clindamycin hydrochloridecapsules, USP

CLINDAMYCIN HYDROCHLORIDE - clindamycin hydrochloride capsule 
Greenstone LLC

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clindamycin hydrochloride
capsules, USP

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin HCl and other antibacterial drugs, clindamycin HCl should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

WARNING

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin HCl 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.

Because clindamycin HCl therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the INDICATIONS AND USAGE section. It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections. 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.

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

DESCRIPTION

Clindamycin hydrochloride is the hydrated hydrochloride salt 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.

Clindamycin hydrochloride capsules, USP contain clindamycin hydrochloride equivalent to 150 mg or 300 mg of clindamycin.

Inactive ingredients: 150 mg– corn starch, FD&C blue no.1, FD&C yellow no. 5, gelatin, lactose, magnesium stearate, talc and titanium dioxide; 300 mg– corn starch, FD&C blue no. 1, gelatin, lactose, magnesium stearate, talc and titanium dioxide.

The structural formula is represented below:

Chemical Structure

The chemical name for clindamycin hydrochloride is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside monohydrochloride.

CLINICAL PHARMACOLOGY

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 nonpenicillinase 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 nonsporeforming 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, eg, 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.

Human Pharmacology

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 mcg/mL was reached in 45 minutes; serum levels averaged 1.51 mcg/mL at 3 hours and 0.70 mcg/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 h) in the elderly compared to 3.2 hours (range 2.1–4.2 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 function1.

INDICATIONS AND USAGE

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, as described in the WARNING box, before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (eg, erythromycin).

Anaerobes: Serious respiratory tract infections such as empyema, anaerobic pneumonitis and lung abscess; serious skin and soft tissue infections; septicemia; intra-abdominal 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, nongonococcal tubo-ovarian abscess, pelvic cellulitis and postsurgical 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.

In Vitro Susceptibility Testing

A standardized disk testing procedure1 is recommended for determining susceptibility of aerobic bacteria to clindamycin. A description is contained in the CLEOCIN® Susceptibility Disk insert. Using this method, the laboratory can designate isolates as resistant, intermediate, or susceptible. Tube or agar dilution methods may be used for both anaerobic and aerobic bacteria. When the directions in the CLEOCIN® Susceptibility Powder insert are followed, an MIC of 1.6 mcg/mL may be considered susceptible; MICs of 1.6 to 4.8 mcg/mL may be considered intermediate and MICs greater than 4.8 mcg/mL may be considered resistant.

CLEOCIN Susceptibility Disks 2 mcg. See package insert for use.

CLEOCIN Susceptibility Powder 20 mg. See package insert for use.

For anaerobic bacteria the minimal inhibitory concentration (MIC) of clindamycin can be determined by agar dilution and broth dilution (including microdilution) techniques. If MICs 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.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Clindamycin HCl and other antibacterial drugs, Clindamycin HCl 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.


1
Bauer AW, Kirby WMM, Sherris JC, et al: Antibiotic susceptibility testing by a standardized single disc method. Am J Clin Pathol 45:493–496, 1966. Standardized disc susceptibility test. Federal Register 37:20527–29, 1972.

CONTRAINDICATIONS

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

WARNINGS

See WARNING box.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin HCl, 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.

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

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

Usage in Meningitis

Since clindamycin does not diffuse adequately into the cerebrospinal fluid, the drug should not be used in the treatment of meningitis.

PRECAUTIONS

General

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 hydrochloride should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Clindamycin hydrochloride should be prescribed with caution in atopic individuals.

Indicated surgical procedures should be performed in conjunction with antibiotic therapy.

The use of clindamycin hydrochloride occasionally results in overgrowth of nonsusceptible organisms — particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation.

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.

The 150 mg capsules contain FD&C yellow no. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C yellow no. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

Prescribing clindamycin HCl 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.

Information for Patients

Patients should be counseled that antibacterial drugs including clindamycin HCl should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When clindamycin HCl 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 HCl 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.

Laboratory Tests

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

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.

Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.

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 1.6 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.

Pregnancy

Teratogenic effects

Pregnancy category B

Reproduction studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (3.2 and 1.6 times the highest recommended adult human dose based on mg/m2, respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (1.3 and 0.7 times the highest recommended adult human dose based on mg/m2, 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.

Nursing Mothers

Clindamycin has been reported to appear in breast milk in the range of 0.7 to 3.8 mcg/mL.

Pediatric Use

When clindamycin hydrochloride is administered to the pediatric population (birth to 16 years), appropriate monitoring of organ system functions is desirable.

