Opzelura® (ruxolitinib) cream side effects

Opzelura® cream was generally well tolerated in eligible patients with non-segmental vitiligo in clinical trials, with few side effects and low treatment-related discontinuations of <1%.^1,2

The most common side effect was acne at the application site (5.8% across the TRuE-V1 and TRuE-V2 trials).²

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Select adverse events (AEs) in TRuE-V1²

	Double-blind period^†		Extension period^‡
n (%)	Vehicle (N=109)	Opzelura® (N=221)	Vehicle to Opzelura® (N=90)	Opzelura® (N=193)
Most common treatment-related adverse events (TEAE)^§	10 (9.2)	38 (17.2)	5 (5.6)	7 (3.6)
Application site acne	0	12 (5.4)	0	1 (0.5)
Application site pruritus	4 (3.7)	11 (5.0)	1 (1.1)	0
Application site exfoliation	0	0	0	0
Serious adverse event^¶	1 (0.9)	6 (2.7)	1 (1.1)	1 (0.5)
Patients with TEAE leading to discontinuation	1 (0.9)	1 (0.5)	0	0

Adapted from Rosmarin et al. 2022.

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This table is not an exhaustive list of all adverse events experienced.

Treatment-related safety data in TRuE-V2 were similar to TRuE-V1 except the occurrence of application-site exfoliation in both the vehicle and ruxolitinib group in the double-blind period in TRuE-V2.² The safety data from the TRuE-V1 and TRuE-V2 trials, where AEs were mainly mild to moderate in severity in the double blind phase, demonstrate that Opzelura® was generally well tolerated.²

TRuE-V1 and TRuE-V2 Opzelura® side effects data

Across both TRuE-V1 and TRuE-V2 trials, application site acne was observed in 5.8% of patients receiving Opzelura®.¹ Further to this, other AEs in patients taking Opzelura® in TRuE-V1 included COVID-19 (5.7%), nasopharyngitis (1.6%), headache (1.6%) and sinusitis (1.6%).^1,2

Opzelura® (ruxolitinib) cream – no treatment-related serious side effects observed in the trials

No serious AEs that occurred in the TRuE-V1 and TRuE-V2 trials were considered by investigators to be related to Opzelura® according to criteria prespecified in the protocol.²

On the basis of the prevalence of COVID-19 at the time the trials were conducted, the incidence of COVID-19 was not considered to be relevant to Opzelura® application.²

TRuE-V1 and TRuE-V2 serious AEs

In TRuE-V1, serious AEs recorded in participants treated with Opzelura® included anal fistula, appendicitis, concussion, hepatitis due to infectious mononucleosis, hypersensitivity, kidney contusion, myocarditis, prostate cancer and subacute combined cord degeneration (in one patient each); hypersensitivity and subacute combined cord degeneration occurred in the same patient.²

In TRuE-V2, serious AEs in participants treated with Opzelura® included appendiceal abscess, coronary-artery stenosis, joint dislocation, papillary thyroid cancer, rhabdomyolysis and ureterolithiasis (in one patient each).²

Opzelura® safety information

No laboratory monitoring is required with Opzelura® treatment.¹ As Opzelura® is a topical Janus kinase (JAK) inhibitor there is limited systemic exposure of ruxolitinib to the body.¹

No haematopoietic AEs were considered to be related to Opzelura®.²

Ruxolitinib plasma concentrations were similar in TRuE-V1 and TRuE-V2 (mean at Week 4 and Week 24: 55.8 and 58.0 nM, respectively) and were well below the IC₅₀ for thrombopoietin-stimulated STAT3 phosphorylation, a proxy for JAK2-mediated bone marrow changes (281 nM).^1,2

Opzelura® contraindications

Opzelura® is contraindicated during pregnancy due to no, or a limited amount of, data on the use of ruxolitinib in pregnant women.¹

No data is available investigating the presence of ruxolitinib in human milk, the effects on milk production after ruxolitinib administration and the effects on the breastfed child. Opzelura® is therefore contraindicated during breastfeeding and must be discontinued around four weeks prior to the commencement of breastfeeding. For all information on fertility, pregnancy and lactation please refer to the Summary of Product Characteristics.¹

In addition, Opzelura® is contraindicated in patients with hypersensitivity to the active ingredient ruxolitinib or to any of its excipients.¹

Excipients in Opzelura® with known side effects¹

Excipient with known effect	Side effect
Propylene glycol (E1529)	May cause skin irritation
Cetyl/Stearyl alcohol	May cause local skin reactions (e.g. contact dermatitis)
Parahydroxybenzoates (E218)	May cause allergic reactions (possibly delayed)
Butylated hydroxytoluene (E321)	May cause local skin reactions (e.g. contact dermatitis) or irritation to the eyes and mucous membranes

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Opzelura® precautions for use

Opzelura® can be applied on sensitive areas around the eyes, external genitalia and mouth but is not for ophthalmic, oral or intravaginal use. In cases of accidental exposure to the eyes or mucous membranes, the cream should be thoroughly wiped off and/or rinsed with water.¹

No interaction studies have been performed with topically administered ruxolitinib, although the potential for ruxolitinib drug interactions is considered to be low due its limited systemic exposure.¹

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.¹

Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. This is because non-melanoma skin cancers (NMSCs) have been reported in patients treated with topical ruxolitinib, although most of these patients had other risk factors for the disease, including prior phototherapy or prior NMSC. It is important to note that a causal relationship to topical ruxolitinib has not been established.²

Special Populations: Renal Impairment – Opzelura® should not be used by patients with end stage renal disease, due to lack of data regarding the safety.¹

Opzelura® is contraindicated during pregnancy and breastfeeding.

*Patient quotes are fictional.

^†AEs during the double-blind period (up to Week 24) are reported in the safety population (Opzelura® group and vehicle group).

^‡AEs during the open-label treatment extension period (after Week 24) are reported in the treatment-extension evaluable population (Opzelura® group and vehicle-to-Opzelura® group).

^§The relatedness of the AE to Opzelura® was determined by the investigator.

^¶In TRuE-V1, serious AEs with application of Opzelura® were anal fistula, appendicitis, concussion, hepatitis due to infectious mononucleosis, hypersensitivity, kidney contusion, myocarditis, prostate cancer, and subacute combined cord degeneration (in one patient each); hypersensitivity and subacute combined cord degeneration occurred in the same patient.

Abbreviations

AE, adverse event; COVID-19, coronavirus disease 2019; IC₅₀, half maximal inhibitory concentration; JAK, Janus kinase; NMSC, non-melanoma skin cancer; TEAEs, treatment-related adverse events; TRuE-V, topical ruxolitinib evaluation in vitiligo study.

References

Opzelura® (ruxolitinib cream) Summary of Product Characteristics. Incyte Biosciences UK Ltd. November 2023.
Rosmarin D, et al. N Engl J Med. 2022;387(16):1445–1455.
Quintás-Cardama A, et al. Blood. 2010;115(15):3109–3117.

UNITED KINGDOM
Adverse events should be reported. Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Incyte immediately by calling 03301003677 (Great Britain) 00-800-0002-7423 (United Kingdom (Northern Ireland)).

REPUBLIC OF IRELAND
Adverse events should be reported. Reporting forms and information can be found at: HPRA Pharmacovigilance website: www.hpra.ie Adverse events should also be reported to Incyte by calling 00-800-0002-7423.

Opzelura® (ruxolitinib) cream safety profile and side effects