Advixa 40-MG SC Injection

Adalimumab is a recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Adalimumab binds specifically to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of patients with Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased levels of TNF are also found in psoriasis plaques. In Plaque Psoriasis, treatment with Adalimumab may reduce the epidermal thickness and infiltration of inflammatory cells.

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis: 40 mg every other week Some patients with RA not receiving methotrexate may benefit from increasing the frequency to 40 mg every week.

Juvenile Idiopathic Arthritis:

• 10 kg to <15 kg: 10 mg every other week
• 15 kg to < 30 kg: 20 mg every other week
• ≥ 30 kg: 40 mg every other week

Adult Crohn’s Disease and Ulcerative Colitis:

• Initial dose (Day 1): 160 mg (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days).
• Second dose two weeks later (Day 15): 80 mg.
• Two weeks later (Day 29): Maintenance dose of 40 mg every other week.
• For patients with Ulcerative Colitis only: Adalimumab should only be continued in patients who have shown evidence of clinical remission by eight weeks (Day 57) of therapy.

Pediatric Crohn’s Disease:

• 17 kg to < 40 kg: Initial dose (Day 1): 80 mg (two 40 mg injections in one day) , Second dose two weeks later (Day 15): 40 mg , Two weeks later (Day 29): Maintenance dose of 20 mg every other week.
• ≥ 40 kg: Initial dose (Day 1): 160 mg (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) , Second dose two weeks later (Day 15): 80 mg (two 40 mg injections in one day) , Two weeks later (Day 29): Maintenance dose of 40 mg every other week.

Plaque Psoriasis:

• 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose.
• Hidradenitis Suppurativa: Initial dose (Day 1): 160 mg (given as four 40 mg injection on Day 1 or as two 40 mg injections per day on Days 1 and 2, Second dose two weeks later (Day 15): 80 mg (two 40 mg injections in one day), Third (Day 29) and subsequent doses: 40 mg every week.

Administered by subcutaneous injection.

Abatacept: Increased risk of serious infection
Anakinra: Increased risk of serious infection
Live vaccines: Advixa use should be avoided

Adalimumab should not be administered to patients with known hypersensitivity to Adalimumab or any of its components.

The most common adverse reaction with Advixa was injection site reactions (erythema and/or itching, hemorrhage, pain or swelling). The most common adverse reactions leading to discontinuation of Advixa in rheumatoid arthritis were clinical flare reaction, rash and pneumonia.

• Other adverse reactions of Advixa includes- Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis.
• General disorders and administration site conditions: Pyrexia.
• Hepato-biliary disorders: Liver failure, hepatitis.
• Immune system disorders: Sarcoidosis.
• Neoplasms benign, malignant and unspecified (including cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin).
• Nervous system disorders: Demyelinating disorders (e.g., optic neuritis, Guillain-Barré syndrome).
• Cerebrovascular accident Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis.
• Pulmonary embolism Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia.
• Vascular disorders: Systemic vasculitis, deep vein thrombosis.

Pregnancy Category B. Adequate and well controlled studies with Adalimumab have not been conducted in pregnant women. Adalimumab is an IgG1 monoclonal antibody and IgG1 is actively transferred across the placenta during the third trimester of pregnancy. Limited data from published literature indicate that Adalimumab is present in low levels in human milk and is not likely to be absorbed by a breastfed infant. However, no data is available on the absorption of Adalimumab from breast milk in newborn or preterm infants. Caution should be exercised when Adalimumab is administered to a nursing woman.

• Serious infections: Advixa should not be started during an active infection. If an infection develops, should be carefully monitored and if infection becomes serious Advixa should be stopped.
• Invasive fungal infections: For patients who develop a systemic illness on Advixa, empiric antifungal therapy should be considered for those who reside or travel to regions where mycoses are endemic
• Malignancies: Incidence of malignancies was greater in Advixa-treated patients than in controls
• Anaphylaxis or serious allergic reactions may occur Hepatitis B virus reactivation: HBV carriers should be monitored during and several months after therapy. If reactivation occurs, Advixa should be stopped and antiviral therapy should be started
• Demyelinating disease: Exacerbation or new onset, may occur Cytopenias, pancytopenia: Patients should be advised to seek immediate medical attention if symptoms develop, and should be considered stopping Advixa
• Heart failure: Worsening or new onset, may occur
• Lupus-like syndrome: Advixa should be stopped if syndrome develops

Pediatric Use: Safety and efficacy of Advixa in pediatric patients for uses other than polyarticular juvenile idiopathic arthritis (JIA) and pediatric Crohn’s disease have not been established.

Geriatric Use: A total of 519 patients 65 years of age and older, including 107 patients 75 years and older, received Advixa in clinical studies. No overall difference in effectiveness was observed between these subjects and younger subjects. The frequency of serious infection and malignancy among Advixa treated subjects over age 65 was higher than for those under age 65. Because there is a higher incidence of infections and malignancies in the elderly population in general, caution should be used when treating the elderly.

The maximum tolerated dose of Advixa has not been established in humans. Multiple doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

Disease-modifying antirheumatic drugs (DMARDs), Immunosuppressant

Do not use beyond the expiration date on the container. Advixa must be refrigerated at 2-8° C. Do not freeze. Protect the pre-filled syringe from exposure to light. Store in original carton until time of administration.