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Ruxolitinib Phosphate (Topical) (Monograph)

Brand name: Opzelura
Drug class: Janus Kinase Inhibitors

Medically reviewed by Drugs.com on Aug 10, 2024. Written by ASHP.

Warning

    Serious Infection
  • Serious and sometimes fatal infections, including tuberculosis (pulmonary or extrapulmonary disease), bacterial and viral infections, invasive fungal infections, and other opportunistic infections, reported in patients receiving oral Janus kinase (JAK) inhibitors to treat inflammatory conditions.1

  • Avoid use in patients with a serious active infection, including localized infections.1 Carefully consider risks and benefits prior to initiating topical ruxolitinib therapy in patients with a chronic or recurring infection.1

  • Closely monitor patients for infection during and after treatment.1 If a serious infection develops, interrupt ruxolitinib therapy until infection is controlled.1

    Mortality
  • Higher overall mortality rate reported in patients receiving oral JAK inhibitors to treat inflammatory conditions.1 5

    Malignancies
  • Lymphoma and other malignancies reported in patients receiving oral JAK inhibitors to treat inflammatory conditions.1 5

    Cardiovascular Events
  • Major adverse cardiovascular events (MACE) including MI, stroke, and sudden cardiovascular death reported in patients receiving oral JAK inhibitors to treat inflammatory conditions.1 5

    Thrombosis
  • Serious and sometimes fatal thrombotic events, including DVT, PE, and arterial thrombosis, reported in patients receiving oral JAK inhibitors to treat inflammatory conditions.1 5

  • Promptly evaluate patients if symptoms of thrombosis develop.1

Introduction

Selective inhibitor of Janus kinase (JAK) 1 and 2.1 2 3 4

Uses for Ruxolitinib Phosphate (Topical)

Atopic Dermatitis

Used topically as a 1.5% cream for short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and pediatric patients ≥12 years of age whose disease is not adequately controlled with topical prescription agents or when these therapies are not advisable.1 2 7

Concomitant use of ruxolitinib with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants (e.g., azathioprine or cyclosporine) is not recommended.1

American Academy of Dermatology guideline for use of topical therapies for atopic dermatitis strongly recommends ruxolitinib cream for mild-to-moderate disease.8

Vitiligo

Used topically as a 1.5% cream for treatment of nonsegmental vitiligo in adults and pediatric patients ≥12 years of age.1 9

Concomitant use of ruxolitinib with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants (e.g., azathioprine or cyclosporine) is not recommended.1

Ruxolitinib Phosphate (Topical) Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Other General Considerations

Administration

Topical Administration

Apply topically as a 1.5% cream.1 Not for ophthalmic, oral, or intravaginal use.1

Do not use more than a single 60 g tube per week or a single 100 g tube per 2 weeks.1

Dosage

Available as ruxolitinib phosphate; dosage expressed in terms of ruxolitinib.1

Pediatric Patients

Atopic Dermatitis
Topical

Pediatric patients ≥12 years of age: Apply thin layer of 1.5% cream to affected area(s) (up to 20% BSA) twice daily.1

Discontinue treatment following resolution of signs and symptoms (e.g., pruritus, rash, erythema).1 If no improvement within 8 weeks, reevaluate patient.1

Vitiligo
Topical

Pediatric patients ≥12 years of age: Apply thin layer of 1.5% cream to affected area(s) (up to 10% BSA) twice daily.1

May need to treat for >24 weeks for satisfactory response.1 If no meaningful repigmentation by 24 weeks, reevaluate patient.1

Adults

Atopic Dermatitis
Topical

Apply thin layer of 1.5% cream to affected area(s) (up to 20% body surface area) twice daily.1

Discontinue treatment following resolution of signs and symptoms (e.g., pruritus, rash, erythema).1 If no improvement within 8 weeks, reevaluate patient.1

Vitiligo
Topical

Apply thin layer of 1.5% cream to affected area(s) (up to 10% body surface area) twice daily.1

May need to treat for >24 weeks for satisfactory response.1 If no meaningful repigmentation by 24 weeks, reevaluate patient.1

Special Populations

Hepatic Impairment

No dosage recommendations at this time.1

Renal Impairment

No dosage recommendations at this time.1

Geriatric Patients

No dosage recommendations at this time.1

Cautions for Ruxolitinib Phosphate (Topical)

