certolizumab pegol

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certolizumab pegol

Cimzia

Pharmacologic class: Tumor necrosis factor (TNF) blocker

Therapeutic class: Immunomodulator

Pregnancy risk category B

FDA Box Warning

Serious infections

• Patients treated with certolizumab are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.

• Discontinue drug if patient develops serious infection or sepsis.

• Reported infections include active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Perform test for latent TB and if positive, start treatment for TB before starting drug. Monitor all patients for active TB during treatment, even if initial latent TB test is negative.

• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis, have been reported. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.

• Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria species, have occurred.

• Carefully consider risks and benefits of treatment with certolizumab before initiating therapy in patients with chronic or recurrent infection.

• Closely monitor patients for signs and symptoms of infection during and after treatment with certolizumab.

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with TNF blockers, of which certolizumab is a member.

• Drug isn't indicated for use in children.

Action

Binds to human TNF with a dissociation constant of 90 pM. TNF is a key proinflammatory cytokine with a central role in inflammatory processes. Selectively neutralizes TNF (IC90 of 4 ng/ml for inhibition of human TNF in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but doesn't neutralize lymphotoxin.

Availability

Powder for reconstitution, lyophilized: 200 mg in single-use vials

Prefilled syringe: 200 mg/ml in 1-ml single-use prefilled syringes

Indications and dosages

Moderate to severe Crohn's disease in patients with inadequate response to conventional therapy

Adults: Initially, 400 mg subcutaneously (given as two 200-mg injections), then at weeks 2 and 4. In patients with a clinical response, maintenance dosage is 400 mg q 4 weeks.

Moderate to severe rheumatoid arthritis
Adults: Initially, 400 mg subcutaneously (given as two 200-mg injections), then at weeks 2 and 4 followed by 200 mg q other week. Consider 400 mg q 4 weeks for maintenance dosing.

Contraindications

None

Precautions

Use cautiously in:
• hypersensitivity reactions
• congestive heart failure (CHF)
• chronic or recurrent infection, serious infections
• chronic hepatitis B virus (HBV) carriers
• preexisting or recent-onset central or peripheral nervous system demyelinating disorders
• significant hematologic abnormalities
• development of positive antinuclear antibody (ANA) titers
• concurrent use of anakinra, abatacept, rituximab, natalizumab, other TNF blockers, or other biological disease-modifying antirheumatics (use not recommended)
• concurrent use of live or attenuated vaccines (don't use)
• immunosuppression and concurrent use of immunosuppressants, such as corticosteroids or methotrexate
• elderly patients (don't use)
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

Be aware that patients with active infections shouldn't start treatment with certolizumab. Also, consider risks and benefits of treatment before starting drug in patients with chronic or recurrent infection; in those who have been exposed to TB; in those with 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 those with underlying conditions that may predispose to infection.
• Evaluate patients for TB risk factors and test for latent infection before starting drug.

Evaluate patients at risk 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; exercise caution when considering resumption of therapy.

Discontinue drug in patients who develop other serious infections or sepsis.

Discontinue drug in patients who develop signs and symptoms suggestive of a lupus-like syndrome following treatment.
• Consider discontining drug in patients with confirmed significant hematologic abnormalities.

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

Adverse reactions

CNS: headache, fatigue, anxiety, bipolar disorder, suicide attempt, transient ischemic attack, stroke

CV: hypertension, hypertensive heart disease, angina pectoris, MI, myocardial ischemia, pericardial effusion, pericarditis, arrhythmias, atrial fibrillation, CHF

EENT: optic neuritis, uveitis, retinal hemorrhage, nasopharyngitis, pharyngitis

GU: menstrual disorder, urinary tract infection, nephrotic syndrome, renal failure Hematologic: anemia, leukopenia, pancytopenia, thrombophilia, bleeding, thrombophlebitis, vasculitis

Hepatic: elevated liver enzyme levels, hepatitis

Musculoskeletal: arthralgia, back pain

Respiratory: upper respiratory tract infection, acute bronchitis

Skin: rash, alopecia totalis, dermatitis, erythema nodosum, urticaria

Other: pyrexia, injection-site reactions, lymphadenopathy, serious infections, malignancies, lupus-like syndrome, hypersensitivity

Interactions

Drug-drug.Abatacept, anakinra, natalizumab, rituximab, TNF blockers or other biological disease-modifying

antirheumatics: increased risk of serious infections

Live vaccines: increased risk of secondary transmission of disease and unknown response

Drug-diagnostic tests. ANA titers: increased risk of developing positive titers

APPT: elevated results

Patient monitoring

Continue to closely monitor patients for hypersensitivity reactions and treat appropriately.
• Closely monitor patients for 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 an immunocompromised patient, and be given appropriate antimicrobial therapy.
• Continue to evaluate patients for TB risk factors; test for latent infection periodically during therapy.
• For patients who reside or travel in regions where mycoses are endemic, suspect invasive fungal infection if serious systemic illness develops. Consider appropriate empiric antifungal therapy while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to institute empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in diagnosis and treatment of invasive fungal infections and should take into account both the risk of severe fungal infection and the risks of antifungal 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.
• Closely monitor patients who are carriers of HBV and require treatment with certolizumab for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.

