CLINDAMYCIN HYDROCHLORIDE

Clindamycin hydrochloride USP 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 USP contain clindamycin hydrochloride USP equivalent to 75 mg, 150 mg, or 300 mg of clindamycin. Inactive ingredients: corn starch, lactose monohydrate, magnesium stearate and talc. Composition of empty hard gelatin capsule shells: For 75 mg strength-size ‘3’: FD&C Blue 1, D&C Yellow 10, gelatin and water. For 150 mg Strength-Size ‘2’: titanium dioxide, FD&C Blue 1, D&C Yellow 10, gelatin and water. For 300 mg Strength-Size ‘0’: FD&C Blue 1, titanium dioxide, gelatin and water. The empty hard gelatin capsules are printed with TekPrint ™ SW-0012 White Ink. Composition of imprinting ink [TekPrint ™ SW-0012 White Ink] utilized for printing on the capsule shell are presented below: Shellac–NF, Dehydrated alcohol–USP, Isopropyl alcohol–USP, Butyl alcohol–NF, Propylene glycol–USP, Strong ammonia solution–NF, Purified water–USP, Potassium hydroxide–NF, Titanium dioxide USP. The structural formula is represented below: The chemical name for clindamycin hydrochloride is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans -4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L- threo - α -D- galacto -octopyranoside monohydrochloride. structure

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 BOXED WARNING , before selecting clindamycin, the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin). 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. To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin hydrochloride capsules USP and other antibacterial drugs, clindamycin hydrochloride capsules USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

If significant diarrhea occurs during therapy, this antibiotic should be discontinued (see BOXED WARNING ). Adults: Serious infections - 150 to 300 mg every 6 hours. More severe infections - 300 to 450 mg every 6 hours. Pediatric Patients (for children who are able to swallow capsules): Serious infections - 8 to 16 mg/kg/day (4 to 8 mg/lb/day) divided into three or four equal doses. More severe infections - 16 to 20 mg/kg/day (8 to 10 mg/lb/day) divided into three or four equal doses. To avoid the possibility of esophageal irritation, clindamycin hydrochloride capsules should be taken with a full glass of water. Clindamycin hydrochloride Capsules are not suitable for children who are unable to swallow them whole. The capsules do not provide exact mg/kg doses therefore it may be necessary to use the clindamycin palmitate oral solution in some cases. 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 β-hemolytic streptococcal infections, treatment should continue for at least 10 days.

Clindamycin hydrochloride is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin.

The following reactions have been reported with the use of clindamycin. Infections and Infestations: Clostridium difficile colitis Gastrointestinal: Abdominal pain, pseudomembranous colitis, esophagitis, nausea, vomiting, and diarrhea (see BOXED WARNING ). The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS ). Esophageal ulcer has been reported. An unpleasant or metallic taste has been reported after oral administration. 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. Severe skin reactions such as Toxic Epidermal Necrolysis, some with fatal outcome, have been reported (See WARNINGS ). Cases of Acute Generalized Exanthematous Pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, anap h ylactic shoc k, anaph ylactic reaction a nd h ypersensitivity have also been reported. Skin and Mucous Membranes: Pruritus, vaginitis, angioedema and rare instances of exfoliative dermatitis have been reported. (See Hypersensitivity Reactions.) 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. 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. Immune System: Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported. Musculoskeletal: Cases of polyarthritis have been reported. To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA Inc. at 1-855-839-8195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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. Clindamycin is metabolized predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N-desmethylclindamycin. Therefore inhibitors of CYP3A4 and CYP3A5 may increase plasma concentrations of clindamycin and inducers of these isoenzymes may reduce plasma concentrations of clindamycin. In the presence of strong CYP3A4 inhibitors, monitor for adverse reactions. In the presence of strong CYP3A4 inducers such as rifampicin, monitor for loss of effectiveness. In vitro studies indicate that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4. Antagonism has been demonstrated between clindamycin and erythromycin in vitro . Because of possible clinical significance, these two drugs should not be administered concurrently.