LEMTRADA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEMTRADA (LEMTRADA).
Alemtuzumab is a humanized monoclonal antibody that binds to CD52, a protein expressed on the surface of mature lymphocytes (T and B cells) and to a lesser extent on monocytes, macrophages, and NK cells. Binding to CD52 induces antibody-dependent cell-mediated cytolysis and complement-mediated lysis, resulting in prolonged depletion of circulating lymphocytes.
| Metabolism | Alemtuzumab is a monoclonal antibody; it is not metabolized by cytochrome P450 enzymes. Clearance occurs via intracellular catabolism and proteolytic degradation. |
| Excretion | Renal (primarily via catabolism to peptides and amino acids, minimal intact drug in urine). No specific biliary or fecal elimination data. |
| Half-life | 12.7 days (range 7.7–22.1 days) after multiple doses; clinically relevant for prolonged lymphocyte depletion. |
| Protein binding | Not determined; likely low due to monoclonal antibody nature (primarily binds to CD52 antigen). |
| Volume of Distribution | Approximately 0.1 L/kg; indicates limited extravascular distribution, primarily in serum and lymphoid tissues. |
| Bioavailability | IV only; not applicable (100% bioavailability via IV infusion). |
| Onset of Action | IV: Lymphocyte depletion occurs within hours; maximal depletion of CD52-bearing lymphocytes by day 7. |
| Duration of Action | Lymphocyte recovery typically begins after 3–6 months, but may take >12 months to return to baseline; sustained immunosuppression. |
12 mg/day intravenously over 4 hours on 5 consecutive days (total 60 mg), followed by 12 mg/day intravenously over 4 hours on 3 consecutive days (total 36 mg) 12 months later.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended in severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. |
| Geriatric use | No specific dose adjustment recommended; limited data available in patients ≥65 years; use with caution due to higher risk of infections and immune-mediated disorders. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEMTRADA (LEMTRADA).
| Breastfeeding | Excreted in human milk in low amounts; M/P ratio not available. Given the high molecular weight (approx. 150 kDa) and potential for immunosuppression in the nursing infant, breastfeeding is not recommended during treatment and for at least 4 months after the last dose. |
| Teratogenic Risk | Pregnancy category: Contraindicated in pregnancy. Alemtuzumab is an IgG1 monoclonal antibody that crosses the placenta. First trimester: Fetal IgG exposure begins around week 13 of gestation; prior to that, transfer is minimal. Second and third trimesters: IgG actively transported across placenta, increasing fetal exposure. Cases of fetal harm (spontaneous abortion, fetal death) reported. Risk of profound lymphopenia and other immune alterations in the newborn. No adequate human studies; animal studies show embryolethality and developmental toxicity. |
■ FDA Black Box Warning
WARNING: SERIOUS AUTOIMMUNE CONDITIONS, INFUSION REACTIONS, AND MALIGNANCIES. Alemtuzumab can cause serious, potentially fatal autoimmune conditions (e.g., immune thrombocytopenia, glomerulonephropathies, autoimmune hemolytic anemia, autoimmune pancytopenia), infusion reactions, and an increased risk of malignancies including thyroid cancer, melanoma, and lymphoproliferative disorders. Only prescribers enrolled in a restricted distribution program should prescribe alemtuzumab.
| Serious Effects |
["Hypersensitivity to alemtuzumab or any of its excipients.","Active infection (except minor localized infections).","Known history of progressive multifocal leukoencephalopathy (PML).","Concurrent treatment with other immunosuppressive therapies (not recommended)."]
| Precautions | ["Autoimmune conditions: Monitor for immune thrombocytopenia, glomerulonephropathies, autoimmune hemolytic anemia, and autoimmune pancytopenia.","Infusion reactions: Premedicate and monitor; reactions can be severe.","Infections: Increased risk due to lymphopenia; monitor for Listeria, herpes, and other opportunistic infections.","Malignancies: Monitor for thyroid cancer, melanoma, and lymphoproliferative disorders.","Vaccination: Avoid live vaccines during and after treatment.","Reproductive risk: Advise women of childbearing age to use contraception during and for 4 months after treatment."] |
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| Fetal Monitoring | Pre-treatment: Confirm negative pregnancy test before initiation. Monitor complete blood counts, renal function, thyroid function, and signs of autoimmunity. During pregnancy: If exposure occurs, monitor fetal growth and wellbeing by ultrasound. Postpartum: Monitor infant for lymphopenia, increased infection risk, and autoimmune conditions. Long-term monitoring of the infant's immune function recommended. |
| Fertility Effects | No direct studies on human fertility. Animal studies: Increased pre-implantation loss and reduced fertility indices at clinically relevant doses. Menstrual irregularities reported. May impair fertility in females; effect reversible upon discontinuation? Not established. |