CLEOCIN PHOSPHATE

CLEOCIN PHOSPHATE Sterile Solution in vials contains clindamycin phosphate, a water soluble ester of clindamycin and phosphoric acid. Each mL contains the equivalent of 150 mg clindamycin, 0.5 mg disodium edetate and 9.45 mg benzyl alcohol added as preservative in each mL. Clindamycin is a semisynthetic antibacterial drug produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin. The chemical name of clindamycin phosphate is L- threo -α-D- galacto- Octopyranoside, methyl-7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl] amino]-1-thio-, 2-(dihydrogen phosphate), (2 S-trans )-. The molecular formula is C 18 H 34 CIN 2 0 8 PS and the molecular weight is 504.96. The structural formula is represented below: Chemical Structure

CLEOCIN PHOSPHATE products are indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. CLEOCIN PHOSPHATE products are 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 antibacterial drug-associated pseudomembranous 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). Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin. Indicated surgical procedures should be performed in conjunction with antibacterial drug therapy. CLEOCIN PHOSPHATE is indicated in the treatment of serious infections caused by susceptible strains of the designated organisms in the conditions listed below: Lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by anaerobes, Streptococcus pneumoniae, other streptococci (except E. faecalis ), and Staphylococcus aureus. Skin and skin structure infections caused by Streptococcus pyogenes, Staphylococcus aureus , and anaerobes. Gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes. Intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms. Septicemia caused by Staphylococcus aureus , streptococci (except Enterococcus faecalis ), and susceptible anaerobes. Bone and joint infections including acute hematogenous osteomyelitis caused by Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms. To reduce the development of drug-resistant bacteria and maintain the effectiveness of CLEOCIN PHOSPHATE and other antibacterial drugs, CLEOCIN PHOSPHATE 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 diarrhea occurs during therapy, this antibacterial drug should be discontinued (see WARNING box). Clindamycin phosphate IM administration should be used undiluted . Clindamycin phosphate IV administration should be diluted (see Dilution for IV use and IV infusion rates below). Adults Parenteral (IM or IV Administration) Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis , Peptococcus species and Clostridium species other than Clostridium perfringens ): 600–1200 mg/day in 2, 3 or 4 equal doses. More severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus species, or Clostridium species other than Clostridium perfringens : 1200–2700 mg/day in 2, 3 or 4 equal doses. For more serious infections, these doses may have to be increased. In life-threatening situations due to either aerobes or anaerobes these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults. (see Dilution for IV use and IV Infusion Rates section below). Single intramuscular injections of greater than 600 mg are not recommended. Alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous IV infusion as follows: Table 2: Serum Clindamycin Levels Maintained, Rapid Infusion Rate and Maintenance Infusion Rate To maintain serum clindamycin levels Rapid infusion rate Maintenance infusion rate Above 4 mcg/mL 10 mg/min for 30 min 0.75 mg/min Above 5 mcg/mL 15 mg/min for 30 min 1.00 mg/min Above 6 mcg/mL 20 mg/min for 30 min 1.25 mg/min Pediatric Patients 1 month of age to 16 years Parenteral (IM or IV) Administration 20 to 40 mg/kg/day in 3 or 4 equal doses. The higher doses would be used for more severe infections. Clindamycin should be dosed based on total body weight regardless of obesity. As an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m 2 /day for serious infections and 450 mg/m 2 /day for more severe infections. Parenteral therapy may be changed to oral CLEOCIN PEDIATRIC ® Flavored Granules (clindamycin palmitate hydrochloride) or CLEOCIN HCl ® Capsules (clindamycin hydrochloride) when the condition warrants and at the discretion of the physician. In cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days. Pediatric Patients less than 1 month The recommended dosage is 15 to 20 mg/kg/day in 3 to 4 equal doses. (see Table 3) regarding the dosing regimen for pediatric patients with post-menstrual age (PMA) less than or equal to 32 weeks, or greater than 32 weeks to less than or equal to 40 weeks. Table 3: Dosing Regimens for Pediatric Patients with PMA less than or equal to 32 weeks, or greater than 32 weeks to less than or equal to 40 weeks PMA (weeks) Dose (mg/kg) Dosing Interval (hours) PMA: Post-Menstrual age Less than or equal to 32 5 8 Greater than or equal to 32 to less than or equal to 40 7 8 Dilution for IV use and IV Infusion Rates The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL. Infusion rates should not exceed 30 mg per minute. The usual infusion dilutions and rates are as follows: Dose Diluent Time 300 mg 50 mL 10 min 600 mg 50 mL 20 min 900 mg 50–100 mL 30 min 1200 mg 100 mL 40 min Administration of more than 1200 mg in a single 1-hour infusion is not recommended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Dilution and Compatibility Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of CLEOCIN PHOSPHATE Sterile Solution (clindamycin phosphate) in IV solutions containing sodium chloride, glucose, calcium or potassium, and solutions containing vitamin B complex in concentrations usually used clinically. No incompatibility has been demonstrated with the antibacterial drugs cephalothin, kanamycin, gentamicin, penicillin or carbenicillin. The following drugs are physically incompatible with clindamycin phosphate: ampicillin sodium, phenytoin sodium, barbiturates, aminophylline, calcium gluconate, and magnesium sulfate. The compatibility and duration of stability of drug admixtures will vary depending on concentration and other conditions. Physico-Chemical Stability of Diluted Solutions of CLEOCIN PHOSPHATE Room Temperature 6, 9 and 12 mg/mL (equivalent to clindamycin base) in dextrose injection 5%, sodium chloride injection 0.9%, or Lactated Ringers Injection in glass bottles, demonstrated physical and chemical stability for at least 16 days at 25°C. Refrigeration 6, 9 and 12 mg/mL (equivalent to clindamycin base) in dextrose injection 5%, sodium chloride injection 0.9%, or Lactated Ringers Injection in glass bottles, demonstrated physical and chemical stability for at least 32 days at 4°C. IMPORTANT: This chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

This drug 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: Clostridioides difficile colitis Gastrointestinal: Antibacterial drug-associated colitis (see WARNINGS ), pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS ). An unpleasant or metallic taste has been reported after intravenous administration of the higher doses of clindamycin phosphate. Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. 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, have been associated with clindamycin. Anaphylactic shock, anaphylactic reaction, hypersensitivity, and Kounis syndrome (acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction) have also been reported (see WARNINGS ). Cutaneous vasculitis and symmetrical drug-related intertriginous and flexural exanthema 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: Acute kidney injury (see WARNINGS ). 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. Local Reactions: Injection site irritation, pain, induration and sterile abscess have been reported after intramuscular injection and thrombophlebitis after intravenous infusion. Reactions can be minimized or avoided by giving deep intramuscular injections and avoiding prolonged use of indwelling intravenous catheters. Musculoskeletal: Polyarthritis cases have been reported. Cardiovascular: Cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration (see DOSAGE AND ADMINISTRATION ).

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.

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].