Alemtuzumab
Indications
Alemtuzumab is used for:
B cell chronic lymphocytic leukaemia, Relapsing-remitting multiple sclerosis
Adult Dose
Intravenous
B cell chronic lymphocytic leukaemia
Adult: Initially, 3 mg daily via infusion over 2 hr (up to 8 hr in some patients). Repeat dose daily until tolerated then increase gradually to 10 mg daily. Dose escalation usually takes 3-7 days. Maintenance: 30 mg given 3 times wkly on alternate days, up to 12 wk. Modify dose according to haematological toxicity.
Relapsing-remitting multiple sclerosis
Adult: Initial treatment course: 12 mg daily via infusion over 4 hr for 5 consecutive days to a total dose of 60 mg. 2nd treatment course: 12 mg daily via infusion over 4 hr for 3 consecutive days to a total dose of 36 mg given 12 mth after the initial treatment course.
Child Dose
Renal Dose
Administration
Reconstitution: Dilute in 100 mL of NaCl 0.9% or glucose 5%.
IV Administration
Administer by IV infusion only, do NOT give as IV push or bolus
Contra Indications
Active systemic infection or underlying immunodeficiency.
Precautions
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 wkly. Conduct serum creatinine levels and urinalysis w/ microscopy prior to treatment initiation and at mthly intervals thereafter. TSH level should be done prior to treatment initiation and every 3 mth thereafter.
Lactation
No data on presence of alemtuzumab in human milk, effects on the breastfed infant, or effects of the drug on milk production
Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice administered 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
Pregnancy-Lactation
Pregnancy
Unknown whether 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
No adequate data on developmental risk associated with use in pregnant women
When administer during organogenesis, 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 presence of alemtuzumab in human milk, effects on the breastfed infant, or effects of the drug on milk production
Lemtrada: Alemtuzumab was detected in the milk of lactating huCD52 transgenic mice administered 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
Interactions
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.
Adverse Effects
Side effects of Alemtuzumab :
CHF, pyrexia, chills, hypotension, rigors, pruritus, shortness of breath, headache, urticaria, rash, tachycardia, dyspnoea, neutropenia, lymphopenia, thrombocytopenia, anaemia, cytomegalovirus (CMV) viraemia and CMV infection, GI disturbances (nausea, vomiting, diarrhoea, abdominal pain), insomnia, anxiety, acute cytokine release syndrome.
Potentially Fatal: Autoimmune anaemia, autoimmune thrombocytopenia, prolonged myelosuppression, severe idiopathic thrombocytopenic purpura, pancytopenia, bone marrow hypoplasia, serious infusion reactions.
Mechanism of Action
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.