CHLORAMPHENICOL

CHLORAMPHENICOL (klor-am-fen'i-kole) Chloromycetin, Novo-chlorocap  CHLORAMPHENICOL SODIUM SUCCINATE Chloromycetin Sodium Succinate Classifications: antibiotic; Therapeutic: antibiotic Pregnancy Category: C

Availability

250 mg capsules; 100 mg/mL injection; 5 mg/mL ophth solution; 10 mg/g ointment

Action

Synthetic broad-spectrum antibiotic that is principally bacteriostatic but may be bactericidal in certain species (e.g., Haemophilus influenzae) or when given in higher concentrations. Believed to act by binding to the 50S ribosome of bacteria and thus interfering with protein synthesis.

Therapeutic Effect

Effective against a wide variety of gram-negative and gram-positive bacteria and most anaerobic microorganisms.

Uses

Severe infections when other antibiotics are ineffective or are contraindicated. Particularly effective against Salmonella typhi and other Salmonella sp., Streptococcus pneumoniae, Neisseria, meningeal infections caused by H. influenzae, and infections involving Bacteroides fragilis and other anaerobic organisms, Rickettsia rickettsii (cause of Rocky Mountain spotted fever) and other rickettsiae, the lymphogranuloma-psittacosis group (Chlamydia), and Mycoplasma. Also used in cystic fibrosis antiinfective regimens and topically for infections of skin, eyes, and external auditory canal.

Contraindications

History of hypersensitivity or toxic reaction to chloramphenicol; treatment of minor infections, prophylactic use; typhoid carrier state, history or family history of drug-induced bone marrow depression, concomitant therapy with drugs that produce bone marrow depression; pregnancy (category C); lactation.

Cautious Use

Impaired hepatic or renal function, premature and full-term infants, children; intermittent porphyria; patients with G6PD deficiency; patient or family history of drug-induced bone marrow depression.

Route & Dosage

Serious Infections Adult: PO/IV 50 mg/kg/d in 4 divided doses. Neonate: IV 25–50 mg/kg/d divided q12–24h Infant/Child: PO/IV 50–75 mg/kg/d divided q6h (max: 4 g/d) Meningitis Adult/Child: IV 75–100 mg/kg/d divided q6h

Administration

Oral

• Give preferably with a full glass of water on an empty stomach, at least 1 h before or 2 h after a meal, to achieve optimum blood levels.

Ophthalmic

• Apply light pressure to lacrimal duct after instillation for 1–2 min to prevent drainage into nasopharynx and systemic absorption. This is an extremely important step to decrease absorption. Several cases of aplastic anemia have been associated with use of ophthalmic preparations.

Intravenous IV administration to neonates, infants, children: Verify correct IV concentration and rate of infusion with physician. PREPARE: Direct: Dilute each 1 g with 10 mL of sterile water or D5W.  Intermittent: Further dilute in 50–100 mL of D5W.   ADMINISTER: Direct: Give slowly over a period of at least 1 min.  Intermittent: Give over 30–60 min.   INCOMPATIBILITIES Solutions/additives: Chlorpromazine, glycopyrrolate, metoclopramide, polymyxin B, prochlorperazine, promethazine, tetracyclines, vancomycin. Y-site: Fluconazole. Solution for infusion may form crystals or a second layer when stored at low temperatures. Solution can be clarified by shaking vial. Do not use cloudy solutions.

• Store topical ophthalmic, otic, and skin preparations, PO forms, and unopened ampuls at room temperature and protected from light unless otherwise directed by manufacturer.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity, angioedema, dyspnea, fever, anaphylaxis, superinfections, Gray syndrome. GI: Nausea, vomiting, diarrhea, perianal irritation, enterocolitis, glossitis, stomatitis, unpleasant taste, xerostomia. Hematologic: Bone marrow depression (dose-related and reversible): reticulocytosis, leukopenia, granulocytopenia, thrombocytopenia, increased plasma iron, reduced Hgb, hypoplastic anemia, hypoprothrombinemia. Non-dose-related and irreversible pancytopenia, agranulocytosis, aplastic anemia, paroxysmal nocturnal hemoglobinuria, leukemia. CNS: Neurotoxicity: headache, mental depression, confusion, delirium, digital paresthesias, peripheral neuritis. Skin: Urticaria, contact dermatitis, maculopapular and vesicular rashes, fixed-drug eruptions. Special Senses: Visual disturbances, optic neuritis, optic nerve atrophy, contact conjunctivitis.

