Introduction
Opzelura (ruxolitinib) is a topical Janus kinase (JAK) inhibitor cream approved by the U.S. Food and Drug Administration (FDA). It represents a novel therapeutic approach for dermatological conditions characterized by inflammation and immune dysregulation. As the first topical JAK inhibitor available in the United States, Opzelura offers targeted therapy with potentially reduced systemic exposure compared to oral JAK inhibitors.
Mechanism of Action
Ruxolitinib is a selective inhibitor of JAK1 and JAK2, which mediate signaling of cytokines and growth factors involved in immune function and hematopoiesis. By inhibiting JAK-mediated phosphorylation of signal transducer and activator of transcription (STAT) proteins, Opzelura modulates the inflammatory cascade at the site of application. This mechanism reduces the production of pro-inflammatory cytokines (including IL-4, IL-13, IL-31, and others) that contribute to the pathogenesis of dermatological conditions like atopic dermatitis and vitiligo.
Indications
FDA-approved indications:
- Short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable
- Topical treatment of non-segmental vitiligo in patients 12 years of age and older
Dosage and Administration
Standard dosing:- Apply a thin layer to affected areas twice daily
- Total body surface area should not exceed 20%
- For atopic dermatitis: Use for up to 8 weeks continuously, then as needed
- For vitiligo: May require longer treatment duration (24-52 weeks demonstrated in clinical trials)
- Renal impairment: No dosage adjustment necessary for mild to moderate impairment
- Hepatic impairment: Use with caution in severe hepatic impairment
- Pediatric: Safety and effectiveness not established in patients <12 years
- Geriatric: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Minimal systemic absorption with topical application. Mean maximum plasma concentrations (Cmax) were approximately 1.4% of the Cmax achieved with the lowest approved oral ruxolitinib dose. Distribution: Primarily local tissue distribution. Plasma protein binding is approximately 97%, mainly to albumin. Metabolism: Primarily metabolized by cytochrome P450 enzymes CYP3A4 and CYP2C9. Elimination: Mean elimination half-life is approximately 3 hours. Excreted primarily in urine (74%) and feces (22%).Contraindications
- Hypersensitivity to ruxolitinib or any component of the formulation
- Patients with active, serious infections (including localized infections)
Warnings and Precautions
Serious Infections: Increased risk of serious bacterial, fungal, viral, and other opportunistic infections. Avoid use in patients with active serious infections. Consider risks and benefits before initiating treatment in patients with chronic or recurrent infections. Mortality, Malignancy, and Major Adverse Cardiovascular Events: Oral JAK inhibitors have been associated with increased risks. While systemic exposure with topical application is significantly lower, these risks cannot be excluded. Thrombocytopenia, Anemia, and Neutropenia: Monitor complete blood counts as clinically appropriate. Thrombosis: Increased risk of thrombosis has been observed with JAK inhibitors used for inflammatory conditions. Hypersensitivity Reactions: Discontinue if hypersensitivity reactions occur.Drug Interactions
Strong CYP3A4 Inhibitors: May increase ruxolitinib exposure. Consider monitoring for adverse reactions. Immunosuppressants: Concurrent use may increase risk of immunosuppression and infection. Live Vaccines: Avoid use with live vaccines during and immediately prior to therapy.Adverse Effects
Common adverse reactions (≥1%):- Application site reactions (acne, itching, redness, burning)
- Nasopharyngitis
- Headache
- Urinary tract infection
- Folliculitis
- Diarrhea
- Fever
- Serious infections
- Thrombocytopenia
- Anemia
- Neutropenia
- Thrombosis
- Malignancy
Monitoring Parameters
- Clinical response and disease improvement
- Signs and symptoms of infection
- Complete blood count (at baseline and as clinically indicated)
- Lipid parameters (as clinically indicated)
- Liver function tests (as clinically indicated)
- Local skin reactions at application sites
Patient Education
- Use only as prescribed; apply a thin layer to affected areas twice daily
- Wash hands after application unless hands are treated areas
- Avoid contact with eyes, mouth, and mucous membranes
- Do not occlude treated areas with bandages or dressings
- Report any signs of infection (fever, sweats, chills, muscle aches, cough, shortness of breath, skin sores)
- Inform healthcare providers of all medications being taken
- Avoid live vaccines during treatment
- Not for ophthalmic, oral, or intravaginal use
- Store at room temperature (20-25°C/68-77°F)
References
1. FDA prescribing information: Opzelura (ruxolitinib) cream. September 2021. 2. Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85(4):863-872. 3. Rosmarin D, Pandya AG, Lebwohl M, et al. Ruxolitinib cream for treatment of vitiligo: A randomised, controlled, phase 2 trial. Lancet. 2020;396(10244):110-120. 4. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145(2):572-582. 5. Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N Engl J Med. 2021;384(12):1101-1112. 6. National Vitiligo Foundation. Vitiligo: Diagnosis and Treatment. 2021. 7. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol. 2014;71(1):116-132.