Adalimumab

Name: Adalimumab

Do I need a prescription for adalimumab?

Yes

Uses for Adalimumab

Rheumatoid Arthritis in Adults

Used to manage the signs and symptoms of rheumatoid arthritis, to induce a major clinical response, to improve physical function, and to inhibit progression of structural damage associated with the disease in adults with moderate to severe active rheumatoid arthritis.1 3 11 Use alone or in combination with methotrexate or other nonbiologic DMARDs.1

Juvenile Arthritis

Management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.1 20 Use with or without methotrexate.1 20

Psoriatic Arthritis

Used to manage the signs and symptoms of psoriatic arthritis, to improve physical function, and to inhibit progression of structural damage associated with the disease in adults with active psoriatic arthritis.1 14 15 Use alone or in combination with other nonbiologic DMARDs.1

Ankylosing Spondylitis

Management of the signs and symptoms of active ankylosing spondylitis.1 16

Crohn’s Disease

Used to reduce signs and symptoms of Crohn’s disease and to induce and maintain clinical remission in adults with moderately to severely active disease who have had inadequate response to conventional therapy.1 Also used to reduce signs and symptoms of the disease and to induce clinical remission in adults with moderately to severely active Crohn’s disease who have lost response to or are intolerant to infliximab.1

Ulcerative Colitis

Used to induce and sustain clinical remission in adults with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressive agents such as corticosteroids, azathioprine, or mercaptopurine.1 32 33 35

Efficacy in patients who have lost response to or were intolerant to TNF blocking agents not established.1 33

Plaque Psoriasis

Management of moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and in whom other systemic therapies are medically less appropriate.1 Use only in patients who will be closely monitored and who will have regular follow-up visits with a clinician.1

Interactions for Adalimumab

Administered concomitantly with aminosalicylates, methotrexate, other DMARDs, corticosteroids, other immunomodulatory agents (e.g., azathioprine, mercaptopurine), and/or NSAIAs in clinical studies.1 (See Concomitant Therapy under Dosage and Administration.)

Drugs Metabolized by Hepatic Microsomal Enzymes

Because increased levels of TNF during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF activity by adalimumab may normalize formation of CYP enzymes.1 29

Drugs metabolized by CYP isoenzymes that have a low therapeutic index: Monitor therapeutic effect and/or serum concentrations following initiation or discontinuance of adalimumab; adjust dosage as needed.1

Biologic Antirheumatic Agents

For abatacept, anakinra, rituximab, and tocilizumab, see Specific Drugs under Interactions. For other biologic agents used in the management of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, or plaque psoriasis, manufacturer states data regarding concomitant use with adalimumab are insufficient.1

Concomitant use of adalimumab and other biologic DMARDs not recommended.1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase the risk of infection.29

Vaccines

Patients may receive inactivated vaccines.1

Avoid live vaccines.1 (See also Pediatric Use under Cautions.) No data available on secondary transmission of infection by live vaccines in adalimumab-treated patients.1

Specific Drugs

Drug

Interaction

Comments

Abatacept

Increased incidence of infection and serious infection, without additional clinical benefit, reported with abatacept and TNF blocking agents in rheumatoid arthritis1 17

Concomitant use not recommended1 17

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Anakinra

Increased incidence of serious infections and neutropenia, without additional clinical benefit, reported with anakinra and etanercept (another TNF blocking agent) in rheumatoid arthritis1 10

Concomitant use not recommended1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Cyclosporine

Possible effect on cyclosporine metabolism; because increased levels of TNF during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF activity by adalimumab may normalize formation of CYP enzymes1 29

Monitor therapeutic effect and concentrations of cyclosporine following initiation or discontinuance of adalimumab; adjust dosage as needed1

Influenza virus vaccine inactivated

Antibody titers in adalimumab-treated rheumatoid arthritis patients were protective, albeit lower than in placebo-treated patients1

Methotrexate

Decreased adalimumab clearance1

Dosage adjustment not necessary1

Natalizumab

Increased risk of progressive multifocal leukoencephalopathy (PML) or other serious infections28

Avoid concomitant use in the management of Crohn’s disease28

Pneumococcal polysaccharide vaccine

No difference in antibody response between adalimumab- and placebo-treated rheumatoid arthritis patients1

