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Clindamycin
Clindamycin hydrochloride is the hydrated hydrochloride salt of clindamycin. Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin. Clindamycin hydrochloride capsules contain clindamycin hydrochloride equivalent to 150 mg of clindamycin. Inactive ingredients: corn starch, FD&C Blue No.1, FD&C Yellow No. 5, gelatin, lactose, magnesium stearate, talc and titanium dioxide. The chemical name for clindamycin hydrochloride is Methyl 7-chloro-6,7,8-trideoxy-6-(1 -methyl-trans-4-propyl-L-2-pyrrolidine-carboxamido)-1 -thio-L-threo-a-o-galacto-octopyranoside monohydrochloride.
Microbiology Clindamycin has been shown to have in vitro activity against isolates of the following organisms: Aerobic gram-positive cocci, including:
Anaerobic gram-negative bacilli, including:
Anaerobic gram-positive nonsporeforming bacilli, including:
Anaerobic and microaerophilic gram-positive cocci, including:
Clostridia: Clostridia are more resistant than most anaerobes to clindamycin. Most Clostridium perfringens are susceptible, but other species, e.g., Clostridium sporogenes and Clostridium tertium are frequently resistant to clindamycin. Susceptibility testing should be done. Human PHARMACOLOGY Serum level studies with a 150 mg oral dose of clindamycin hydrochloride in 24 normal adult volunteers showed that clindamycin was rapidly absorbed after oral administration. An average peak serum level of 2.50 mcg/mL was reached in 45 minutes; serum levels averaged 1.51 mcg/mL at 3 hours and 0.70 mcg/mL at 6 hours. Absorption of an oral dose is virtually complete (90%), and the concomitant administration of food does not appreciably modify the serum concentrations; serum levels have been uniform and predictable from person to person and dose to dose. Serum level studies following multiple doses of clindamycin hydrochloride for up to 14 days show no evidence of accumulation or altered metabolism of drug. Serum half-life of clindamycin is increased slightly in patients with markedly reduced renal function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Concentrations of clindamycin in the serum increased linearly with increased dose. Serum levels exceed the MIC (minimum inhibitory concentration) for most indicated organisms for at least six hours following administration of the usually recommended doses. Clindamycin is widely distributed in body fluids and tissues (including bones). The average biological half-life is 2.4 hours. Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the feces; the remainder is excreted as bioinactlve metabolites. Doses of up to 2 grams of clindamycin per day for 14 days have been well tolerated by healthy volunteers, except that the incidence of gastrointestinal side effects is greater with the higher doses. No significant levels of clindamycin are attained in the cerebro-spinal fluid, even in the presence of inflamed meninges. TOXICOLOGY Animal toxicity studies showed the following: One year oral toxicity studies in Spartan Sprague-Dawley rats and Beagle dogs at levels of 30, 100, and 300 mg/kg/day (3 grams/day per dog) have shown clindamycin hydrochloride to be well tolerated. No appreciable difference in pathological findings has been obtained in groups of animals treated with clindamycin hydrochloride from comparable control groups. Rats receiving clindamycin hydrochloride at 600 mg/kg/day for six months tolerated the drug well; however, dogs dosed at this level vomited, would not eat and lost weight.
Clindamycin is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Clindamycin is also indicated in the treatment
of serious infections due to susceptible
strains of streptococci, pneumococci, and staphylococci. Its use
should be reserved for penicillin
allergic patients or
other patients for whom, in the judgment
of the physician,
a penicillin is inappropriate.
