CLINDAZED 300

Indications

• Acne vulgaris
• Skin and soft tissue infections
• Respiratory tract infections
• Bone and joint infections
• Serious bacterial infections

Dosage

Adults: The dosage of clindamycin for adults varies depending on the severity and type of infection. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the bacterial ribosome. This action impedes ribosome assembly and the translation process. Clindamycin acts as a structural analog of tRNA, disrupting peptide chain initiation and potentially stimulating the dissociation of peptidyl-tRNA from the ribosome. Its mechanism in treating acne vulgaris is less clear but may involve its activity against Propionibacterium acnes.

Pharmacodynamics

Clindamycin exerts its bacteriostatic effect by inhibiting microbial protein synthesis. It has a relatively short half-life and time to maximum concentration (Tmax), requiring administration every six hours to maintain effective drug levels. A significant risk associated with clindamycin use is the potential development of Clostridium difficile-associated diarrhea (CDAD), which can occur from mild diarrhea to severe colitis. Clindamycin is generally reserved for serious infections when less toxic alternatives are inappropriate.

Pharmacokinetics

Clindamycin is rapidly absorbed after oral administration, with peak plasma concentrations achieved within 1-2 hours. It is widely distributed in body tissues and fluids, including bone, and has a half-life of approximately 2-3 hours. Clindamycin is metabolized by the liver and excreted primarily in urine, with some excretion in bile. The use of clindamycin may lead to the development of resistance, particularly through base modification within the ribosomal RNA.

Contra-indications

• Hypersensitivity to clindamycin or lincomycin
• History of antibiotic-associated colitis, particularly caused by _Clostridium difficile_

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Rash
• Clostridium difficile associated diarrhea (CDAD)
• Severe colitis

Interactions

• May enhance the effect of neuromuscular blocking agents
• Potential for cross-resistance with macrolides and lincomycin

Precautions

• Use with caution in patients with a history of gastrointestinal disease, particularly colitis
• Monitor for signs of CDAD
• Assess renal and hepatic function prior to use

Pregnancy

Clindamycin is classified as category B. Studies in animals have not demonstrated a risk to the fetus, but there are no well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

Clindamycin is excreted in breast milk. Caution is advised when administering to nursing mothers, as the effects on the infant are unknown.

Storage

Store in a cool, dry place below 25°C. Protect from light. Keep out of reach of children.

Formulations

• Capsules: 150 mg, 300 mg
• Oral solution: 75 mg/5 mL
• Topical gel: 1% clindamycin phosphate
• Injectable solution: 300 mg/6 mL

Mechanism of action

Clindamycin inhibits bacterial protein synthesis by binding to 23S RNA of the 50S subunit of the bacterial ribosome. It impedes both the assembly of the ribosome and the translation process. The molecular mechanism through which this occurs is thought to be due to clindamycin's three-dimensional structure, which closely resembles the 3'-ends of L-Pro-Met-tRNA and deacylated-tRNA during the peptide elongation cycle - in acting as a structural analog of these tRNA molecules, clindamycin impairs peptide chain initiation and may stimulate dissociation of peptidyl-tRNA from bacterial ribosomes. The mechanism through which topical clindamycin treats acne vulgaris is unclear, but may be related to its activity against _Propionibacterium acnes_, a bacteria that has been associated with acne. Clindamycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Clindamycin palmitate hydrochloride and clindamycin phosphate are inactive until hydrolyzed to free clindamycin. This hydrolysis occurs rapidly in vivo. Clindamycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of erythromycin, chloramphenicol, and lincomycin. Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. ... Clindamycin is not a substrate for macrolide efflux pumps, and strains that are resistant to macrolides by this mechanism are susceptible to clindamycin.

Pharmacodynamics

Clindamycin exerts its bacteriostatic effect via inhibition of microbial protein synthesis. Clindamycin has a relatively short T_max and half-life necessitating administration every six hours to ensure adequate antibiotic concentrations. _Clostridium difficile_ associated diarrhea (CDAD) has been observed in patients using clindamycin, ranging in severity from mild diarrhea to fatal colitis and occasionally occurring over two months following cessation of antibiotic therapy. Overgrowth of _C. difficile_ resulting from antibiotic use, along with its production of A and B toxins, contributes to morbidity and mortality in these patients. Because of the associated risks, clindamycin should be reserved for serious infections for which the use of less toxic antimicrobial agents are inappropriate. Clindamycin is active against a number of gram-positive aerobic bacteria, as well as both gram-positive and gram-negative anaerobes. Resistance to clindamycin may develop, and is generally the result of base modification within the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete, and may also occur between clindamycin and macrolide antibiotics (e.g. [erythromycin]) due to similarities in their binding sites. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.