Clindamycin Information
Clindamycin ()
Clindamycin ()
Clindamycin () Description
Clindamycin () Injection, USP, a water soluble ester of Clindamycin () and phosphoric acid, is a sterile solution for intramuscular or intravenous use.
Clindamycin () is a semisynthetic antibiotic 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 methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl--4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L--α-D--octopyranoside 2-(dihydrogen phosphate).
The molecular formula is CHClNOPS and the molecular weight is 504.97.
The structural formula is represented below:
Each mL contains Clindamycin () phosphate equivalent to 150 mg Clindamycin () , 0.5 mg disodium edetate and 9.45 mg benzyl alcohol added as a preservative. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. pH is 6.5 range 5.5 to 7.0.
The Pharmacy Bulk Package is a sterile dosage form which contains multiple single doses in the preparation of admixtures for intravenous infusion (see ,).
Clindamycin () Clinical Pharmacology
Biologically inactive Clindamycin () phosphate is rapidly converted to active Clindamycin () .
By the end of short-term intravenous infusion, peak serum levels of active Clindamycin () are reached. Biologically inactive Clindamycin () phosphate disappears rapidly from the serum; the average elimination half-life is 6 minutes; however, the serum elimination half-life of active Clindamycin () is about 3 hours in adults and 2½ hours in pediatric patients.
After intramuscular injection of Clindamycin () phosphate, peak levels of active Clindamycin () are reached within 3 hours in adults and 1 hour in pediatric patients. Serum level curves may be constructed from I.V. peak serum levels as given in Table 1 by application of elimination half-lives listed above.
Serum levels of Clindamycin () can be maintained above the 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.
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.
No significant levels of Clindamycin () are attained in the cerebrospinal fluid, even in the presence of inflamed meninges.
Pharmacokinetic studies in elderly volunteers (61 to 79 years) and younger adults (18 to 39 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 I.V. administration of Clindamycin () phosphate. After oral administration of Clindamycin () hydrochloride, elimination half-life is increased to approximately 4 hours (range 3.4 to 5.1 h) in the elderly compared to 3.2 hours (range 2.1 to 4.2 h) in younger adults. The extent of absorption, however, is not different between the age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function.
Serum assays for active Clindamycin () require an inhibitor to prevent hydrolysis of Clindamycin () phosphate.
Clindamycin () has been shown to have activity against isolates of the following organisms:
Cross resistance has been demonstrated between Clindamycin () and lincomycin.
Antagonism has been demonstrated between Clindamycin () and erythromycin.
Disk diffusion technique―Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure has been recommended for use with disks to test susceptibility to Clindamycin () .
Reports from a laboratory using the standardized single-disk susceptibility test with a 2 mcg Clindamycin () disk should be interpreted according to the following criteria:
Susceptible organisms produce zones of 17 mm or greater, indicating that the tested organism is likely to respond to therapy.
Organisms of intermediate susceptibility produce zones of 15-16 mm, indicating that the tested organism would be susceptible if a high dosage is used or if the infection is confined to tissues and fluids (e.g., urine), in which high antibiotic levels are attained.
Resistant organisms produce zones of 14 mm or less, indicating that other therapy should be selected.
Standardized procedures require the use of control organisms. The 2 mcg Clindamycin () disk should give a zone diameter between 24 and 30 mm for ATCC 25923.
Dilution techniques―A bacterial isolate may be considered susceptible if the minimum inhibitory concentration (MIC) for Clindamycin () is not more than 1.6 mcg/mL. Organisms are considered moderately susceptible if the MIC is greater than 1.6 mcg/mL and less than or equal to 4.8 mcg/mL. Organisms are considered resistant if the MIC is greater than 4.8 mcg per mL. The range of MIC’s for the control strains are as follows:
For anaerobic bacteria the minimum inhibitory concentration (MIC) of Clindamycin () can be determined by agar dilution and broth dilution (including microdilution) techniques. If MIC’s are not determined routinely, the disk broth method is recommended for routine use. The KIRBY-BAUER DISK DIFFUSION METHOD AND ITS INTERPRETIVE STANDARDS ARE NOT RECOMMENDED FOR ANAEROBES.
Clindamycin () Indications And Usage
Clindamycin () Injection, USP is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.
Clindamycin () Injection, USP 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 antibiotic-associated pseudomembranous colitis, as described in the box, 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 antibiotic therapy.
Clindamycin () Injection, USP 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, , other streptococci (except ), and .
