Adalimumab

Trade Names:Humira- Injection 20 mg per 0.4 mL- Injection 40 mg per 0.8 mL

Pharmacology

Blocks interaction of human tumor necrosis factor (TNF)–alpha with receptors and modulates biological responses induced or regulated by TNF.

Pharmacokinetics

Absorption

C _max is approximately 4.7 mcg/mL following a single 40 mg subcutaneous injection. T _max is approximately 131 h. The average absolute bioavailability is 64%.

Distribution

Vd _ss is 4.7 to 6 L.

Elimination

Mean terminal half-life is approximately 14 days. Systemic Cl is approximately 12 mL/h.

Special Populations

No pharmacokinetic data are available.

No pharmacokinetic data are available.

In patients with rheumatoid arthritis (RA), there was a trend toward lower Cl with increasing age in patients 40 to older than 75 yr of age.

No differences in pharmacokinetics were observed based on gender.

Indications and Usage

Reduce signs and symptoms, induce major clinical response, inhibit the progression of structural damage, and improve physical function in patients with moderate to severe active RA; reduce signs and symptoms of active arthritis, inhibit the progression of structural damage, and improve physical function in patients with psoriatic arthritis; reduce signs and symptoms in patients with active ankylosing spondylitis; reduce signs and symptoms and induce and maintain clinical remission in patients with moderately to severely active Crohn disease; reduce signs and symptoms of moderate to severe active polyarticular juvenile idiopathic arthritis; treatment of moderate to severe chronic plaque psoriasis in patients who are candidates for systemic treatment or phototherapy when other systemic therapies are medically less appropriate.

Contraindications

None well documented.

Dosage and Administration

Subcutaneous 40 mg every other wk. Patients with RA not receiving methotrexate concurrently may benefit from 40 mg every wk.

Subcutaneous 160 mg initially, then 80 mg at wk 2 followed by a maintenance dosage of 40 mg every other wk starting at wk 4.

Subcutaneous Administer 20 mg every other wk.

Administer 40 mg every other wk.

Subcutaneous 80 mg initially, followed by 40 mg every other wk starting 1 wk after the initial dose.

General Advice

• Visually inspect solution before administering dose. Do not administer if particulate matter, cloudiness, or discoloration is noted.
• Rotate injection sites (abdomen, thigh, upper arm). Give new injections at least 1 inch from old site and never into areas where the skin is tender, bruised, red, or hard.
• Do not rub injection site after injection has been completed.
• Discard any unused solution. Do not save unused solution.

Storage/Stability

Refrigerate syringes at 36° to 46°F. Do not freeze. Store in original carton until time of administration. Protect from light.

Drug Interactions

Do not use in combination; increased risk of serious infections and neutropenia.

Do not give concurrently.

Reduces apparent Cl of adalimumab; however, adjustments in the dose of either drug do not appear necessary.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (5%); arrhythmia, atrial fibrillation, cardiovascular disorder, chest pain, CHF, coronary artery disorder, heart arrest, hypertensive encephalopathy, MI, palpitation, pericardial effusion, pericarditis, syncope, tachycardia, vascular disorder (less than 5%).

CNS

Headache (12%); confusion, multiple sclerosis, paresthesia, subdural hematoma, tremor (less than 5%).

Dermatologic

Rash (12%); cellulitis, erysipelas, herpes zoster (less than 5%); cutaneous vasculitis, erythema multiforme (postmarketing).

EENT

Cataract (less than 5%); streptococcal pharyngitis.

GI

Nausea (9%); abdominal pain (7%); cholecystitis, cholelithiasis, esophagitis, gastroenteritis, GI disorder and hemorrhage, vomiting (less than 5%); appendicitis.

Genitourinary

UTI (8%); cystitis, kidney calculus, menstrual disorder, pyelonephritis (less than 5%); metrorrhagia.

Hematologic

Agranulocytosis, granulocytopenia, leukopenia, lymphoma-like reaction, pancytopenia, polycythemia (less than 5%); neutropenia, thrombocytopenia (postmarketing).

Hepatic

Hepatic necrosis (less than 5%).

