Limitations: This safety classification applies only to preparations containing dexamethasone in combination with tobramycin, chloramphenicol or neomycin/polymyxin. The same ATC code (S01CA01) can in some countries be used for different combinations of dexamethasone and other drugs, which in theory may or may not be porphyrinogenic. Please refer to the classification and monograph of each individual substance.

Following ocular administration, dexamethasone, tobramycin, neomycin, polymyxin B, and chloramphenicol have a very low systemic concentration and therefore an insignificant hepatic exposure. With this administration all substances are individually classified as not or probably not porphyrinogenic. The different combinations of these substances are also regarded as probably not porphyrinogenic.

Dexamethasone is a 9-fluoro glucocorticoid. Tobramycin is a broad-spectrum aminoglycoside antibiotic. Chloramphenicol is a broad-spectrum antibiotic Neomycin is an aminoglycoside antibiotic Polymyxin is an anti-bacterial agent (cyclic peptide)

Eye drops containing dexamethasone in combinations with various antibacterial agents are used postoperative and to treat ocular damage.

Plasma concentrations of both dexamethasone and tobramycin are well below 1,0 µM concentrations (SPC) and hepatic exposure is therefore regarded as insignificant. Only a negligible amount of chloramphenicol, neomycin and polymyxin B is absorbed after topical application and the hepatic exposure is therefore also insignificant.

Dexamethasone is a substrate and an inducer of multiple CYP enzymes, and a potent inducer of CYP3A4. For details on the metabolism of dexamethasone, please refer to the monograph of the substance for systemic use (ATC code: H02AB02). Tobramycin is a non-CYP ligand and is eliminated in unchanged form by glomerular filtration (SPC). In vitro studies indicate that chloramphenicol has a potent inhibitory effect on CYP2C19, CYP3A4, and, to a lesser extent, CYP2D6 (Park 2003). However systemic exposure to chloramphenicol occurs at a very low level after topical ophthalmic use (SPC). An insufficient amount of neomycin is absorbed to produce systemic effects and is rapidly excreted by the kidneys in the unchanged form (SPC). Polymyxin B is not absorbed through mucous membranes, or intact or denuded skin, and systemic exposure is insignificant. Polymyxin B is excreted mainly in the unchanged form by glomerular filtration in the kidneys.

Uneventful use reported in 3 patients with acute porphyria.