Be aware that pancytopenia, including aplastic anemia, has been reported (rare) with TNF-blocker use. Watch for leukopenia, pancytopenia, or thrombocytopenia.

Watch for neurologic complications (rare), including new-onset or exacerbation of clinical symptoms or radiographic evidence of CNS demyelinating disease (including multiple sclerosis), peripheral demyelinating disease (including Guillain-Barré syndrome), seizure disorder, optic neuritis, and peripheral neuropathy.

Patient teaching

• Instruct patient who may self-inject on proper use of prefilled syringe, suitable injection sites (including thigh or abdomen), rotation of sites, and appropriate handling and disposal of syringe. Instruct patient to discard unused portions remaining in syringe.

Advise patient to seek immediate medical attention if signs or symptoms of severe allergic reactions occur.
• Advise patient to report new or worsening medical conditions, such as heart disease, neurologic disease, or autoimmune disorders, and to promptly report signs and symptoms suggestive of a cytopenia (such as bruising, bleeding, or persistent fever).
• Inform patient that drug may lower ability of immune system to fight infections. Instruct patient 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 while taking certolizumab.
• Tell patient to avoid taking live vaccines while using this drug.
• 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.

certolizumab pegol

(ser-toe-liz-u-mab pey-gol) ,

Cimzia

(trade name)

Classification

Therapeutic: gastroinestinal anti inflammatories
Pharmacologic: tumor necrosis factor blockers
Pregnancy Category: B

Indications

Moderately-to-severely active Crohn's disease when response to conventional therapy has been inadequate.Moderately-to-severely active rheumatoid arthritis.Active psoriatic arthritisActive ankylosing spondylitis

Action

Neutralizes tumor necrosis factor (TNF), a prime mediator of inflammation; pegylation provides a long duration of action.

Therapeutic effects

Decreased signs/symptoms of Crohn's disease.
Decreased pain and swelling, decreased rate of joint destruction and improved physical function in rheumatoid arthritis.
Decreased joint swelling and pain in psoriatic arthritis
Decreased spinal pain and inflammation in ankylosing spondylitis

Pharmacokinetics

Absorption: 80% absorbed following SC administration.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 14 days.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
Subcutunknown50–120 hr2–4 wk

Contraindications/Precautions

Contraindicated in: Active infection (including localized);Concurrent use of anakinra.
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 demyelinating disorders (may exacerbate);History of heart failure; Geriatric: May ↑ risk of infections; Obstetric: Use in pregnancy only if clearly needed; avoid breast feeding; Pediatric: Safety not established; ↑ risk of lymphoma (including hepatosplenic T-cell lymphoma [HSTCL] in patients with Crohn's disease), leukemia, and other malignancies.

Adverse Reactions/Side Effects

Dermatologic

  • psoriasis
  • skin reactions (rarely severe)

Hematologic

  • hematologic reactions

Musculoskeletal

  • arthralgia (most frequent)

Miscellaneous

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

Interactions

Drug-Drug interaction

Concurrent use with anakinra ↑ risk of serious infections (contraindicated).Concurrent use with azathioprine and/or methotrexate may ↑ risk of HSTCL.May ↓ antibody response to or ↑ risk of adverse reactions to live vaccines (contraindicated).

Route/Dosage

Crohn's Disease

Subcutaneous (Adults) 400 mg initially, repeat 2 and 4 wk later; may be followed by maintenance dose of 400 mg every 4 wk.

Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

Subcutaneous (Adults) 400 mg initially, repeat 2 and 4 wk later; then maintenance dose of 200 mg every 2 wk (400 mg every 4 wk may be used alternatively).

Availability

Lyophilized powder for subcutaneous injection (requires reconstitution): 200 mg/vial
Prefilled syringe: 200 mg/mL