Rituximab

Increased risk of serious infection reported in patients who received rituximab and subsequently received a TNF blocking agent1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Theophylline

Possible effect on theophylline metabolism; because increased levels of TNF during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF activity by adalimumab may normalize formation of CYP enzymes1 29

Monitor therapeutic effect and serum concentrations of theophylline following initiation or discontinuance of adalimumab; adjust dosage as needed1

TNF blocking agents

Concomitant use not recommended1

Tocilizumab

Concomitant use not studied; possibility of increased immunosuppression and increased risk of infection25

Avoid concomitant use25

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection29

Warfarin

Possible effect on warfarin metabolism; because increased levels of TNF during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF activity by adalimumab may normalize formation of CYP enzymes1 29

Monitor therapeutic effect of warfarin following initiation or discontinuance of adalimumab; adjust dosage as needed1

Stability

Storage

Parenteral

Injection

2–8°C.1 Do not freeze; do not use solutions that have been frozen.1 During travel, store in a cool carrier with an ice pack.1 Protect from light; store in original carton until time of administration.1

Actions

  • Potent antagonist of TNF biologic activity.1 3 8

  • Has high specificity and affinity for TNF (TNF-α); does not bind to or inactivate lymphotoxin α (TNF-β).1 3 8 Prevents the binding of TNF to cell surface TNF receptors, thereby blocking the biologic activity of TNF.1 3 8

  • An immunoglobulin G1 (IgG1) made by phage display technology with amino acid sequences from the human germline; does not contain nonhuman components or artificially fused human peptide sequences.3 8 Indistinguishable in structure and function from naturally occurring human IgG.3 8

  • Produced by recombinant DNA technology in a mammalian cell expression system; purified by a process that includes specific viral inactivation and removal steps.1

Pronunciation

(a da LIM yoo mab)

Adverse Reactions

>10%:

Central nervous system: Headache (12%)

Dermatologic: Skin rash (6% to 12%)

Hematologic & oncologic: Positive ANA titer (12%)

Immunologic: Antibody development (3% to 26%; significance unknown)

Local: Injection site reaction (12% to 20%; includes erythema, itching, hemorrhage, pain, swelling)

Neuromuscular & skeletal: Increased creatine phosphokinase (15%)

Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)

1% to 10%:

Cardiovascular: Hypertension (5%), atrial fibrillation (<5%), cardiac arrest (<5%), cardiac arrhythmia (<5%), chest pain (<5%), coronary artery disease (<5%), deep vein thrombosis (<5%), hypertensive encephalopathy (<5%), myocardial infarction (<5%), palpitations (<5%), pericardial effusion (<5%), pericarditis (<5%), peripheral edema (<5%), subdural hematoma (<5%), syncope (<5%), tachycardia (<5%)

Central nervous system: Confusion (<5%), myasthenia (<5%), paresthesia (<5%), torso pain (<5%)

Dermatologic: Cellulitis, erysipelas

Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%), dehydration (<5%), ketosis (<5%), menstrual disease (<5%), parathyroid disease (<5%)

Gastrointestinal: Nausea (9%), abdominal pain (7%), cholecystitis (<5%), cholelithiasis (<5%), esophagitis (<5%), gastrointestinal hemorrhage (<5%), vomiting (<5%), diverticulitis

Genitourinary: Urinary tract infection (≤8%), hematuria (5%), cystitis (<5%), pelvic pain (<5%)

Hematologic & oncologic: Adenoma (<5%), agranulocytosis (<5%), paraproteinemia (<5%), polycythemia (<5%), carcinoma (including breast, gastrointestinal, skin, urogenital), malignant lymphoma, malignant melanoma

Hepatic: Increased serum alkaline phosphatase (5%), hepatic necrosis (<5%)

Hypersensitivity: Hypersensitivity reaction (children 6%; adults 1%)

Infection: Serious infection (9%; including dental caries, gastroenteritis, rotavirus, varicella), herpes simplex infection (≤4%), herpes zoster (≤4%), sepsis

Local: Injection site reaction (8%; other than erythema, itching, hemorrhage, pain, swelling)

Neuromuscular & skeletal: Back pain (6%), arthritis (<5%), arthropathy (<5%), bone disease (<5%), bone fracture (<5%), limb pain (<5%), muscle cramps (<5%), myasthenia (<5%), osteonecrosis (<5%), septic arthritis (<5%), synovitis (<5%), tendon disease (<5%), tremor (<5%), arthralgia (3%; plaque psoriasis)

