Golimumab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Simponi Aria: 50 mg/4 mL (4 mL) [latex free; contains polysorbate 80]

Solution Auto-injector, Subcutaneous [preservative free]:

Simponi: 50 mg/0.5 mL (0.5 mL); 100 mg/mL (1 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Simponi: 50 mg/0.5 mL (0.5 mL); 100 mg/mL (1 mL) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Human monoclonal antibody that binds to human tumor necrosis factor alpha (TNFα), thereby interfering with endogenous TNFα activity. Biological activities of TNFα include the induction of proinflammatory cytokines (interleukin [IL]-6, IL-8, Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor), expression of adhesion molecules (E-selectin, vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1) necessary for leukocyte infiltration, activation of neutrophils and eosinophils.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: IV: 151 ± 61 mL/kg (distributed primarily to circulatory system with limited extravascular distribution)

Metabolism

Pathway unknown

Time to Peak

SubQ: 2-6 days

Half-Life Elimination

~2 weeks

Use in Specific Populations

Special Populations Note

Body weight: Following IV administration, patients with higher body weights tend to have higher serum golimumab concentrations (compared to lower body weights).

Use: Labeled Indications

Ankylosing spondylitis (Simponi, Simponi Aria): Treatment of adults with active ankylosing spondylitis (alone or in combination with methotrexate).

Psoriatic arthritis (Simponi, Simponi Aria): Treatment of adults with active psoriatic arthritis (alone or in combination with methotrexate).

Rheumatoid arthritis (Simponi, Simponi Aria): Treatment of adults with moderately-to-severely active rheumatoid arthritis (in combination with methotrexate).

Ulcerative colitis (Simponi): Treatment of moderately to severely active ulcerative colitis in adults with corticosteroid dependence or who have had an inadequate response to conventional therapy (to induce and maintain clinical response, improve mucosal appearance during induction, induce clinical remission, and achieve and sustain remission in induction responders).

Use: Off Label

Axial spondyloarthritis (active, nonradiographic)b

Data from a randomized, double-blind, placebo-controlled study supports the use of golimumab in the management of patients with active, nonradiographic axial spondyloarthritis who have a positive MRI and/or elevated CRP at baseline Sieper 2015.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to golimumab, latex, or any other component of formulation or packaging; patients with severe infections (eg, sepsis, tuberculosis, opportunistic infections); moderate or severe heart failure (NYHA class III/IV)

Dosage and Administration

Dosing: Adult

Note: Corticosteroids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and/or NSAIDs may be continued for the treatment of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Golimumab should not be used in combination with biologic DMARDs.

Ankylosing spondylitis:

IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter (either alone or in combination with methotrexate or other nonbiologic DMARDs)

SubQ: 50 mg once a month (either alone or in combination with methotrexate or other nonbiologic DMARDs)

Psoriatic arthritis:

IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter (either alone or in combination with methotrexate or other nonbiologic DMARDs)

SubQ: 50 mg once a month (either alone or in combination with methotrexate or other nonbiologic DMARDs)

Rheumatoid arthritis:

IV: 2 mg/kg at weeks 0, 4, and then every 8 weeks thereafter (in combination with methotrexate)

SubQ: 50 mg once a month (in combination with methotrexate)

Ulcerative colitis: SubQ: Induction: 200 mg at week 0, then 100 mg at week 2, followed by maintenance therapy of 100 mg every 4 weeks

Axial spondyloarthritis (active, nonradiographic) (off-label use): SubQ: 50 mg once every 4 weeks for 16 weeks (Sieper 2015).

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Intact solution should be colorless to light yellow; solution may develop a few fine, translucent particles.

SubQ: Bring to room temperature by allowing syringe/autoinjector to sit at room temperature outside the carton for ≥30 minutes prior to administration (do not warm in any other way). Do not use if discolored, cloudy, or if foreign particles are present.

IV: Do not use if solution is discolored, or contains opaque or foreign particles. Dilute for infusion by slowly adding calculated dose/volume to NS or ¹/₂ NS to a total volume of 100 mL. Gently mix.

