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CERTOLIZUMAB PEGOL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Certolizumab pegol is a tumor necrosis factor (TNF) inhibitor (specifically TNF-alpha), which results in an interference in the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide.

Specific Substances

    1) CDP-870
    2) Certolizumabum Pegolum
    3) PHA-738144
    4) CAS 428863-50-7
    1.2.1) MOLECULAR FORMULA
    1) C2115H3252N556O673S16

Available Forms Sources

    A) FORMS
    1) Certolizumab pegol is available in the US as 200 mg lyophilized powder for reconstitution with 1 mL of sterile water for injection and as 200 mg/mL in a single-use prefilled glass syringe (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) USES
    1) Certolizumab pegol is indicated for maintaining clinical response and reducing signs and symptoms of moderate to severe Crohn's disease in adults who had inadequate response to conventional therapy (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    2) It is also indicated for treatment of adults with moderate to severe active rheumatoid arthritis (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Certolizumab pegol is indicated for the treatment of adults with moderate to severe active rheumatoid arthritis. It is also approved for maintaining clinical response and reducing signs and symptoms of moderate to severe Crohn's disease in adults who had inadequate response to conventional therapy.
    B) PHARMACOLOGY: Certolizumab pegol is a tumor necrosis factor (TNF) inhibitor (specifically TNF-alpha), which results in an interference in the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide.
    C) EPIDEMIOLOGY: Overdose is very rare.
    D) WITH THERAPEUTIC USE
    1) COMMON: Upper respiratory infections (eg; nasopharyngitis, laryngitis, viral infection), urinary tract infections (eg; bladder infection, bacteriuria, cystitis), and arthralgia. LESS COMMON: Although the causal relationship to certolizumab pegol is not clear, the following adverse reactions were reported during studies of patients receiving certolizumab pegol therapy: angina pectoris, dysrhythmias, cardiac failure, myocardial infarction, myocardial ischemia, pericardial effusion, pericarditis, bleeding and injection site reaction, alopecia totalis, dermatitis, erythema nodosum, urticaria, abdominal pain, diarrhea, intestinal obstruction, nephrotic syndrome, renal failure, optic neuritis, uveitis, retinal hemorrhage, anemia, leukopenia, pancytopenia, lymphadenopathy, thrombophilia, elevated liver enzymes, hepatitis, seizure, peripheral neuropathy, and anxiety. Tuberculosis (TB), including disseminated and pulmonary TB, some cases fatal, has been reported with certolizumab pegol therapy.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: There are no reports of toxicity following acute overdose. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.
    0.2.20) REPRODUCTIVE
    A) Certolizumab pegol is classified as FDA pregnancy category B.
    0.2.21) CARCINOGENICITY
    A) In studies, more cases of malignancies have been observed among patients receiving TNF blockers compared to controls. However, the cases have been reported in children and young adults and certolizumab pegol is not approved for use in pediatric patients.

Laboratory Monitoring

    A) Monitor patients for clinical signs of infection.
    B) Monitor ECG, liver enzymes and renal function in symptomatic patients.
    C) Monitor serial CBC with differential.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor patients for clinical signs of infection.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Myelosuppression has been reported. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg; filgrastim, sargramostim). Transfusions as needed for severe thrombocytopenia, bleeding.
    C) DECONTAMINATION
    1) Decontamination is not necessary.
    D) AIRWAY MANAGEMENT
    1) Endotracheal intubation and mechanical ventilation may be required in patients with severe allergic reactions, but this is rare.
    E) ANTIDOTE
    1) None
    F) ACUTE ALLERGIC REACTION
    1) MILD to MODERATE effects: Monitor airway. Administer antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE Effects: Administer oxygen, aggressive airway management may be necessary. Administer antihistamines, epinephrine, corticosteroids as needed. Treatment includes IV fluids and ECG monitoring.
    G) MYELOSUPPRESSION
    1) For severe neutropenia, administer colony stimulating factor. Filgrastim 5 mcg/kg/day subQ or IV over 15 to 30 minutes OR sargramostim 250 mcg/meter(2)/day IV over 4 hours. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage.
    H) PATIENT DISPOSITION
    1) OBSERVATION CRITERIA: Mild to moderately symptomatic patients should be sent to a health care facility for evaluation and treated until symptoms resolve.
    2) ADMISSION CRITERIA: Patients who remain symptomatic despite adequate treatment should be admitted.
    3) CONSULT CRITERIA: Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    I) PITFALLS
    1) When managing a suspected certolizumab pegol overdose, the possibility of multi-drug involvement should be considered.
    J) PHARMACOKINETICS
    1) Subcutaneous bioavailability: 80%. Volume of distribution 6 to 8 L. Elimination half-life was approximately 14 days for all doses tested. Following subcutaneous administration of certolizumab pegol (up to 800 mg), the peak plasma concentrations were reached in 54 to 171 hours.
    K) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause myelosuppression (eg; methotrexate), elevated liver enzymes (eg; ethanol, acetaminophen), dysrhythmias, or renal dysfunction (eg; NSAIDs).