Hypersensitivity

Anaphylaxis, angioneurotic edema (postmarketing)

Lab Tests

Mild to moderate increase in CPK (15%); hyperlipidemia (7%); hypercholesterolemia (6%); hematuria, increased alkaline phosphatase (5%); increased aminotransferases.

Local

Injection-site pain (19%); injection-site reactions (16%).

Metabolic

Abnormal healing, dehydration, ketosis, paraproteinemia, peripheral edema (less than 5%).

Musculoskeletal

Back pain (6%); arthralgia (3%); arthritis, bone disorder, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis, synovitis, tendon disorder (less than 5%); myositis.

Respiratory

Upper respiratory tract infection (17%); sinusitis (11%); flu syndrome (7%); asthma, bronchospasm, decreased lung function, dyspnea, lung disorder, pleural effusion, pneumonia (less than 5%); interstitial lung disease, including pulmonary fibrosis (postmarketing).

Miscellaneous

Patients with negative antinuclear antibody titers who developed positive titers (12%); accidental injury (10%); low-titer antibodies to adalimumab (5%); adenoma, carcinoma, fever, infection, leg thrombosis, lupus erythematosus syndrome, lymphoma, malignancies, melanoma, pain in extremity, parathyroid disorder, pelvic pain, reactivated tuberculosis (TB), sepsis, surgery, thorax pain (less than 5%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 4 yr of age, and there are limited data in treating children who weigh less than 15 kg (7 lb).

Safety and efficacy not established.

Elderly

Because of higher incidence of infections and malignancies in elderly patients, use with caution.

Hypersensitivity

Anaphylaxis and angioedema have been reported rarely.

Heart failure

Worsening of CHF and new-onset CHF have occurred.

Hematologic events

Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF-blocking agents.

Hepatitis B

Risk of reactivation of HBV may be increased in chronic carriers of this virus. Use with caution in known HBV carriers. In patients who develop HBV reactivation, stop treatment with this drug and initiate effective antiviral therapy.

Immunizations

If possible, bring juvenile idiopathic arthritis patients up to date with all immunizations prior to initiating therapy.

Immunogenicity

May result in formation of autoantibodies and, rarely, in the development of a lupus-like syndrome.

Immunosuppression

May affect host defenses against infection and malignancies.

Infection

Serious, fatal infections and sepsis have occurred. Do not initiate treatment in patients with active infections, including chronic or local infections.

Latex allergy

The needle cover of the syringe contains dry rubber (latex).

Malignancy

Lymphoma and nonmelanoma skin cancer have occurred. Patients with highly active RA are at high risk for developing lymphoma.

Neurologic events

Rare cases of exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease have occurred.

Overdosage

Symptoms

Doses of up to 10 mg/kg have been administered without evidence of toxicity.

Patient Information

• Advise patient or caregiver to review the Medication Guide before starting therapy and with each refill.
• If administered at home, ensure patient or caregiver understands how to store, prepare, and administer the dose and how to dispose of used equipment and supplies. Inform patient or caregiver that a qualified health care provider will supervise the administration of the first injection.
• Caution patient or caregiver that the needle cover contains dry rubber (latex) that should not be handled by patients sensitive to latex.
• Advise patient that if a dose is missed, to inject the missed dose as soon as remembered and inject the next dose at the regularly scheduled time.
• Instruct patient to continue taking other arthritis medications prescribed by health care provider.
• Advise patient to seek immediate medical attention if any of the following occur: bleeding, paleness, persistent fever, rash or other signs or symptoms of an allergic reaction, or unusual bruising.
• Advise patient to report any of the following to health care provider: dizziness, fever or other signs of infection, intolerable injection-site reactions, leg weakness, low-grade fever, new or worsening joint pain, numbness or tingling, persistent chest pain, persistent cough, rash on cheeks or arms that is sensitive to the sun, sore throat, swelling of ankles or feet, unexplained shortness of breath, vision problems, or wasting or weight loss.
• Counsel patients about the risk of lymphoma and other malignancies while receiving adalimumab.

Copyright © 2009 Wolters Kluwer Health.