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) 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.

ADVERSE REACTIONS

The following reactions have been reported with the use of clindamycin.

Gastrointestinal

Abdominal pain, pseudomembranous colitis, esophagitis, nausea, vomiting and diarrhea (see WARNING box). The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS).

Hypersensitivity Reactions

Generalized mild to moderate morbilliform-like (maculopapular) skin rashes are the most frequently reported adverse reactions. Vesiculobullous rashes, as well as urticaria, have been observed during drug therapy. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, and a few cases of anaphylactoid reactions have also been reported.

Skin and Mucous Membranes

Pruritus, vaginitis, and rare instances of exfoliative dermatitis have been reported. (See Hypersensitivity Reactions.)

Liver

Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.

Renal

Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.

Hematopoietic

Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing.

Musculoskeletal

Rare instances of polyarthritis have been reported.

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.

DOSAGE AND ADMINISTRATION

If significant diarrhea occurs during therapy, this antibiotic should be discontinued (see WARNING box).

Adults

Serious infections— 150 to 300 mg every 6 hours. More severe infections— 300 to 450 mg every 6 hours.

Pediatric Patients

Serious infections— 8 to 16 mg/kg/day (4 to 8 mg/lb/day) divided into three or four equal doses. More severe infections— 16 to 20 mg/kg/day (8 to 10 mg/lb/day) divided into three or four equal doses.

To avoid the possibility of esophageal irritation, clindamycin hydrochloride capsules, USP should be taken with a full glass of water.

Serious infections due to anaerobic bacteria are usually treated with CLEOCIN PHOSPHATE® Sterile Solution. However, in clinically appropriate circumstances, the physician may elect to initiate treatment or continue treatment with clindamycin hydrochloride capsules, USP.

In cases of β-hemolytic streptococcal infections, treatment should continue for at least 10 days.

HOW SUPPLIED

clindamycin hydrochloride capsules, USP are available in the following strengths, colors and sizes:

150 mg Light Blue and Green

    Bottles of 100          NDC 59762-3328-1

300 mg Light Blue

    Bottles of 16            NDC 59762-5010-1
    Bottles of 100          NDC 59762-5010-2

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

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 1.6 and 5.4 times the highest recommended adult human dose based on mg/m2, 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 3.2 times the highest recommended adult human dose based on mg/m2) for 6 months tolerated the drug well; however, dogs dosed at this level (approximately 10.8 times the highest recommended adult human dose based on mg/m2) vomited, would not eat, and lost weight.

REFERENCES

  1. Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.

Rx only

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Manufactured by Patheon Inc.
Toronto, Ontario M3B 1Y5
Canada

LAB-0051-6.0
June 2008


CLINDAMYCIN HYDROCHLORIDE 
clindamycin hydrochloride   capsule
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)59762-3328
Route of AdministrationORALDEA Schedule    
INGREDIENTS
Name (Active Moiety)TypeStrength
clindamycin hydrochloride (clindamycin) Active150 MILLIGRAM  In 1 CAPSULE
corn starchInactive 
FD&C blue no. 1Inactive 
FD&C yellow no. 5Inactive 
gelatinInactive 
lactoseInactive 
magnesium stearateInactive 
talcInactive 
titanium dioxideInactive 
Product Characteristics
Colorblue (light blue) , greenScore no score
ShapeCAPSULESize19mm
FlavorImprint Code G150;mg;3328
Contains    
CoatingfalseSymbolfalse
Packaging
#NDCPackage DescriptionMultilevel Packaging
159762-3328-1100 CAPSULE In 1 BOTTLENone

CLINDAMYCIN HYDROCHLORIDE 
clindamycin hydrochloride   capsule
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)59762-5010
Route of AdministrationORALDEA Schedule    
INGREDIENTS
Name (Active Moiety)TypeStrength
clindamycin hydrochloride (clindamycin) Active300 MILLIGRAM  In 1 CAPSULE
corn starchInactive 
FD&C blue no. 1Inactive 
gelatinInactive 
lactoseInactive 
magnesium stearateInactive 
talcInactive 
titanium dioxideInactive 
Product Characteristics
Colorblue (light blue) Score no score
ShapeCAPSULESize22mm
FlavorImprint Code G300;mg;5010
Contains    
CoatingfalseSymbolfalse
Packaging
#NDCPackage DescriptionMultilevel Packaging
159762-5010-116 CAPSULE In 1 BOTTLENone
259762-5010-2100 CAPSULE In 1 BOTTLENone

Revised: 07/2008Greenstone LLC