA at the A site. This action blocks the formation of peptide bonds, a critical step in protein synthesis, leading to bacteriostatic inhibition of bacterial growth.
3. Indications & Uses
- Severe Typhoid Fever (caused by *Salmonella typhi*) resistant to first-line drugs like fluoroquinolones and third-generation cephalosporins.
- Bacterial Meningitis (caused by *Haemophilus influenzae*, *Neisseria meningitidis*, or *Streptococcus pneumoniae*) when patient is allergic to penicillins/cephalosporins or organism is resistant.
- Rickettsial infections (e.g., Scrub typhus, Rocky Mountain spotted fever) where tetracyclines are contraindicated (e.g., in pregnancy/children).
- Cystic Fibrosis patients with lung infections due to multidrug-resistant bacteria.
4. Dosage & Administration
Adult Dosage: Oral/IV: 50-100 mg/kg/day in divided doses every 6 hours. For severe infections (e.g., meningitis, typhoid): Up to 4-6 grams per day in divided doses. Typical 500mg capsule dose: 1-2 capsules every 6 hours. MUST NOT EXCEED MAXIMUM DOSE.
Administration: Oral: Take on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption, but can be taken with food to reduce GI upset. Capsule should be swallowed whole with a full glass of water. IV: Administer as a slow intravenous infusion over at least 15-30 minutes. NEVER GIVE INTRAVENOUSLY AS A BOLUS. Complete the prescribed course even if feeling better.
5. Side Effects
Common side effects may include:
- Nausea, vomiting, diarrhea.
- Unpleasant or bitter taste.
- Headache, mild depression.
- Topical: Transient stinging/burning (eye/ear drops).
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin, Acenocoumarol | Chloramphenicol inhibits hepatic metabolism of coumarins, potentiating anticoagulant effect leading to increased risk of bleeding. | Major |
| Phenytoin, Phenobarbital | Chloramphenicol inhibits metabolism of phenytoin/phenobarbital, increasing their levels and risk of toxicity (ataxia, nystagmus). Conversely, these drugs may decrease chloramphenicol levels. | Major |
| Sulfonylureas (e.g., Glibenclamide) | Increased risk of hypoglycemia due to inhibited metabolism. | Moderate |
| Rifampicin | Rifampicin induces chloramphenicol metabolism, decreasing its plasma concentration and efficacy. | Moderate |
| Paracetamol (Acetaminophen) | May increase risk of bone marrow suppression and prolong half-life of chloramphenicol. | Moderate |
| Other Myelosuppressive drugs (e.g., Chemotherapy, Zidovudine) | Additive risk of bone marrow toxicity. | Major |
7. Patient Counselling
- DO complete the full course of medication as prescribed by your doctor.
- DO inform all your doctors and your dentist that you are taking chloramphenicol before any surgery or new treatment.
- DO get regular blood tests (CBC) as advised by your doctor.
- DONT use this medicine for colds, flu, or other viral infections.
- DONT give this medicine to anyone else, even if they have similar symptoms.
- DONT stop taking the medicine early even if you feel better.
8. Toxicology & Storage
Overdose: Symptoms of dose-dependent toxicity: Nausea, vomiting, anorexia, abdominal distension, metabolic acidosis. In neonates: Gray Baby Syndrome (pallor, cyanosis, vomiting, irregular respiration, hypothermia, vasomotor collapse, death). Signs of bone marrow suppression may be delayed.
Storage: Store at room temperature (15-25°C), protected from light and moisture. Keep the container tightly closed. Do not store in the bathroom. Keep out of reach of children and pets. Do not use after the expiry date printed on the pack. Dispose of unused medicine properly; do not flush or pour down the drain.