Discard unused portion of vial/syringe/autoinjector.

Administration

Note: The safety and efficacy of switching between the IV and SubQ formulations and routes have not been studied.

IV: Dilute prior to use. Infuse over 30 minutes, using an infusion set with an in-line low protein-binding 0.22 micron filter. Do not infuse in the same line with other medications.

Subcutaneous injection: Hold autoinjector firmly against skin and inject subcutaneously into thigh, lower abdomen (below navel), or upper arm. A loud click is heard when injection has begun. Continue to hold autoinjector against skin until second click is heard (may take 3 to 15 seconds). Following second click, lift autoinjector from injection site. Rotate injection sites and avoid injecting into tender, red, scaly, hard, or bruised skin, or areas with scars or stretch marks. If multiple injections are required for a single dose, administer at different sites on body.

Storage

Store intact vials and syringes refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. May also store at room temperature (≤25°C [77°F]) for ≤30 days; do not return to refrigerator. Do not shake. Store product in original carton to protect from light.

IV: Solutions diluted for infusion may be stored at room temperature for 4 hours.

Drug Interactions

Abatacept: Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Avoid combination

Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: May enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Avoid combination

Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Avoid combination

Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

InFLIXimab: May enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Thiopurine Analogs: Anti-TNF Agents may enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Monitor therapy

Tocilizumab: May enhance the immunosuppressive effect of Anti-TNF Agents. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Vedolizumab: Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab. Avoid combination

Adverse Reactions

As reported with combination therapy.

>10%:

Hematologic & oncologic: Positive ANA titer (IV: 17%, anti-dsDNA: <1%; subcutaneous: 4%, anti-dsDNA: <1%)

Immunologic: Antibody development (subcutaneous: Drug-tolerant EIA: 16% to 38%; IV: Drug-tolerant EIA: 19% to 21%; approximately ¹/₃ were neutralizing)

Infection: Infection (27% to 28%)

Respiratory: Upper respiratory tract infection (13% to 16%)

1% to 10%:

Cardiovascular: Hypertension (3%)

Central nervous system: Dizziness (≤2%), paresthesia (≤2%)

Dermatologic: Skin rash (3%)

Gastrointestinal: Constipation (≤1%)

Hematologic & oncologic: Decreased neutrophils (≤5%), leukopenia (1%)

Hepatic: Increased serum alanine aminotransferase (≤8%), increased serum aspartate aminotransferase (≤5%)

Infection: Viral infection (4% to 5%; includes herpes and influenza), fungal infection (≤2%; may be invasive or superficial), bacterial infection (1%)

Local: Injection site reaction (subcutaneous: 3% to 6%)

Respiratory: Nasopharyngitis (≤6%), bronchitis (2% to 3%), sinusitis (≤2%)

Miscellaneous: Fever (2%), infusion-related reaction (intravenous: 1%)

Frequency not defined:

Dermatologic: Cellulitis

Infection: Opportunistic infections, sepsis, serious infection

Respiratory: Activated tuberculosis, reactivated tuberculosis

<1%, postmarketing, and/or case reports: Abscess, agranulocytosis, anaphylaxis, aplastic anemia, atypical serious infection, bullous skin disease, cardiac failure, demyelinating disease of the central nervous system, dyspnea, exfoliation of skin, Guillain-Barre syndrome, hepatitis B, hepatotoxicity (idiosyncratic), hypersensitivity angiitis, hypersensitivity reaction, infective bursitis, interstitial pulmonary disease, leukemia, lichenoid eruption, lupus-like syndrome, malignant lymphoma, malignant melanoma, malignant neoplasm, Merkel cell carcinoma, multiple sclerosis, mycobacterial infection, nausea, neutropenia, non-Hodgkin's lymphoma, optic neuritis, pancytopenia, peripheral demyelinating polyneuropathy, pneumonia, pruritus, psoriasis (including new onset, palmoplantar, pustular, or exacerbation), pyelonephritis, sarcoidosis, septic arthritis, septic shock, thrombocytopenia, urticaria, vasculitis

