AMJEVITA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMJEVITA (AMJEVITA).
Adalimumab is a recombinant human IgG1 monoclonal antibody that binds specifically to tumor necrosis factor-alpha (TNF-α) and blocks its interaction with p55 and p75 cell surface TNF receptors. It also modulates biological responses that are induced or regulated by TNF-α, including expression of adhesion molecules, chemotaxis, and pro-inflammatory cytokine release.
| Metabolism | Adalimumab is a monoclonal antibody; it is not metabolized by cytochrome P450 enzymes. Clearance occurs via catabolism to small peptides and amino acids. |
| Excretion | Adalimumab (AMJEVITA) is eliminated primarily via intracellular catabolism, with negligible renal or biliary excretion. No intact drug is excreted in urine. The Fe receptor-mediated recycling contributes to long half-life. |
| Half-life | Terminal elimination half-life is approximately 14 days (range 10-20 days) in patients receiving 40 mg every other week. This long half-life supports biweekly dosing. |
| Protein binding | Adalimumab is a monoclonal antibody; protein binding is negligible as it is not bound to serum proteins. However, it may bind to soluble TNF-alpha with high affinity. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 4.7-6.0 L (0.06-0.08 L/kg for a 70 kg adult). This small Vd reflects distribution primarily in the vascular and interstitial spaces, consistent with a large protein. |
| Bioavailability | Subcutaneous bioavailability: 64% (range 50-80%) after 40 mg SC injection. No intravenous formulation is approved; absolute bioavailability determined by comparison to IV administration. |
| Onset of Action | Subcutaneous administration: Clinical improvement may be observed within 2 weeks for many indications (e.g., rheumatoid arthritis, psoriasis), but maximal effect may require 12-24 weeks. |
| Duration of Action | Duration of effect: After a single 40 mg SC dose, therapeutic concentrations persist for approximately 2-3 weeks. Steady-state is achieved by week 12-16 with every-other-week dosing. |
Subcutaneous injection: 40 mg every other week; for patients with Crohn disease, an initial dose of 160 mg (given as four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) followed by 80 mg at week 2 and 40 mg every other week starting at week 4.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for any degree of hepatic impairment. |
| Pediatric use | For pediatric patients weighing ≥40 kg: 40 mg subcutaneously every other week; for weight <40 kg: 20 mg subcutaneously every other week. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to higher risk of infections. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMJEVITA (AMJEVITA).
| Breastfeeding | Adalimumab is excreted in breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.04. Limited data indicate that infants are exposed to less than 1% of the maternal dose, and no adverse effects have been reported in breastfed infants. Because adalimumab is a large protein, it undergoes proteolysis in the infant's gastrointestinal tract and is not systemically absorbed. Therefore, breastfeeding is considered compatible with adalimumab therapy. |
| Teratogenic Risk | Amjevita (adalimumab) is an IgG1 monoclonal antibody that crosses the placenta during the third trimester, with highest fetal exposure in the third trimester. In the first and second trimesters, placental transfer is limited. Available data from the OTIS autoimmune diseases in pregnancy study and other cohort studies do not indicate a substantially increased risk of major birth defects or miscarriage with adalimumab exposure during pregnancy. However, there is a potential risk of immunosuppression in the neonate, including increased risk of infections, if the mother is exposed during the second and third trimesters. Infants should not be vaccinated with live vaccines for at least 5 months after maternal last dose. |
■ FDA Black Box Warning
Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), invasive fungal infections, and other opportunistic pathogens. Patients should be tested for latent TB before and during therapy. Malignancies, including lymphoma, have been reported in children and adolescents treated with TNF blockers.
| Serious Effects |
["Known hypersensitivity to adalimumab or any component of the formulation","Active serious infection including sepsis"]
| Precautions | ["Serious infections (bacterial, viral, fungal, including reactivation of HBV)","Invasive fungal infections (e.g., histoplasmosis, coccidioidomycosis, candidiasis)","Malignancies (lymphoma, leukemia, melanoma, Merkel cell carcinoma, other)","Anaphylaxis and allergic reactions","Demyelinating disease (new onset or exacerbation of CNS demyelinating disorders)","Hematologic reactions (pancytopenia, aplastic anemia)","Congestive heart failure (new onset or worsening)","Lupus-like syndrome (autoantibodies, rarely clinical disease)","Hepatitis B reactivation","Use with abatacept or anakinra (increased risk of infection)"] |
| Food/Dietary |
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| Fetal Monitoring | Monitor infants for signs of infections and immunosuppression following in utero exposure to adalimumab. Live vaccines should not be administered to infants until 5 months after the mother's last dose during pregnancy. For the mother, monitor for adverse reactions including infections, allergic reactions, and injection site reactions. No specific fetal monitoring is required other than routine prenatal care. |
| Fertility Effects | No formal studies have been conducted on the effects of adalimumab on human fertility. Animal reproduction studies did not show impairment of fertility. In clinical trials, no significant effects on fertility have been reported. It is not known whether adalimumab can cause reproductive harm in humans. |
| No specific food interactions. No dietary restrictions required. |
| Clinical Pearls | AMJEVITA (adalimumab-atto) is a biosimilar to Humira. Administer subcutaneously; rotate injection sites. Do not administer live vaccines. Screen for TB and hepatitis B before initiation. Consider withholding for serious infections. Monitor for allergic reactions and blood dyscrasias. |
| Patient Advice | Store in refrigerator, do not freeze; protect from light. · Inject at room temperature; allow to sit out 15-30 minutes. · Rotate injection sites; avoid tender, bruised, or scarred skin. · Report signs of infection (fever, chills, cough) or allergic reaction immediately. · Do not receive live vaccines while on this medication. · Inform all healthcare providers of your use of AMJEVITA. |