Adalimumab

Name: Adalimumab

Is adalimumab available as a generic drug?

GENERIC AVAILABLE: No

Adalimumab side effects

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

Stop using adalimumab and call your doctor right away if you have any of these symptoms of lymphoma:

  • fever, night sweats, weight loss, tiredness;

  • feeling full after eating only a small amount;

  • pain in your upper stomach that may spread to your shoulder;

  • easy bruising or bleeding, pale skin, feeling light-headed, rapid heart rate; or

  • liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Also call your doctor at once if you have:

  • signs of infection--fever, chills, sore throat, vomiting, diarrhea, flu symptoms, pain or burning when you urinate;

  • signs of tuberculosis--fever with ongoing cough, weight loss (fat or muscle);

  • pale skin, easy bruising or bleeding (nosebleeds, bleeding gums);

  • numbness, tingly feeling, weakness or prickly feeling;

  • vision problems;

  • shortness of breath with swelling of your ankles or feet; or

  • new or worsening psoriasis (raised, silvery flaking of the skin).

Older adults may be more likely to develop an infection while using adalimumab.

Common side effects may include:

  • headache;

  • cold symptoms such as stuffy nose, sinus pain, sneezing, sore throat;

  • rash; or

  • redness, bruising, itching, or swelling where the injection was given.

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.

Pharmacologic Category

  • Antirheumatic, Disease Modifying
  • Gastrointestinal Agent, Miscellaneous
  • Monoclonal Antibody
  • Tumor Necrosis Factor (TNF) Blocking Agent

ALERT U.S. Boxed Warning

Serious infections:

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

Discontinue adalimumab if a patient develops a serious infection or sepsis. Reported infections include the following:

Active tuberculosis (TB), including reactivation of latent TB. Patients with TB frequently have presented with disseminated or extrapulmonary disease. Test patients for latent TB before adalimumab use and during therapy. Initiate treatment for latent infection prior to adalimumab use.

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

Bacterial, viral, and other infections caused by opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with adalimumab prior to initiating therapy in patients with chronic or recurrent infection.

Monitor patients closely for the development of signs and symptoms of infection during and after treatment with adalimumab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Malignancy:

Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF)–blockers, including adalimumab. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF-blockers, including adalimumab. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF-blocker cases have occurred in patients with Crohn disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF-blocker or a TNF-blocker in combination with these other immunosuppressants.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: May rarely cause hypersensitivity, anaphylaxis, anaphylactoid reactions, or angioneurotic edema; medications for the treatment of hypersensitivity reactions should be available for immediate use.

• 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, peripheral demyelinating disease, including Guillain-Barré syndrome) have been reported; there is a known association between intermediate uveitis and central demyelinating disorders. Consider discontinuing use in patients who develop peripheral or central nervous system demyelinating disorders during treatment. Use with caution in patients with preexisting or recent onset central or peripheral nervous system demyelinating disorders.

• Heart failure: Worsening and new-onset heart failure (HF) has been reported with adalimumab and other TNF blockers. 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 disorders: Rare cases of pancytopenia and aplastic anemia have been reported with TNF-blockers. Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with a history of significant hematologic abnormalities.

• Hepatitis B: Rare reactivation of hepatitis B (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants (some have been fatal); evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of 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.

• Infections: [US Boxed Warning]: Patients receiving adalimumab 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, corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (including 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. Monitor closely for signs/symptoms of infection during and after treatment. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to initiating therapy in patients with chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infections who develop severe systemic illness. Caution should be exercised when considering use in the elderly, patients with a history of an opportunistic infection, patients taking concomitant immunosuppressants (eg, corticosteroids, methotrexate), or in patients with conditions that predispose them to infections (eg, advanced or poorly controlled diabetes) or residence/travel in areas of endemic tuberculosis or mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent infections. Do not initiate adalimumab in patients with an active infection, including clinically important localized infection. 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 adolescents receiving TNF-blocking agents, including adalimumab. Half of the malignancies reported in children and adolescents were lymphomas (Hodgkin and non-Hodgkin) while other cases varied and included rare malignancies usually associated with immunosuppression and malignancies not typically observed in this population. Most patients were receiving concomitant immunosuppressants. [US Boxed Warning]: Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has been reported (some fatal) primarily in patients with Crohn disease or ulcerative colitis treated with adalimumab and who received concomitant azathioprine or mercaptopurine; reports occurred predominantly in adolescent and young adult males. The impact of adalimumab on the development and course of malignancy is not fully defined. Compared to 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 and leukemia. A higher incidence of nonmelanoma skin cancers was noted in adalimumab-treated patients (0.7/100 patient years), when compared to the control group (0.2/100 patient years).

