Cimzia

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category B. There are no well-done studies that have been done in humans with this medication. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Cimzia during pregnancy. To enroll, healthcare providers or patients can call 1-877-311-8972.

Lyophilized Powder for Reconstitution:

• If your doctor prescribes the Cimzia powder for reconstitution, Cimzia should be injected by a healthcare provider. Each dose of Cimzia will be given as one or two separate injections under the skin in your stomach area (abdomen) or upper leg (thigh).
• Make sure to keep all of your injection and follow-up appointments with your doctor.

Prefilled Syringe:

• If your doctor prescribes the Cimzia prefilled syringe, see the booklet called "Patient Instructions for Use" packed in your Cimzia  prefilled syringe kit for complete instructions for use.
• Do not give yourself an injection of Cimzia unless you have been shown by your doctor or nurse. Call your doctor if you have questions. Someone you know can also help you with your injection after they have been trained by your doctor or nurse.
• Cimzia is given by an injection under the skin. Your doctor will tell you how much Cimzia to inject and how often to inject Cimzia, based on your condition to be treated. Do not use more Cimzia or inject more often than prescribed.
• Depending on the amount of Cimzia prescribed by your doctor, you may need more than one injection at a time.
• If you are prescribed to take 400 mg of Cimzia, you will need two injections. You will need to use two Cimzia prefilled syringes.
• Cimzia may be injected into your abdomen or thigh area. If you are prescribed to have more than one injection, each injection should be given at a different site in your abdomen or thigh.
• Make sure the solution in the prefilled syringe is clear and colorless to light yellow. The solution should be essentially free from particles. Do not use the Cimzia prefilled syringe if the medicine looks cloudy or if there are large or colored particles.
• Do not miss any doses of Cimzia. If you forget to take Cimzia, inject a dose as soon as you remember. Then, take your next dose at your regularly scheduled time.
• Make sure to keep all follow-up appointments with your doctor.

Certolizumab reduces the effects of a substance in the body that can cause inflammation.

Certolizumab is used to treat the symptoms of Crohn's disease after other drugs have been tried without successful treatment of symptoms. Certolizumab is also used to treat moderate to severe rheumatoid arthritis in adults.

Certolizumab may also be used for purposes not listed in this medication guide.

Before you start treatment with certolizumab, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Certolizumab is given as two injections under the skin of your stomach or thigh. This medication is usually given every 2 to 4 weeks. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to give the injection and properly dispose of used needles and syringes.

Do not use the medicine if it looks cloudy or has particles in it. Call your pharmacist for new medication.

Certolizumab can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill.

Your blood may need to be tested often. Your skin may also need to be checked for signs of skin cancer.

If you have ever had hepatitis B, certolizumab can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

Store this medicine in its original carton in the refrigerator. Protect from light and do not freeze.

Each single-use prefilled syringe is for one use only. Throw away after one use, even if there is still medicine left inside.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Call your doctor for instructions if you miss a dose of certolizumab.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• abatacept;

• adalimumab;

• anakinra;

• etanercept;

• golimumab;

• infliximab;

• natalizumab; or

• rituximab.

This list is not complete. Other drugs may interact with certolizumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

A nurse or other trained health professional will give you this medicine. This medicine is given as a shot under your skin, usually on the abdomen (stomach) or upper thighs.

This medicine comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Certolizumab may also be given at home. If you are using this medicine at home, your doctor or nurse will teach you how to prepare and inject the medicine. Be sure that you understand how to use the medicine.

To use the prefilled syringe:

