CLINDAMYCIN PHOSPHATE- clindamycin phosphate_injection, solution

CLINICAL PHARMACOLOGY
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 IV peak serum concentrations as given in Table 1 by application of elimination half-lives (see Excretion 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. No significant concentrations of clindamycin are attained in the cerebrospinal fluid even in the presence of inflamed meninges. In vitro studies in human liver and intestinal microsomes indicated that clindamycin is predominantly metabolized by Cytochrome P450 3A4 (CYP3A4), with minor contribution from CYP3A5, to form clindamycin sulfoxide and a minor metabolite, N-desmethylclindamycin. Biologically inactive clindamycin phosphate disappears from the serum with 6 minutes of the average elimination half-life; however, the average serum elimination half-life of active clindamycin is about 3 hours in adults and 2½ hours in pediatric patients. The elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease. Pharmacokinetic studies in elderly volunteers (61en dash79 years) and younger adults (18en dash39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration-time curve) after IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, the average elimination half-life is increased to approximately 4. 0 hours (range 3. 1 h) in the elderly, compared to 3. 2 hours (range 2. 2 h) in younger adults. The extent of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function 1 Table 1. Average Peak and Trough Serum Concentrations of Active Clindamycin After Dosing with Clindamycin Phosphate Dosage Regimen Peak Trough Healthy Adult Males (Post equilibrium) 600 mg IV in 30 min q6h 10. 0 600 mg IV in 30 min q8h 10. 1 900 mg IV in 30 min q8h 14. 7 600 mg IM q12h Data in this group from patients being treated for infection. 9 Pediatric Patients (first dose) 5en dash7 mg/kg IV in 1 hour 10 5en dash7 mg/kg IM 8 3en dash5 mg/kg IM 4 An analysis of pharmacokinetic data in obese children and obese young adults (2-20 years) demonstrated that clindamycin clearance and volume of distribution normalized by total body weight in these patients are comparable to those in children (and young adults) with normal body weight. Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic. Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Because the binding sites for these antibacterial drugs overlap, cross-resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria. Macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should be screened for induction of clindamycin resistance using the D-zone test. Clindamycin has been shown to be active against most of the isolates of the following microorganisms, both in vitro and in clinical infections [ INDICATIONS AND USAGE ] Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Clostridium perfringens The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for clindamycin against isolates of a similar genus or organism group. However, the efficacy of clindamycin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials. Staphylococcus epidermidis Streptococcus agalactiae Actinomyces israelii For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.
Distribution
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 IV peak serum concentrations as given in Table 1 by application of elimination half-lives (see Excretion 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. No significant concentrations of clindamycin are attained in the cerebrospinal fluid even in the presence of inflamed meninges.
Metabolism
In vitro studies in human liver and intestinal microsomes indicated that clindamycin is predominantly metabolized by Cytochrome P450 3A4 (CYP3A4), with minor contribution from CYP3A5, to form clindamycin sulfoxide and a minor metabolite, N-desmethylclindamycin.
Excretion
Biologically inactive clindamycin phosphate disappears from the serum with 6 minutes of the average elimination half-life; however, the average serum elimination half-life of active clindamycin is about 3 hours in adults and 2½ hours in pediatric patients.
Microbiology
Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic. Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Because the binding sites for these antibacterial drugs overlap, cross-resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria. Macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should be screened for induction of clindamycin resistance using the D-zone test. Clindamycin has been shown to be active against most of the isolates of the following microorganisms, both in vitro and in clinical infections [ INDICATIONS AND USAGE ] Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Clostridium perfringens The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for clindamycin against isolates of a similar genus or organism group. However, the efficacy of clindamycin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials. Staphylococcus epidermidis Streptococcus agalactiae Actinomyces israelii For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.
Mechanism of Action
Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic.
Resistance
Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Because the binding sites for these antibacterial drugs overlap, cross-resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria. Macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should be screened for induction of clindamycin resistance using the D-zone test.
Antimicrobial Activity
Clindamycin has been shown to be active against most of the isolates of the following microorganisms, both in vitro and in clinical infections [ INDICATIONS AND USAGE ] Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes Clostridium perfringens The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for clindamycin against isolates of a similar genus or organism group. However, the efficacy of clindamycin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials. Staphylococcus epidermidis Streptococcus agalactiae Actinomyces israelii.
Gram-positive bacteria
Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes
Anaerobic bacteria
Clostridium perfringens The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for clindamycin against isolates of a similar genus or organism group. However, the efficacy of clindamycin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.
Gram-positive bacteria
Staphylococcus epidermidis Streptococcus agalactiae
Anaerobic bacteria
Actinomyces israelii

