golimumab


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golimumab

Simponi

Pharmacologic class: Tumor necrosis factor (TNF) blocker

Therapeutic class: Immunomodulator

Pregnancy risk category B

Action

A human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNF. This interaction prevents binding of TNF to its receptors, thereby inhibiting biological activity of TNFα (a cytokine protein). Elevated TNF levels in blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. TNF is an important mediator of articular inflammation characteristic of these diseases.

Availability

Injection: 50 mg/0.5 ml in single-dose prefilled SmartJect® Autoinjector; 50 mg/0.5 ml in single-dose prefilled syringe

Indications and dosages

Moderate to severe rheumatoid arthritis (with methotrexate); psoriatic arthritis, ankylosing spondylitis (with or without methotrexate or other nonbiological disease-modifying antirheumatics)

Adults: 50 mg subcutaneously monthly

Contraindications

None

Precautions

Use cautiously in:
• hypersensitivity reactions
• congestive heart failure (CHF)
• patients at risk for infection
• chronic hepatitis B virus (HBV) carriers
• central or peripheral nervous system demyelinating disorders
• cytopenia, including pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia
• concurrent use of abatacept or anakinra (use not recommended)
• concurrent use of immunosuppressants, such as corticosteroids or methotrexate
• concurrent use of live vaccines (don't use)
• patients switching from other disease-modifying antirheumatics
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).

Administration

Be aware that patients with active infections shouldn't start treatment with golimumab. Also, consider risks and benefits of starting golimumab in patients with chronic or recurrent infection, in those who have been exposed to TB, in those with a history of opportunistic infection, in those who have resided or traveled in areas of endemic TB or endemic mycoses (such as histoplasmosis, coccidioidomycosis, or blastomycosis), and in patients with underlying conditions that may predispose to infection. Be aware that when switching from one biological agent to another, overlapping biological activity may further increase risk of infection. Discontinue drug if patients develop other serious infections or sepsis.

Test for HBV infection before initiating TNF-blocker therapy. Discontinue drug in patients who develop HBV reactivation and initiate effective antiviral therapy with appropriate supportive treatment. Know that safety of resuming TNF-blocker therapy after HBV reactivation has been controlled isn't known; therefore, exercise caution when considering resumption of therapy.
• Before starting treatment, evaluate patient for TB risk factors and test for latent infection. Consider induration of 5 mm or greater with tuberculin skin testing a positive test when assessing if treatment for latent TB is needed, even for patient who has previously received bacille Calmette-Guérin vaccine. Treatment of latent TB infection before therapy with TNF blockers has been shown to reduce risk of TB reactivation during therapy.
• Consider anti-TB therapy before starting golimumab in patients with history of latent or active TB in whom adequate course of treatment can't be confirmed and in patients with negative test for latent TB but with risk factors for TB infection.

Consider discontinuing drug if central or peripheral nervous system demyelinating disorders develop.

Immediately discontinue drug if severe hypersensitivity reactions occur and initiate appropriate therapy.

Adverse reactions

CNS: dizziness, paresthesia, central or peripheral nervous system demyelinating disorders

CV: hypertension, CHF

EENT: nasopharyngitis, pharyngitis, laryngitis, rhinitis, sinusitis

GI: constipation

Hematologic: pancytopenia, leukopenia, neutropenia, aplastic anemia, thrombocytopenia

Hepatic: hepatic dysfunction, acute hepatic failure

Respiratory: upper respiratory tract infection, bronchitis

Skin: urticaria, bruising, pruritus, irritation, induration

Other: injection-site reactions, viral infections, superficial fungal infections, pain, serious infections, malignancies, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug.Abatacept, anakinra: increased risk of serious infection

Anakinra: increased risk of neutropenia and serious infection

CYP450 substrates: possible altered golimumab level due to antagonized TNFα activity

Live vaccines: increased risk of infection

Drug-diagnostic tests.ALT, AST: increased levels

Patient monitoring

• Monitor CBC with differential and hepatic function tests closely.
• Continue to watch for signs and symptoms of TB and test for latent TB periodically during therapy. Strongly consider TB in patients who develop new infection during treatment, especially in those who have previously or recently traveled to countries with high prevalence of TB or who have had close contact with a person with active TB.
• Closely observe for signs and symptoms of infection during and after treatment. Know that patients who develop new infection during treatment should be closely monitored, undergo prompt and complete diagnostic workup appropriate for immunocompromised patients, and be given appropriate antimicrobial therapy.
• Observe for signs and symptoms of malignancies. Be aware that lymphomas, including Hodgkin's and non-Hodgkin's lymphoma, and leukemia have been reported.