• Tuberculosis: [US Boxed Warnings]: Active tuberculosis (disseminated or extrapulmonary), including reactivation of latent tuberculosis, has been reported in patients receiving adalimumab. Evaluate patients for tuberculosis risk factors and latent tuberculosis infection (with a skin test) prior to and during therapy. Treatment for latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis during and after treatment. Consider antituberculosis treatment if an adequate course of treatment cannot be confirmed in patients with a history of latent or active tuberculosis or with risk factors despite negative skin test. Some patients who tested negative prior to therapy have developed active infection; tests for latent tuberculosis infection may be falsely negative while on adalimumab therapy. Use with caution in patients who have traveled to or resided in regions where tuberculosis is endemic. Monitor for signs and symptoms of tuberculosis in all patients.

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: Infection and malignancy has been reported at a higher incidence; use caution in elderly patients.

• Pediatric: Malignancies have been reported among children and adolescents.

• Surgery patients: Limited experience with patients undergoing surgical procedures while on therapy; consider long half-life with planned procedures. Monitor closely for infection.

Dosage form specific issues:

• Latex: The packaging (needle cover of prefilled syringe and autoinjector) may contain 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:

• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy; live vaccines should not be given concurrently. There are no data available concerning the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.

Monitoring Parameters

Monitor improvement of symptoms and physical function assessments. Latent TB screening prior to initiating and during therapy; signs/symptoms of active infection, including tuberculosis (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); 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 Considerations

Adalimumab crosses the placenta and can be detected in cord blood at birth at concentrations higher than those in the maternal serum. In one study of pregnant women with inflammatory bowel disease, adalimumab was found to be measurable in a newborn for up to 11 weeks following delivery. Maternal doses of adalimumab were 40 mg every other week (n=9) or 40 mg weekly (n=1) and the last dose was administered 0.14 to 8 weeks prior to delivery (median 5.5 weeks) (Mahadevan 2013). If therapy for inflammatory bowel disease is needed during pregnancy, adalimumab should be discontinued before 30 weeks gestation in order to decrease exposure to the newborn. In addition, the administration of live vaccines should be postponed until anti-TNF concentrations in the infant are negative (Habal 2012; Mahadeven 2013; Zelinkova 2013).

Women exposed to adalimumab during pregnancy for the treatment of an autoimmune disease (eg, inflammatory bowel disease) may contact the OTIS Autoimmune Diseases Study at 877-311-8972.

Usual Adult Dose for Psoriatic Arthritis

40 mg subcutaneously every other week

Comments:
-In the treatment of rheumatoid arthritis, some patients not taking concomitant methotrexate may derive additional benefit from increasing the dosing frequency to 40 mg every week.
-Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory drugs, analgesics, or other disease modifying agents may be given concomitantly.

Uses:
-To reduce signs and symptoms in adult patients with active ankylosing spondylitis (AS)
-Alone or in combination with non-biologic DMARDs to inhibit the progression of structural damage and improve physical function in adult patients with active psoriatic arthritis
-Alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs) to reduce signs and symptoms, inducing major clinical response, inhibit the progression of structural damage, and improve physical function in adult patients with moderately to severely active rheumatoid arthritis (RA)

Usual Adult Dose for Crohn's Disease - Maintenance

-Initial dose: 160 mg subcutaneously on Day 1 (given in one day or split over 2 consecutive days), followed by 80 mg subcutaneously 2 weeks later (Day 15)
-Maintenance dose (beginning 2 weeks later [Day 29]): 40 mg subcutaneously every other week

Comments:
-Aminosalicylates and/or corticosteroids may be continued during treatment.
-Azathioprine, 6-mercaptopurine (6-MP), or methotrexate (MTX) may be continued during treatment if necessary.
-Treatment beyond one year in Crohn's Disease has not been established.
-Treatment in ulcerative colitis should only be continued in patients who have shown evidence of clinical remission by eight weeks (Day 57) of therapy.

Uses:
-To reduce signs and induce and maintain remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy; to reduce signs and induce remission in these patients if they have also lost response to or are intolerant to infliximab
-To induce and maintain remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine (6-MP) (the effectiveness of this drug in patients who have lost response to or were intolerant to TNF blockers has not been established)

Usual Adult Dose for Uveitis

-Initial dose: 80 mg subcutaneously
-Maintenance dose: 40 mg subcutaneously every other week, starting one week after the initial dose

Comments:
-Treatment beyond one year for moderate to severe chronic plaque psoriasis has not been studied.

Uses:
-For the treatment of adult patients with moderate to severe chronic plaque psoriasis (Ps) who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate
-For the treatment of noninfectious intermediate, posterior, and panuveitis in adult patients

Liver Dose Adjustments

Data not available

Adalimumab Identification

Substance Name

Adalimumab

CAS Registry Number

331731-18-1

Drug Class

Antibodies, Monoclonal, Humanized

Antirheumatic Agents

Dermatologic Agents

Gastrointestinal Agents

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