common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are abdominal pain, nausea, vomiting and diarrhoea.

Clindamycin is suspected to have triggered an acute porphyric attack in a woman with AIP. Case reports on drug-drug interactions indicate that clindamycin can induce CYP3A4 in vivo and in vitro studies of human PXR activation showed that clindamycin exhibits a clear propensity to induce CYP3A4.

Clindamycin is a lincosamide antibiotic

Clindamycin is an antibiotic indicated for the treatment of severe infections.

Clindamycin is metabolized by CYP3A4 and CYP3A5 (del Carmen Carrasco-Portugal 2008) to the active N-demethyl metabolite and other inactive metabolites (SPC). The half-life elimination is 2-3 hours. In vitro data indicates that clindamycin has a moderate inhibitory effect on CYP3A4, but not on other CYP enzymes (CYP1A2, CYP2C9, CYP2C19) (Wynalda 2003). In vitro studies of human PXR activation showed that clindamycin exhibits a clear propensity to induce CYP3A4 (Yasuda 2008). Although clindamycin elicited substantial increases in PXR activation, CYP3A4mRNA, and CYP3A4 protein, it failed to produce a significant increase in the CYP3A4 activity, which could reflect its modest ability to inhibit CYP3A4 (Yasuda 2008). Clindamycin is listed as a clinically significant inducer of CYP3A4 (Anaizi 2001). A case study showed that when clindamycin was co-administrated with tacrolimus, a CYP3A4 substrate, clindamycin decreased its blood trough level (Jouret 2010). Two other case studies also showed the same tendency when cyclosporine, also a CYP3A4 substrate, was co-administrated with clindamycin. The daily doses of cyclosporine had to be increased to maintain the desired serum concentrations of cyclosporine (Thurnheer 1999) and other authors report drug-drug interactions between cyclosporine and clindamycin in ICU (Askari 2013). All the cases can be explained by induction of CYP3A4 by clindamycin. In regard to the substantial increases in PXR activation and CYP3A4 induction found in vitro (Yasuda 2008), a relatively low number of drug-drug interactions have been described. A possible explanation is the dual effect of clindamycin, being both an inducer and moderate inhibitor of CYP3A4 (Yasuda 2008, Wynalda 2003), which may result in only moderate or no net effect in CYP3A4 activity. For an evaluation of the porphyrinogenicity of clindamycin, it is important to realize that the inhibitory effect of clindamycin can mask the inductive power of this drug and that an increased de novo synthesis of CYP3A4 can take place irrespective of negative results from in vivo DDI-studies. Regarding evaluation of induction of CYP3A4 by clindamycin, in vitro studies should therefore be taken more into account than in vivo studies.

Uneventful use is described in a patient with HCP (Moore 2000).

There is one report of an acute porphyric attack in a Norwegian woman with AIP after having been treated with iv clindamycin for three days. The woman was admitted to the ICU with symptoms including severe abdominal pain, nausea, vomiting, constipation, urinary retention, muscle weakness, hypertension, tachycardia, hyponatremia and hypomagnesemia. After withdrawal of clindamycin and treatment with iv glucose the symptoms subsided. The attack report was assessed according to the WHO-UMC causality assessment system, and the causality was found to be probable. Uneventful use reported in 3 patients with acute porphyria.