• Gather the items you will need on a clean, flat surface using a cloth or towel in a well-lighted area.
• Remove the carton with the syringe from the refrigerator and place it on the clean cloth.
• Allow 30 minutes for the syringe to warm up to room temperature. Do not warm this medicine in any other way.
• Wash your hands with soap and water before and after using this medicine.
• Choose an injection site on your body. Use a different body area for each shot. Keep track of where you give each shot so you can rotate body areas.
• Clean the injection site with an alcohol swab, and do not touch the area until you are ready for injection.
• Remove the needle cover when you are ready to inject.
• Hold the syringe with one hand between the thumb and index fingers. Do not to touch the needle or let it touch any surface.
• Use your free hand to pinch and hold the skin at the injection site.
• Inject the medicine in a dart-like motion into the pinched skin at a 45-degree angle.
• Use your thumb to push the plunger and inject the full dose of the medicine. Pull the needle out of the skin.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form (prefilled syringe):
  • For ankylosing spondylitis:
    • Adults—At first, 400 milligrams (mg) given as 2 doses of 200 mg injected under the skin. This dose is repeated after 2 weeks and 4 weeks. Your doctor may continue the dose as 200 mg every 2 weeks or 400 mg every 4 weeks.
    • Children—Use and dose must be determined by your doctor.
  • For Crohn disease:
    • Adults—At first, 400 milligrams (mg) given as 2 doses of 200 mg injected under the skin. This dose is repeated after 2 weeks and 4 weeks. Your doctor may continue the dose as 400 mg every 4 weeks.
    • Children—Use and dose must be determined by your doctor.
  • For psoriatic arthritis:
    • Adults—At first, 400 milligrams (mg) given as 2 doses of 200 mg injected under the skin. This dose is repeated after 2 weeks and 4 weeks. Your doctor may continue the dose as 200 mg every other week or 400 mg every 4 weeks.
    • Children—Use and dose must be determined by your doctor.
  • For rheumatoid arthritis:
    • Adults—At first, 400 milligrams (mg) given as 2 doses of 200 mg injected under the skin. This dose is repeated after 2 weeks and 4 weeks. Your doctor may continue the dose as 200 mg every other week or 400 mg every 4 weeks.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

Protect the medicine from direct light. Keep your medicine in the original package until you are ready to use it.

Throw away used syringes in a hard, closed container (puncture-resistant) that the needles cannot poke through. Keep this container away from children and pets.

Clinical Trials Experience

The most serious adverse reactions were:

• Serious Infections [see Warnings and Precautions (5.1)]
• Malignancies [see Warnings and Precautions (5.2)]
• Heart Failure [see Warnings and Precautions (5.3)]

Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug, and may not predict the rates observed in a broader patient population in clinical practice.

In premarketing controlled trials of all patient populations combined the most common adverse reactions (≥ 8%) were upper respiratory infections (18%), rash (9%) and urinary tract infections (8%).

Adverse Reactions Most Commonly Leading to Discontinuation of Treatment in Premarketing Controlled Trials

The proportion of patients with Crohn's disease who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for Cimzia and 7% for placebo. The most common adverse reactions leading to the discontinuation of Cimzia (for at least 2 patients and with a higher incidence than placebo) were abdominal pain (0.4% Cimzia, 0.2% placebo), diarrhea (0.4% Cimzia, 0% placebo), and intestinal obstruction (0.4% Cimzia, 0% placebo).

The proportion of patients with rheumatoid arthritis who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for Cimzia and 2.5% for placebo. The most common adverse reactions leading to discontinuation of Cimzia were tuberculosis infections (0.5%); and pyrexia, urticaria, pneumonia, and rash (0.3%).

Controlled Studies with Crohn's Disease

The data described below reflect exposure to Cimzia at 400 mg subcutaneous dosing in studies of patients with Crohn's disease. In the safety population in controlled studies, a total of 620 patients with Crohn's disease received Cimzia at a dose of 400 mg, and 614 subjects received placebo (including subjects randomized to placebo in Study CD2 following open label dosing of Cimzia at Weeks 0, 2, 4). In controlled and uncontrolled studies, 1,564 patients received Cimzia at some dose level, of whom 1,350 patients received 400 mg Cimzia. Approximately 55% of subjects were female, 45% were male, and 94% were Caucasian. The majority of patients in the active group were between the ages of 18 and 64.

During controlled clinical studies, the proportion of patients with serious adverse reactions was 10% for Cimzia and 9% for placebo. The most common adverse reactions (occurring in ≥ 5% of Cimzia-treated patients, and with a higher incidence compared to placebo) in controlled clinical studies with Cimzia were upper respiratory infections (e.g. nasopharyngitis, laryngitis, viral infection) in 20% of Cimzia-treated patients and 13% of placebo-treated patients, urinary tract infections (e.g. bladder infection, bacteriuria, cystitis) in 7% of Cimzia-treated patients and in 6% of placebo-treated patients, and arthralgia (6% Cimzia, 4% placebo).