Because of the risk of
colitis, as described
in the Anaerobes: Serious respiratory tract infections such as empyema, anaerobic pneumonitis and lung abscess; serious skin and soft tissue infections; septicemia; intra-abdominal infections such as peritonitis and intra-abdominal abscess (typically resulting from anaerobic organisms resident in the normal gastrointestinal tract); infections of the female pelvis and genital tract such as endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis and postsurgical vaginal cuff infection. Streptococci: Serious respiratory tract infections; serious skin and soft tissue infections. Staphylococci: Serious respiratory tract infections; serious skin and soft tissue infections. Pneumococci: Serious respiratory tract infections. Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin. In Vitro Susceptibility Testing: A standardized disk testing procedure* is recommended for determining susceptibility of aerobic bacteria to clindamycin. A description is contained in the CLEOCIN Susceptibility Disk insert. Using this method, the laboratory can designate isolates as resistant, intermediate, or susceptible. Tube or agar dilution methods may be used for both anaerobic and aerobic bacteria. When the directions in the CLEOCIN Susceptibility Powder insert are followed, an MIC of 1.6 mcg/mL may be considered susceptible; M.C. of 1.6 to 4.8 mcg/mL may be considered intermediate and M.C. greater than 4.8 mcg/ mL may be considered resistant. *Bauer AW, Kirby WMM, Sherris JC, et al: Antibiotic susceptibility testing by a standardized single disc method. AM J Clin Pathol 45: 493-496 1966. Standardized disc susceptibility test. Federal Register 37: 20527-29, 1972. For anaerobic bacteria the minimal inhibitory concentration (MIC) of clindamycin can be determined by agar dilution and broth dilution (including microdilution) techniques. If M.C. are not determined routinely, the disk broth method is recommended for routine use. THE KIRBY-BAUER DISK DIFFUSION METHOD AND ITS INTERPRETIVE STANDARDS ARE NOT RECOMMENDED FOR ANAEROBES.
If significant
diarrhea occurs during
therapy, this antibiotic
should be discontinued (see To avoid the possibility of esophageal irritation, clindamycin hydrochloride capsules should be taken with a full glass of water. Serious infections due to anaerobic bacteria are usually treated with CLEOCIN PHOSPHATE Sterile Solution. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with clindamycin hydrochloride capsules. In cases of B- hemolytic streptococcal infections, treatment should continue for at least 10 days HOW SUPPLIED Clindamycin hydrochloride capsules, 150 mg, are available in bottles of 100 (light blue and green). NDC 59762-3328-l Store at controlled room temperature 15° to 30° C (59° to 86° F). Caution: Federal law prohibits dispensing without prescription.
The following reactions have been reported with the use of clindamycin. Gastrointestinal: Abdominal pain,
esophagitis, nausea,
vomiting and diarrhea
(see Hypersensitivity Reactions: Generalized mild to moderate morbilliform-like (maculopapular) skin rashes are the most frequently reported adverse reactions. Vesiculobullous rashes, as well as urticaria, have been observed during drug therapy. Rare instances of erythema muttiforme, some resembling Stevens-Johnson syndrome, and a few cases of anaphylactoid reactions have also been reported. Skin and Mucous Membranes: Pruritus, vaginitis, and rare instances of exfoliative dermatitis have been reported. (See Hypersensitivity Reactions above) Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy. Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances. Hematopoietic: Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing. Musculoskeletal: Rare instances of polyarthritis
have been reported.
No information provided.
See Studies indicate a toxin(s) produced by Clostridia is one primary cause of antibiotic associated colitis.1-5 Cholestyramine and colestipol resins have been shown to bind the toxin in vitro. Mild cases of colitis may respond to drug discontinuance alone. Moderate to severe cases should be managed with fluid, electrolyte and protein supplementation as indicated. Vancomycin has been found to be effective in the treatment of antibiotic associated pseudomembranous colitis produced by Clostridium difficile. The usual adult dose is 500 milligrams to 2 grams of vancomycin orally per day in three to four divided doses administered for 7 to 10 days. Cholestyramine or colestipol resins bind vancomycin in vitro. If both a resin and vancomycin are to be administered concurrently, it may be advisable to separate the time of administration of each drug. Other causes of colitis should also be considered. A careful inquiry should be made concerning previous sensitivities to drugs and other allergens. Usage in Pregnancy - Safety for use in pregnancy has not been established. Usage in Newborns and Infants - When clindamycin hydrochloride is administered to newborns and infants, appropriate monitoring of organ system functions is desirable. Nursing Mothers - Clindamycin has been reported to appear in breast milk in ranges of 0.7 to 3.8 mcg/mL. Usage in Meningitis - Since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis. Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.
Review of experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhea less well. When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency. Clindamycin hydrochloride should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. Clindamycin hydrochloride should be prescribed with caution in atopic individuals. During prolonged therapy, periodic liver and kidney function tests and blood counts should be performed. Indicated surgical procedures should be performed in conjunction with antibiotic therapy. The use of clindamycin hydrochloride occasionally results in over growth of nonsusceptible organisms - particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation. Patients with very severe renal disease and/or very severe hepatic disease accompanied by severe metabolic aberrations should be dosed with caution, and serum clindamycin levels monitored during high-dose therapy. Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents. The capsules contain FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No.5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. |
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