Alemtuzumab


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV B cell chronic lymphocytic leukaemia As 30 mg/mL solution: Initial: 3 mg daily via infusion over 2 hours. Repeat daily until tolerated then increase gradually to 10 mg daily; if tolerated, start maintenance dose of 30 mg 3 times weekly given on alternate days. Total treatment duration (including dose escalation): 12 weeks. Relapsing-remitting multiple sclerosis In patients with highly active disease despite full and adequate treatment course with at least 1 disease modifying therapy, or in patients with rapidly evolving severe cases (≥2 disabling relapses in 1 year, and with ≥1 Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load compared to a previous MRI). As 12 mg/1.2 mL solution: Initial treatment course: 12 mg daily for 5 consecutive days (60 mg total dose). 2nd treatment course: 12 mg daily for 3 consecutive days (36 mg total dose), given 12 months after the initial treatment course. Up to 2 additional treatment courses may be considered as needed: 12 mg daily for 3 consecutive days (36 mg total dose), given at least 12 months after the prior treatment course. Doses are administered via infusion over 4 hours. Dosing interruption or discontinuation, or infusion time extension may be required according to individual safety or tolerability (refer to detailed product guideline).
Dosage Details
Intravenous
B cell chronic lymphocytic leukaemia
Adult: As 30 mg/mL solution: Initially, 3 mg daily via infusion over 2 hours. Repeat dose daily until tolerated then increase gradually to 10 mg daily; if tolerated, start maintenance dose of 30 mg 3 times weekly given on alternate days (dose escalation usually takes 3-7 days). Total treatment duration (including dose escalation): 12 weeks. Premedicate with antihistamine and paracetamol before dosing. Administer prophylaxis for herpes virus infections and Pneumocystis jirovecii pneumonia (PCP) and continue for a minimum of 2 months after therapy. Dosing interruption or discontinuation, or infusion time extension may be required according to individual safety or tolerability (refer to detailed product guideline).