Ophthalmic: Cataract (<5%)

Renal: Nephrolithiasis (<5%), pyelonephritis

Respiratory: Flu-like symptoms (7%), asthma (<5%), bronchospasm (<5%), dyspnea (<5%), pleural effusion (<5%), respiratory depression (<5%), pharyngitis (juvenile idiopathic arthritis: ≤4%), pneumonia (≤4%), tuberculosis (including reactivation of latent infection; disseminated, miliary, lymphatic, peritoneal, and pulmonary)

Miscellaneous: Accidental injury (10%), abnormal healing (<5%), postoperative complication (infection)

<1% (Limited to important or life-threatening): Abscess (limb, perianal), alopecia, anal fissure, anaphylactoid reaction, anaphylaxis, angioedema, aplastic anemia, appendicitis, bacterial infection, basal cell carcinoma, cardiac failure, cerebrovascular accident, cervical dysplasia, circulatory shock, cytopenia, dermal ulcer, endometrial hyperplasia, erythema multiforme, fixed drug eruption, fulminant necrotizing fasciitis, fungal infection, Guillain-Barré syndrome, hepatic failure, hepatitis B (reactivation), hepatosplenic T-cell lymphomas (children, adolescents, and young adults), hepatotoxicity (idiosyncratic) (Chalasani 2014), histoplasmosis, hypersensitivity angiitis, increased serum transaminases, interstitial pulmonary disease (eg, pulmonary fibrosis), intestinal obstruction, intestinal perforation, leukemia, leukopenia, liver metastases, lupus-like syndrome, lymphadenopathy, lymphocytosis, malignant neoplasm of ovary, meningitis (viral), Merkel cell carcinoma, multiple sclerosis, mycobacterium avium complex, myositis (children and adolescents), neutropenia, optic neuritis, pancreatitis, pancytopenia, protozoal infection, psoriasis (including new onset, palmoplantar, pustular, or exacerbation), pulmonary embolism, respiratory failure, sarcoidosis, septic shock, skin granuloma (annulare; children and adolescents), Stevens-Johnson syndrome, streptococcal pharyngitis (children and adolescents), systemic lupus erythematosus, testicular neoplasm, thrombocytopenia, vasculitis (systemic), viral infection

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinitis, rhinorrhea, abdominal pain, nausea, or back pain. Have patient report immediately to prescriber signs of infection, signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), signs of heart problems (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), angina, severe headache, severe loss of strength and energy, burning or numbness feeling, severe dizziness, passing out, seizures, vision changes, extremity weakness, bruising, bleeding, excessive weight loss, night sweats, persistent fever, swollen glands, mole changes, skin growth, hematuria, pale skin, skin eczema, severe injection site irritation, or signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Usual Adult Dose for Plaque Psoriasis

-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

Adalimumab Pregnancy Warnings

Animal studies have revealed no teratogenic, embryotoxic or fetotoxic effects. There are no controlled data in human pregnancy. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

AU, UK: Use is not recommended. US: Benefit should outweigh risk. AU TGA pregnancy category: C US FDA pregnancy category: Not assigned. Risk Summary: This drug is actively transferred across the placenta and may affect immune response in the in utero exposed infant. In animal studies, no fetal harm or malformations were observed with IV administration during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD). Comments: -The use of effective contraception is advised during treatment and for at least 5 months after discontinuation. -This drug crosses the placenta in pregnant women. -This drug inhibits TNF alpha; therefore, if it is administered during pregnancy it could affect the immune response in the infant. -Administration of live vaccines to infants exposed to this drug in utero is not recommended for 5 months following the mother's last injection during pregnancy.

Adalimumab Breastfeeding Warnings

AU, UK: Use should be avoided. US: Benefit should outweigh risk. Excreted into human milk: Yes Comments: -Human immunoglobulins are excreted in breast milk. -Some manufacturers recommend that a woman receiving this drug not breast-feed for at least 5 months after the last treatment.

Limited information indicates that maternal use of this drug produces low levels in milk that do not adversely affect the nursing infant. Because it is a large protein molecule, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant GI tract. Most experts recommend that the drug is probably safe during nursing but caution should be exercised while nursing a newborn or preterm infant.

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