LEMTRADA
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEMTRADA (LEMTRADA).
Comprehensive clinical and safety monograph for LEMTRADA (LEMTRADA).
Treatment of relapsing forms of multiple sclerosis (MS), for patients who have had an inadequate response to two or more drugs indicated for MS.Treatment of B-cell chronic lymphocytic leukemia (B-CLL) (off-label in many regions due to regulatory changes).
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. |
| Molecular Weight | 150000 |
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 | Alemtuzumab is an IgG1 monoclonal antibody and is actively transported across the placenta during the first trimester. Human data are limited, but there is a risk of fetal lymphopenia and potential for immune-mediated adverse effects. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Active transport increases; exposure may lead to fetal B-cell and T-cell depletion. Use only if clearly needed and no safer alternative exists. |
| 3rd trimester | Highest placental transfer; can cause neonatal lymphopenia and increased infection risk. Avoid use near term; consider risk of neonatal immunosuppression. |
Clinical note
Comprehensive clinical and safety monograph for LEMTRADA (LEMTRADA).
| Placental transfer | Alemtuzumab, as a humanized IgG1 monoclonal antibody, is actively transported across the placenta via FcRn receptors. Transfer is lowest in the first trimester and increases progressively in the second and third trimesters, leading to significant fetal exposure. |
| Breastfeeding | Alemtuzumab is excreted into breast milk in small amounts, but the potential for infant absorption and systemic effects (e.g., immunosuppression) is unknown. The manufacturer recommends against breastfeeding during treatment and for at least 4 months after the last dose. |
| Lactation Rating | L4 - Possibly Hazardous |
| 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. |
| 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. |
■ 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 |
Known hypersensitivity to alemtuzumab or any excipientsActive systemic infections (e.g., tuberculosis, hepatitis B, listeriosis, HIV)Human immunodeficiency virus (HIV) infectionUntreated or active tuberculosisSevere active infections
| 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. |
| Food/Dietary | No specific food interactions. Grapefruit and other CYP450 substrates are not relevant; alemtuzumab is not metabolized by CYP enzymes. Avoid alcohol due to potential immune effects. |
| Clinical Pearls | Lemtrada (alemtuzumab) is a CD52-directed cytolytic monoclonal antibody for relapsing-remitting multiple sclerosis (RRMS). Administer via IV infusion over 4 hours for 5 consecutive days (first course) and 3 consecutive days (second course, 12 months later). Premedicate with corticosteroids (e.g., methylprednisolone 1 g IV) for 3 days each course to mitigate infusion reactions. Monitor for autoimmune adverse effects: immune thrombocytopenia (ITP), thyroid disorders, nephropathies. Obtain baseline and monthly CBC, serum creatinine, urinalysis with microscopy, and thyroid function for 48 months after last dose. Vaccinate for varicella zoster virus (VZV) at least 6 weeks prior if seronegative; avoid live vaccines during and after treatment. Pregnancy category C—contraindicated in pregnancy; effective contraception required during and 4 months after treatment. |
| Patient Advice | This drug is given as an intravenous infusion for five days in a row for the first course, and three days in a row one year later. Each infusion takes about 4 hours. · You will receive steroid medications before each infusion to reduce the risk of infusion reactions (fever, chills, rash, breathing problems). · Serious side effects include autoimmune conditions affecting blood cells (low platelets), thyroid, or kidneys. You need monthly blood and urine tests for at least four years after the last dose. · You may be at higher risk for infections; report any signs of infection (fever, cough, painful urination) immediately. · Do not receive live vaccines (e.g., chickenpox, nasal flu vaccine) during treatment and for at least 12 months after. |
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