chloramphenicol
Chloromycetin, Chloroptic, Fenicol ◆, Ocu-Chlor, Pentamycetin ◆

chloramphenicol sodium succinate
Chloromycetin Sodium Succinate, Pentamycetin ◆

Available forms
Available by prescription only
Injection: 1-g vial
Ophthalmic ointment: 1%
Ophthalmic solution: 0.5%
Otic solution: 0.5%
Powder for solution: 25 mg/vial

Indications and dosages
 Severe meningitis, brain abscesses, bacteremia, other serious infections. Adults and children: 50 to 100 mg/kg I.V. daily, divided q 6 hours. Maximum dose is 100 mg/kg daily.
Premature infants and neonates who weigh less than 2 kg (4.4 lb) or are younger than age 7 days: 25 mg/kg I.V. daily.
Neonates who weigh more than 2 kg and are age 7 days and older: 25 mg/kg I.V. q 12 hours. I.V. route must be used to treat meningitis.
 Superficial infections of the skin caused by susceptible bacteria. Adults and children: Rub into affected area b.i.d. or t.i.d.
 Infection of external ear canal. Adults and children: Instill 2 to 3 drops into ear canal t.i.d.
 Surface bacterial infection involving conjunctiva or cornea. Adults and children: Instill 2 drops of solution in eye q hour until condition improves, or instill q.i.d., depending on severity of infection. Apply small amount of ointment to lower conjunctival sac h.s. as supplement to drops. To use ointment alone, apply small amount to lower conjunctival sac q 3 to 6 hours or more frequently, if needed. Continue with treatment up to 48 hours after condition improves.

Pharmacodynamics
Antibacterial action: Chloramphenicol palmitate and chloramphenicol sodium succinate must be hydrolyzed to chloramphenicol before antimicrobial activity can take place. The active compound then inhibits bacterial protein synthesis by binding to the 50S subunit of the ribosome, thus inhibiting peptide bond formation.
  Drug usually produces bacteriostatic effects on susceptible bacteria, including Rickettsia, Chlamydia,Mycoplasma, and certain Salmonella strains, as well as most gram-positive and gram-negative organisms. Chloramphenicol is used to treat Haemophilus influenzae infection, Rocky Mountain spotted fever, meningitis, lymphogranuloma, psittacosis, severe meningitis, and bacteremia.

Pharmacokinetics
Absorption: With I.V. administration, serum levels vary greatly, depending on patient’s metabolism.
Distribution: Distributed widely to most body tissues and fluids, including CSF, liver, and kidneys; it readily crosses the placental barrier. About 50% to 60% of drug binds to plasma proteins.
Metabolism: Parent drug is metabolized primarily by hepatic glucuronyl transferase to inactive metabolites.
Excretion: About 8% to 12% of dose is excreted by the kidneys as unchanged drug; the remainder is excreted as inactive metabolites. Plasma half-life ranges from about 1 1/2 to 4 1/2 hours in adults with normal hepatic and renal function. Plasma half-life of parent drug is prolonged in patients with hepatic dysfunction. Peritoneal hemodialysis doesn’t remove significant drug amounts. Plasma chloramphenicol levels may be elevated in patients with renal impairment after I.V. chloramphenicol administration.

Contraindications and precautions
Contraindicated in patients hypersensitive to chloramphenicol. Use cautiously in patients taking drugs that suppress bone marrow function and those with impaired renal or hepatic function, acute intermittent porphyria, or G6PD deficiency.

Interactions
Drug-drug. Chlorpropamide, cyclophosphamide, dicumarol, phenobarbital, phenytoin, tolbutamide: Inhibits hepatic metabolism by inhibiting microsomal enzyme activity, thus prolonging plasma half-life of these drugs and increasing risk of toxicity from increased serum drug levels. Avoid use together.
Folic acid, iron salts, vitamin B₂: Reduces hematologic response to these substances. Monitor patient closely.
Penicillin: May antagonize bactericidal activity. Give penicillin 1 hour or more before chloramphenicol to avoid reducing bactericidal activity of penicillin.

