Ruxolitinib (Topical) (Monograph)

Brand name: Opzelura
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical name: (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile;phosphoric acid
Molecular formula: C₁₇H₂₁N₆O₄P
CAS number: 1092939-17-7

Medically reviewed by Drugs.com on Aug 29, 2022. Written by ASHP.

Introduction

Selective inhibitor of Janus kinase (JAK) 1 and 2.

Uses for Ruxolitinib (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 patients ≥12 years of age whose disease is not adequately controlled with topical prescription agents or when these therapies are not advisable.

Ruxolitinib (Topical) Dosage and Administration

General

Pretreatment Screening

• Consider benefits and risks of serious infections (observed in patients receiving oral JAK inhibitors) prior to initiating therapy. Do not initiate topical ruxolitinib therapy in patients with active HBV or HCV infection.

• Consider evaluating for latent and active tuberculosis infection prior to initiating therapy.

• Consider benefits and risks of increased mortality (observed in clinical trials of oral JAK inhibitors) prior to initiating therapy.

• Consider benefits and risks of increased malignancies (observed in clinical trials of oral JAK inhibitors) prior to initiating therapy.

• Consider benefits and risks of major adverse cardiovascular events (MACE) prior to initiating therapy, particularly in patients who are current or past smokers and those with other cardiovascular risk factors.

• Consider benefits and risks of thrombocytopenia, anemia, and neutropenia in patients who have a known history of these events prior to initiating therapy.

Patient Monitoring

• Monitor closely for signs or symptoms of infection, including active tuberculosis.

• Perform dermatologic examinations periodically during therapy and following discontinuance of therapy as appropriate.

• Perform CBC monitoring as clinically indicated.

Other General Considerations

• Do not use concomitantly with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants (e.g., azathioprine or cyclosporine).

Administration

Topical Administration

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

Apply a thin layer to affected area(s) of skin (up to 20% body surface area).

Dosage

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

Pediatric Patients

Atopic Dermatitis

Topical

Pediatric patients ≥12 years of age: Apply thin layer to affected area(s) (up to 20% body surface area) twice daily. Do not use more than 60 g per week.

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

Adults

Atopic Dermatitis

Topical

Apply thin layer to affected area(s) (up to 20% body surface area) twice daily. Do not use more than 60 g per week.

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

Prescribing Limits

Pediatric Patients

Atopic Dermatitis

Topical

Maximum 60 g per week.

Adults

Atopic Dermatitis

Topical

Maximum 60 g per week.

Cautions for Ruxolitinib (Topical)

Contraindications

• Manufacturer states none known.

Warnings/Precautions

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. Serious lower respiratory infections reported in patients receiving topical ruxolitinib.

Avoid use of topical ruxolitinib in patients with a serious active infection, including localized infections. Consider risks and benefits prior to initiating topical ruxolitinib therapy in patients with a chronic or recurring infection, patients with a history of a 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.

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

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

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

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

Increased Mortality.

Higher overall mortality rate, including sudden cardiovascular death, observed in patients receiving oral JAK inhibitors for inflammatory conditions. Consider risks and benefits of ruxolitinib prior to initiating or continuing therapy.

Malignancies and Lymphoproliferative Disorders.

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

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

Periodic dermatologic examinations recommended during and after treatment as appropriate.

Cardiovascular Effects.

Major adverse cardiovascular events (MACE) including MI, stroke, and sudden cardiovascular death observed in patients receiving oral JAK inhibitors for inflammatory conditions.

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.

Thrombosis.

Serious and sometimes fatal thrombotic complications, including DVT, PE, and arterial thrombosis reported in patients receiving oral JAK inhibitors for inflammatory conditions. Thromboembolic events also reported in patients receiving topical ruxolitinib; however, there was no clear correlation between increased platelet counts and thromboembolic events.

Use with caution in patients at risk for thrombosis.

Hematologic Effects

Thrombocytopenia, neutropenia, and anemia reported.

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

Lipid Abnormalities.

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

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. Adverse developmental effects observed in animal reproduction studies.

Lactation

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

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

Pediatric Use

Safety and efficacy established in pediatric patients ≥12 years of age. No overall differences in safety or efficacy relative to adults observed.

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

Geriatric Use

No overall differences in safety or efficacy observed between geriatric patients and younger adults.

Common Adverse Effects

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

Interactions for Ruxolitinib (Topical)

No formal drug interaction studies to date with topical ruxolitinib.

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

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

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. Also, not a substrate for P-gp.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors (e.g., erythromycin, ketoconazole): Potential pharmacokinetic interaction (increased ruxolitinib exposure and increased risk of adverse reactions). Avoid concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole).

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

Specific Drugs

Ruxolitinib (Topical) Pharmacokinetics

Absorption

Bioavailability

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

Distribution

Extent

Distributed into milk in rats; not known whether distributed into human milk.

Plasma Protein Binding

Approximately 97%.

Elimination

Metabolism

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

Elimination Route

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

Half-life

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

Stability

Storage

Topical

Cream

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

Actions

• Selectively inhibits JAK 1 and 2, which mediate signaling of cytokines and growth factors important for hematopoiesis and immune function.

• JAK enzymes also mediate signaling of cytokines associated with inflammation of atopic dermatitis and may act directly on sensory neurons and mediate itch response.

• JAK signaling involves recruitment of signal transducers and activators of transcription (STAT) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression.

• Relevance of inhibition of specific JAK enzymes to therapeutic efficacy of topical ruxolitinib not known.

Advice to Patients

• Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide).

• Inform patients that they may be at increased risk for developing infections, including serious infections, when taking JAK inhibitors. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection.

• Advise patients that JAK inhibitors may increase the risk of herpes zoster, and some cases can be serious.

• Inform patients that JAK inhibitors may increase the risk for developing lymphomas and other malignancies including skin cancer. Instruct patients to inform their health care provider if they have ever had any type of cancer. Inform patients that periodic skin examinations should be performed during treatment with ruxolitinib.

• Advise patients that major adverse cardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, have been reported in clinical studies with JAK inhibitors used to treat inflammatory conditions. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events.

• Advise patients that thrombotic events such as DVT and PE have been reported in clinical studies with JAK inhibitors. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of DVT or PE.

• Advise patients of the risk of thrombocytopenia, anemia, and neutropenia. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of these hematologic disorders.

• Advise patients or caregivers that ruxolitinib phosphate (Opzelura) is for topical use only.

• Advise patients to limit treatment to 60 g of cream per week.

• Inform patients to report any pregnancies to Incyte Corporation at 1-855-463-3463.

• Advise patients not to breastfeed during treatment with ruxolitinib phosphate and for approximately 4 weeks after the last dose.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

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.

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