Adalimumab,Humira

U.S. BRAND NAMES — Humira®
PHARMACOLOGIC CATEGORY Antirheumatic, Disease ModifyingMonoclonal AntibodyTumor Necrosis Factor (TNF) Blocking Agent
DOSING: ADULTS Rheumatoid arthritis: SubQ: 40 mg every other week; may be administered with other DMARDs; patients not taking methotrexate may increase dose to 40 mg every week
Ankylosing spondylitis, psoriatic arthritis: SubQ: 40 mg every other week
Crohn's disease: Initial: 160 mg divided into 4 doses given on day 1 or over 2 days, then 80 mg at week 2; Maintenance: 40 mg every other week beginning at week 4
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL) [prefilled glass syringe or Humira® pen; packaged with alcohol preps; needle cover contains latex]
DOSAGE FORMS: CONCISE Injection, solution [preservative free]: Humira®: 40 mg/0.8 mL (1 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — For SubQ injection; rotate injection sites. Do not use if solution is discolored. Do not administer to skin which is red, tender, bruised, or hard; rotate injection sites.
USE Treatment of active rheumatoid arthritis, active psoriatic arthritis (moderate-to-severe), or ankylosing spondylitis; may be used alone or in combination with disease-modifying antirheumatic drugs (DMARDs).
Treatment of moderate-to-severe active Crohn's disease which has inadequate response to conventional treatment, or which has lost response to or is intolerant of infliximab
ADVERSE REACTIONS SIGNIFICANT — Frequency > placebo in rheumatoid arthritis studies:
>10%: Central nervous system: Headache (12%) Dermatologic: Rash (12%) Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling) Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)
5% to 10%: Cardiovascular: Hypertension (5%) Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%) Gastrointestinal: Nausea (9%), abdominal pain (7%) Genitourinary: Urinary tract infection (8%) Hepatic: Alkaline phosphatase increased (5%) Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling) Neuromuscular & skeletal: Back pain (6%) Renal: Hematuria (5%) Miscellaneous: Accidental injury (10%), flu-like syndrome (7%)
<5%: Cardiovascular: Arrhythmia, atrial fibrillation, chest pain, CHF, coronary artery disorder, heart arrest, MI, palpitation, pericardial effusion, pericarditis, peripheral edema, syncope, tachycardia, thrombosis (leg), vascular disorder Central nervous system: Confusion, fever, hypertensive encephalopathy, multiple sclerosis, subdural hematoma Dermatologic: Cellulitis, erysipelas Endocrine & metabolic: Dehydration, menstrual disorder, parathyroid disorder Gastrointestinal: Diverticulitis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, vomiting Genitourinary: Cystitis, pelvic pain Hematologic: Agranulocytosis, granulocytopenia, leukopenia, pancytopenia, paraproteinemia, polycythemia Hepatic: Cholecystitis, cholelithiasis, hepatic necrosis Neuromuscular & skeletal: Arthritis, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, paresthesia, pyogenic arthritis, synovitis, tendon disorder, tremor Ocular: Cataract Renal: Kidney calculus, pyelonephritis Respiratory: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, pneumonia Miscellaneous: Adenoma, allergic reactions (1%), carcinoma (including breast, gastrointestinal, skin, urogenital), healing abnormality, herpes zoster, ketosis, lupus erythematosus syndrome, lymphoma, melanoma, postsurgical infection, sepsis, tuberculosis (reactivation of latent infection; miliary, lymphatic, peritoneal and pulmonary)
Postmarketing and/or case reports: Anaphylactoid reaction, anaphylaxis, angioneurotic edema, aplastic anemia, cutaneous vasculitis, cytopenia, fixed drug eruption, infections (viral, fungal and protozoal), interstitial lung disease (eg, pulmonary fibrosis), septic arthritis, thrombocytopenia, transaminases increased, urticaria
CONTRAINDICATIONS — Hypersensitivity to adalimumab or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Fatal infections: See "Concerns related to adverse effects" below. Tuberculosis evaluation: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; 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. Fatal infections: [U.S. Boxed Warning]: Serious and potential fatal infections (including invasive fungal and other opportunistic infections) have been reported in patients receiving TNF-blocking agents, including adalimumab. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy. Other opportunistic infections included Histoplasma, Aspergillus, and Nocardia. Use with caution in patients who have resided in regions where histoplasmosis is endemic. Caution should be exercised when considering the use in patients with chronic infection, history of recurrent infection, or predisposition to infection. Do not give to patients with an active chronic or localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Hepatitis B: Rare reactivation of hepatitis B has occurred in chronic virus carriers; evaluate prior to initiation and during treatment. Malignancy: Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. Pancytopenia: Rare cases of pancytopenia (including aplastic anemia) have been reported with TNF-blocking agents; with significant hematologic abnormalities, consider discontinuing therapy. Tuberculosis evaluation: Tuberculosis (disseminated or extrapulmonary) has been reactivated while on adalimumab; most cases have been reported within the first 8 months of treatment. [U.S. Boxed Warnings]: Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test prior to therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment; active tuberculosis has developed in this population during treatment.
Disease-related concerns: Congestive heart failure: Use with caution in patients with CHF or decreased left ventricular function; worsening and new-onset CHF has been reported. Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease have been reported.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues: Latex: The packaging (needle cover) contains latex.
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 is no data available concerning the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS Abatacept: Concurrent use may increase the risk of infection; avoid concurrent use.
Abciximab: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA; may also cause thrombocytopenia or decreased therapeutic effect.
Anakinra: Concomitant use may increase risk of infections; not recommended.
Vaccines (killed organism or component): Adalimumab may decrease the effect of vaccines; monitor.
Vaccines (live organism): Adalimumab may increase the risk of vaccinal infection; avoid concurrent use.
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/nutraceutical: Echinacea may decrease the therapeutic effects of adalimumab; avoid concurrent use.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to adalimumab during pregnancy (877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — It is not known whether adalimumab is secreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
PRICING — (data from drugstore.com)Kit (Humira) 40 mg/0.8 mL (2): $1415.88
MONITORING PARAMETERS — Place and read PPD before initiation. Monitor improvement of symptoms and physical function assessments; CBC; signs of infection, bleeding or bruising.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Doses of up to 10 mg/kg have been tolerated in clinical trials. In case of overdose, treatment should be symptom-directed and supportive.
CANADIAN BRAND NAMES — Humira®
INTERNATIONAL BRAND NAMES — Humira (AE, AR, AT, AU, BE, BG, BH, CA, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HU, IE, IL, IQ, IR, IT, JO, KW, LB, LY, MX, NL, NO, NZ, OM, PE, PT, PY, QA, RU, SA, SE, SG, SY, TR, UY, YE); Trudexa (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFalpha receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4.7-6 L; Synovial fluid concentrations: 31% to 96% of serum
Bioavailability: Absolute: 64%
Half-life elimination: Terminal: ~2 weeks (range 10-20 days)
Time to peak, serum: SubQ: 131 +/- 56 hours
Excretion: Clearance increased in the presence of antiadalimumab antibodies; decreased in patients 40 years and older
PATIENT INFORMATION — May cause headache, nausea, or stomach pain. Notify prescriber of any signs of infection.