Retapamulin

In human liver microsomes, retapamulin was shown to be a strong inhibitor of CYP3A4. However, since plasma concentrations of retapamulin during topical application have been low, it is not expected that concurrent systemic administration of CYP3A4 substrates will result in clinically important inhibition of their metabolism by retapamulin.

Co-administration of oral ketoconazole 200mg twice daily increased mean retapamulin AUC and C_max by 81% after topical application of retapamulin 10 mg/g ointment on the abraded skin of healthy adult males. Nevertheless, the highest plasma concentrations recorded were low (<10.5 ng/ml in the absence of ketoconazole and <17 ng/ml in the presence of ketoconazole.

No clinical data on exposed pregnancies are available. Animal studies have shown reproductive toxicity after oral administration and are insufficient with respect to effects on parturition and fetal/postnatal development.

Retapamulin ointment should only be used in pregnancy when topical antibacterial therapy is clearly indicated and the use of retapamulin is considered to be preferable to administration of a systemic antibacterial medicinal product.

It is unknown whether retapamulin is excreted in human breast milk. Minimal systemic exposure is observed in adults, therefore exposure of the breast-feeding infant is likely to be negligible. The excretion of retapamulin in milk has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with retapamulin should be made taking into account the benefit of breast-feeding to the child and the benefit of retapamulin therapy to the woman.

Fertility

There are no data on the effects of retapamulin on human fertility. No treatment-related effects on male or female fertility have been shown in animal studies.

Retapamulin has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

In clinical studies in which 2150 patients with superficial skin infections applied retapamulin, the most commonly reported adverse reaction was application site irritation, which affected approximately 1% of patients.

List of adverse reactions

The following convention has been used for the classification of frequency: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10,000 to <1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Immune system disorders

Not known: Hypersensitivity, including angioedema

Skin and subcutaneous tissue disorders

Uncommon: Contact dermatitis

Medicinal product no longer authorised

General disorders and administration site conditions

Common: Application site reactions: Irritation

Uncommon: Application site reactions: Pain, Pruritus, Erythema

Not known: Application site irritation (including burning sensation)

Paediatric population

Frequency, type and severity of adverse reactions in the paediatric population are the same as in adults.