Clindamycin Hydrochloride

CLINDAMYCIN HYDROCHLORIDE- clindamycin hydrochloride capsule
Lannett Company, Inc.

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clindamycin hydrochloride 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 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 75 mg, 150 mg, or 300 mg of clindamycin.

Inactive ingredients: 75 mg — lactose monohydrate, corn starch, magnesium stearate, talc, D&C Yellow No. 10, FD&C Green No. 3, and gelatin; 150 mg — lactose monohydrate, corn starch, magnesium stearate, talc, D&C Yellow No. 10, FD&C Green No. 3, D&C Red No. 33, FD&C Blue No. 1, titanium dioxide, and gelatin; 300 mg — lactose monohydrate, corn starch, magnesium stearate, talc, D&C Red No. 33, FD&C Blue No. 1, FD&C Green No. 3, titanium dioxide, and gelatin.

The capsule imprinting ink contains: shellac glaze in ethanol, titanium dioxide, isopropyl alcohol, ammonium hydroxide, n-butyl alcohol, propylene glycol, and simethicone.

The structural formula is represented below:

clindamycin-hcl-molecular-structure
(click image for full-size original)

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 -╬▒-D-galacto -octopyranoside monohydrochloride.

CLINICAL PHARMACOLOGY

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 HCl 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 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-┬şdesmethylclindamycin.

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 Impairment
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.

Elderly Patients
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, the average 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.

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 vitro and in clinical infections (see INDICATIONS AND USAGE):

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 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 (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
Propionibacterium 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.

Page 1 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.