Clindamycin phosphate products are indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Clindamycin 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 antibiotic-associated pseudomembranous colitis, as described in the BOXED WARNING Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin. Indicated surgical procedures should be performed in conjunction with antibiotic therapy. Clindamycin 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, E. faecalis Staphylococcus aureus. Skin and skin structure infections caused by Streptococcus pyogenes, Staphylococcus aureus 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 Enterococcus faecalis Bone and joint infections including acute hematogenous osteomyelitis caused by Staphylococcus aureus To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin phosphate and other antibacterial drugs, clindamycin 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.

DOSAGE AND ADMINISTRATION
If diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING Clindamycin phosphate IM administration should be used undiluted. Clindamycin phosphate IV administration should be diluted Dilution for IV use and IV infusion rates Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis Peptococcus Clostridium Clostridium perfringens 600en dash1200 mg/day in 2, 3 or 4 equal doses. More severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus Clostridium Clostridium perfringens 1200en dash2700 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 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: 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 15 to 20 mg/kg/day in 3 to 4 equal doses. The lower dosage may be adequate for small prematures. 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 2 Parenteral therapy may be changed to oral clindamycin palmitate hydrochloride granules or clindamycin hydrochloride capsules when the condition warrants and at the discretion of the physician. In cases of beta-hemolytic streptococcal infections, treatment should be continued for at least 10 days. The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL. Infusion rates should not exceed 30 mg per minute. Dose Diluent Time 300 mg 50 mL 10 min 600 mg 50 mL 20 min 900 mg 50en dash100 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. Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of 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 antibiotics 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. For current information regarding compatibilities of clindamycin phosphate under specific conditions, please contact Almaject Inc. 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 or Mini-Bag containers, demonstrated physical and chemical stability for at least 16 days at 25°C. Also, 18 mg/mL (equivalent to clindamycin base) in dextrose injection 5%, in Mini-Bag containers, demonstrated physical and chemical stability for at least 16 days at 25°C. 9%, or Lactated Ringers Injection in glass bottles or Mini-Bag containers, 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. 9%, or Lactated Ringers Injection in Mini-Bag containers demonstrated physical and chemical stability for at least eight weeks at -10°C. Frozen solutions should be thawed at room temperature and not refrozen.
Adults
Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis Peptococcus Clostridium Clostridium perfringens 600en dash1200 mg/day in 2, 3 or 4 equal doses. More severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus Clostridium Clostridium perfringens 1200en dash2700 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 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: 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
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. Dose Diluent Time 300 mg 50 mL 10 min 600 mg 50 mL 20 min 900 mg 50en dash100 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.

Anaphylactic and Severe Hypersensitivity Reactions
Anaphylactic shock and anaphylactic reactions have been reported ( ADVERSE REACTIONS 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 ( ADVERSE REACTIONS 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.
ADVERSE REACTIONS
The following reactions have been reported with the use of clindamycin. Infections and Infestations: Clostridium difficile Gastrointestinal: WARNINGS WARNINGS Hypersensitivity Reactions: Severe skin reactions such as Toxic Epidermal Necrolysis, some with fatal outcome, have been reported (see WARNINGS WARNINGS Skin and Mucous Membranes: Hypersensitivity Reactions Liver: Renal: Hematopoietic: Immune System: Local Reactions: Musculoskeletal: Cardiovascular: DOSAGE AND ADMINISTRATION