Other Adverse Reactions

The most commonly occurring adverse reactions in controlled trials of Crohn's disease were described above. Other serious or significant adverse reactions reported in controlled and uncontrolled studies in Crohn's disease and other diseases, occurring in patients receiving Cimzia at doses of 400 mg or other doses include:

Blood and lymphatic system disorders: Anemia, leukopenia, lymphadenopathy, pancytopenia, and thrombophilia.

Cardiac disorders: Angina pectoris, arrhythmias, atrial fibrillation, cardiac failure, hypertensive heart disease, myocardial infarction, myocardial ischemia, pericardial effusion, pericarditis, stroke and transient ischemic attack.

Eye disorders: Optic neuritis, retinal hemorrhage, and uveitis.

General disorders and administration site conditions: Bleeding and injection site reactions.

Hepatobiliary disorders: Elevated liver enzymes and hepatitis.

Immune system disorders: Alopecia totalis.

Psychiatric disorders: Anxiety, bipolar disorder, and suicide attempt.

Renal and urinary disorders: Nephrotic syndrome and renal failure.

Reproductive system and breast disorders: Menstrual disorder.

Skin and subcutaneous tissue disorders: Dermatitis, erythema nodosum, and urticaria.

Vascular disorders: Thrombophlebitis, vasculitis.

Controlled Studies with Rheumatoid Arthritis

Cimzia was studied primarily in placebo-controlled trials and in long-term follow-up studies. The data described below reflect the exposure to Cimzia in 2,367 RA patients, including 2,030 exposed for at least 6 months, 1,663 exposed for at least one year and 282 for at least 2 years; and 1,774 in adequate and well-controlled studies. In placebo-controlled studies, the population had a median age of 53 years at entry; approximately 80% were females, 93% were Caucasian and all patients were suffering from active rheumatoid arthritis, with a median disease duration of 6.2 years. Most patients received the recommended dose of Cimzia or higher.

Table 1 summarizes the reactions reported at a rate of at least 3% in patients treated with Cimzia 200 mg every other week compared to placebo (saline formulation), given concomitantly with methotrexate.

Hypertensive adverse reactions were observed more frequently in patients receiving Cimzia than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs.

Patients receiving Cimzia 400 mg as monotherapy every 4 weeks in rheumatoid arthritis controlled clinical trials had similar adverse reactions to those patients receiving Cimzia 200 mg every other week.

Other Adverse Reactions

Other infrequent adverse reactions (occurring in less than 3% of RA patients) were similar to those seen in Crohn's disease patients.

Psoriatic Arthritis Clinical Study

Cimzia has been studied in 409 patients with psoriatic arthritis (PsA) in a placebo-controlled trial. The safety profile for patients with PsA treated with Cimzia was similar to the safety profile seen in patients with RA and previous experience with Cimzia .

Ankylosing Spondylitis Clinical Study

Cimzia has been studied in 325 patients with axial spondyloarthritis of whom the majority had ankylosing spondylitis (AS) in a placebo-controlled study (AS-1). The safety profile for patients in study AS-1 treated with Cimzia was similar to the safety profile seen in patients with RA.

Infections

The incidence of infections in controlled studies in Crohn's disease was 38% for Cimzia-treated patients and 30% for placebo-treated patients. The infections consisted primarily of upper respiratory infections (20% for Cimzia, 13% for placebo). The incidence of serious infections during the controlled clinical studies was 3% per patient-year for Cimzia-treated patients and 1% for placebo-treated patients. Serious infections observed included bacterial and viral infections, pneumonia, and pyelonephritis.

The incidence of new cases of infections in controlled clinical studies in rheumatoid arthritis was 0.91 per patient-year for all Cimzia-treated patients and 0.72 per patient-year for placebo-treated patients. The infections consisted primarily of upper respiratory tract infections, herpes infections, urinary tract infections, and lower respiratory tract infections. In the controlled rheumatoid arthritis studies, there were more new cases of serious infection adverse reactions in the Cimzia treatment groups, compared to the placebo groups (0.06 per patient-year for all Cimzia doses vs. 0.02 per patient-year for placebo). Rates of serious infections in the 200 mg every other week dose group were 0.06 per patient-year and in the 400 mg every 4 weeks dose group were 0.04 per patient-year. Serious infections included tuberculosis, pneumonia, cellulitis, and pyelonephritis. In the placebo group, no serious infection occurred in more than one subject. There is no evidence of increased risk of infections with continued exposure over time [see Warnings and Precautions (5.1)] .