Range Of Toxicity

    A) TOXICITY: A toxic dose has not been established. Certolizumab pegol doses up to 800 mg subcutaneous and 20 mg/kg intravenous have been used in therapeutic trials with no adverse effects.
    B) THERAPEUTIC DOSE: Initial, 400 mg given as 2 subcutaneous injections of 200 mg. Crohn's Disease: 400 mg initially and at weeks 2 and 4, followed by 400 mg every 4 weeks. Rheumatoid Arthritis: 400 mg initially and at weeks 2 and 4, followed by 200 mg every other week. Maintenance dose: 400 mg every 4 weeks.

Clinical Effects

Summary Of Exposure

    A) USES: Certolizumab pegol is indicated for the treatment of adults with moderate to severe active rheumatoid arthritis. It is also approved for maintaining clinical response and reducing signs and symptoms of moderate to severe Crohn's disease in adults who had inadequate response to conventional therapy.
    B) PHARMACOLOGY: Certolizumab pegol is a tumor necrosis factor (TNF) inhibitor (specifically TNF-alpha), which results in an interference in the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide.
    C) EPIDEMIOLOGY: Overdose is very rare.
    D) WITH THERAPEUTIC USE
    1) COMMON: Upper respiratory infections (eg; nasopharyngitis, laryngitis, viral infection), urinary tract infections (eg; bladder infection, bacteriuria, cystitis), and arthralgia. LESS COMMON: Although the causal relationship to certolizumab pegol is not clear, the following adverse reactions were reported during studies of patients receiving certolizumab pegol therapy: angina pectoris, dysrhythmias, cardiac failure, myocardial infarction, myocardial ischemia, pericardial effusion, pericarditis, bleeding and injection site reaction, alopecia totalis, dermatitis, erythema nodosum, urticaria, abdominal pain, diarrhea, intestinal obstruction, nephrotic syndrome, renal failure, optic neuritis, uveitis, retinal hemorrhage, anemia, leukopenia, pancytopenia, lymphadenopathy, thrombophilia, elevated liver enzymes, hepatitis, seizure, peripheral neuropathy, and anxiety. Tuberculosis (TB), including disseminated and pulmonary TB, some cases fatal, has been reported with certolizumab pegol therapy.
    E) WITH POISONING/EXPOSURE
    1) TOXICITY: There are no reports of toxicity following acute overdose. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, optic neuritis, uveitis and retinal hemorrhage were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CONGESTIVE HEART FAILURE
    1) WITH THERAPEUTIC USE
    a) Cases of new onset or worsening congestive heart failure (CHF) have been reported with tumor necrosis factor (TNF) blockers. Although certolizumab pegol has not been formerly studied in patients with CHF, cardiac failure has been observed with certolizumab pegol treatment during controlled or uncontrolled studies of Crohn's disease and other diseases under investigation (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) CARDIOVASCULAR FINDING
    1) WITH THERAPEUTIC USE
    a) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, the following adverse reactions were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear:
    1) Angina pectoris, dysrhythmias, cardiac failure, myocardial infarction, myocardial ischemia, pericardial effusion, and pericarditis (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) TUBERCULOSIS
    1) WITH THERAPEUTIC USE
    a) Tuberculosis (TB), including disseminated and pulmonary TB, some cases fatal, has been reported with certolizumab pegol therapy. The rate of TB was 0.5 per 100 patient-years from collective study data in completed and ongoing clinical trials (n=4650) and 0.3 per 100 patient-years among Crohn's disease patients (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) UPPER RESPIRATORY INFECTION
    1) WITH THERAPEUTIC USE
    a) During clinical studies in patients with Crohn's disease, upper respiratory infection (eg; nasopharyngitis, laryngitis, viral infection) was reported in 20% of patients receiving certolizumab pegol (n=620) compared with 13% of patients receiving placebo (n=614) (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) DEMYELINATING DISEASE OF CENTRAL NERVOUS SYSTEM
    1) WITH THERAPEUTIC USE
