Clindamycin hydrochloride is the hydrated hydrochloride salt of clindamycin. Each capsule contains clindamycin hydrochloride equivalent to 300 mg of clindamycin.
Clindamycin is a semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin.
Excipients/Inactive Ingredients: 300 mg capsule: Maize starch, talc, magnesium stearate, lactose monohydrate.
Pharmacology: Pharmacokinetics: Serum level studies with a 150 mg oral dose of clindamycin hydrochloride in 24 normal adult volunteers showed that clindamycin was rapidly absorbed after oral administration. An average peak serum level of 2.50 μg/mL was reached in 45 minutes; serum levels averaged 1.51 μg/mL at 3 hours and 0.70 μg/mL at 6 hours. Absorption of an oral dose is virtually complete (90%), and the concomitant administration of food does not appreciably modify the serum concentrations; serum levels have been uniform and predictable from person to person and dose to dose. Serum level studies following multiple doses of clindamycin hydrochloride for up to 14 days show no evidence of accumulation or altered metabolism of drug. Serum half-life of clindamycin is increased slightly in patients with markedly reduced renal function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Concentrations of clindamycin in the serum increased linearly with increased dose. Serum levels exceed the MIC (minimum inhibitory concentration) for most indicated organisms for at least six hours following administration of the usually recommended doses. Clindamycin is widely distributed in body fluids and tissues (including bones). The average biological half-life is 2.4 hours. Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the feces; the remainder is excreted as bioinactive metabolites. Doses of up to 2 grams of clindamycin per day for 14 days have been well tolerated by healthy volunteers, except that the incidence of gastrointestinal side effects is greater with the higher doses. No significant levels of clindamycin are attained in the cerebrospinal fluid, even in the presence of inflamed meninges. Pharmacokinetic studies in elderly volunteers (61-79 years) and younger adults (18-39 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 IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, elimination half-life is increased to approximately 4.0 hours (range 3.4-5.1 hours) in the elderly compared to 3.2 hours (range 2.1-4.2 hours) 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.
Toxicology: Preclinical Safety Data: Carcinogenesis: Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.
Mutagenesis: Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Impairment of Fertility: 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.
In oral embryo fetal development studies in rats and subcutaneous embryo fetal development studies in rats and rabbits, no developmental toxicity was observed except at doses that produced maternal toxicity.
Microbiology: Clindamycin has been shown to have in vitro activity against isolates of the following organisms: Aerobic gram-positive cocci, including: Staphylococcus aureus; Staphylococcus epidermidis (penicillinase and non-penicillinase producing strains); When tested by in vitro methods some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin; Streptococci (except Streptococcus faecalis); Pneumococci.
Anaerobic gram-negative bacilli, including: Bacteroides species (including Bacteroides fragilis group and Bacteroides melaninogenicus group); Fusobacterium species.
Anaerobic gram-positive non-sporeforming bacilli, including: Propionibacterium; Eubacterium; Actinomyces species.
Anaerobic and microaerophilic gram-positive cocci, including: Peptococcus species; Peptostreptococcus species; Microaerophilic streptococci
Clostridia: Clostridia are more resistant than most anaerobes to clindamycin. Most Clostridium perfringens are susceptible, but other species, e.g., Clostridium sporogenes and Clostridium tertium are frequently resistant to clindamycin.
Susceptibility testing should be done.
Cross resistance has been demonstrated between clindamycin and lincomycin. Antagonism has been demonstrated between clindamycin and erythromycin.
Clindamycin is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.
Clindamycin 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 colitis, before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).
Anaerobes: Serious respiratory tract infections such as empyema, anaerobic pneumonitis infections such as peritonitis and intra-abdominal abscess (typically resulting from anaerobic organisms resident in the normal gastrointestinal tract); infections of the female pelvis and genital tract such as endometritis, non-gonococcal tubo-ovarian abscess, pelvic cellulitis and post-surgical vaginal cuff infection.
Streptococci: Serious respiratory tract infections; serious skin and soft tissue infections.
Staphylococci: Serious respiratory tract infections; serious skin and soft tissue infections.
Pneumococci: Serious respiratory tract infections.
Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin.
Dosage in Adults: Clindamycin hydrochloride capsules (oral administration): 600-1800 mg/day divided in 2, 3 or 4 equal doses. To avoid the possibility of esophageal irritation, clindamycin HCl capsules should be taken with a full glass of water.
Dosage in Children (over 1 month of age): Clindamycin hydrochloride capsules (oral administration): To avoid the possibility of esophageal irritation, clindamycin HCl capsules should be taken with a full glass of water.
Serious infection: Doses of 8-16 mg/kg/day in 3 or 4 equal doses.
More severe infections: 16-20 mg/kg/day in 3 or 4 equal doses.
Dosage in Elderly: 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. Therefore, dosage adjustments are not necessary in the elderly with normal hepatic function and normal (age-adjusted) renal function (see Pharmacology: Pharmacokinetics under Actions).
Dosage in Renal Impairment: Clindamycin dosage modification is not necessary in patients with renal insufficiency.
Dosage in Hepatic Impairment: Clindamycin dosage modification is not necessary in patients with hepatic insufficiency.
Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
Clindamycin is contraindicated in patients previously found to be sensitive to clindamycin or lincomycin or to any component of the formulation.
Pseudomembraneous colitis has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider the diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis". After the primary diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate-to-severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
Since clindamycin does not diffuse adequately into cerebrospinal fluid, the drug should not be used in the treatment of meningitis.
If therapy is prolonged, liver and kidney function tests should be performed.
The use of clindamycin phosphate may result in overgrowth of non-susceptible organisms, particularly yeasts.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, 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 strains 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 antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Effects on Ability to Drive and Use Machines: The effect of clindamycin on the ability to drive or operate machinery has not been systematically evaluated.
Use in Pregnancy: Oral and subcutaneous reproductive toxicity studies in rats and rabbits revealed no evidence of impaired fertility or harm to the fetus due to clindamycin, except at doses that caused maternal toxicity. Animal reproduction studies are not always predictive of human response.
Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal blood concentrations.
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. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy.
Clindamycin should be used in pregnancy only if clearly needed.
Use in Nursing Mothers: Clindamycin has been reported to appear in human breast milk in ranges from 0.7 to 3.8 μg/mL. Because of the potential for serious adverse reactions in nursing infants, clindamycin should not be taken by nursing mothers.
All undesirable effects listed in the label are presented by MedDRA SOC. Within each frequency category, the undesirable effects are presented in the order of frequency* and then of clinical importance. (See table.)
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Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.
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.
Instructions for Use/Handling: Not applicable.
Incompatibilities: Not applicable.
J01FF01 - clindamycin ; Belongs to the class of lincosamides. Used in the systemic treatment of infections.
Cap 300 mg (white hard gelatin capsule filled with white powder marked "Clin 300" and "Pfizer") x 100's.