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

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, USP equivalent to 150 mg or 300 mg of clindamycin.

Inactive ingredients: 150 mg- black iron oxide, corn starch, D&C Yellow #10, FD&C Blue no. 1, gelatin, lactose monohydrate, magnesium stearate, potassium hydroxide, propylene glycol, shellac, talc, and titanium dioxide; 300 mg- black iron oxide, corn starch, FD&C Blue no. 1, gelatin, lactose monohydrate, magnesium stearate, potassium hydroxide, propylene glycol, shellac, talc, and titanium dioxide.

The structural formula is represented below:

1. C 18H 33ClN 2O 5S•HCl M.W. 461.45

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.

Human Pharmacology

Absorption

Pharmacokinetic 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 concentration of 2.50 mcg/mL was reached in 45 minutes; serum concentrations 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 concentrations have been uniform and predictable from person to person and dose to dose. Pharmacokinetic studies following multiple doses of clindamycin hydrochloride for up to 14 days show no evidence of accumulation or altered metabolism of drug. 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.

Distribution

Concentrations of clindamycin in the serum increased linearly with increased dose. Serum concentrations 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). No significant concentrations of clindamycin are attained in the cerebrospinal fluid, even in the presence of inflamed meninges.

Metabolism

In vitrostudies 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

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.

Specific Populations

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 do not need to be modified in patients with renal disease.

Geriatric Patients

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 IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, the average 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 age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function 1.

Obese Pediatric Patients Aged 2 to Less than 18 Years and Obese Adults Aged 18 to 20 Years

An analysis of pharmacokinetic data in obese pediatric patients aged 2 to less than 18 years and obese adults aged 18 to 20 years demonstrated that clindamycin clearance and volume of distribution, normalized by total body weight, are comparable regardless of obesity.

Microbiology

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 vitroand in clinical infections [see Indications and Usage (1)]:

Gram-positive bacteria

• Staphylococcus aureus(methicillin-susceptible strains)
• Streptococcus pneumoniae(penicillin-susceptible strains)
• Streptococcus pyogenes
• Anaerobic bacteria
• Clostridium perfringens
• Fusobacterium necrophorum
• Fusobacterium nucleatum
• Peptostreptococcus anaerobius
• Prevotella melaninogenica

The following in vitrodata are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitrominimum 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(methicillin-susceptible strains)
• Streptococcus agalactiae
• Streptococcus anginosus
• Streptococcus mitis
• Streptococcus oralis
• Anaerobic bacteria
• Actinomyces israelii
• Clostridium clostridioforme
• Eggerthella lenta
• Finegoldia (Peptostreptococcus) magna
• Micromonas (Peptostreptococcus) micros
• Prevotella bivia
• Prevotella intermedia
• Cutibacterium acnes

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.

Clindamycin hydrochloride capsules, USP are indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.

Clindamycin hydrochloride capsules, USP 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 colitis, as described in the BOXED WARNING, 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, 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.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin hydrochloride capsules, USP and other antibacterial drugs, clindamycin hydrochloride capsules, USP 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 hydrochloride capsules are contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin.

See BOXED WARNING

Clostridioides difficile-Associated Diarrhea

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin hydrochloride, 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. difficileproduces toxins A and B, which contribute to the development of CDAD. Hypertoxin producing strains of C. difficilecause 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. difficilemay 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.

Anaphylactic and Severe Hypersensitivity Reactions

Anaphylactic shock and anaphylactic reactions have been reported (see 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 (see 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.

Nephrotoxicity

Clindamycin is potentially nephrotoxic and cases with acute kidney injury have been reported. Consider monitoring of renal function particularly in patients with pre-existing renal dysfunction or those taking concomitant nephrotoxic drugs. In case of acute kidney injury, discontinue clindamycin hydrochloride when no other etiology is identified.

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

Infections and Infestations: Clostridioides difficile colitis

Gastrointestinal: Abdominal pain, pseudomembranous colitis, nausea, vomiting, and diarrhea (See BOXEDWARNING). The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (See WARNINGS). Esophagitis and esophageal ulcer have been reported, particularly when taken in a lying position or with a small amount of water. An unpleasant or metallic taste has been reported after oral administration.

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. Severe skin reactions such as Toxic Epidermal Necrolysis, some with fatal outcome, have been reported (See WARNINGS). Cases of Acute Generalized Exanthematous Pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, anaphylactic shock, anaphylactic reaction and hypersensitivity have also been reported.

Skin and Mucous Membranes: Pruritus, vaginitis, angioedema 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: Acute kidney injury (See WARNINGS).

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.

Immune System: Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported.

Musculoskeletal: Cases of polyarthritis have been reported.

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.

If significant diarrhea occurs during therapy, this antibacterial drug should be discontinued (See BOXED WARNING).

Administer clindamycin hydrochloride capsules with a full glass of water (6 to 8 ounces, approximately 200 to 250 mL) and at least 30 minutes before lying down to reduce the potential for esophageal irritation (See ADVERSE REACTIONS).

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

Pediatric Patients (who are able to swallow capsules): 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. Clindamycin should be dosed based on total body weight regardless of obesity.

Clindamycin hydrochloride capsules are not suitable for pediatric patients who are unable to swallow them whole. The capsules do not provide exact mg/kg doses therefore it may be necessary to use the clindamycin palmitate oral solution in some cases.

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

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

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

Clindamycin hydrochloride capsules, USP, 150 mgare size ‘1’ capsules with turquoise blue opaque cap and light green body imprinted with “RX692”on cap and body in black ink containing white to off white powder. They are supplied as follows:

1. NDC 63304-692-03 Bottles of 10
2. NDC 63304-692-01 Bottles of 100
3. NDC 63304-692-05 Bottles of 500
4. NDC 63304-692-77 Carton of 100 (10 X 10 Unit-Dose blister)

Clindamycin hydrochloride capsules, USP, 300 mgare size ‘0’ capsules with turquoise blue opaque cap and turquoise blue opaque body imprinted with “RX693”on cap and body in black ink containing white to off white powder. They are supplied as follows:

1. NDC 63304-693-03 Bottles of 10
2. NDC 63304-693-16 Bottles of 16
3. NDC 63304-693-01 Bottles of 100
4. NDC 63304-693-62 Carton of 60 (3 X 20 Unit-Dose blister)
5. NDC 63304-693-77 Carton of 100 (10 X 10 Unit-Dose blister)
6. NDC 63304-693-05 Bottles of 500

Store at 20° - 25° C (68° - 77° F) [See USP Controlled Room Temperature].

To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1-800-FDA-1088or www.fda.gov/medwatch.

1. Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.
2. Manufactured by:
3. Ohm Laboratories Inc.
4. New Brunswick, NJ 08901
5. Distributed by:
6. Sun Pharmaceutical Industries, Inc.
7. Cranbury, NJ 08512
8. August 2024 FDA-15

For 150 mg Strength

NDC 63304-692-01

CLINDAMYCIN HYDROCHLORIDE CAPSULES, USP

150 mg *

Rx only 100 Capsules

Ohm ®

For 300 mg Strength

NDC 63304-693-01

CLINDAMYCIN HYDROCHLORIDE CAPSULES, USP

300 mg*

Rx only 100 Capsules

Ohm ®

NDC 63304-693-01

CLINDAMYCIN HYDROCHLORIDE CAPSULES, USP

300 mg*

Rx only 60 Unit-Dose Capsules (3X20 Unit-Dose Blister Cards)

SUN PHARMA

Clindamycin Hydrochloride Capsules, USP

63304-693-11

1. 300 mg Rx only