certolizumab pegol
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.