    a) Rare cases of new-onset or exacerbation of clinical and/or radiologic evidence of demyelinating disease have been reported in association with tumor necrosis factor (TNF) blockers, including certolizumab pegol (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) SEIZURE
    1) WITH THERAPEUTIC USE
    a) Although the causal relationship to certolizumab pegol is not clear, neurologic disorders, including seizure disorders, have been observed with certolizumab pegol treatment (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    C) DISORDER OF THE PERIPHERAL NERVOUS SYSTEM
    1) WITH THERAPEUTIC USE
    a) Although the causal relationship to certolizumab pegol is not clear, neurologic disorders, including peripheral neuropathy, have been observed with certolizumab pegol treatment (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH THERAPEUTIC USE
    a) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, abdominal pain, diarrhea, and intestinal obstruction were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TYPE B VIRAL HEPATITIS
    1) WITH THERAPEUTIC USE
    a) Hepatitis B virus (HBV) reactivation (in patients who are chronic carriers) may occur with tumor necrosis factor (TNF) blocker therapy, including certolizumab pegol. Fatalities have been reported as a result of HBV reactivation in patient receiving treatment with a TNF blocker. The majority of these cases occurred in patients who were also receiving other immunosuppressant drugs (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) INFLAMMATORY DISEASE OF LIVER
    1) WITH THERAPEUTIC USE
    a) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, elevated liver enzymes and hepatitis were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) URINARY TRACT INFECTIOUS DISEASE
    1) WITH THERAPEUTIC USE
    a) During clinical studies in patients with Crohn's disease, urinary tract infection (eg; bladder infection, bacteriuria, cystitis) was reported in 7% of patients receiving certolizumab pegol (n=620) compared with 6% of patients receiving placebo (n=614) (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) UROGENITAL FINDING
    1) WITH THERAPEUTIC USE
    a) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, nephrotic syndrome and renal failure were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) WITH THERAPEUTIC USE
    a) Tumor necrosis factor (TNF) blockers have been rarely associated with cases of pancytopenia, including aplastic anemia. Medically-significant cytopenias (eg, thrombocytopenia, pancytopenia, leukopenia) have been reported infrequently with the use of certolizumab pegol (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    b) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, anemia, leukopenia, pancytopenia, and thrombophilia were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) DERMATOLOGICAL FINDING
    1) WITH THERAPEUTIC USE
    a) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, the following adverse reactions were reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear:
    1) Bleeding and injection site reaction, alopecia totalis, dermatitis, erythema nodosum, and urticaria (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) WITH THERAPEUTIC USE
    a) During clinical studies in patients with Crohn's disease, arthralgia was reported in 6% of patients receiving certolizumab pegol (n=620) compared with 4% of patients receiving placebo (n=614) (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) LYMPHADENOPATHY
    1) WITH THERAPEUTIC USE
    a) During controlled or uncontrolled studies of Crohn's disease and other diseases under investigation, lymphadenopathy has been reported in patients receiving certolizumab pegol therapy; however, the causal relationship to certolizumab pegol is not clear (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).
    B) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reactions (eg, allergic dermatitis, angioedema, dizziness, dyspnea, hot flush, injection-site reaction, malaise, postural hypotension, pyrexia, rash, serum sickness, syncope, and urticaria) have been reported rarely following certolizumab pegol administration (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Reproductive

