Clindaver

Approved Indications (Systemic Use):

• Skin and Skin Structure Infections:
• Cellulitis, abscesses, and infected wounds caused by susceptible Staphylococcus aureus (including some MRSA), Streptococcus spp.
• Respiratory Tract Infections:
• Pneumonia, empyema, lung abscess, pharyngitis, and sinusitis caused by anaerobes or Gram-positive cocci.
• Bone and Joint Infections:
• Osteomyelitis and septic arthritis.
• Gynecologic Infections:
• Pelvic inflammatory disease (PID), endometritis, vaginal cuff infection, bacterial vaginosis (topical and oral).
• Intra-abdominal Infections:
• Peritonitis and intra-abdominal abscesses (usually in combination with aminoglycosides).
• Septicemia and Bacteremia caused by susceptible Gram-positive cocci.
• Dental Infections:
• Acute oral infections, periodontal abscesses.
• Surgical Prophylaxis:
• For patients allergic to beta-lactams.

Topical Indications:

• Acne Vulgaris:
• Inflammatory and non-inflammatory acne lesions (topical 1% solution or gel).
• Bacterial Vaginosis:
• Intravaginal clindamycin cream or ovules.

Clinically Accepted Off-Label Uses:

• Toxoplasmosis (in combination with pyrimethamine) for sulfonamide-intolerant patients.
• Malaria (with quinine):
• For chloroquine-resistant Plasmodium falciparum.
• Pneumocystis jirovecii Pneumonia (PCP):
• In combination with primaquine.
• Necrotizing Fasciitis:
• As adjunct to beta-lactams to inhibit toxin production.
• Prophylaxis of Endocarditis in penicillin-allergic patients undergoing dental procedures.

Adults:

• Oral (systemic infections):
  150–450 mg every 6 hours.
• IV/IM:
  600–900 mg every 8 hours (max 4.8 g/day in divided doses).
• Topical (acne):
  Apply thin layer of 1% clindamycin gel or lotion to affected areas twice daily.
• Vaginal cream (bacterial vaginosis):
  One applicator (5 g of 2% cream) intravaginally at bedtime for 3–7 days.
• Vaginal ovules:
  One 100 mg ovule intravaginally once daily for 3 days.

Pediatrics:

• Oral (systemic):
  8–20 mg/kg/day in 3–4 divided doses.
• IV/IM:
  20–40 mg/kg/day in 3–4 divided doses.

Neonates:

• 15–20 mg/kg/day IV in divided doses every 8–12 hours.

Elderly:

• No specific adjustment, but monitor organ function and adverse effects.

Renal Impairment:

• No adjustment usually required.
  Monitor with prolonged therapy or severe renal failure.

Hepatic Impairment:

• Use with caution in moderate to severe hepatic dysfunction.
  Adjust dose based on clinical response and liver enzyme levels.

Administration Notes:

• Take oral formulations with a full glass of water to avoid esophageal irritation.
• IV clindamycin must be diluted and administered slowly to avoid thrombophlebitis.
• Do not refrigerate reconstituted IV solution; use within 24 hours.

Clindamycin is a lincosamide antibiotic that binds to the 50S subunit of the bacterial ribosome, thereby inhibiting the translocation step in protein synthesis. This results in inhibition of bacterial growth (bacteriostatic effect), although it may be bactericidal at high concentrations or against particularly susceptible organisms. It is effective against Gram-positive cocci (including MRSA), anaerobic bacteria, and certain protozoa. Clindamycin also inhibits the synthesis of bacterial toxins, making it a useful adjunct in toxin-mediated infections such as necrotizing fasciitis.

