CLINDAMYCIN PHOSPHATE

Clindamycin Phosphate in Sodium Chloride Injection contains clindamycin phosphate, a water-soluble ester of clindamycin. Clindamycin is a semisynthetic antibacterial produced by a 7( S )-chloro-substitution of the 7( R )-hydroxyl group of the parent antibacterial 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]01-thio-, 2-(dihydrogen phosphate), (2S- trans )-. The molecular formula is C 18 H 34 CIN 2 O 8 PS and the molecular weight is 504.96. The structural formula is represented below: Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution for intravenous infusion available in three strengths, 300 mg/50 mL, 600 mg/50 mL, and 900 mg/50 mL, containing 300 mg, 600 mg or 900 mg clindamycin, respectively (as clindamycin phosphate, USP). Each 50 mL of all the strengths of Clindamycin Phosphate in Sodium Chloride Injection also contains, 450 mg of sodium chloride USP, 2 mg of edetate disodium dihydrate USP, and water for Injection USP. The pH is adjusted with sodium hydroxide and /or hydrochloric acid. Clindamycin Phosphate in Sodium Chloride Injection is filled in GALAXY plastic container fabricated from a specially designed multilayer plastic. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies. Clindamycin Structural Formula

Clindamycin Phosphate in Sodium Chloride Injection contains clindamycin, a lincosamide antibacterial indicated for the treatment of the following in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved: • Serious infections caused by susceptible anaerobic bacteria ( 1.1 ) • Infections Due to Susceptible Isolates of Streptococci, Pneumococci and Staphylococci. ( 1.2 ) • Lower Respiratory Tract Infections. ( 1.3 ) • Skin and Skin Structure Infections. ( 1.4 ) • Gynecological Infections. ( 1.5 ) • Intra-abdominal Infections. ( 1.6 ) • Septicemia. ( 1.7 ) • Bone and Joint Infections. ( 1.8 ) Limitation of use Since clindamycin does not diffuse adequately into the cerebrospinal fluid, Clindamycin Phosphate in Sodium Chloride Injection should not be used in the treatment of meningitis ( 1.9 ) Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Clindamycin Phosphate in Sodium Chloride Injection and other antibacterial drugs, Clindamycin Phosphate in Sodium Chloride Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.10 ) 1.1 Infections Due to Susceptible Anaerobic Bacteria Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious infections caused by susceptible anaerobic bacteria in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.3 - 1.7) ] . 1.2 Infections Due to Susceptible Isolates of Streptococci, Pneumococci and Staphylococci Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious infections due to susceptible isolates of streptococci, pneumococci, and staphylococci in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 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-associated pseudomembranous colitis, [see 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 therapy. 1.3 Lower Respiratory Tract Infections Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by susceptible isolates of anaerobes, Streptococcus pneumoniae , other streptococci (except E. faecalis ), and Staphylococcus aureus in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 1.4 Skin and Skin Structure Infections Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious skin and skin structure infections caused by susceptible isolates of Streptococcus pyogenes , Staphylococcus aureus , and anaerobes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 1.5 Gynecological Infections Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 1.6 Intra-abdominal Infections Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 1.7 Septicemia Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious septicemia caused by susceptible isolates of Staphylococcus aureus , streptococci (except Enterococcus faecalis ), and susceptible anaerobes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 1.8 Bone and Joint Infections Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious bone and joint infections including acute hematogenous osteomyelitis caused by susceptible isolates of Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. 1.9 Limitations of Use Since clindamycin does not diffuse adequately into the cerebrospinal fluid, Clindamycin Phosphate in Sodium Chloride Injection should not be used in the treatment of meningitis [see Clinical Pharmacology (12.3) ] . 1.10 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Clindamycin Phosphate in Sodium Chloride Injection and other antibacterial drugs, Clindamycin Phosphate in Sodium Chloride Injection 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 a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg 600 mg or 900 mg, this product is not recommended for use and an alternative formulation of clindamycin should be considered. ( 2.1 ) • Recommended Adult Dosage: Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis , Peptococcus species and Clostridioides species other than Clostridium perfringens ): 600–1200 mg/day in 2, 3 or 4 equal doses by intravenous infusion. ( 2.2 ) • 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 by intravenous infusion. ( 2.2 ) • Dosage in Pediatric Patients (1 Month of Age to 16 Years): 20 to 40 mg/kg/day in 3 or 4 equal doses by intravenous infusion. ( 2.3 ) • Alternative Pediatric Patients Dosing: 350 mg/m 2 /day for serious infections and 450 mg/m2/day for more severe infections. ( 2.3 ) • Dosage in Neonates (Less than 1 Month of Age): 15 to 20 mg/kg/day in 3 to 4 equal doses by intravenous infusion. ( 2.3 ) 2.1 Important Administration and Discontinuation Instructions If a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg 600 mg or 900 mg, this product is not recommended for use and an alternative formulation of clindamycin should be considered. Administer Clindamycin Phosphate in Sodium Chloride Injection by intravenous infusion over at least 10 minutes. Infusion rates should NOT exceed 30 mg per minute. The usual infusion rates are described in Table 1 . Table 1: Usual Infusion Rates for the Administration of Clindamycin Phosphate in Sodium Chloride Injection Dose Time 300 mg 10 min 600 mg 20 min 900 mg 30 min Discontinue Clindamycin Phosphate in Sodium Chloride Injection if diarrhea occurs during therapy [see Boxed Warning ]. 2.2 Recommended Adult Dosage The recommended dosing regimen for Clindamycin Phosphate in Sodium Chloride Injection is 600-1200 mg/day in 2, 3, or 4 equal doses by intravenous infusion for 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 ). For more severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus species, or Clostridium species other than Clostridium perfringens, the recommended dosing regimen is 1200-2700 mg/day in 2, 3, or 4 equal doses by intravenous infusion. In life-threatening situations, these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults. Alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous intravenous infusion as follows: Table 2: Infusion Rates for the Administration of Clindamycin Injection by Single Rapid Infusion followed by Continuous Intravenous Infusion for the Maintenance of Serum Clindamycin Levels 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 2.3 Dosage in Pediatric Patients If a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg, 600 mg or 900 mg, this product is not recommended for use and an alternative formulation of clindamycin should be considered. The recommended pediatric dosing regimen of Clindamycin Phosphate in Sodium Chloride Injection is as follows: Pediatric patients (1 month of age to 16 years old): The recommended dosage is 20 to 40 mg/kg/day in 3 or 4 equal doses. The higher doses would be used for more severe infections. 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 formulations of clindamycin 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) Less than or equal to 32 5 8 Greater than or equal to 32 weeks to less than or equal to 40 7 8 PMA: Post-Menstrual Age 2.4 Directions for Use of Clindamycin Phosphate in Sodium Chloride Injection in GALAXY Plastic Container Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Premixed Clindamycin Phosphate in Sodium Chloride Injection is for intravenous infusion using sterile equipment. Check for minute leaks prior to use by squeezing bag firmly. If leaks are found, discard solution as sterility may be impaired. Do NOT add supplementary medication. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do NOT use unless solution is clear and seal is intact. Do NOT use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. Clindamycin Phosphate in Sodium Chloride Injection should not be injected intravenously undiluted as a bolus, but should be infused over at least 10 minutes. Preparation for Administration: 1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set.