    3.20.1) SUMMARY
    A) Certolizumab pegol is classified as FDA pregnancy category B.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Certolizumab pegol is classified as FDA pregnancy category B (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    B) PREGNANCY REGISTRY
    1) A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to certolizumab pegol during pregnancy. Patients may be registered by calling 1-877-311-8972 (Prod Info CIMZIA(R) subcutaneous injection powder, 2013)
    C) PLACENTAL TRANSFER
    1) Certolizumab pegol administration in pregnant women with Crohn's disease resulted in measurable certolizumab pegol concentrations in infant, cord, and maternal blood. The last dose of certolizumab pegol (400 mg for every mother) was administered 19 days prior to delivery on average (range, 5 to 42 days) and resulted in certolizumab pegol concentrations of less than 0.41 to 1.66 mcg/mL, less than 0.41 to 1.58 mcg/mL, and 1.87 to 59.57 mcg/mL in cord blood, infant blood, and maternal blood, respectively (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    D) ANIMAL STUDIES
    1) There was no evidence of fetal harm during animal studies with certolizumab pegol doses up to 100 mg/kg (Prod Info CIMZIA(R) subcutaneous injection powder, 2013)
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is unknown whether certolizumab pegol is excreted in human milk. Due to the potential for adverse reactions in the nursing infant, either discontinue nursing or discontinue certolizumab pegol taking into account the importance of the drug to the mother (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    3.20.5) FERTILITY
    A) LACK OF EFFECT
    1) There was no evidence impaired fertility during animal studies with certolizumab pegol doses up to 100 mg/kg (Prod Info CIMZIA(R) subcutaneous injection powder, 2013)

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) In studies, more cases of malignancies have been observed among patients receiving TNF blockers compared to controls. However, the cases have been reported in children and young adults and certolizumab pegol is not approved for use in pediatric patients.
    3.21.3) HUMAN STUDIES
    A) RATE OF MALIGNANCY
    1) In controlled and open-labeled portions of certolizumab pegol trials of Crohn's disease and other investigational uses, the rate of malignancy (other than non-melanoma skin cancer) was 0.5 (95% confidence interval (CI), 0.4 to 0.7) per 100 patient-years among 4650 certolizumab-treated patients and 0.6 (95% CI, 0.1 to 1.7) per 100 patient-years for 1319 placebo-treated patients (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    2) Malignancies, some fatal, have been reported in children and young adults who received tumor necrosis factor (TNF) blockers (Prod Info CIMZIA(R) subcutaneous injection powder, 2013). Over a 10-year period, there were 30 reports of cancer in children and young adults who received TNF blockers and other immunosuppressive agents (eg, methotrexate, azathioprine or 6-mercaptopurine) for Juvenile Idiopathic Arthritis, Crohn's disease or other diseases (US Food and Drug Administration, 2008). Approximately 50% of the cancers were lymphomas (both Hodgkin's and non-Hodgkin's lymphoma), and others reported included rare malignancies usually associated with immunosuppression and malignancies not observed in children and adolescents. The malignancies occurred after a median duration of therapy of 30 months (range, 1 to 84 months). Certolizumab pegol is not approved for use in pediatric patients (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    B) LYMPHOMA
    1) During controlled studies of Crohn's disease and other diseases under investigation, lymphoma was reported in 1 patient who received certolizumab pegol (n=2657) and 1 patient (with Hodgkin lymphoma) in the placebo group (n=1319). During placebo-controlled and open label studies of patients with rheumatoid arthritis, lymphoma was reported in 3 patients who received certolizumab pegol (n=2367), which is approximately 2-fold higher than expected in the general population(Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    2) Hepatosplenic T-cell lymphoma, a rare but very aggressive and usually fatal type of T-cell lymphoma, has been reported during postmarketing surveillance of patients who received tumor necrosis factor (TNF) blockers, including certolizumab pegol. Most of the reported cases occurred in adolescent and young adult male patients with Crohn's disease or ulcerative colitis who received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF blocker (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor patients for clinical signs of infection.
    B) Monitor ECG, liver enzymes and renal function in symptomatic patients.
    C) Monitor serial CBC with differential.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients who remain symptomatic despite adequate treatment should be admitted.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Mild to moderately symptomatic patients should be sent to a health care facility for evaluation and treatment as necessary.

Monitoring

    A) Monitor patients for clinical signs of infection.
    B) Monitor ECG, liver enzymes and renal function in symptomatic patients.
    C) Monitor serial CBC with differential.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not necessary.