Skin and skin structure infections caused by , , 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 , streptococci (except ), and susceptible anaerobes.
Bone and joint infections including acute hematogenous osteomyelitis caused by 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 Clindamycin () and other antibacterial drugs, Clindamycin () 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.
Clindamycin () Contraindications
This drug is contraindicated in individuals with a history of hypersensitivity to preparations containing Clindamycin () or lincomycin.
Clindamycin () Warnings
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
A careful inquiry should be made concerning previous sensitivities to drugs and other allergens.
This product contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants (see –).
SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN AND INTRAVENOUS CORTICOSTEROIDS SHOULD ALSO BE ADMINISTERED AS INDICATED.
Clindamycin () Precautions
Review of experience to date suggests that a subgroup of older patients with associated severe illness may tolerate diarrhea less well. When Clindamycin () is indicated in these patients, they should be carefully monitored for change in bowel frequency.
Clindamycin () phosphate should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Clindamycin () phosphate should be prescribed with caution in atopic individuals.
Certain infections may require incision and drainage or other indicated surgical procedures in addition to antibiotic therapy.
The use of Clindamycin () phosphate may result in overgrowth of nonsusceptible organisms−particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation.
Clindamycin () phosphate should not be injected intravenously undiluted as a bolus, but should be infused over at least 10 to 60 minutes as directed in the section.
Clindamycin () dosage modification may not be 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.
Prescribing Clindamycin () 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.
Patients should be counseled that antibacterial drugs including Clindamycin () should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Clindamycin () is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Clindamycin () or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
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.
Antagonism has been demonstrated between Clindamycin () and erythromycin . Because of possible clinical significance, the two drugs should not be administered concurrently.
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) revealed no effects on fertility or mating ability.
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, respectively) or subcutaneous doses of Clindamycin () up to 250 mg/kg/day (0.9 and 0.5 times the highest recommended adult human dose based on mg/m, respectively) revealed no evidence of teratogenicity.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed.
This product contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal “Gasping Syndrome” in premature infants.
The potential for the toxic effect in the pediatric population from chemicals that may leach from the single dose premixed I.V. preparation in plastic has not been evaluated.
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 ) seen in association with most antibiotics 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.
Clindamycin () Adverse Reactions
The following reactions have been reported with the use of Clindamycin () .
Clindamycin () 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.
Clindamycin () Dosage And Administration
If diarrhea occurs during therapy, this antibiotic should be discontinued. (See box.)
Parenteral (I.M. or I.V.) Administration:
Serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including , species and species other than ):
600 to 1200 mg/day in 2, 3 or 4 equal doses.
More severe infections, particularly those due to proven or suspected , species, or species other than :
1200 to 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 section below.
Single I.M. 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 I.V. infusion as follows:
15 to 20 mg/kg/day in three to four equal doses. The lower dosage may be adequate for small prematures.
Parenteral (I.M. or I.V.) administration: 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/day for serious infections and 450 mg/m/day for more severe infections.
Parenteral therapy may be changed to Clindamycin () palmitate hydrochloride for oral solution or Clindamycin () hydrochloride capsules 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.
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 I.V. 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.
Room temperature: 6, 9, and 12 mg/mL (equivalent to Clindamycin () base) in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bottles or minibags, demonstrated physical and chemical stability for at least 16 days at 25°C. Also, 18 mg/mL (equivalent to Clindamycin () base) in 5% Dextrose Injection, in minibags, 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 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in glass bottles or minibags, 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 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer’s Injection in minibags demonstrated physical and chemical stability for at least eight weeks at -10°C.
Frozen solutions should be thawed at room temperature and not refrozen.
Clindamycin () How Supplied
Clindamycin () Injection, USP (150 mg/mL) is supplied as follows:
Clindamycin () Animal Toxicology
One year oral toxicity studies in Spartan Sprague− Dawley rats and beagle dogs at dose levels up to 300 mg/kg/day (approximately 1.1 and 3.6 times the highest recommended adult human dose based on mg/m, respectively) have shown Clindamycin () to be well tolerated. No appreciable difference in pathological findings has been observed between groups of animals treated with Clindamycin () and comparable control groups. Rats receiving Clindamycin () hydrochloride at 600 mg/kg/day (approximately 2.1 times the highest recommended adult human dose based on mg/m) for 6 months tolerated the drug well; however, dogs dosed at this level (approximately 7.2 times the highest recommended adult human dose based on mg/m) vomited, would not eat, and lost weight.
Revised: March, 2008