Closely monitor patients with CHF during therapy. Discontinue drug if new or worsening CHF signs and symptoms develop.
• Closely monitor patients who are carriers of HBV and require treatment with golimumab for clinical and laboratory signs of active HBV infection throughout therapy and for several months after treatment ends.
• Continue to monitor patients for hypersensitivity reactions.

Observe for signs and symptoms (although rare) of new-onset or exacerbation of CNS demyelinating diseases, including multiple sclerosis, and of peripheral demyelinating diseases, including Guillain-Barré syndrome.

Patient teaching

• Instruct patient who may self-inject on proper use of prefilled syringe, suitable sites for injection (including thigh and abdomen), rotation of sites, appropriate handling and disposal of syringe, and discarding unused portions of drug remaining in syringe.
• Advise latex-sensitive patient that needle cover on prefilled syringe and prefilled syringe in prefilled SmartJect Autoinjector contain dry natural rubber (a latex derivative).

Advise patient to seek immediate medical attention if signs and symptoms of severe allergic reactions occur.

Advise patient to promptly report new or worsening medical conditions (such as heart disease, neurological disease, or autoimmune disorders) and to promptly report signs and symptoms suggestive of cytopenia (such as bruising, bleeding, or persistent fever).
• Inform patient that drug may lower ability of immune system to fight infection and of importance of informing prescriber about new or previous infections, including TB and reactivation of HBV infection.
• Counsel patient about possible risk of lymphoma and other malignancies during therapy.
• Tell patient to avoid live vaccines during golimumab therapy.
• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

golimumab

(go-li-mu-mab) ,

Simponi

(trade name),

Simponi Aria

(trade name)

Classification

Therapeutic: antirheumatics
Pharmacologic: dmards
Pregnancy Category: B

Indications

Simponi and Simponi Aria: Treatment of moderately to severely active rheumatoid arthritis (with methotrexate).Simponi: Treatment of active psoriatic arthritis (alone or with methotrexate).Simponi: Treatment of active ankylosing spondylitis.Simponi: Moderately to severely active ulcerative colitis in patients who have demonstrated corticosteroid dependence or have responded inadequately to immunosuppressants such as aminosalicylates, corticosteroids, azathioprine, or 6–mercaptopurine.

Action

Inhibits binding of TNFα to receptors inhibiting activity and resulting in anti-inflammatory and antiproliferative activity.

Therapeutic effects

Decreased pain and swelling with decreased joint destruction in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Induction and maintenance of clinical remission of ulcerative colitis.

Pharmacokinetics

Absorption: Well absorbed following subcutaneous administration. IV administration results in complete bioavailability.
Distribution: Distributed primarily in the circulatory system with limited extravascular distribution.
Metabolism and Excretion: Unknown.
Half-life: 2 wk.

Time/action profile (improvement)

ROUTEONSETPEAKDURATION
Subcutwithin 3 mo2–7 days†unknown
IVwithin 3 mounknownunknown
† Blood levels

Contraindications/Precautions

Contraindicated in: Active infection (including localized);Concurrent use of abatacept or anakinra (↑ risk of infections); Lactation: Avoid during breast feeding.
Use Cautiously in: History of chronic or recurrent infection or underlying illness/treatment predisposing to infection;History of exposure to tuberculosis;History of opportunistic infection;Patients residing, or who have resided, where tuberculosis, histoplasmosis, coccidioidomycoses, or blastomycosis is endemic;History of HF (may worsen);Pre-existing or recent-onset CNS demyelinating disorders;History of cytopenias (may worsen);History of psoriasis (may exacerbate);Hepatitis B virus carriers (risk of reactivation); Geriatric: Use cautiously in elderly patients due to ↑ risk of infection; Obstetric: Use during pregnancy only if clearly needed; Pediatric: Safety not established; ↑ risk of lymphoma (including hepatosplenic T-cell lymphoma [HSTCL]), leukemia, and other malignancies.

Adverse Reactions/Side Effects

Central nervous system

  • central nervous system demyelinating disorders (life-threatening)
  • Guillain-Barre syndrome
  • multiple sclerosis

Ear, Eye, Nose, Throat

  • nasopharyngitis
  • optic neuritis

Respiratory

  • upper respiratory tract infection

Cardiovascular

  • HF (life-threatening)
  • hypertension

Gastrointestinal

  • ↑ liver enzymes

Dermatologic

  • psoriasis

Hematologic

  • aplastic anemia
  • leukopenia
  • neutropenia
  • pancytopenia
  • thrombocytopenia

Local

  • injection site reactions

Neurologic

  • paresthesia

Miscellaneous

  • anaphylaxis (life-threatening)
  • hypersensitivity reactions (life-threatening)
  • infections (including reactivation tuberculosis and other opportunistic infections due to bacterial, invasive fungal, viral, mycobacterial, and parasitic pathogens) (life-threatening)
  • malignancy (including lymphoma, HSTCL, leukemia, and skin cancer) (life-threatening)
  • fever

Interactions

Drug-Drug interaction

Abatacept, anakinra, corticosteroids, or methotrexate ↑ risk of serious infections; concurrent use with anakinra or abatacept is not recommended.↓ antibody response and ↑ risk of adverse reactions with live-virus vaccines.Concurrent use with azathioprine and/or methotrexate may ↑ risk of HSTCL.May normalize previously suppressed levels of CYP450 enzymes, following initiation or discontinuation of golimumab, effects of substrates of this system may be altered and should be monitored, including warfarin, theophylline, and cyclosporine.