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

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 antibiotic-associated colitis and diarrhea (due to Clostridium difficile 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.
Neonates (less than 1 month)
15 to 20 mg/kg/day in 3 to 4 equal doses. The lower dosage may be adequate for small prematures.
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 2 Parenteral therapy may be changed to oral clindamycin palmitate hydrochloride granules or clindamycin hydrochloride capsules when the condition warrants and at the discretion of the physician. In cases of beta-hemolytic streptococcal infections, treatment should be continued for at least 10 days.">Specific Populations
The elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease. Pharmacokinetic studies in elderly volunteers (61en dash79 years) and younger adults (18en dash39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration-time curve) after IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, the average elimination half-life is increased to approximately 4. 0 hours (range 3. 1 h) in the elderly, compared to 3. 2 hours (range 2. 2 h) in younger adults. The extent of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function 1 Table 1. Average Peak and Trough Serum Concentrations of Active Clindamycin After Dosing with Clindamycin Phosphate Dosage Regimen Peak Trough Healthy Adult Males (Post equilibrium) 600 mg IV in 30 min q6h 10. 0 600 mg IV in 30 min q8h 10. 1 900 mg IV in 30 min q8h 14. 7 600 mg IM q12h Data in this group from patients being treated for infection. 9 Pediatric Patients (first dose) 5en dash7 mg/kg IV in 1 hour 10 5en dash7 mg/kg IM 8 3en dash5 mg/kg IM 4 An analysis of pharmacokinetic data in obese children and obese young adults (2-20 years) demonstrated that clindamycin clearance and volume of distribution normalized by total body weight in these patients are comparable to those in children (and young adults) with normal body weight.
Patients with Renal/Hepatic Impairment
The elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease.
Elderly Patients
Pharmacokinetic studies in elderly volunteers (61en dash79 years) and younger adults (18en dash39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration-time curve) after IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, the average elimination half-life is increased to approximately 4.0 hours (range 3.4en dash5.1 h) in the elderly, compared to 3.2 hours (range 2.1en dash4.2 h) in younger adults. The extent of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function 1 Table 1. Average Peak and Trough Serum Concentrations of Active Clindamycin After Dosing with Clindamycin Phosphate Dosage Regimen Peak Trough Healthy Adult Males (Post equilibrium) 600 mg IV in 30 min q6h 10.9 2.0 600 mg IV in 30 min q8h 10.8 1.1 900 mg IV in 30 min q8h 14.1 1.7 600 mg IM q12h Data in this group from patients being treated for infection. 9 Pediatric Patients (first dose) 5en dash7 mg/kg IV in 1 hour 10 5en dash7 mg/kg IM 8 3en dash5 mg/kg IM 4
Obese Children and Obese Young Adults
An analysis of pharmacokinetic data in obese children and obese young adults (2-20 years) demonstrated that clindamycin clearance and volume of distribution normalized by total body weight in these patients are comparable to those in children (and young adults) with normal body weight.
Pregnancy
In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters, has not been associated with an increased frequency of congenital abnormalities. Clindamycin should be used during the first trimester of pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed. Reproduction studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (2.1 and 1.1 times the highest recommended adult human dose based on mg/m 2 2 Clindamycin Injection contains benzyl alcohol. Benzyl alcohol can cross the placenta (see WARNINGS
Nursing Mothers
Limited published data based on breast milk sampling reports that clindamycin appears in human breast milk in the range of less than 0.5 to 3.8 mcg/mL at dosages of 150 mg orally to 600 mg intravenously. Clindamycin has the potential to cause adverse effects on the breast-fed infant''s gastrointestinal flora. If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. Monitor the breast-fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis. The developmental and health benefits of breastfeeding should be considered along with the mother''s clinical need for clindamycin and any potential adverse effects on the breast-fed child from clindamycin or from the underlying maternal condition.
Pediatric Use
When clindamycin Injection is administered to the pediatric population (birth to 16 years) appropriate monitoring of organ system functions is desirable.
Usage in Newborns and Infants
This product contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal "Gasping Syndrome" in premature infants (see WARNINGS The potential for the toxic effect in the pediatric population from chemicals that may leach from the single dose premixed IV preparation in plastic has not been evaluated (see WARNINGS
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 antibiotic-associated colitis and diarrhea (due to Clostridium difficile 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.
Neonates (less than 1 month)
15 to 20 mg/kg/day in 3 to 4 equal doses. The lower dosage may be adequate for small prematures.
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 2 Parenteral therapy may be changed to oral clindamycin palmitate hydrochloride granules or clindamycin hydrochloride capsules when the condition warrants and at the discretion of the physician. In cases of beta-hemolytic streptococcal infections, treatment should be continued for at least 10 days.