Warnings/Precautions

Concerns related to adverse effects:

• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.
• Demyelinating disease: Rare cases of new-onset or exacerbation of demyelinating disorders (eg, multiple sclerosis, optic neuritis, Guillain-Barré syndrome, polyneuropathy) have been reported. Consider discontinuing in patients who develop peripheral or CNS demyelinating disorders during treatment. Use with caution in patients with pre-existing or recent onset central or peripheral nervous system demyelinating disorders.
• Heart failure: Worsening and new-onset heart failure (HF) (some fatal) have been reported with golimumab and other TNF-blockers. Monitor closely and discontinue with onset or worsening of symptoms. Use with caution in patients with HF or decreased left ventricular function. In a scientific statement from the American Heart Association, TNF blockers have been determined to be agents that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).
• Hematologic effects: Cases of pancytopenia and other significant cytopenias, including aplastic anemia, have been reported with TNF-blocking agents. Pancytopenia, leukopenia, neutropenia, and thrombocytopenia have occurred with golimumab. Consider discontinuing with significant hematologic abnormalities. Use with caution in patients with underlying hematologic disorders.
• Hepatitis B: Rare reactivation of hepatitis B virus (HBV), sometimes fatal, has occurred in chronic virus carriers, usually in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients. Patients who test positive for HBV surface antigen should be referred for hepatitis B evaluation/treatment prior to golimumab initiation. Monitor for clinical and laboratory signs of active infection during and for several months following discontinuation of golimumab treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.
• Hypersensitivity reactions: Severe systemic hypersensitivity reactions (including anaphylaxis) have been reported (some have occurred with the first dose) following intravenous and subcutaneous administration. Symptoms associated with reactions may include dyspnea, hives, nausea, and pruritus; reactions occurred during and within 1 hour of the start of IV infusion. Discontinue immediately if signs develop and initiate appropriate treatment.
• Infections: [US Boxed Warning]: Patients receiving golimumab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids). Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral, or other opportunistic infections (including legionellosis and listeriosis) have been reported in patients receiving TNF-blocking agents, including golimumab. May present as disseminated (rather than local) disease. Histoplasmosis testing (antigen or antibody) may be negative in some patients with active infection. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised (consider risks versus benefits) when considering use in the elderly, patients taking concomitant immunosuppressants, patients with chronic or recurrent infection, patients who have been exposed to tuberculosis, patients with a history of opportunistic infection, patients with comorbid conditions that predispose them to infections (eg, diabetes), or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis). Do not initiate golimumab therapy in patients with active infection, including localized infection, which is clinically important. Patients who develop a new infection while undergoing treatment should be monitored closely.
• Malignancy: [US Boxed Warning]: Lymphoma and other malignancies (some fatal) have been reported in children and adolescent patients receiving TNF-blocking agents. Half of the malignancies reported in children were lymphomas (Hodgkin and non-Hodgkin) while other cases varied and included malignancies not typically observed in this population. The onset of malignancy was after a median of 30 months (range: 1 to 84 months) after the initiation of the TNF-blocking agent; most patients were receiving concomitant immunosuppressants. The impact of golimumab on the development and course of malignancy is not fully defined. Compared with the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Lymphomas and other malignancies were also observed (at rates higher than expected for the general population) in adult patients receiving TNF-blocking agents. Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has also been associated with TNF-blocking agents, primarily reported in adolescent and young adult males with Crohn disease or ulcerative colitis treated with a TNF-blocking agent and concurrent or prior azathioprine or mercaptopurine. Melanoma and Merkel cell carcinoma have been reported in patients receiving TNF-blocking agents including golimumab. Perform periodic skin examinations in all patients during therapy, particularly those at increased risk for skin cancer. Consider risks versus benefits in patients with a known malignancy (other than a successfully treated nonmelanoma skin cancer) and if considering continuing treatment in a patient who develops a malignancy.
• Tuberculosis: [US Boxed Warning]: Tuberculosis (disseminated or extrapulmonary) has been reported in patients receiving golimumab; both reactivation of latent infection and new infections have been reported. Patients should be evaluated for tuberculosis risk factors and latent tuberculosis infection (with a tuberculin skin test) prior to and during therapy. Treatment of latent tuberculosis should be initiated before use. Monitor for development of tuberculosis throughout treatment in patients with initial negative tuberculin skin tests, patients currently receiving treatment for latent tuberculosis, or patients previously treated for tuberculosis; active tuberculosis has developed in this population during treatment with TNF-blocking agents. Use with caution in patients who have resided in regions where tuberculosis is endemic. Consider antituberculosis therapy if an adequate course of treatment cannot be confirmed in patients with a history of latent or active tuberculosis or for patients with risk factors despite negative skin test. Prior to use, consider risks versus benefits in patients who have been exposed to tuberculosis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution; general incidence of infection is higher in elderly patients.
• Pediatric: [US Boxed Warning]: Lymphoma and other malignancies (some fatal) have been reported in children and adolescent patients receiving TNF-blocking agents.