Intravenous
Relapsing-remitting multiple sclerosis
Adult: In patients with highly active disease despite full and adequate treatment course with at least 1 disease modifying therapy, or in patients with rapidly evolving severe cases (≥2 disabling relapses in 1 year, and with ≥1 Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load compared to a previous MRI). As 12 mg/1.2 mL solution: Initial treatment course: 12 mg daily for 5 consecutive days (60 mg total dose). 2nd treatment course: 12 mg daily for 3 consecutive days (36 mg total dose), given 12 months after the initial treatment course. Up to 2 additional treatment courses may be considered as needed: 12 mg daily for 3 consecutive days (36 mg total dose), given at least 12 months after the prior treatment course. Doses are administered via infusion over 4 hours. Premedicate with corticosteroids prior to dosing. Give oral antiviral prophylaxis for herpes infections on the 1st day of each treatment course and continue for a minimum of 1 or 2 months after therapy. Dosing interruption or discontinuation, or infusion time extension may be required according to individual safety or tolerability (refer to detailed product guideline).
Reconstitution
As 30 mg/mL solution for infusion: Withdraw the appropriate dose for infusion from the vial then add into a 100 mL bag of 0.9% NaCl or 5% dextrose in water. As 12 mg/1.2 mL solution for infusion: Withdraw 1.2 mL from the vial and add into 100 mL bag of 0.9% NaCl or 5% glucose solution for infusion. Mix bag by gentle inversion.
Contraindications
As 12 mg/1.2 mL solution used in relapsing-remitting multiple sclerosis (RRMS): HIV infection, severe active infection (until complete resolution), other autoimmune diseases, coagulopathy, uncontrolled hypertension; history of stroke, angina pectoris, MI or arterial dissection of the cervicocephalic arteries. Concurrent antiplatelet or anticoagulant therapy.
Special Precautions
Patient with hepatitis B or C; latent TB, pre-existing or ongoing malignancies. Concomitant administration with live vaccines. Not recommended for use in multiple sclerosis (MS) patients with inactive disease or those who are stable on other treatment. Treatment guidelines may vary among individual products (refer to product-specific recommendations). Pregnancy and lactation.
Adverse Reactions
Significant: Hepatic injury, including acute liver failure; malignancies (e.g. thyroid cancer, melanoma, lymphoproliferative disorders, lymphoma), pneumonitis, emesis, suicidal ideation; CHF, cardiomyopathy, decreased ejection fraction, severe bleeding reactions; other infections (e.g. cervical HPV infection, nasopharyngitis, upper respiratory tract infection, pneumonia, sinusitis, herpes viral infections, influenza, bronchitis, appendicitis, gastroenteritis, tooth infection, UTI, oral or vaginal candidiasis).
Blood and lymphatic system disorders: Lymphadenopathy, leukocytosis, leucopenia.
Cardiac disorders: Tachycardia, bradycardia, palpitations, chest pain or discomfort.
Ear and labyrinth disorders: Ear infection, vertigo.
Eye disorders: Conjunctivitis, endocrine ophthalmopathy, blurred vision.
Gastrointestinal disorders: Abdominal pain, nausea, diarrhoea, dyspepsia, oropharyngeal pain, dysgeusia, stomatitis.
General disorders and administration site conditions: Pyrexia, fatigue, peripheral oedema, asthenia, influenza-like illness, malaise, infusion site pain.
Immune system disorders: Cytokine release syndrome.
Injury, poisoning and procedural complications: Contusion.
Investigations: Decreased haematocrit, increased AST/ALT, increased blood creatinine.
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, chills, muscle weakness, back or neck pain, pain in extremity, muscle spasms, musculoskeletal pain.
Nervous system disorders: Headache, dizziness, hypoaesthesia, paraesthesia, tremor, migraine, MS relapse.
Psychiatric disorders: Anxiety, depression, insomnia.
Renal and urinary disorders: Haematuria, proteinuria.
Reproductive system and breast disorders: Menorrhagia, irregular menstruation.
Respiratory, thoracic and mediastinal disorders: Lower respiratory tract infections, epistaxis, hiccups, cough, asthma, dyspnoea.
Skin and subcutaneous tissue disorders: Urticaria, rash, pruritus, erythema, ecchymosis, alopecia, hyperhidrosis, acne, skin lesion, dermatitis.
Vascular disorders: Flushing, hypotension or hypertension.
Potentially Fatal: Autoimmune conditions [e.g. immune thrombocytopenic purpura (ITP), haemolytic anaemia, thrombocytopenia, bone marrow hypoplasia, neutropenia, pancytopenia, lymphopenia, thyroid disorders, glomerular nephropathies including anti-glomerular basement membrane (anti-GBM) disease, autoimmune hepatitis (AIH), acquired haemophilia A], haemophagocytic lymphohistiocytosis (HLH), progressive multifocal leukoencephalopathy (PML), acute acalculous cholecystitis; ischaemic or haemorrhagic stroke, cervicocephalic arterial dissection, serious infusion-related reactions (e.g. syncope, pulmonary infiltrates, pulmonary alveolar haemorrhage, acute respiratory distress syndrome, respiratory arrest, cardiac arrhythmias, MI, myocardial ischaemia, pericarditis, acute cardiac insufficiency, cardiac arrest, anaphylaxis, angioedema, anaphylactic shock); serious bacterial (e.g. TB, listeriosis/listeria meningitis), viral [e.g. varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation], fungal and protozoan infections; severe EBV-associated hepatitis.
MonitoringParameters
Monitor patients closely for signs of infection, infusion-related reactions, vital signs, depression, and suicidal behaviour or ideation. For RRMS: Obtain CBC with differential, serum creatinine, urinalysis with urine cell counts, serum ALT/AST, and total bilirubin prior to treatment initiation and monthly thereafter until ≥48 months after the last infusion; thyroid function test before initiation and every 3 months thereafter until 48 months after the last infusion. Perform skin exams at baseline then yearly for melanoma; TB screening according to local guidelines; human papilloma virus (HPV) screening annually in females. Evaluate patient for history of varicella or vaccination for VZV; if none, test for VZV antibodies and consider vaccinations for antibody-negative patients; complete necessary immunisations at least 6 weeks prior to treatment initiation. For B-CLL: Monitor CBC with differential and platelets weekly or as clinically indicated; CD4+ lymphocyte counts following treatment until recovery; CMV antigen during and for at least 2 months after therapy.
Overdosage
Symptoms: As 30 mg/mL solution used in B-cell chronic lymphocytic leukaemia (B-CLL): Bone marrow aplasia, infections or severe infusion-related reactions; acute bronchospasm, cough, and dyspnoea may occur. As 12 mg/1.2 mL solution used in RRMS: Headache, rash, hypotension or sinus tachycardia. Management: Supportive treatment.
Drug Interactions
Increased risk of immunosuppression with concurrent antineoplastic or immunosuppressive therapies.
Potentially Fatal: May enhance the effects of anticoagulant or antiplatelet therapy. May diminish the effects of live vaccines.
Lab Interference
May interfere with diagnostic serum tests that utilise antibodies.
Action
Description: Alemtuzumab is a recombinant humanised monoclonal antibody that binds to CD52, a nonmodulating cell-surface antigen found on B and T lymphocytes, a majority of monocytes, macrophages, natural killer (NK) cells and a subpopulation of granulocytes. The binding to CD52+ cells results in an antibody-dependent malignant cell lysis. It produces immunomodulatory effects through lymphocyte depletion and repopulation, including alteration in the proportions, number, and properties of some subsets after the treatment in MS.
Pharmacokinetics:
Distribution: Mainly distributed into the blood and interstitial space. Volume of distribution: 0.18 L/kg (30 mg/mL solution); 14.1 L (12 mg/mL solution).
Excretion: Elimination half-life: 30 mg/mL solution: Approx 11 hours (after 1st 30 mg dose); 6 days (after the last 30 mg dose); 12 mg/1.2 mL solution: Approx 2 weeks.
Storage
Store between 2-8°C. Do not freeze. Protect from light.
ATC Classification
L04AA34 - alemtuzumab ; Belongs to the class of selective immunosuppressive agents. Used to induce immunosuppression.
References
Anon. Alemtuzumab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 24/07/2020.

Buckingham R (ed). Alemtuzumab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 24/07/2020.

Campath Injection (Genzyme Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 24/07/2020.

Lemtrada 12 mg Concentrate for Solution for Infusion (Sanofi Belgium). European Medicines Agency [online]. Accessed 24/07/2020.

Lemtrada Injection, Solution, Concentrate (Genzyme Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 24/07/2020.

Sanofi-Aventis New Zealand Limited. Lemtrada, Concentrate for Infusion 10 mg/mL data sheet 31 January 2020. Medsafe. http://www.medsafe.govt.nz/. Accessed 24/07/2020.

Disclaimer: This information is independently developed by MIMS based on Alemtuzumab from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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