Nursing implications

Nursing assessment

  • Crohn's Disease: Assess abdominal pain and frequency, quantity, and consistency of stools at beginning and during therapy.
  • Arthritis/Ankylosing Spondylitis: Assess pain and range of motion before and periodically during therapy.
  • Assess for signs of infection (fever, sore throat, dyspnea, WBC) prior to and during therapy. Monitor all patients for active TB during therapy, even if initial test was negative. Do not begin certolizumab during an active infection, including chronic or localized infections. If infection develops, monitor closely and discontinue certolizumab if infection becomes serious.
  • Evaluate patients at risk for hepatitis B virus (HBV) infection for prior evidence of HBV infection before initiating therapy. Monitor carriers of HBV closely for clinical and lab signs of active HBV infection during and for several months following discontinuation of therapy. If HBV reactivation occurs, discontinue certolizumab and initiate antiviral therapy.
  • Monitor for signs of hypersensitivity reactions (angioedema, dyspnea, hypotension, rash, serum sickness, urticaria). If reactions occur, discontinue certolizumab and treat symptomatically.
  • 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 certolizumab until the infection has been diagnosed and adequately treated.
  • Lab Test Considerations: May cause anemia, leukopenia, pancytopenia, and thrombocytopenia.
    • Monitor CBC with differential periodically during therapy. May cause leukopenia, neutropenia, thrombocytopenia, and pancytopenia. Discontinue certolizumab if symptoms of blood dyscrasias (persistent fever) occur.
    • May cause ↑ liver enzymes.
    • May cause erroneously ↑ aPTT.

Potential Nursing Diagnoses

Risk for infection (Side Effects)

Implementation

  • Perform test for latent TB. If positive, begin treatment for TB prior to starting certolizumab therapy. Monitor for TB throughout therapy, even if latent TB test is negative.
    • Bring medication to room temperature prior to reconstituting. Reconstitute 2 vials for each dose by adding 1 mL of Sterile Water for injection to each vial, using a 20-gauge needle, for a concentration of 200 mg/mL. Gently swirl so all powder comes into contact with sterile water; do not shake. Leave vials undisturbed for as long as 30 min to fully reconstitute. Solution is clear and colorless to pale yellow; do not administer solutions that are discolored or contain particulate matter. Do not leave reconstituted solution at room temperature for >2 hr prior to injection. May be refrigerated for up to 24 hr prior to injection; do not freeze.
  • Subcutaneous: Bring solution to room temperature prior to injection. Using a new 20-gauge needle for each vial, withdraw reconstituted solution into 2 separate syringes each containing 1 mL (200 mg/mL) of certolizumab. Switch each 20-gauge needle to a 23-gauge needle and inject the full contents of each syringe subcut into separate sides of the abdomen or thigh.

Patient/Family Teaching

  • Advise patient of potential benefits and risks of certolizumab. Advise patient to read the Medication Guide prior to starting therapy.
  • Inform patient of risk of infection. Advise patient to notify health care professional if symptoms of infection (fever, cough, flu-like symptoms, or open cuts or sores), including TB or reactivation of HBV infection, occur.
  • Counsel patient about possible risk of lymphoma and other malignancies while receiving certolizumab.
  • Advise patient to notify health care professional if signs of hypersensitivity reactions (rash, swollen face, difficulty breathing), or new or worsening medical conditions such as heart or neurological disease or autoimmune disorders occur and to report signs of bone marrow depression (bruising, bleeding, or persistent failure).
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional prior to taking any Rx, OTC, vitamins, or herbal products.
  • Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • Decrease in signs and symptoms of Crohn's disease.
  • Decreased pain and swelling with decreased rate of joint destruction in patients with rheumatoid arthritis.
  • Decreased joint swelling and pain in psoriatic arthritis
  • Decreased spinal pain and inflammation in ankylosing spondylitis
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References in periodicals archive ?
or Europe through partnerships with leading biopharmaceutical companies, including AstraZeneca's MOVANTIK(TM), Baxalta's ADYNOVATE(TM), UCB's Cimzia for Crohn's disease and rheumatoid arthritis, Roche's PEGASYS for hepatitis C and Amgen's Neulasta for neutropenia.
Certoliumabum pegol - Cimzia - roztrwEr for injection13.
Cimzia, Vimpat and Neupro generated combined net sales of EUR 433 million, while anti-epilepticA drugA Keppra reached EUR 190 million.
During experiments, the Cimzia jabs showed rapid improvements in pain, stiffness and mobility, the Daily Express reported.
The TNF blockers that will receive the warnings include Remicade (infliximab), Enbrel (etanercept), Humira (adali-mumab), Cimzia (certolizumab pegol), and Simponi (golimumab), according to the FDA announcement.
Cimzia is used in treatment of Crohn's disease and rheumatoid arthritis, Vimpat is an anti-epileptic drug, while Neupro is prescribed for Parkinson's disease.
It is also available to Crohn's disease patients taking Cimzia for subcutaneous self-administration.
NICE last month recommended use of Cimzia for rheumatoid arthritis after the manufacturer, Belgium's UCB SA, said it would provide the treatment for free for the first 12 weeks of use.
The FDA has just approved Cimzia, an extremely dangerous drug (already used for Crohn's disease), to treat rheumatoid arthritis.
These injectable drugs--Enbrel, Remicade, Humira, and Cimzia suppress the immune system to keep it from attacking the body.
However, active tuberculosis has developed in patients receiving Cimzia whose tuberculin test was negative.
The FDA has granted approval to Cimzia (certolizumab pegol) for adults with moderate to severe Crohn's disease who have not responded to conventional therapies.