Tuberculosis and Opportunistic Infections

In completed and ongoing global clinical studies in all indications including 5,118 Cimzia-treated patients, the overall rate of tuberculosis is approximately 0.61 per 100 patient-years across all indications.

The majority of cases occurred in countries with high endemic rates of TB. Reports include cases of miliary, lymphatic, peritoneal, as well as pulmonary TB. The median time to onset of TB for all patients exposed to Cimzia across all indications was 345 days. In the studies with Cimzia in RA, there were 36 cases of TB among 2,367 exposed patients, including some fatal cases. Rare cases of opportunistic infections have also been reported in these clinical trials [see Warnings and Precautions (5.1)].

Malignancies

In clinical studies of Cimzia, the overall incidence rate of malignancies was similar for Cimzia-treated and control patients. For some TNF blockers, more cases of malignancies have been observed among patients receiving those TNF blockers compared to control patients [see Warnings and Precautions (5.2)].

Heart Failure

In placebo-controlled and open-label rheumatoid arthritis studies, cases of new or worsening heart failure have been reported for Cimzia-treated patients. The majority of these cases were mild to moderate and occurred during the first year of exposure [see Warnings and Precautions (5.3)].

Autoantibodies

In clinical studies in Crohn's disease, 4% of patients treated with Cimzia and 2% of patients treated with placebo that had negative baseline ANA titers developed positive titers during the studies. One of the 1,564 Crohn's disease patients treated with Cimzia developed symptoms of a lupus-like syndrome.

In clinical trials of TNF blockers, including Cimzia, in patients with RA, some patients have developed ANA. Four patients out of 2,367 patients treated with Cimzia in RA clinical studies developed clinical signs suggestive of a lupus-like syndrome. The impact of long-term treatment with Cimzia on the development of autoimmune diseases is unknown [see Warnings and Precautions (5.9)].

Immunogenicity

Patients with Crohn's disease were tested at multiple time points for antibodies to certolizumab pegol during Studies CD1 and CD2. In patients continuously exposed to Cimzia,the overall percentage of patients who were antibody positive to Cimzia on at least one occasion was 8%; approximately 6% were neutralizing in vitro. No apparent correlation of antibody development to adverse events or efficacy was observed. Patients treated with concomitant immunosuppressants had a lower rate of antibody development than patients not taking immunosuppressants at baseline (3% and 11%, respectively). The following adverse events were reported in Crohn's disease patients who were antibody-positive (N = 100) at an incidence at least 3% higher compared to antibody-negative patients (N = 1,242): abdominal pain, arthralgia, edema peripheral, erythema nodosum, injection site erythema, injection site pain, pain in extremity, and upper respiratory tract infection.

In two long-term (up to 7 years of exposure), open-label Crohn's disease studies, overall 23% (207/903) of patients developed antibodies against certolizumab pegol on at least one occasion. Of the 207 patients who were antibody positive, 152 (73%) had a persistent reduction of drug plasma concentration, which represents 17% (152/903) of the study population. The data from these two studies do not suggest an association between the development of antibodies and adverse events.

The overall percentage of patients with antibodies to certolizumab pegol detectable on at least one occasion was 7% (105 of 1,509) in the rheumatoid arthritis placebo-controlled trials. Approximately one third (3%, 39 of 1,509) of these patients had antibodies with neutralizing activity in vitro. Patients treated with concomitant immunosuppressants (MTX) had a lower rate of antibody development than patients not taking immunosuppressants at baseline. Patients treated with concomitant immunosuppressant therapy (MTX) in RA-I, RA-II, RA-III had a lower rate of neutralizing antibody formation overall than patients treated with Cimzia monotherapy in RA-IV (2% vs. 8%). Both the loading dose of 400 mg every other week at Weeks 0, 2 and 4 and concomitant use of MTX were associated with reduced immunogenicity.