Contraindications

Warnings/Precautions

Warnings

Infectious Complications

Serious and sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, or other opportunistic infections) reported in patients receiving oral JAK inhibitors for inflammatory conditions (see Boxed Warning).1 5 Serious lower respiratory infections reported in patients receiving topical ruxolitinib.1

Avoid use of topical ruxolitinib in patients with serious active infection, including localized infections.1 Consider risks and benefits prior to initiating therapy in patients with chronic or recurring infection, patients with a history of serious or opportunistic infection, patients with an underlying condition that may predispose them to infection, and patients who have been exposed to tuberculosis or have resided or traveled in regions where tuberculosis or mycoses are endemic.1

Closely monitor patients for infection during and after treatment.1 If serious infection, opportunistic infection, or sepsis develops, interrupt therapy until infection is controlled.1

Tuberculosis reported in patients receiving oral JAK inhibitors for inflammatory conditions.1 No cases reported in patients receiving topical ruxolitinib.1 Consider evaluating patients for tuberculosis prior to initiating therapy.1 Monitor patients for tuberculosis during therapy.1

Viral reactivation, including herpes virus reactivation (e.g., herpes zoster) reported with JAK inhibitors including topical ruxolitinib.1 If herpes zoster develops, consider interrupting therapy until episode has resolved.1

Effect of JAK inhibition on reactivation of chronic viral hepatitis not known.1 Clinical trials excluded patients with a history of HBV or HCV infection.1 Increased HBV DNA titers, with or without increased ALT/AST, reported in patients with chronic HBV infection taking oral ruxolitinib.1 Do not initiate topical ruxolitinib therapy in patients with active HBV or HCV infection.1

Mortality

Higher all-cause mortality rate, including sudden cardiovascular death, observed in patients receiving oral JAK inhibitors for rheumatoid arthritis (see Boxed Warning).1 5 Consider risks and benefits of ruxolitinib prior to initiating or continuing therapy.1

Malignancy and Lymphoproliferative Disorders

Lymphoma and other malignancies observed in patients receiving oral JAK inhibitors for inflammatory conditions (see Boxed Warning).1 5 Nonmelanoma skin cancers (e.g., basal cell and squamous cell carcinoma) reported in patients receiving topical ruxolitinib.1

Consider risks and benefits of ruxolitinib prior to initiating or continuing therapy in patients who are current or past smokers, those who develop malignancy while on treatment, and in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer).1

Periodic dermatologic examinations recommended during and after treatment as appropriate.1 Advise patients to limit exposure to sunlight and UV light by wearing protective clothing and using broad-spectrum sunscreen.1

Cardiovascular Effects

Major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, and non-fatal stroke observed in patients receiving oral JAK inhibitors for rheumatoid athritis (see Boxed Warning).1 5

Consider risks and benefits of ruxolitinib prior to initiating or continuing therapy in patients who are current or past smokers and in patients with other cardiovascular risk factors.1 Discontinue ruxolitinib in patients who have experienced MI or stroke.1

Thrombosis

Serious and sometimes fatal thrombotic complications, including DVT, PE, and arterial thrombosis reported in patients receiving oral JAK inhibitors for inflammatory conditions (see Boxed Warning).1 5

Avoid use in patients at increased risk for thrombosis.1 Discontinue therapy in patients who have symptoms of thrombosis.1

Hematologic Effects

Thrombocytopenia, neutropenia, and anemia reported.1

Consider risks and benefits of ruxolitinib prior to initiating therapy in patients with a history of thrombocytopenia, neutropenia, or anemia.1 Monitor CBCs as clinically indicated.1 If clinically significant thrombocytopenia, anemia, or neutropenia occurs, discontinue therapy.1

Lipid Abnormalities

Increases in total cholesterol, LDL-cholesterol, and triglycerides reported in patients receiving oral ruxolitinib.1

Specific Populations

Pregnancy

Data are inadequate to assess whether use of topical ruxolitinib during pregnancy is associated with major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1 Adverse developmental effects observed in animal reproduction studies.1

Pregnancy registry is available; contact registry at 1-855-463-3463.1

Lactation

Distributes into milk in rats.1 Not known whether ruxolitinib distributes into human milk, affects nursing infants, or affects milk production.1

