Alemtuzumab

Alemtuzumab is used for: B cell chronic lymphocytic leukaemia, Relapsing-remitting multiple sclerosis

Intravenous B cell chronic lymphocytic leukemia Adult: 30mg/mL (1mL/vial) Indicated as a single agent for treatment of B-cell chronic lymphocytic leukemia (B-CLL) Gradually escalate to a maximum recommended single dose of 30 mg (typically over 3-7 days) Escalation is required at the initiation of dosing or if the dose is held >7 days during treatment Escalation strategy Administer 3 mg IV once daily until infusion reactions are Grade <2, THEN Administer 10 mg IV once daily until infusion reactions are Grade <2, THEN Administer 30 mg IV three times per week (on alternate days [eg, Mon-Wed-Fri]) Duration of treatment: 12 weeks (including escalation periods) Not to exceed 30 mg/dose OR 90 mg/week Relapsing-remitting multiple sclerosis Adult: 10mg/mL (1.2mL/vial [12mg/1.2mL]) The recommended dose is administered as 2 separate treatment courses First course: 12 mg/day IV on 5 consecutive days (60 mg total dose) Second course: 12 mg/day IV on 3 consecutive days (36 mg total dose) Subsequent courses: Administer 12 mg/day IV on 3 consecutive days (36 mg total dose) as needed, at least 12 months after last dose of any prior treatment courses

IV Preparation Visually inspect for particulate matter and discoloration; if particulate matter is present or solution is discolored, do use vial Do not shake vial Withdraw the necessary amount from the vial into a syringe Campath To prepare 3-mg or 10-mg dose, withdraw calculated amount into a 1-mL syringe calibrated in increments of 0.01 mL To prepare 30-mg dose, withdraw 1 mL in either a 1-mL or 3-mL syringe Lemtrada Withdraw 1.2 mL from vial into a syringe Inject syringe contents into 100 mL sterile 0.9% NaCl USP or D5W Gently invert bag to mix solution IV Administration Administer by IV infusion only, do NOT give as IV push or bolus

Active systemic infection or underlying immunodeficiency.

Patient w/ autoimmune disorder, ischaemic heart disease, pre-existing malignancy; hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers. Pregnancy and lactation. Monitoring Parameters Monitor BP; CBCs and platelet counts weekly. Conduct serum creatinine levels and urinalysis w/ microscopy prior to treatment initiation and at monthly intervals thereafter. TSH level should be done prior to treatment initiation and every 3 months thereafter. Monitoring Parameters Check liver, thyroid, and kidney function, urinalysis with microscopy, blood counts, and vital signs (including blood pressure, heart rate, and ECG) before infusions. Monitor blood pressure and heart rate continuously or at least once every hour during infusions—discontinue infusion if severe adverse reactions occur. Monitor patients for infusion-related reactions for at least 2 hours after infusions; patients should be informed of the risk of delayed infusion-related reactions and to seek immediate medical attention if these occur. Monitor platelet counts after treatment. Conduct laboratory tests (ie, CBC with differential, serum creatinine, urinalysis with urine cell counts) at baseline and at periodic intervals for 48 months following the last treatment course. Test thyroid function (eg, TSH) before treatment and q3mo thereafter. HPV screening should be carried out annually in female patients. Screening patients at high risk of hepatitis B or C is recommended before treatment. All patients should be evaluated for active or latent tuberculosis before starting treatment. Obtain a baseline ECG; monitor vital signs before infusion and periodically during the infusion. Complete any necessary immunizations >6 weeks. Determine whether patients have a history of varicella or were vaccinated for varicella zoster virus (VZV); if not, test for antibodies to VZV and consider vaccination for those who are antibody-negative; postpone initiating treatment until 6 weeks after VZV vaccination. Instruct to avoid potential sources of Listeria monocytogenes.

Pregnancy Campath: Unknown whether the drug can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity; administer to a pregnant woman only if clearly needed Lemtrada: No adequate data on the developmental risk associated with use in pregnant women When administered during organogenesis, the drug was embryolethal in pregnant huCD52 transgenic mice Auto-antibodies may develop after administration; placental transfer of antithyroid antibodies resulting in neonatal Graves’ disease reported Contraception Women of childbearing potential should use effective contraceptive measures during treatment and for 4 months following that course of treatment Infertility In huCD52 transgenic mice, administration prior to and during the mating period resulted in adverse effects on sperm parameters in males and reduced number of corpora lutea and implantations in females Lactation No data on the presence of alemtuzumab in human milk, its effects on the breastfed infant, or the effects of the drug on milk production Lemtrada: Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice administered the drug Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

May reduce efficacy of inactivated vaccines. Not recommended for use w/in 3 wk of other chemotherapy drugs. Live viral vaccines should not be used for at least 12 mth after alemtuzumab therapy.

Side effects of Alemtuzumab : Common or very common: Abdominal pain. anxiety. asthma. cytokine release syndrome. endocrine ophthalmopathy. goitre. haemorrhage. hiccups. hyperhidrosis. hyperthyroidism. hypothyroidism. influenza-like illness. leucocytosis. lymphadenopathy. lymphopenia. malaise. meningitis. menstrual cycle irregularities. multiple sclerosis exacerbated. muscle complaints. muscle weakness. neoplasms. nephropathy. oropharyngeal pain. peripheral edema. sensation abnormal. skin reactions. stomatitis. thyroiditis. tremor. urine abnormalities. vertigo. vision disorders Uncommon: Acquired hemophilia. appetite decreased. cervical dysplasia. dry mouth. dysphagia. ear pain. facial swelling. gallbladder disorders. gastrointestinal disorders. Goodpasture’s syndrome. limb discomfort. musculoskeletal stiffness. nephrolithiasis. pancytopenia. pneumonitis. tension headache. throat irritation. weight changes Rare or very rare: Haemophagocytic lymphohistiocytosis Frequency not known: Artery dissection. cerebrovascular insufficiency. hepatitis autoimmune (including fatal cases). liver injury. myocardial ischemia. reactivation of infections. thyroid disorder autoimmune Potentially Fatal: Autoimmune anemia, autoimmune thrombocytopenia, prolonged myelosuppression, severe idiopathic thrombocytopenic purpura, pancytopenia, bone marrow hypoplasia, serious infusion reactions.

Alemtuzumab is a recombinant humanised monoclonal antibody that binds to CD52, a nonmodulating antigen found on the surface of B and T lymphocytes, a majority of monocytes, macrophages, natural killer (NK) cells and subpopulation of granulocytes. Upon binding to CD52+, an antibody-dependent malignant cell lysis occurs.