golimumab (Simponi, Simponi Aria)

Dosing and uses of Simponi, Simponi Aria (golimumab)

• Adult
• Pediatric

 

Adult dosage forms and strengths

SC solution (prefilled syringe/autoinjector)

• Simponi
• 50mg/0.5mL
• 100mg/1mL

IV solution (vial)

• Simponi Aria
• 50mg/4mL

 

Rheumatoid Arthritis

Indicated for moderately-to-severely active rheumatoid arthritis in combination with methotrexate

Simponi: 50 mg SC qMonth

Simponi Aria: 2 mg/kg IV infused over 30 minutes at weeks 0 and 4, then q8weeks

 

Psoriatic Arthritis

Indicated alone or in combination with methotrexate for active psoriatic arthritis

50 mg SC qMonth

 

Ankylosing Spondylitis

Indicated for active ankylosing spondylitis with or without methotrexate

50 mg SC qMonth

 

Ulcerative Colitis

Indicated for adults with moderate-to-severe ulcerative colitis that is resistant to prior treatment or requires continuous corticosteroid therapy

Initial: 200 mg SC at Week 0, followed by 100 mg SC at Week 2, THEn

Maintenance: 100 mg SC q4weeks

 

Pediatric dosage forms and strengths

<18 years: Safety and efficacy not established

 

Polyarticular Juvenile Idiopathic Arthritis (Orphan)

Orphan designation for treatment of polyarticular juvenile idiopathic arthritis in pediatric patients aged ≤16 yr

Sponsor

• Janssen Research & Development, LLC; Welsh & McKean Roads; P. O. Box 776; Spring House, PA 19477

 

Simponi, Simponi Aria (golimumab) adverse (side) effects

>10%

Upper respiratory infections (13-16%)

 

1-10%

Injection site reactions, SC (6%)

Increased ALT/AST (3-4%)

Viral infections (4-5%)

Hypertension (3%)

Bronchitis (2-3%)

Rash (3%)

Sinusitis (2%)

Superficial fungal infections (2%)

Dizziness (2%)

Paresthesia (2%)

Pyrexia (2%)

Leukopenia (1%)

Bacterial infections (1%)

Constipation (1%)

 

Postmarketing Reports

Neoplasm benign and malignant: Melanoma

Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction), sarcoidosis

Respiratory, thoracic and mediastinal disorders: Interstitial lung disease

Skin and subcutaneous tissue disorders: Skin exfoliation, rash, bullous skin reactions

 

Warnings

Black box warnings

Serious infection risk

• Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
• Patients older than 65 years may be at greater risk
• Discontinue if patient develops serious infection or sepsis
• Reported infections include:
• 1) Active TB, including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat latent infection prior to use
• 2) Invasive fungal infections (eg, histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease; antigen/antibody testing for histoplasmosis may be negative in some patients with active infection; initiate empiric antifungal therapy if severe systemic illness develops
• 3) Other bacterial (eg, Legionella, Listeria), mycobacterial (eg, tuberculosis), and viral (eg, hepatitis B) opportunistic pathogens

Malignancy

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with TNF blockers
• Manufacturer required to report all malignancies to FDA in order for complete and consistent analysis

 

Contraindications

Active serious infection

Concomitant live vaccines

 

Cautions

Risk of infections, reactivation of latent hepatitis/TB; interrupt if serious infection develops (eg, bacterial sepsis, severe invasive fungal infections, opportunistic infections)

Infection risk increases when coadministered with abatacept, anakinra, or rituximaB

May decrease humoral response to live-virus vaccines (eg, MMR)

Administration of live virus vaccines and therapeutic agents (eg, BCG bladder instillation) may result in disseminated infections

Increased risk of lymphoma and other cancers reported in children and adolescents

Occurrence of leukemia and new-onset psoriasis in patients treated with TNF blockers

Skin cancer (melanoma, Merkel cell carcinoma) reported with TNF blockers; perform periodic skin examination for all patients, particularly those with risk factors for skin cancer

Enhanced safety surveillance requirements to capture malignancy data: Manufacturers required to report all malignancies to FDA in order for complete and consistent analysis

Risk of exacerbation of or new onset heart failure; discontinue therapy if worsening symptoms occur

Risk of exacerbation of or new onset demyelinating disease

Lupus-like syndrome may occur; discontinue therapy if it develops

Given with or without methotrexate depending on indication

No added benefits, but increased adverse effects, if given with other immunosuppressive biologics

Serious systemic hypersensitivity reactions including anaphylaxis may occur

Hepatosplenic T-cell lymphomas (HSTCL)

• Rare postmarketing cases reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with TNF blockers
• Reports have also included a patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
• HSTCL is an aggressive, rare type of T-cell lymphoma (usually fatal)
• Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-mercaptopurine, although there have been cases reported receiving azathioprine or mercaptopurine alone
• The following HSTCL cases have been identified in the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), and mercaptopurine (3)

 

Pregnancy and lactation

Pregnancy category: B

Lactation: not known if excreted in breast milk, do not nurse

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Simponi, Simponi Aria (golimumab)

Mechanism of action

Human anti-TNF-alpha monoclonal antibody, blocks inflammatory activity of TNF-alpha

 

Absorption

Bioavailability: 53% (SC)

Peak Plasma Time (50 mg dose): 2-6 days

Peak Plasma Concentration: 2.5 mcg/mL

 

Distribution

Vd: 58-126 mL/kg

 

Elimination

Half Life: 2 wk

Clearance: 4.0-6.7 mL/kg/day

 

Administration

IV Preparation

Inspect vial; solution is colorless to light yellow and opalescent

The solution may develop a few fine translucent particles, as golimumab is a protein; do not use if opaque particles, discoloration or other foreign particles are present

Dilute calculated dose volume with 0.9% NaCl to a final volume of 100 mL; alternatively, 0.45% NaCl Injection, USP can also be used; gently mix (DO NOT SHAKE)

Discard any unused drug remaining in the vials

 

IV Administration

Use only an infusion set with an in-line, sterile, nonpyrogenic, low protein-binding filter (pore size 0.22 micrometer or less)

Do not administer concomitantly in same IV line with other agents

Infuse over 30 minutes

 

SC Preparation & Administration

Warm by sitting at room temperature for 30 min; do NOT heat or microwave

If multiple injections required, administer at different site on the body

Rotate injection sites for each administration

Do not administer in area where the skin is tender, bruised, red, or hard

 

Storage

Refrigerate unopened IV and SC products at 2-8ºC (36-46ºF); do not freeze

Keep the product in the original carton to protect from light until the time of use

Once diluted, IV infusion solution may be stored for 4 hr at room temperature