Because of potential for serious adverse effects in nursing infants, breastfeeding is not recommended during topical ruxolitinib therapy and for approximately 4 weeks after the last dose.1

Pediatric Use

Safety and efficacy established in pediatric patients ≥12 years of age for both atopic dermatitis and nonsegmental vitiligo.1 No overall differences in safety or efficacy relative to adults observed.1

Safety and efficacy not established in pediatric patients <12 years of age.1

Geriatric Use

No overall differences in safety or efficacy observed between geriatric patients and younger adults with atopic dermatitis.1 Insufficient number of geriatric patients in clinical trials for vitiligo to determine whether they respond differently from younger adults.1

Common Adverse Effects

Adverse effects occurring in ≥1% of patients with atopic dermatitis: Nasopharyngitis, bronchitis, ear infection, increased eosinophil count, urticaria, diarrhea, folliculitis, tonsillitis, rhinorrhea.1

Adverse effects occurring in ≥1% of patients with vitiligo: Application site acne, pruritus, and erythema, nasopharyngitis, headache, urinary tract infection, pyrexia.1

Drug Interactions

No formal drug interaction studies to date with topical ruxolitinib.1

Metabolized mainly by CYP3A4 and to a minor extent by CYP2C9.1

In vitro, does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4;1 does not induce CYP1A2, 2B6, or 3A4.1

In vitro, does not inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion-transporting polypeptides (OATP) 1B1 and 1B3, organic cation transporters (OCT) 1 and 2, and organic anion transporters (OAT) 1 and 3 at clinically relevant concentrations.1 Also, not a substrate for P-gp.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors (e.g., erythromycin, ketoconazole): Potential pharmacokinetic interaction (increased ruxolitinib exposure and increased risk of adverse reactions).1 Avoid concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole).1 No clinical studies conducted with mild CYP3A4 inhibitors.1

CYP3A4 inducers: Potential pharmacokinetic interaction (decreased ruxolitinib exposure).1

Ruxolitinib Phosphate (Topical) Pharmacokinetics

Absorption

Bioavailability

Topically applied ruxolitinib cream can be absorbed through skin.1 Following topical application, mean bioavailability is low (approximately 6%).4 No evidence of drug accumulation following topical application for 28 days in patients with atopic dermatitis.1

Distribution

Extent

Not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 97%.1

Elimination

Metabolism

Metabolized principally by CYP3A4 and to a lesser extent by CYP2C9.1

Elimination Route

Excreted in urine (74%) and feces (22%), mainly as metabolites (<1% excreted as unchanged drug).1

Half-life

Mean half-life following topical application approximately 116 hours.1

Stability

Storage

Topical

Cream

20–25°C (excursions permitted between 15–30°C).1

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Ruxolitinib Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

1.5% (of ruxolitinib)

Opzelura (available in 60 and 100 g tubes )

Incyte

AHFS DI Essentials™. © Copyright 2024, Selected Revisions August 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Incyte Corporation. Opzelura (ruxolitinib) cream 1.5% prescribing information. Wilmington, DE; 2023 Sept.

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; 85:863-72. http://www.ncbi.nlm.nih.gov/pubmed/33957195?dopt=AbstractPlus

3. 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; 145:572-82. http://www.ncbi.nlm.nih.gov/pubmed/31629805?dopt=AbstractPlus

4. Gong, X, Chen X, Kuligowski ME et al. Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies. Am J Clin Dermatol. 2021; 22:555-66. http://www.ncbi.nlm.nih.gov/pubmed/33982267?dopt=AbstractPlus

5. US Food and Drug Administration. FDA Drug Safety Communication: FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. 2021 Sept 1. From FDA website. Accessed 2024 May 30. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

6. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 215309Orig1s000: Multi-discipline review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/215309Orig1s000MultidisciplineR.pdf

7. Papp K, Szepietowski JC, Kircik L, et al. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: results from two phase 3 studies. J Am Acad Dermatol. 2023;88:1008-16.

8. Sidbury R, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):E1-E20.

9. Rosmarin D, Passeron T, Pandya AG, et al for the TRuE-V Study Group. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387(16):1445-55.