Route/Dosage

Rheumatoid Arthritis

Subcutaneous (Adults) 50 mg once monthly.
Intravenous (Adults) 2 mg/kg initially and 4 wk later, then 2 mg/kg every 8 wk

Psoriatic Arthritis and Ankylosing Spondylitis

Subcutaneous (Adults) 50 mg once monthly.

Ulcerative Colitis

Subcutaneous (Adults) 200 mg initially, then 100 mg 2 wk later, then 100 mg every 4 wk.

Availability

Solution for subcutaneous injection: 50 mg/0.5 mL in single-dose prefilled syringes and Smartject autoinjectors, 100 mg/mL in single-dose prefilled syringes and Smartject autoinjectors
Solution for intravenous injection: 12.5 mg/mL

Nursing implications

Nursing assessment

  • Assess for signs and symptoms of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound) prior to, during, and after therapy. Discontinue therapy if serious or opportunistic infection or sepsis occurs. If new infection develops during therapy, assess patient and institute antimicrobial therapy. Patients who tested negative for latent tuberculosis (TB) prior to therapy may develop TB during therapy. Initiate treatment for latent TB prior to initiating therapy.
  • Test for HBV prior to therapy and monitor carriers of HBV for signs of reactivation during and for several months after therapy. If reactivation occurs, discontinue golimumab and institute antiviral therapy.
  • Monitor patients with HF for new or worsening symptoms. Discontinue therapy if symptoms occur.
  • Assess for exacerbations and new onset psoriasis. Discontinue therapy of these occur.
  • Assess patient for latex allergy. Needle cover of syringe contains latex and should not be handled by persons sensitive to latex.
  • Assess for signs and symptoms of systemic fungal infections (fever, malaise, weight loss, sweats, cough, dypsnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Ascertain if patient lives in or has traveled to areas of endemic mycoses. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until the pathogens are identified. Consult with an infectious diseases specialist. Consider stopping golimumab until the infection has been diagnosed and adequately treated.
  • Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician or other health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
  • Rheumatoid Arthritis: Assess pain and range of motion prior to and periodically during therapy.
  • Ulcerative Colitis: Assess for signs and symptoms before, during, and after therapy.
  • Lab Test Considerations: Monitor liver function tests periodically during therapy. May cause ↑ serum AST and ALT.
    • Monitor CBC with differential periodically during therapy. May cause leukopenia, neutropenia, thrombocytopenia, and pancytopenia. Discontinue golimumab if symptoms of blood dyscrasias (persistent fever) occur.
    • Monitor for HBV blood tests before starting during, and for several months after therapy is completed.

Potential Nursing Diagnoses

Chronic pain (Indications)
Risk for infection (Adverse Reactions)

Implementation

  • Administer a tuberculin skin test prior to administration of golimumab. Assess if treatment for latent tuberculosis is needed; an induration of 5 mm or greater is a positive tuberculin skin test, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG). Consider antituberculosis therapy prior to therapy in patients with a history of latent or active tuberculosis if an adequate course of treatment cannot be confirmed, and for patients with risk factors for tuberculosis infection.
  • Initial injection should be supervised by health care professional.
  • Refrigerate solution; do not freeze. Allow prefilled syringe or autoinjector to sit at room temperature for 30 min prior to injection; do not warm in any other way. Do not shake. Solution is clear to slightly opalescent and colorless to light yellow. Do not administer solutions that are discolored, cloudy, or contain particulate matter. Discard unused solution.
  • Subcutaneous: Remove the needle cover or autoinjector cap just prior to injection. Inject into front of middle thigh, lower part of abdomen 2 inches from navel, or caregiver may administer into outer area of upper arm. Do not inject in areas where skin is tender, bruised, red, scaly, or hard; avoid scars or stretch marks. Press a cotton ball or gauze over injection site for 10 sec; do not rub.
    • Autoinjector: Press open end of autoinjector against skin at 90° angle. Use free hand to pinch and hold skin at injection site. Press button with fingers or thumb; button will stay pressed and does not need to be held. Injection will begin following a loud click. Keep holding the autoinjector against skin until a second loud click is heard (usually 3–6 sec, but may take up to 15 sec). Lift autoinjector from skin following second click. Yellow indicator in viewing window indicates autoinjector worked correctly. If yellow does not appear in viewing window call 1-800-457-6399 for help.
    • Prefilled syringe: Hold body of syringe between thumb and index finger. Do not pull back on plunger at any time. Pinch skin. Using a dart-like motion, insert needle into pinched skin at 45° angle. Inject all medication by pushing plunger until plunger head is between needle guard wings. Take needle out of skin and let go of skin. Slowly take thumb off plunger to allow empty syringe to move up until entire needle is covered by needle guard.

