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.

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.

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:

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/m2/day for serious infections and 450 mg/m2/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.

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.

5.1 Clostridioides difficile-Associated Diarrhea

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Clindamycin Phosphate in Sodium Chloride Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Boxed Warning].

5.2 Anaphylactic and Severe Hypersensitivity Reactions

Anaphylactic shock and anaphylactic reactions have been reported [see Adverse Reactions (6)]. Severe hypersensitivity reactions, including severe skin reactions such as toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS), some with fatal outcome, have been reported [see Adverse Reactions (6)].

In case of such an anaphylactic or severe hypersensitivity reaction, discontinue treatment permanently and institute appropriate therapy.

A careful inquiry should be made concerning previous sensitivities to drugs and other allergens.

5.3 Nephrotoxicity

Clindamycin is potentially nephrotoxic and cases with acute kidney injury have been reported. Consider monitoring of renal function particularly in patients with pre-existing renal dysfunction or those taking concomitant nephrotoxic drugs. In case of acute kidney injury, discontinue Clindamycin Phosphate in Sodium Chloride Injection when no other etiology is identified [see Adverse Reactions (6)].

5.4 Diarrhea in Elderly Patients with Associated Severe Illness

Elderly patients with associated severe illness may have a greater risk of developing adverse reactions from diarrhea. When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency [see Use in Specific Populations (8.5)].

5.5 Use in Patients with Gastrointestinal Disease

Clindamycin Phosphate in Sodium Chloride Injection products should be avoided in individuals with a history of gastrointestinal disease, particularly colitis.

5.6 Use in Atopic Individuals

Clindamycin Phosphate in Sodium Chloride Injection should be avoided in atopic individuals.

5.7 Laboratory Tests: Monitoring to Assess Safety

During prolonged therapy periodic liver and kidney function tests and blood counts should be performed.

Clindamycin dosage modification is not necessary in patients with renal disease. In patients with moderate to severe liver disease, prolongation of clindamycin half-life has been found. However, it was postulated from studies that when given every eight hours, accumulation should rarely occur.
Therefore, dosage modification in patients with liver disease may not be necessary. However, periodic liver enzyme determinations should be made when treating patients with severe liver disease.

5.8 Overgrowth of Nonsusceptible Organisms

The use of Clindamycin Phosphate in Sodium Chloride Injection may result in overgrowth of nonsusceptible organisms-particularly yeasts. If such infections occur, appropriate measures should be taken as indicated by the clinical situation.

5.9 Development of Drug-Resistant Bacteria

Prescribing Clindamycin Phosphate in Sodium Chloride Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

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.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious infections caused by susceptible anaerobic bacteria, infections due to susceptible isolates of streptococci, pneumococci and staphylococci, lower respiratory tract Infections, skin and skin structure infections, gynecological infections, intra-abdominal infections, septicemia and bone and joint infections in pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1-1.8)] and Dosage and Administration (2.3)].

When Clindamycin Phosphate in Sodium Chloride Injection is administered to the pediatric population (less than 1 month to 16 years old) appropriate dosing and monitoring of organ system functions is desirable. Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Clindamycin Phosphate in Sodium Chloride Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg 600 mg or 900 mg is required and an alternative formulation of clindamycin should be considered [see Dosage and Administration (2.3)].

The potential for the toxic effect in the pediatric population from chemicals that may leach from the single dose premixed Clindamycin Phosphate in Sodium Chloride Injection preparation in plastic has not been evaluated.

8.5 Geriatric Use

Clinical studies of clindamycin did not include sufficient numbers of patients age 65 and over to determine whether they respond differently from younger patients. However, other reported clinical experience indicates that antibacterial-associated colitis and diarrhea (due to Clostridioides difficile) seen in association with most antibacterial drugs occur more frequently in the elderly (>60 years) and may be more severe. These patients should be carefully monitored for the development of diarrhea.

Pharmacokinetic studies with clindamycin have shown no clinically important differences between young and elderly subjects with normal hepatic function and normal (age-adjusted) renal function after oral or intravenous administration [see Clinical Pharmacology (12.3)].

12.1 Mechanism of Action

Clindamycin is an antibacterial drug [see Microbiology (12.4)].

12.3 Pharmacokinetics

Clindamycin phosphate is a water-soluble ester prodrug of clindamycin. Biologically inactive clindamycin phosphate is converted to active clindamycin. By the end of short-term intravenous infusion, peak serum concentrations of active clindamycin are reached.

After intramuscular injection of clindamycin phosphate, peak concentrations of active clindamycin are reached within 3 hours in adults and 1 hour in pediatric patients. Serum concentration-time curves may be constructed from intravenous peak serum concentrations by application of elimination half-lives described in the elimination section below.

Serum concentrations of clindamycin can be maintained above the in vitro minimum inhibitory concentrations for most indicated organisms by administration of clindamycin phosphate every 8 to 12 hours in adults and every 6 to 8 hours in pediatric patients, or by continuous intravenous infusion. An equilibrium state is reached by the third dose.

12.4 Microbiology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.1 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.