Clindamycin

Key points

• The boxed warning reserves clindamycin for serious infections where less toxic antimicrobial agents are inappropriate, and states it should not be used in patients with nonbacterial infections such as most upper respiratory tract infections.
• Clostridioides difficile-associated diarrhoea has been reported to occur over two months after antibacterial treatment, which is why the label calls for a careful medical history rather than only asking about current medicines.
• Clindamycin is metabolised predominantly by cytochrome P450 3A4, with a minor contribution from CYP3A5, to clindamycin sulfoxide and the minor metabolite N-desmethylclindamycin.
• Its average elimination half-life is longer in older people: approximately 4.0 hours after an oral dose, against 3.2 hours in younger adults.

How it works

The UK summary of product characteristics states that lincosamides such as clindamycin bind to the 50S subunit of the bacterial ribosome and inhibit protein synthesis. Its action is predominantly bacteriostatic, although the same document notes that high concentrations may be slowly bactericidal against sensitive strains. Clindamycin phosphate is inactive in the test tube, and rapid hydrolysis in the body converts it to the antibacterially active form.

Safety specific to clindamycin

The boxed warning on the oral label has four parts.

It opens by stating that Clostridioides difficile-associated diarrhoea has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which lets C. difficile overgrow.

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

The third part explains why the risk outlasts the course. C. difficile produces toxins A and B, and hypertoxin-producing strains cause increased morbidity and mortality because those infections can resist antimicrobial therapy and may require colectomy. The warning states that C. difficile-associated diarrhoea must be considered in all patients who present with diarrhoea following antibacterial drug use, and that a careful medical history is necessary since it has been reported to occur over two months after the antibacterial was given. Two months, not two weeks, is the window the label sets.

The fourth part sets out the response. If C. difficile-associated diarrhoea is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued, and appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile and surgical evaluation should be instituted as clinically indicated.

Outside the box, the summary of product characteristics warns of severe hypersensitivity reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome and toxic epidermal necrolysis. The oral label separately records that vesiculobullous rashes and urticaria have been observed during therapy, and that jaundice and abnormalities in liver function tests have been seen.

When to seek urgent care

Diarrhoea that develops during a course of clindamycin, or at any point in the two months after one finishes, needs medical assessment rather than an anti-diarrhoeal bought over the counter, particularly when it is severe, persistent, or contains blood or mucus. A spreading rash with blistering or peeling, or yellowing of the skin or eyes, also warrants prompt attention.

Further reading

• CLINDAMYCIN HYDROCHLORIDE capsule
• Clindamycin 75 mg Capsules