Dosage & Administration
Atopic Dermatitis
Adult and Pediatric Patients 12 Years of Age and Older
Pediatric Patients 2 to 11 Years of Age
Nonsegmental Vitiligo
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Opzelura Prescribing Information
SERIOUS INFECTIONS
Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions and Adverse Reactions ].
Reported infections include:
- Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
- Invasive fungal infections, including cryptococcosis, and pneumocystosis.
- Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of OPZELURA in patients with an active, serious infection, including localized infections. If a serious infection develops, interrupt OPZELURA until the infection is controlled.
The risks and benefits of treatment with OPZELURA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with OPZELURA [see Warnings and Precautions ].
MORTALITY
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing an oral JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor [see Warnings and Precautions ].
MALIGNANCIES
Malignancies were reported in patients treated with OPZELURA. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with an oral JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions ].
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue OPZELURA in patients who have experienced a myocardial infarction or stroke [see Warnings and Precautions ].
THROMBOSIS
Thromboembolic events were observed in trials with OPZELURA. Thrombosis, including pulmonary embolism (PE), deep venous thrombosis (DVT), and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with an oral JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid OPZELURA in patients at risk. If symptoms of thrombosis occur, discontinue OPZELURA and treat appropriately [see Warnings and Precautions ].
Atopic Dermatitis
OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adult and pediatric patients 2 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
Nonsegmental Vitiligo
OPZELURA is indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older.
Limitations of Use
Use of OPZELURA in combination with therapeutic biologics, other Janus kinase (JAK) inhibitors, or potent immunosuppressants such as azathioprine or cyclosporine is not recommended.
Recommended Dosage andAdministration for Atopic Dermatitis
OPZELURA is for topical use only. OPZELURA is not for ophthalmic, oral, or intravaginal use.
Instruct patients to apply a thin layer of OPZELURA twice daily to affected areas of up to 20% body surface area.
Do not use OPZELURA with occlusive dressings.
Stop using when signs and symptoms (e.g., itch, rash, and redness) of atopic dermatitis resolve. If signs and symptoms do not improve within 8 weeks, patients should be re-examined by their healthcare provider [see Clinical Studies ( 14.1)].
Adult and Pediatric Patients 12 Years of Age and Older
Do not use more than one 60 gram tube of OPZELURA per week or one 100 gram tube per 2 weeks.
Pediatric Patients 2 to 11 Years of Age
Do not use more than one 60 gram tube of OPZELURA per 2 weeks.
Recommended Dosage and Administration for Nonsegmental Vitiligo
OPZELURA is for topical use only. OPZELURA is not for ophthalmic, oral, or intravaginal use.
Instruct patients to apply a thin layer of OPZELURA twice daily to affected areas of up to 10% body surface area.
Do not use more than one 60 gram tube of OPZELURA per week or one 100 gram tube per 2 weeks.
Satisfactory patient response may require treatment with OPZELURA for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be re‑evaluated by the healthcare provider [see Clinical Studies ( 14.2)].
Cream: 15 mg of ruxolitinib per gram (1.5%) of white to off-white cream supplied in 60 g and 100 g tubes
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy registry that monitors pregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy. Pregnant persons exposed to OPZELURA and healthcare providers should report OPZELURA exposure by calling 1-855-463-3463 or visiting www.opzelura.pregnancy.incyte.com.
Risk Summary
Available data from pregnancies reported in clinical trials with OPZELURA are not sufficient to evaluate a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of ruxolitinib to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes at doses associated with maternal toxicity (see Data).
The background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risk in the U.S. general population of major birth defects and miscarriage is 2-4% and 15-20%, respectively.
Data
Animal Data
Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. There were no treatment-related malformations at any dose. A decrease in fetal weight of approximately 9% was noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 22 times the clinical systemic exposure at the maximum recommended human dose (MRHD; the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 25-40% atopic dermatitis-affected body surface area is used for calculation of multiples of human exposure). In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemic exposure approximately 70% the MRHD clinical systemic exposure.