Antibody formation was associated with lowered drug plasma concentration and reduced efficacy. In patients receiving the recommended Cimzia dosage of 200 mg every other week with concomitant MTX, the ACR20 response was lower among antibody positive patients than among antibody-negative patients (Study RA-I, 48% versus 60%; Study RA-II 35% versus 59%, respectively). In Study RA-III, too few patients developed antibodies to allow for meaningful analysis of ACR20 response by antibody status. In Study RA-IV (monotherapy), the ACR20 response was 33% versus 56%, antibody-positive versus antibody-negative status, respectively [see Clinical Pharmacology (12.3)]. No association was seen between antibody development and the development of adverse events.

The data reflect the percentage of patients whose test results were considered positive for antibodies to certolizumab pegol in an ELISA, and are highly dependent on the sensitivity and specificity of the assay. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to certolizumab pegol with the incidence of antibodies to other products may be misleading.

Hypersensitivity Reactions

The following symptoms that could be compatible with hypersensitivity reactions have been reported rarely following Cimzia administration to patients: angioedema, dermatitis allergic, dizziness (postural), dyspnea, hot flush, hypotension, injection site reactions, malaise, pyrexia, rash, serum sickness, and (vasovagal) syncope [see Warnings and Precautions (5.4)] .

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Cimzia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Vascular disorder: systemic vasculitis has been identified during post-approval use of TNF blockers.

Skin: case of severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and new or worsening psoriasis (all sub-types including pustular and palmoplantar) have been identified during post-approval use of TNF blockers.

Immune System Disorders: sarcoidosis

Neoplasms benign, malignant and unspecified (including cysts and polyps): Melanoma, Merkel cell carcinoma (neuroendocrine carcinoma of the skin) [see Warnings and Precautions (5.2)].

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Cimzia during pregnancy. For more information, healthcare providers or patients can contact:

MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS). The OTIS AutoImmune Diseases Study at 1-877-311-8972 or visit http://mothertobaby.org/pregnancy-studies/

Risk Summary

Limited data from the ongoing pregnancy registry on use of Cimzia in pregnant women are not sufficient to inform a risk of major birth defects or other adverse pregnancy outcomes. Certolizumab pegol plasma concentrations obtained from 10 women treated with Cimzia during pregnancy and their newborn infants demonstrated low placental transfer of certolizumab pegol. Cimzia may be eliminated at a slower rate in exposed infants than in adult patients [see Data] . There are risks to the mother and fetus associated with active rheumatoid arthritis or Crohn's disease. The theoretical risks of administration of live or live-attenuated vaccines to the infants exposed in utero to Cimzia should be weighed against the benefits of vaccinations [see Clinical Considerations] . No adverse developmental effects were observed in animal reproduction studies during which pregnant rats were administered intravenously a rodent anti-murine TNFα pegylated Fab' fragment (cTN3 PF) similar to certolizumab pegol during organogenesis at up to 2.4 times the recommended human dose of 400 mg per month.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Published data suggest that the risk of adverse pregnancy outcomes in women with rheumatoid arthritis or Crohn's disease is correlated with maternal disease activity and that active disease increases the risk of adverse pregnancy outcomes, including fetal loss, preterm delivery (before 37 weeks of gestation), low birth weight (<2500 g) and small for gestational age birth.

Fetal/Neonatal Adverse Reactions

Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant. Although certolizumab pegol levels were low in 12 infants exposed to Cimzia in utero, the clinical significance of these low levels is unknown. Additional data available from one exposed infant suggests that Cimzia may be eliminated at a slower rate in infants than in adults [see Data]. The safety of administering live or live-attenuated vaccines in exposed infants is unknown.

Data

Human Data

A limited number of pregnancies have been reported in the ongoing pregnancy exposure registry. Due to the small number of Cimzia-exposed pregnancies with known outcomes (n=23), no meaningful comparisons between the exposed group and control groups may be conducted to determine an association with Cimzia and major birth defects or adverse pregnancy outcomes.

In an independent clinical study conducted in 10 pregnant women with Crohn´s disease treated with Cimzia, certolizumab pegol concentrations were measured in maternal blood as well as in cord and infant blood (n=12) at the day of birth. The last dose of Cimzia (400 mg for every mother) was given on average 19 days prior to delivery (range 5-42 days). Plasma certolizumab pegol concentrations were <0.41 –1.66 μg/mL in cord blood, <0.41 – 1.58 μg/mL in infant blood, and 1.87–59.57 μg/mL in maternal blood. Plasma certolizumab pegol concentrations were lower (by at least 75%) in the infants than in mothers suggesting low placental transfer of certolizumab pegol. In one infant, the plasma certolizumab pegol concentration declined from 1.02 to 0.84 μg /mL over 4 weeks suggesting that Cimzia may be eliminated at a slower rate in infants than adults.