Range Of Toxicity

Summary

    A) TOXICITY: A toxic dose has not been established. Certolizumab pegol doses up to 800 mg subcutaneous and 20 mg/kg intravenous have been used in therapeutic trials with no adverse effects.
    B) THERAPEUTIC DOSE: Initial, 400 mg given as 2 subcutaneous injections of 200 mg. Crohn's Disease: 400 mg initially and at weeks 2 and 4, followed by 400 mg every 4 weeks. Rheumatoid Arthritis: 400 mg initially and at weeks 2 and 4, followed by 200 mg every other week. Maintenance dose: 400 mg every 4 weeks.

Therapeutic Dose

    7.2.1) ADULT
    A) CROHN'S DISEASE: Initially, 400 mg SubQ (as 2 SubQ injections of 200 mg each) once and then repeat at weeks 2 and 4. The maintenance dose of 400 mg SubQ every 4 weeks (Prod Info CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, 2013).
    B) RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS: Initially, 400 mg SubQ (as 2 SubQ injections of 200 mg each) once and then repeat at weeks 2 and 4, followed by 200 mg every other week. The maintenance dose of 400 mg SubQ every 4 weeks can be considered (Prod Info CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, 2013).
    C) ANKYLOSING SPONDYLITIS: Initially, 400 mg subQ (2 subQ injections of 200 mg each) once and then repeat at weeks 2 and 4, followed by 200 mg subQ every 2 weeks OR 400 mg subQ every 4 weeks (Prod Info CIMZIA(R) subcutaneous injection powder, 2013).
    7.2.2) PEDIATRIC
    A) The safety and efficacy of certolizumab pegol have not been established in pediatric patients (Prod Info CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, 2013).

Maximum Tolerated Exposure

    A) A toxic dose has not been established. Certolizumab pegol doses up to 800 mg subcutaneous and 20 mg/kg intravenous have been used in therapeutic trials with no adverse effects (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Certolizumab pegol is a tumor necrosis factor (TNF) inhibitor, which acts by binding and selectively neutralizing TNF-alfa. It does not neutralize TNF-beta. The inhibition of TNF-alfa, which is strongly expressed in the bowel wall and feces of patients with Crohn's disease, results in an interference in the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide (Prod Info CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, 2009).

Physicochemical

Physical Characteristics

    A) Powder for solution is a sterile, white, lyophilized powder. Prefilled syringes contain a sterile, clear to opalescent solution that is colorless to pale yellow and essentially free from particulates (Prod Info CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, 2013).

Ph

    A) Approximately 5.2: when reconstituted with sterile water for injection (Prod Info CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, 2013)

Molecular Weight

    A) Approximately 91 kilodaltons (Prod Info CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, 2013)

References

General Bibliography

    1) Beauchesne MF & Shalansky SJ: Nonchemotherapy drug-induced agranulocytosis: a review of 118 patients treated with colony-stimulating factors. Pharmacotherapy 1999; 19(3):299-305.
    2) Hartman LC, Tschetter LK, Habermann TM, et al: Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.. N Engl J Med 1997; 336:1776-1780.
    3) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    4) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    5) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    6) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    7) Product Information: CIMZIA(R) lyophilized powder for solution, solution for subcutaneous injection, certolizumab pegol lyophilized powder for solution, solution for subcutaneous injection. UCB Inc, Smyrna, GA, 2009.
    8) Product Information: CIMZIA(R) subcutaneous injection lyophilized powder for solution, subcutaneous injection solution, certolizumab pegol subcutaneous injection lyophilized powder for solution, subcutaneous injection solution. UCB, Inc. (per FDA), Smyrna, GA, 2013.
    9) Product Information: CIMZIA(R) subcutaneous injection powder, certolizumab pegol subcutaneous injection powder. UCB, Inc. (per manufacturer), Smyrna, GA, 2013.
    10) Product Information: LEUKINE(R) injection, sargramostim injection. Berlex, Seattle, WA, 2006.
    11) Product Information: NEUPOGEN(R) injection, filgrastim injection. Amgen,Inc, Thousand Oaks, CA, 2006.
    12) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    13) Stull DM, Bilmes R, Kim H, et al: Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm 2005; 62(1):83-87.
    14) US Food and Drug Administration: Early Communication About an Ongoing Safety Review of Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, and Cimzia). US Food and Drug Administration. Rockville, MD. 2008. Available from URL: http://www.fda.gov/cder/drug/early_comm/TNF_blockers.htm.
    15) Vanden Hoek,TL; Morrison LJ; Shuster M; et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.