In a pre-and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse effects on embryofetal survival, postnatal growth, development parameters or offspring reproductive function at the highest dose evaluated (3.1 times the MRHD clinical systemic exposure).
Lactation
Risk Summary
There are no data on the presence of ruxolitinib in human milk, the effects on the breastfed child, or the effects on milk production. Ruxolitinib was present in the milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, thrombocytopenia, anemia, and neutropenia, advise women not to breastfeed during treatment with OPZELURA and for approximately four weeks after the last dose (approximately 5‑6 elimination half-lives).
Data
Lactating rats were administered a single dose of [14C]-labeled ruxolitinib (30 mg/kg) on postnatal Day 10, after which plasma and milk samples were collected for up to 24 hours. The AUC for total radioactivity in milk was approximately 13 times the maternal plasma AUC. Additional analysis showed the presence of ruxolitinib and several of its metabolites in milk, all at levels higher than those in maternal plasma.
Pediatric Use
Atopic Dermatitis
The safety and effectiveness of OPZELURA for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis have been established in non-immunocompromised pediatric patients ages 2 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Use of OPZELURA in this age group is supported by evidence from adequate and well-controlled trials in adults and pediatric subjects ages 2 years and older with mild to moderate atopic dermatitis [see Clinical Studies ( 14.1)]. Trials included 92 subjects 12 to 17 years of age and 130 subjects 2 to 11 years of age treated with OPZELURA.
Application site reactions, pyrexia, and decreased white blood cell were reported more frequently in pediatric subjects ages 2 to ll years compared to adults and pediatric subjects ages 12 years and older [see Adverse Reactions ( 6.1)]. The safety and effectiveness of OPZELURA have not been established in pediatric patients younger than 2 years of age with atopic dermatitis.
Nonsegmental Vitiligo
The safety and effectiveness of OPZELURA for the topical treatment of nonsegmental vitiligo have been established in pediatric patients ages 12 years and older. Use of OPZELURA in this age group is supported by evidence from TRuE-V1 and TRuE-V2, which included 55 subjects ages 12 to 17 years with nonsegmental vitiligo [see Clinical Studies ( 14.2)].
The safety and effectiveness of OPZELURA have not been established in pediatric patients younger than 12 years of age with nonsegmental vitiligo.
Juvenile Animal Toxicity Data
Oral administration of ruxolitinib to juvenile rats resulted in effects on growth and bone measures. When administered starting at postnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, evidence of fractures occurred at doses ≥ 30 mg/kg/day, and effects on body weight and other bone measures [e.g., bone mineral content, peripheral quantitative computed tomography, and x-ray analysis] occurred at doses ≥ 5 mg/kg/day. When administered starting at postnatal day 21 (the equivalent of a human 2-3 years of age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at doses ≥ 15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were more severely affected than females in all age groups, and effects were generally more severe when administration was initiated earlier in the postnatal period. These findings were observed at systemic exposures that are at least 45% the MRHD in pediatric subjects 2 to 11 years of age (the clinical systemic exposure from ruxolitinib cream, 1.5% applied twice daily to 35-50% atopic dermatitis-affected body surface area in pediatric subjects 2 to 11 years of age is used for the calculation of multiples of human exposure in this subsection).
Geriatric Use
Of the 1249 total subjects with atopic dermatitis in clinical trials with OPZELURA, 115 (9%) were 65 years of age and older [see Clinical Studies ]. No clinically meaningful differences in safety or effectiveness were observed between subjects less than 65 years and subjects 65 years and older.
Of the 831 total subjects enrolled with nonsegmental vitiligo in clinical trials with OPZELURA, 65 (8%) were 65 years of age and older [see Clinical Studies ( 14.2)]. Clinical trials of OPZELURA in subjects with nonsegmental vitiligo did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.
None.