Patient/Family Teaching

  • Instruct patient on correct technique for administration. Review patient information sheet, preparation of dose, administration sites and technique, and disposal of equipment into a puncture-resistant container. Advise patient of risks and benefits of golimumab therapy. Inject missed doses as soon as remembered, then return to regular schedule. Instruct patient to read Medication Guide before starting therapy and with each Rx refill; new information may be available.
  • Caution patient not to share this medication with others, even with the same symptoms; may be harmful.
  • Inform patient of increased risk of infections, malignancies, cardiac and nervous system disorders during therapy.
  • Caution patient to notify health care professional promptly if any signs of infection, including TB, invasive fungal infections (fever, malaise, weight loss, sweats, cough, dypsnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock), reactivation of HBV (muscle aches, clay-colored bowel movements, feeling very tired, fever, dark urine, chills, skin or eyes look yellow, stomach discomfort, little or no appetite, skin rash, vomiting), hypersensitivity reactions, or nervous system problems (vision changes, weakness in arms or legs, numbness or tingling in any part of the body) develop.
  • Advise patient to examine skin periodically during therapy and notify health care professional of any changes in appearance of skin or growths on skin.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Inform patient to avoid receiving live vaccinations; other vaccinations may be given.
  • Advise patient to notify health care professional of pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • Decreased pain and swelling with decreased rate of joint destruction in patients with rheumatoid arthritis.
  • Decreased signs and symptoms, slowed progression of joint destruction, and improved physical function in patients with psoriatic arthritis.
  • Reduced signs and symptoms of ankylosing spondylitis.
  • Decreased symptoms, maintaining remission and mucosal healing with decreased corticosteroid use in ulcerative colitis.
References in periodicals archive ?
Drugs profile mention in this report includes : adalimumab biosimilar, apremilast, BI-655066, certolizumab pegol biosimilar, COVA-322, DNX-114, DNX-514, etanercept biosimilar, golimumab, IBI-303, IBPM-004AM, IBPM-005IX, infliximab biobetter, INV-17, secukinumab, thalidomide, tofacitinib, VTP-43742.
Supply of low molecular weight heparins - Enoxaparinum Natrium, antibiotics, albumin, various drugs, contrast agents, drugs for neurological product Avilin Lotion Spray, alcohol, prescription medicines, omeprazole, medicines rheumatic medicinal products: certolizumab, golimumab, Lakcid and water Respiflo.
A Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of Subcutaneous Golimumab in Patients with Active Nonradiographic Axial Spondyloarthritis.
Biologic drugs in South Africa Biologic drug Mechanism of Route of action administration Infliximab Mouse/human IV every (Revellex) chimeric mab 8 weeks against TNF-[alpha] Etanercept Soluble TNF- SC weekly (Enbrel) [alpha] receptor fusion protein Adalimumab Mab against SC every (Humira) TNF-[alpha] other week Golimumab Human mab SC monthly (Simponi) against TNF-[alpha] Certolizumab Human mab SC monthly pego ([dagger]) against TNF-[alpha] Abatacept Receptor fusion IV monthly or (Orencia) protein inhibiting SC weekly T-cell co- stimulation Rituximab Mouse/human IV 6-monthly (Mabthera) chimeric mab against CD [20.
Five studies looked at the association of AABs with ACR response in infliximab, adalimumab, golimumab, abatacept, and rituximab.
Good to excellent responses were achieved with ustekinumab at doses of either 45 mg or 90 mg, depending on body weight, in 9 of 11 psoriasis patients who had experienced treatment failures on multiple biologics, including infliximab (11 patients), etanercept (10), efalizumab (9), adalimumab (7), and golimumab (3) (Int.
The immunomodulators are canakinumab (Ilaris; pregnancy class C), indicated for cryopyrin-associated periodic syndrome, and golimumab (Simponi; B), indicated (with or without methotrexate) for ankylosing spondylitis, active psoriatic arthritis, or rheumatoid arthritis.
Therapeutic use: Golimumab (19-22) is a human monoclonal antibody that binds to TNF-alpha, inhibiting its activity.
The findings may clear the way for European approval of the anti-inflammatory drug, called golimumab, which was approved in the United States in April.
Food and Drug Administration last month approved the sale of the medicine, which has the chemical name of golimumab.