Overview
11 DESCRIPTION Ruxolitinib phosphate is a Janus kinase inhibitor with the chemical name ( R )-3-(4-(7 H -pyrrolo[2,3- d ]pyrimidin-4-yl)-1 H -pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate and a molecular weight of 404.36 g/mol. Ruxolitinib phosphate has the following structural formula: Ruxolitinib phosphate is a white to off-white to light yellow to light pink powder.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ruxolitinib, a Janus kinase (JAK) inhibitor, inhibits JAK1 and JAK2 which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known. 12.2 Pharmacodynamics The pharmacodynamics of OPZELURA is unknown. Cardiac Electrophysiology Under the conditions of clinical use, OPZELURA is not expected to prolong the QT interval. 12.
Indications
- 1 INDICATIONS AND USAGE OPZELURA is a Janus kinase (JAK) inhibitor 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. ( 1.1 ) the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older. ( 1.
Common Doses
- Refer to label
Dosage
2 DOSAGE AND ADMINISTRATION Atopic Dermatitis Apply a thin layer of OPZELURA topically twice daily to affected areas of up to 20% body surface area. ( 2.1 ) Do not use OPZELURA with occlusive dressings. ( 2.1 ) 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. ( 2.1 ) Pediatric Patients 2 to 11 Years of Age Do not use more than one 60 gram tube of OPZELURA per 2 weeks. ( 2.
Black Box Warning
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS 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 ( 5.1 ) and Adverse Reactions ( 6.1 )] . Reported infections include: Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Invasive fungal infections, including cryptococcosis, and pneumocystosis.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS In atopic dermatitis, the most common adverse reactions (incidence ≥ 1%) are nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increased, urticaria, folliculitis, tonsillitis, rhinorrhea, upper respiratory tract infection, COVID-19, application site reactions, pyrexia, and white blood cell decreased. ( 6 ) In nonsegmental vitiligo, the most common adverse reactions (incidence ≥ 1%) are application site acne, application site pruritus, nasopharyngitis, headache, urinary tract infection, application site erythema, and pyrexia.
Interactions
- 7 DRUG INTERACTIONS Drug interaction studies with OPZELURA have not been conducted. Ruxolitinib is known to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 may increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 may decrease ruxolitinib systemic concentrations [see Clinical Pharmacology ( 12.3 )] . Strong Inhibitors of CYP3A4 Avoid concomitant use of OPZELURA with strong inhibitors of CYP3A4 as there is a potential to increase the systemic exposure of ruxolitinib and could increase the risk of OPZELURA adverse reactions [see Clinical Pharmacology ( 12.