Dosage form specific issues:

• Latex: Some dosage forms may contain dry natural rubber (latex).
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Administration formulation/route: The safety and efficacy of switching between the IV and SubQ formulations and routes have not been studied.
• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of infection by live vaccines in patients receiving therapy. In clinical trials, humoral response to pneumococcal vaccine was not suppressed in psoriatic arthritis patients receiving golimumab.

Monitoring Parameters

CBC with differential; latent TB screening (prior to initiating and periodically during therapy); HBV screening (prior to initiating [all patients]; during and for several months following therapy [HBV carriers]); monitor improvement of symptoms and physical function assessments; signs/symptoms of infection (prior to, during, and following therapy); signs/symptoms/worsening of heart failure signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) including periodic skin examination

Pregnancy

Pregnancy Considerations

Golimumab crosses the placenta (Benoit 2019).

Golimumab is a humanized monoclonal antibody (IgG₁). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Following administration of golimumab 100 mg every 2 weeks throughout pregnancy to a patient with ulcerative colitis, cord blood concentrations of golimumab were 121% of the maternal serum concentration at delivery. Delivery occurred 3 days after the last maternal dose (Benoit 2019).

Information related to this class of medications is emerging, but based on available data, tumor necrosis factor alpha (TNFα) blocking agents are considered to have low to moderate risk when used in pregnancy (ACOG 776 2019).

Vaccination with live vaccines (eg, rotavirus vaccine) should be avoided for the first 6 months of life if exposure to a biologic agent occurs during the third trimester of pregnancy (eg, >27 weeks' gestation) (Mahadevan 2019).

Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes (Mahadevan 2019).

Use of immune modulating therapies in pregnancy should be individualized to optimize maternal disease and pregnancy outcomes (ACOG 776 2019). When treatment for inflammatory bowel disease is needed in pregnant women, appropriate biologic therapy can be continued without interruption. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer. Dosing can be adjusted so delivery occurs at the lowest serum concentration. For golimumab, the final injection can be given 4 to 6 weeks prior to the estimated date of delivery, then continued 48 hours' postpartum (Mahadevan 2019).

Treatment algorithms are available for use of biologics in female patients with Crohn disease who are planning a pregnancy (Weizman 2019).

Patient Education

What is this drug used for?

• It is used to treat rheumatoid arthritis.
• It is used to treat ankylosing spondylitis.
• It is used to treat psoriatic arthritis.
• It is used to treat ulcerative colitis.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out.
• Chest pain
• Severe loss of strength and energy
• Mole changes
• Skin changes
• Vision changes
• Swollen glands
• Night sweats
• Excessive weight loss
• Skin growths
• Bruising
• Bleeding
• Pale skin
• Severe headache
• Severe dizziness
• Passing out
• Flu-like symptoms
• Skin sores
• Skin redness
• Skin pain
• Nerve problems like sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet.
• Seizures
• Eczema
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.