The pharmacokinetic data points to low risk for porphyric attacks. There is one clinical report of safe use. There also exist one report of a possible acute attack, but the causal relationship between drug use and attack is too weak to use the report in the safety assessment of spiramycin.

Lactone ring with a ketone group and a sugar moiety.

Macrolide antibiotic used in the treatment of susceptible bacterial infections and some protozoal infections. Gastrointestinal disturbances are the most frequent adverse effects, and can be confused with porphyric symptoms.

Spiramycin is metabolised in the liver to active metabolites. About 10% is excreted in the urine. Spiramycin is reported to have little or no effect on hepatic cytochrome P450 isoenzymes. Zhou et al 2007 classify spiramycin as a substrate for CYP 3A4, but with only a minor/weak inhibitory effect on CYP3A4. In vitro spiramycin has been shown to be a weaker inhibitor of CYP 3A4 than the other macrolides including azithromycin (Ketter 1991). In human liver microsomes, spiramycin was found not to interfere with the hepatic metabolism of ciclosporine, a sepcific substrate for cytochrome P450 3A (Pichard L 1990). Spiramycin is reported not to inhibit CYP 3A4 in a review of macrolides and CYP 3A4 (Von Rosensteil 1995). No information was found about CYP2C9 and spiramycin, but there are no known drug interactions that involve spiramycin and 2C9, and spiramycin is generally considered not to inactivate cytochrome P450 and to be unable to modify the pharmacokinetics of other compounds (in common with some other macrolides ie. rokitamycin, dirithromycin and azithromycin) (Periti 1992).

One report of a possible beginning of an acute porphyric attack in a female with AIP, but the attack is poorly documented and there were several other factors that could have induced the attack. For this reason, we have not given this report any weight in the judgement of spiramycin’s porphyrinogenicity. There is also 2 reports of uneventful use in female AIP-patients, these reports are of good quality and the patients were moderately vulnerable for an attack.