OPZELURA Cream Ref.[115069] Active ingredients: Ruxolitinib

The cream is not for ophthalmic, oral, or intravaginal use (see section 4.2). In cases of accidental exposure in the eyes or mucous membranes, the cream should be thoroughly wiped off and/or rinsed with water.

Non-melanoma skin cancer

Non-melanoma skin cancers (NMSCs), predominantly basal cell carcinomas, have been reported in patients treated with topical ruxolitinib. Most of these patients had risk factors, such as prior phototherapy or prior NMSC. A causal relationship to topical ruxolitinib has not been established. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

Excipients with known effect

Propylene glycol

This medicinal product contains 150 mg propylene glycol (E1520) in each gram of cream which may cause skin irritation.

Cetyl alcohol and stearyl alcohol

This medicinal product contains cetyl alcohol and stearyl alcohol which may cause local skin reactions (e.g. contact dermatitis).

Parahydroxybenzoates

This medicinal product contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed).

Butylated hydroxytoluene

This medicinal product contains butylated hydroxytoluene (E321) which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

No interaction studies have been performed with topically administered ruxolitinib.

The potential for interactions with ruxolitinib is considered to be low because of the limited systemic exposure following topical administration.

Based on in vitro data, ruxolitinib is predominantly cleared by cytochrome P450 3A4 (CYP3A4) metabolism. Interaction potential was evaluated for oral ruxolitinib in dedicated clinical pharmacology studies that included co-administration of strong or moderate CYP3A4 inhibitors or a strong inducer. The plasma AUC is approximately doubled with co-administration of a potent inhibitor of CYP3A4 while only a modest increase was seen with co-administration of a moderate CYP3A4 inhibitor.

The use of ruxolitinib cream in combination with other topical medicinal products used to treat vitiligo has not been evaluated and co-application on the same skin areas is not recommended.

Other topical medicinal products used to treat other conditions on the same skin areas should be applied with a minimum of 2 hours after the application of ruxolitinib cream. This is also applicable to the use of sunscreen or emollients.

Contraception in women of childbearing potential

Women of childbearing potential have to use effective contraception during treatment and for 4 weeks after discontinuation of treatment.

Pregnancy

There are no or limited amount of data from the use of ruxolitinib in pregnant women. Data on systemic absorption of topical ruxolitinib during pregnancy are lacking. There could also be individual factors (e.g. damaged skin barrier, excessive use) that contribute to an increased systemic exposure. Animal studies have shown that ruxolitinib is embryotoxic and foetotoxic following oral administration. Teratogenicity was not observed in rats or rabbits (see section 5.3). Opzelura is contraindicated during pregnancy (see section 4.3).

Breast-feeding

No data are available regarding the presence of ruxolitinib in human milk, the effects on the breastfed child, or the effects on milk production after topical application of Opzelura. Following oral administration of ruxolitinib to lactating rats, ruxolitinib and/or its metabolites were present in the milk with a concentration 13-fold higher than the maternal plasma concentration. In juvenile rat studies, oral administration of ruxolitinib resulted in effects on growth and bone measures (see section 5.3). Opzelura is contraindicated during breast-feeding (see section 4.3) and treatment must be discontinued approximately 4 weeks before the beginning of breastfeeding.

Fertility

There are no human data on the effect of ruxolitinib on fertility. In animal studies, no effect of oral ruxolitinib on fertility was observed.

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

Summary of the safety profile

Safety was primarily evaluated in the pivotal studies, for up to one year. In the long-term extension study (see section 5.1), safety up to 2 years was consistent with the profile reported in the pivotal studies. The most common adverse reaction is application site acne (5.8%).

Tabulated list of adverse reactions

Adverse reactions are ranked under headings of frequency, with the most frequent first, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Table 1. Adverse reactions:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.