Overview
11 DESCRIPTION Brodalumab is a human monoclonal IgG2κ antibody directed against human interleukin-17 receptor A (IL-17RA). It is expressed in a Chinese Hamster Ovary (CHO) cell line. Brodalumab is comprised of 1312 amino acids and has an estimated molecular mass of 144,000 Daltons.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Brodalumab is a human monoclonal IgG2 antibody that selectively binds to human IL-17RA and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. Blocking IL-17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines. 12.2 Pharmacodynamics Elevated levels of IL-17A, IL-17C, and IL-17F are found in psoriatic plaques. Serum IL-17A levels, measured at Weeks 12, 24, and 48 of SILIQ 210 mg every 2 weeks of treatment, were higher than the baseline levels in subjects with moderate to severe plaque psoriasis.
Indications
- 1 INDICATIONS AND USAGE SILIQ ® (brodalumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. SILIQ is a human interleukin-17 receptor A (IL-17RA) antagonist indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. ( 1 )
Common Doses
- 210 mg
- 1.5 mL
Dosage
2 DOSAGE AND ADMINISTRATION Administer 210 mg of SILIQ by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. ( 2.2 ) 2.1 Tuberculosis Assessment Prior to Initiation of SILIQ Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SILIQ [see Warnings and Precautions ( 5.4 )]. 2.2 Dosage The recommended SILIQ dose is 210 mg administered by subcutaneous injection at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks. If an adequate response has not been achieved after 12 to 16 weeks of treatment with SILIQ, consider discontinuing therapy.
Black Box Warning
WARNING: SUICIDAL IDEATION AND BEHAVIOR Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with SILIQ. Prior to prescribing SILIQ, weigh the potential risks and benefits in patients with a history of depression and/or suicidal ideation or behavior. Patients with new or worsening suicidal ideation and behavior should be referred to a mental health professional, as appropriate.
Contraindications
- 4 CONTRAINDICATIONS SILIQ is contraindicated in patients with: Crohn’s disease because SILIQ may cause worsening of disease [see Warnings and Precautions ( 5.7 )] . Clinically significant hypersensitivity to brodalumab or to any of the excipients in SILIQ or component of the container. Hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of SILIQ [see Warnings and Precautions ( 5.3 )] . Crohn’s disease ( 4 ) Clinically significant hypersensitivity to brodalumab or to any of the excipients in SILIQ or component of the container ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of labeling: Suicidal Ideation and Behavior [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Infections [see Warnings and Precautions ( 5.4 )] Crohn’s Disease [see Contraindications ( 4 ), Warnings and Precautions ( 5.7 )] Most common adverse reactions (incidence ≥1%) were arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, and tinea infections. ( 6.
Interactions
- 7 DRUG INTERACTIONS CYP450 Substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Treatment with SILIQ may modulate serum levels of some cytokines. Therefore, upon initiation or discontinuation of SILIQ in patients who are receiving concomitant drugs which are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (e.g., for warfarin) or drug concentration (e.g.