Adverse reactions
CNS: headache, mild depression, confusion, delirium, peripheral neuropathy with prolonged therapy.
EENT: optic neuritis (in patients with cystic fibrosis), glossitis, decreased visual acuity, optic atrophy in children, stinging of eye after instillation, blurred vision (with ointment).
GI: nausea, vomiting, stomatitis, diarrhea, enterocolitis.
GU: hemoglobinuria.
Hematologic: aplastic anemia, hypoplastic anemia, agranulocytosis, thrombocytopenia.
Metabolic: lactic acidosis, gray syndrome in neonates (abdominal distention, gray cyanosis, vasomotor collapse, respiratory distress, death within a few hours of onset of symptoms).
Skin: jaundice; possible contact sensitivity; burning, urticaria, pruritus in hypersensitive patients.
Other: angioedema in hypersensitive patients, hypersensitivity reactions (fever, rash, urticaria, anaphylaxis).

Effects on lab test results
• May decrease hemoglobin, hematocrit, and granulocyte and platelet counts.

Overdose and treatment
Signs and symptoms of parenterally administered overdose include anemia and metabolic acidosis followed by hypotension, hypothermia, abdominal distention, and possible death.
 Treatment is symptomatic and supportive. Drug may be removed by charcoal hemoperfusion.

Special considerations
• Culture and sensitivity tests may be performed with first dose and repeated as needed.
• Use drug only when clearly indicated for severe infection. Because of risk of severe toxicity, it should be reserved for life-threatening infections.
• Refrigerate ophthalmic solution.
• For I.V. administration, reconstitute 1-g vial of powder for injection with 10 ml of sterile water for injection; concentration will be 100 mg/ml. Solution remains stable for 30 days at room temperature; however, refrigeration is recommended. Don’t use cloudy solutions. Administer I.V. infusion slowly, over at least 1 minute. Check injection site daily for phlebitis and irritation.
• Therapeutic range is 10 to 20 mcg/ml for peak levels and 5 to 10 mcg/ml for trough levels.
• False elevation of urinary para-aminobenzoic acid levels will result if chloramphenicol is administered during a bentiromide test for pancreatic function. Drug therapy will cause false-positive results on tests for urine glucose level using cupric sulfate (Clinitest).
• Obtain CBC, platelet count, reticulocyte count, and serum iron level before therapy begins and every 2 days during therapy. Stop drug immediately if results indicate anemia, reticulocytopenia, leukopenia, or thrombocytopenia.
• Assess patient for superinfection by nonsusceptible organisms.
Pregnant patients
• Safe use during pregnancy hasn’t been established.
Breast-feeding patients
• Drug appears in breast milk at low levels, posing a risk of bone marrow depression and slight risk of gray syndrome. An alternative to breast-feeding is recommended during treatment.
Pediatric patients
• Use drug cautiously in children younger than age 2 because of risk of gray syndrome (although most cases occur in first 48 hours after birth). Drug has prolonged half-life in neonates, necessitating special dose.
Geriatric patients
• Administer drug cautiously to elderly patients with impaired liver function.

Patient education
• Instruct patient to report adverse reactions, especially nausea, vomiting, diarrhea, bleeding, fever, confusion, sore throat, or mouth sores.
• Tell patient to take drug for prescribed period and to take it exactly as directed, even after he feels better.
• Instruct patient to wash hands before and after applying topical ointment or solution.
• Warn patient using otic solution not to touch ear with dropper.
• Caution patient using topical cream to avoid sharing washcloths and towels with family members.
• Tell patient using ophthalmic drug to clean eye area of excess exudate before applying drug; show him how to instill drug in eye. Warn him not to touch applicator tip to eye or surrounding tissue.
• Instruct patient to be alert for signs and symptoms of sensitivity, such as itchy eyelids or constant burning, and to discontinue drug and call immediately should any occur.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use