HADLIMA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HADLIMA (HADLIMA).
Adalimumab is a recombinant human IgG1 monoclonal antibody that binds specifically to tumor necrosis factor alpha (TNF-alpha) and neutralizes its biological activity by blocking its interaction with the p55 and p75 cell surface TNF receptors. It also modulates biological responses induced or regulated by TNF, including changes in adhesion molecules and apoptosis.
| Metabolism | Adalimumab is metabolized via proteolytic degradation into small peptides and amino acids. No involvement of cytochrome P450 enzymes. |
| Excretion | Renal: 0.1-0.5% as unchanged drug in urine; biliary/fecal: 70-90% as metabolites; mostly via reticuloendothelial system degradation. |
| Half-life | Terminal elimination half-life approximately 2 weeks (12-16 days); supports every-2-week dosing in maintenance therapy. |
| Protein binding | ~95% bound, primarily to albumin. |
| Volume of Distribution | Central Vd ~3-4 L; peripheral Vd ~6-8 L; total Vd ~10-12 L (0.13-0.17 L/kg), indicating limited extravascular distribution. |
| Bioavailability | SC: ~55-64% relative to IV; IM: not routinely used. |
| Onset of Action | IV: Clinical response observed within 2 weeks; SC: Similar onset, typically within 2-4 weeks. |
| Duration of Action | Duration of clinical effect persists for 8-12 weeks after single dose; dosing interval is every 2 weeks for maintenance. |
40 mg subcutaneously every 2 weeks; may increase to 40 mg weekly if inadequate response.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment; insufficient data for severe renal impairment. |
| Liver impairment | No formal studies in hepatic impairment; caution in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Weight ≥15 kg to <30 kg: 20 mg subcutaneously every 2 weeks; weight ≥30 kg: 40 mg subcutaneously every 2 weeks. For juvenile idiopathic arthritis, same weight-based dosing. |
| Geriatric use | No specific dose adjustment; consider comorbidities and concomitant medications; monitor for infections. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HADLIMA (HADLIMA).
| Breastfeeding | Adalimumab is excreted in human milk in small amounts. The milk-to-plasma ratio is not well established but is likely low due to its large molecular size. Limited data suggest that ingested amounts are low and oral bioavailability is poor. Consider the benefits of breastfeeding, the necessity of the drug to the mother, and the potential for adverse effects in the infant, such as immunosuppression. Monitoring the infant for infections is recommended. |
| Teratogenic Risk | HADLIMA (adalimumab) is an IgG1 monoclonal antibody. Based on its mechanism of action and available data, it is not considered a major teratogen. However, IgG antibodies cross the placenta increasingly after gestational week 20, with highest transfer in the third trimester. Limited human data do not show a clear increase in major congenital anomalies. Theoretical risks include potential immunosuppression in the neonate. Use only if clearly needed, particularly during the second and third trimesters. |
■ FDA Black Box Warning
Serious infections: Patients treated with adalimumab are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), invasive fungal infections, and infections due to other opportunistic pathogens. Malignancy: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including adalimumab.
| Serious Effects |
["Known hypersensitivity to adalimumab or any component of the product","Active serious infections"]
| Precautions | ["Serious infections","Malignancy","Hepatitis B virus reactivation","Demyelinating disease","Cytopenias","Heart failure","Lupus-like syndrome","Vaccinations: Avoid live vaccines"] |
| Food/Dietary | Avoid alcohol; may enhance CNS depression. No specific food restrictions, but maintain adequate fluid intake to prevent dehydration. |
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| Fetal Monitoring | Regular monitoring for signs of infection in the mother and, after delivery, in the infant. Consider monitoring of complete blood counts and liver function tests. Ultrasound monitoring for fetal growth and well-being is recommended if used during pregnancy. Assess for neonatal immunosuppression, including avoidance of live vaccines in the infant for the first 6 months after maternal exposure in utero. |
| Fertility Effects | Adalimumab is not known to impair fertility in males or females. Studies in animals have not shown adverse effects on fertility. In humans, limited data suggest no significant impact on fertility outcomes. However, underlying disease conditions (e.g., rheumatoid arthritis) may affect fertility. |
| Clinical Pearls | HADLIMA (atropine/diphenoxylate) is used for diarrhea; monitor for anticholinergic effects like dry mouth, blurred vision, urinary retention. Avoid in children under 6 years. Use with caution in patients with glaucoma, myasthenia gravis, or hepatic impairment. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · May cause drowsiness or dizziness; avoid driving or operating machinery. · Report severe constipation, abdominal pain, or signs of anticholinergic toxicity. · Not recommended for children under 6 years due to risk of respiratory depression. |