Drug Interactions
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.
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 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 antibiotics 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. For current information regarding compatibilities of clindamycin phosphate under specific conditions, please contact Almaject Inc.

Physico-Chemical Stability of Diluted Solutions of Clindamycin 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 or Mini-Bag containers, demonstrated physical and chemical stability for at least 16 days at 25°C. Also, 18 mg/mL (equivalent to clindamycin base) in dextrose injection 5%, in Mini-Bag containers, 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 or Mini-Bag containers, 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.
Frozen
6, 9 and 12 mg/mL (equivalent to clindamycin base) in dextrose injection 5%, sodium chloride injection 0.9%, or Lactated Ringers Injection in Mini-Bag containers demonstrated physical and chemical stability for at least eight weeks at -10°C. Frozen solutions should be thawed at room temperature and not refrozen.

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/m 2
Teratogenic effects
In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters, has not been associated with an increased frequency of congenital abnormalities. Clindamycin should be used during the first trimester of pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed. Reproduction studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (2.1 and 1.1 times the highest recommended adult human dose based on mg/m 2 2 Clindamycin Injection contains benzyl alcohol. Benzyl alcohol can cross the placenta (see WARNINGS
OVERDOSAGE
Significant mortality was observed in mice at an intravenous dose of 855 mg/kg and in rats at an oral or subcutaneous dose of approximately 2618 mg/kg. In the mice, convulsions and depression were observed. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
DIRECTIONS FOR DISPENSING
The Pharmacy Bulk Package is for use in a Pharmacy Admixture Service only under a laminar flow hood. Entry into the vial should be made with a small diameter sterile transfer set or other small diameter sterile dispensing device, and contents dispensed in aliquots using aseptic technique. Multiple entries with a needle and syringe are not recommended. AFTER ENTRY USE ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 24 HOURS AFTER INITIAL ENTRY.
REFERENCES
Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.">Susceptibility Testing
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.
WARNINGS
See BOXED WARNING Clostridium difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile Anaphylactic shock and anaphylactic reactions have been reported ( ADVERSE REACTIONS 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 ( ADVERSE REACTIONS 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. This product contains benzyl alcohol as a preservative. The preservative benzyl alcohol has been associated with serious adverse events, including the "gasping syndrome", and death in pediatric patients. Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys'' capacity to detoxify the chemical. Premature and low birth weight infants may be more likely to develop toxicity. Since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis.
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/m 2
Teratogenic effects
In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters, has not been associated with an increased frequency of congenital abnormalities. Clindamycin should be used during the first trimester of pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed. Reproduction studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (2.1 and 1.1 times the highest recommended adult human dose based on mg/m 2 2 Clindamycin Injection contains benzyl alcohol. Benzyl alcohol can cross the placenta (see WARNINGS
OVERDOSAGE
Significant mortality was observed in mice at an intravenous dose of 855 mg/kg and in rats at an oral or subcutaneous dose of approximately 2618 mg/kg. In the mice, convulsions and depression were observed. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
DIRECTIONS FOR DISPENSING
The Pharmacy Bulk Package is for use in a Pharmacy Admixture Service only under a laminar flow hood. Entry into the vial should be made with a small diameter sterile transfer set or other small diameter sterile dispensing device, and contents dispensed in aliquots using aseptic technique. Multiple entries with a needle and syringe are not recommended. AFTER ENTRY USE ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 24 HOURS AFTER INITIAL ENTRY.
REFERENCES
Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.

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CLINDAMYCIN PHOSPHATE- clindamycin phosphate_injection, solution Product manual source documgent