Diagnostic Test Interference

Possibility of false-positive results for urine glucose by copper reduction methods (e.g., Benedict's solution, Clinitest). Chloramphenicol may interfere with 17-OHCS (urinary steroid) determinations (modification of Reddy, Jenkins, Thorn procedure not affected), with urobilinogen excretion, and with responses to tetanus toxoid and possibly other active immunizing agents.

Interactions

Drug: The metabolism of chlorpropamide, dicumarol, phenytoin, tolbutamide may be decreased, prolonging their activity. Phenobarbital decreases chloramphenicol levels. The response to iron preparations, folic acid, and vitamin B₁₂ may be delayed.

Pharmacokinetics

Absorption: Rapidly from GI tract. Peak: PO: 1–3 h; IV: 1 h. Distribution: Widely distributed to most body tissues including saliva and ascitic, pleural and synovial fluid; concentrates in liver and kidneys; penetrates CNS; crosses placenta. Metabolism: Primarily inactivated in liver. Elimination: Much longer in neonates; metabolite and free drug excreted in urine; excreted in breast milk. Half-Life: 1.5–4.1 h.

Nursing Implications

Assessment & Drug Effects

• Lab tests: Perform bacterial culture and susceptibility tests prior to first dose and periodically thereafter. Baseline CBC, platelets, serum iron, and reticulocyte cell counts before initiation of therapy, at 48 h intervals during therapy, and periodically. Monitor chloramphenicol blood levels weekly or more frequently with hepatic dysfunction and in patients receiving therapy for longer than 2 wk. Desired concentrations: peak 10–20 mcg/mL; through 5–10 mcg/mL.
• Monitor blood studies. Chloramphenicol should be discontinued upon appearance of leukopenia, reticulocytopenia, thrombocytopenia, or anemia.
• Non-dose-related irreversible bone marrow depression may appear weeks or months after drug therapy is terminated. The potential for this side effect is greatest in patients with impaired hepatic or renal function, infants, children, and premenopausal women.
• Observe the patient closely, because blood studies are not always reliable predictors of irreversible bone marrow depression.
• Check temperature at least q4h. Usually chloramphenicol is discontinued if temperature remains normal for 48 h.
• Monitor I&O ratio or pattern: Report any appreciable change.
• More frequent determinations of serum glucose are recommended in patients receiving oral antidiabetic agents.
• Monitor for S&S of gray syndrome, which has occurred 2–9 d after initiation of high dose chloramphenicol therapy in premature infants and neonates and in children ≤2 y. Report early signs: abdominal distention, failure to feed, pallor, changes in vital signs. Early detection and prompt termination of therapy can interrupt a potentially fatal course.

Patient & Family Education

• A bitter taste may occur 15–20 s after IV injection; it usually lasts only 2–3 min.
• Report immediately sore throat, fever, fatigue, petechiae, nose bleeds, bleeding gums, or other unusual bleeding or bruising, or any other suspicious sign of symptom. Drug therapy should be discontinued if abnormal bleeding occurs.
• Watch for S&S of superinfection (see Appendix F).
• Follow dosage and duration of therapy as prescribed by physician.
• Avoid prolonged or frequent intermittent use of topical preparations because systemic absorption and toxicity can occur.
• Withhold medication and check with physician immediately if signs of hypersensitivity reaction (see Appendix F), irritation, superinfection, or other adverse reactions appear.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug