Chloramphenicol Sodium Succinate

Description

DESCRIPTION: Chloramphenicol is an antibiotic that is clinically useful for, and should be reserved for, serious infections caused by organisms susceptible to its antimicrobial effects when less potentially hazardous therapeutic agents are ineffective or contraindicated. Sensitivity testing is essential to determine its indicated use, but may be performed concurrently with therapy initiated on clinical impression that one of the indicated conditions exists (see INDICATIONS AND USAGE section). When reconstituted as directed, each vial contains a sterile solution equivalent to 100 mg of chloramphenicol per mL (1 g/10 mL). Each gram (10 mL of a 10% solution) of chloramphenicol sodium succinate contains approximately 52 mg (2.25 mEq) of sodium. The chemical name for chloramphenicol sodium succinate is D-threo-(-)-2, 2-Dichloro-N-[β-hydroxy-α-(hydroxymethyl)-p-nitrophenethyl] acetamide α-(sodium succinate). The structural formula is: structure

Side Effects (Adverse Reactions)

ADVERSE REACTIONS: Blood Dyscrasias The most serious adverse effect of chloramphenicol is bone marrow depression. Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) are known to occur after the administration of chloramphenicol. An irreversible type of marrow depression leading to aplastic anemia with a high rate of mortality is characterized by the appearance weeks or months after therapy of bone marrow aplasia or hypoplasia. Peripherally, pancytopenia is most often observed, but in a small number of cases only one or two of the three major cell types (erythrocytes, leukocytes, platelets) may be depressed. A reversible type of bone marrow depression, which is dose related, may occur. This type of marrow depression is characterized by vacuolization of the erythroid cells, reduction of reticulocytes and leukopenia, and responds promptly to the withdrawal of chloramphenicol. An exact determination of the risk of serious and fatal blood dyscrasias is not possible because of lack of accurate information regarding 1) the size of the population at risk, 2) the total number of drug-associated dyscrasias, and 3) the total number of non-drug associated dyscrasias. In a report to the California State Assembly by the California Medical Association and the State Department of Public Health in January 1967, the risk of fatal aplastic anemia was estimated at 1:24,200 to 1:40,500 based on two dosage levels. There have been reports of aplastic anemia attributed to chloramphenicol which later terminated in leukemia. Paroxysmal nocturnal hemoglobinuria has been reported. Gastrointestinal Reactions Nausea, vomiting, glossitis and stomatitis, diarrhea and enterocolitis may occur in low incidence. Neurotoxic Reactions Headache, mild depression, mental confusion, and delirium have been described in patients receiving chloramphenicol. Optic and peripheral neuritis have been reported, usually following long-term therapy. If this occurs, the drug should be promptly withdrawn. Hypersensitivity Reactions Fever, macular and vesicular rashes, angioedema, urticaria, and anaphylaxis may occur. Herxheimer’s reactions have occurred during therapy for typhoid fever. "Gray Syndrome" Toxic reactions including fatalities have occurred in the premature and neonate; the signs and symptoms associated with these reactions have been referred to as the “gray syndrome.” One case of gray syndrome has been reported in a neonate born to a mother having received chloramphenicol during labor. One case has been reported in a 3-month-old infant. The following summarizes the clinical and laboratory studies that have been made on these patients: a) In most cases therapy with chloramphenicol had been instituted within the first 48 hours of life. b) Symptoms first appeared after 3 to 4 days of continued treatment with high doses of chloramphenicol. c) The symptoms appeared in the following order: (1) abdominal distension with or without emesis; (2) progressive pallid cyanosis; (3) vasomotor collapse, frequently accompanied by irregular respiration; (4) death within a few hours of onset of these symptoms. d) The progression of symptoms from onset to exitus was accelerated with higher dose schedules. e) Preliminary blood serum level studies revealed unusually high concentrations of chloramphenicol (over 90 mcg/mL after repeated doses). f) Termination of therapy upon early evidence of the associated symptomatology frequently reversed the process with complete recovery. Blood Dyscrasias The most serious adverse effect of chloramphenicol is bone marrow depression. Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, and granulocytopenia) are known to occur after the administration of chloramphenicol. An irreversible type of marrow depression leading to aplastic anemia with a high rate of mortality is characterized by the appearance weeks or months after therapy of bone marrow aplasia or...

Drug Interactions

Drug Interactions Concurrent therapy with other drugs that may cause bone marrow depression should be avoided.

Contraindications

CONTRAINDICATIONS: Chloramphenicol is contraindicated in individuals with a history of previous hypersensitivity and/or toxic reaction to it. It must not be used in the treatment of trivial infections or where it is not indicated, as in colds, influenza, infections of the throat; or as a prophylactic agent to prevent bacterial infections.

Pregnancy and Breastfeeding

Pregnancy Pregnancy Category C – Animal reproduction studies have not been conducted with chloramphenicol. There are no adequate and well-controlled studies to establish safety of this drug in pregnancy. It is not known whether chloramphenicol can cause fetal harm when administered to a pregnant woman. Orally administered chloramphenicol has been shown to cross the placental barrier. Because of potential toxic effects on the fetus (see ADVERSE REACTIONS, “Gray Syndrome” ), chloramphenicol should be given to a pregnant woman only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers Chloramphenicol is excreted in human milk following oral administration of the drug. Because of the potential for serious adverse reactions in nursing infants from chloramphenicol, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see ADVERSE REACTIONS, “Gray Syndrome” ).

How Supplied

HOW SUPPLIED: Chloramphenicol Sodium Succinate for Injection, USP is freeze-dried in the vial. When reconstituted as directed, each vial contains a sterile solution equivalent to 100 mg of chloramphenicol per mL (1 g/10 mL). Product No. NDC No. 1115 63323-011-15 Available in packages of 10 vials. Preservative Free. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].