Animal Data

Because certolizumab pegol does not cross-react with mouse or rat TNFα, reproduction studies were performed in rats using a rodent anti-murine TNFα pegylated Fab' fragment (cTN3 PF) similar to certolizumab pegol. Animal reproduction studies have been performed in rats during organogenesis at intravenous doses up to 100 mg/kg (about 2.4 times the recommended human dose of 400 mg, based on the surface area) and have revealed no evidence of harm to the fetus due to cTN3 PF.

Lactation

Risk Summary

No data are available regarding the presence of certolizumab pegol in human milk, the effects on the breast fed infant, or the effects on milk production. Published data suggest that the systemic exposure to a breastfed infant is expected to be low because certolizumab pegol is a large molecule and is degraded in the gastrointestinal tract. However, if certolizumab pegol is transferred into human milk, effects of local exposure in the gastrointestinal tract are unknown.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Cimzia and any potential adverse effects on the breastfed child from Cimzia or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant [see Use in Specific Populations (8.1)].

Geriatric Use

Clinical studies of Cimzia did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Population pharmacokinetic analyses of patients enrolled in Cimzia clinical studies concluded that there was no apparent difference in drug concentration regardless of age. Because there is a higher incidence of infections in the elderly population in general, use caution when treating the elderly with Cimzia [see Warnings and Precautions (5.1)] .

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies of Cimzia have not been conducted to assess its carcinogenic potential. Certolizumab pegol was not genotoxic in the Ames test, the human peripheral blood lymphocytes chromosomal aberration assay, or the mouse bone marrow micronucleus assay.

Since certolizumab pegol does not cross-react with mouse or rat TNFα, reproduction studies were performed in rats using a rodent anti-murine TNFα pegylated Fab fragment (cTN3 PF), similar to certolizumab pegol. The cTN3 PF had no effects on the fertility and general reproductive performance of male and female rats at intravenous doses up 100 mg/kg, administered twice weekly.

Cimzia (certolizumab) reduces the effects of a substance in the body that can cause inflammation.

Cimzia is used to treat the symptoms of Crohn's disease after other drugs have been tried without success.

Cimzia is also used to treat moderate to severe rheumatoid arthritis in adults. It is also used to treat psoriatic arthritis and ankylosing spondylitis in adults.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Ask your doctor before receiving any vaccine while you are being treated with Cimzia.

Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Get emergency medical help if you have signs of an allergic reaction to Cimzia: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with Cimzia. Contact your doctor right away if you have signs of infection, such as: fever, chills, cough, sweating, muscle pain, open sores or skin wounds, unusual tiredness, feeling short of breath, painful urination, diarrhea, or weight loss.

Call your doctor right away if you have any of these symptoms of lymphoma:

• chest pain, cough, feeling short of breath;

• swelling in your neck, underarm, or groin (this swelling may come and go);

• fever, night sweats, itching, weight loss, feeling tired;

• feeling full after eating only a small amount; or

• pain in your upper stomach that may spread to your back or shoulder.

Stop using Cimzia and call your doctor at once if you have:

• shortness of breath (even with mild exertion), swelling, rapid weight gain;

• pale skin, easy bruising or bleeding;

• a new growth on your skin (may be red or purple), or any change in the size or color of a mole, freckle, or bump on your skin;

• nerve problems - vision problems, dizziness, numbness or tingly feeling, muscle weakness in your arms or legs;

• liver problems - loss of appetite, right-sided stomach pain, tiredness, jaundice (yellowing of the skin or eyes); or

• lupus-like syndrome - joint pain or swelling, trouble breathing, or a butterfly-shaped skin rash over your cheeks and nose (worsens in sunlight).

Common Cimzia side effects may include:

• pain or burning when you urinate;

• rash; or

• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• abatacept;

• adalimumab;

• anakinra;

• etanercept;

• golimumab;

• infliximab;

• natalizumab; or

• rituximab.

This list is not complete. Other drugs may interact with certolizumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.