• Absorption:
  Oral bioavailability ~90%. Rapid and almost complete after oral administration.
• Distribution:
  Widely distributed in body fluids and tissues including bone, but not cerebrospinal fluid (CSF), even with meningeal inflammation.
• Protein Binding:
  ~90% bound to plasma proteins.
• Metabolism:
  Extensively metabolized in the liver via oxidation and demethylation.
• Active Metabolites:
  Yes; some retain antimicrobial activity.
• Excretion:
  ~10% unchanged in urine, ~4% in feces. Majority eliminated as metabolites.
• Half-Life:
  ~2.4 hours (may be prolonged in hepatic impairment).
• Onset of Action:
  Oral: ~1 hour
  IV: Immediate

• Pregnancy:
  FDA Category B. Animal studies show no risk. Human studies show no increase in fetal anomalies. Safe when used during the second and third trimesters. Use with caution in the first trimester.
• Lactation:
  Clindamycin is excreted into breast milk in small amounts. May cause diarrhea or GI disturbance in infants.
  Recommendation: Use with caution in breastfeeding. Monitor infant for signs of gastrointestinal distress.

• Primary Class: Lincosamide Antibiotic
• Subclass: Protein synthesis inhibitor (50S ribosomal binder)

• Known hypersensitivity to clindamycin or lincomycin
• History of antibiotic-associated colitis (e.g., pseudomembranous colitis)
• Topical formulations: Avoid in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis

• Black Box Warning (Oral/IV):
  Clostridioides difficile–associated diarrhea (CDAD) can occur and be fatal. Monitor for persistent diarrhea.
• Hepatic Impairment:
  Monitor liver function in long-term or high-dose therapy.
• Renal Dysfunction:
  Prolonged serum half-life in severe impairment; monitor accordingly.
• Dermatologic Reactions:
  Risk of severe skin reactions including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN).
• Blood Dyscrasias:
  Rare but possible leukopenia, neutropenia, or agranulocytosis.
• Topical Use:
  May cause local irritation, burning, or contact dermatitis.

Common (Systemic Use):

• GI: Diarrhea, nausea, vomiting, abdominal pain
• Skin: Rash, urticaria
• General: Metallic taste (oral form)

Common (Topical Use):

• Dryness, burning, peeling, erythema at application site

Serious:

• GI: Clostridioides difficile–associated colitis (can be life-threatening)
• Hematologic: Neutropenia, thrombocytopenia
• Hepatic: Elevated liver enzymes, hepatotoxicity
• Dermatologic: SJS, TEN, erythema multiforme
• Hypersensitivity: Anaphylaxis, angioedema

Timing & Dose Dependence:

• GI symptoms can occur early.
• CDAD may present weeks after discontinuation.
• Serious skin reactions are rare but require immediate discontinuation.

Major Drug–Drug Interactions:

• Neuromuscular Blocking Agents:
  Clindamycin may enhance neuromuscular blockade (avoid in patients on muscle relaxants).
• Erythromycin:
  Antagonistic effect due to competition for ribosomal binding sites.
• Rifampin:
  May decrease clindamycin levels by increasing hepatic metabolism.

Drug–Food Interaction:

• Food delays but does not significantly reduce absorption.

Drug–Alcohol Interaction:

• No direct interaction; alcohol may worsen GI upset.

Enzyme Systems:

• Metabolized via CYP3A4 and CYP3A5.
  Potential interactions with CYP3A4 inducers/inhibitors.

• CDC & IDSA (Infectious Diseases Society of America):
  Clindamycin remains a recommended option for skin/soft tissue infections and dental infections, especially in penicillin-allergic patients.
• Rising Resistance:
  Increasing resistance among Staphylococcus aureus (D-test recommended for inducible clindamycin resistance in MRSA).
• Updated Labeling:
  Reinforced black box warning for CDAD; emphasis on appropriate use and stewardship.
• Topical Use:
  Still preferred as a first-line option in combination acne therapy (e.g., with benzoyl peroxide).

Oral Capsules:

• Store at 20°C to 25°C (68°F to 77°F).
  Protect from moisture.

Oral Solution:

• Store at room temperature.
  Do not refrigerate.
  Use within 14 days after reconstitution.

IV Vials:

• Store dry powder vials at 20°C to 25°C.
  Protect from light.
  Use within 24 hours after dilution.

Topical Gel/Lotion:

• Store at 20°C to 25°C.
  Do not freeze.
  Keep container tightly closed.

Vaginal Cream/Ovules:

• Store at 20°C to 25°C.
  Protect from excessive heat.
  Do not freeze.