Clindamycin Phosphate in Sodium Chloride Injection is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin. Individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin. ( 4 )

The following serious adverse reactions to clindamycin are described below and elsewhere in the labeling: • Clostridioides difficile- Associated Diarrhea [see Warnings and Precautions (5.1) ] • Anaphylactic and Severe Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] • Nephrotoxicity [see Warnings and Precautions (5.3) ] The following adverse reactions associated with the use of clindamycin were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably, or to establish a causal relationship to drug exposure. Infections and Infestations Clostridioides difficile colitis Gastrointestinal Antibacterial-associated colitis [see Warnings and Precautions (5.1) ] , pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.1) ] . 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 and Precautions (5.2) ] . Cases of Acute Generalized Exanthematous Pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. Anaphylactic shock, anaphylactic reaction and hypersensitivity have also been reported [see Warnings and Precautions (5.2) ]. Skin and Mucous Membranes Pruritus, vaginitis, angioedema and rare instances of exfoliative dermatitis have been reported [see Warnings and Precautions (5.2) ]. Liver Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy. Renal Acute kidney injury [see Warnings and Precautions (5.3) ]. Hematopoietic Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. Immune System Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported. Local Reactions Thrombophlebitis has been reported after intravenous infusion. Avoid 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 (2) ] . Most common adverse reactions: gastrointestinal (abdominal pain, nausea, vomiting) and hypersensitivity reactions (anaphylaxis, urticaria, skin rash). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. ( 7.1 ) • Monitor for adverse reactions when strong CYP3A4 and/or CYP3A5 inhibitors are coadministered with clindamycin. ( 7.2 ) • In the presence of strong CYP3A4 and/or CYP3A5 inducers such as rifampicin, monitor for loss of effectiveness. ( 7.3 ) 7.1 Neuromuscular Blocking Agents Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be avoided in patients receiving such agents. 7.2 Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. Monitor for adverse reactions when strong CYP3A4 and/or CYP3A5 inhibitors are coadministered with clindamycin. 7.3 Inducers of CYP3A4 and CYP3A5 Inducers of CYP3A4 and/or CYP3A5 may reduce plasma concentrations of clindamycin. In the presence of strong CYP3A4 and/or CYP3A5 inducers such as rifampicin, monitor for loss of effectiveness.