Alemtuzumab

Intravenous
B cell chronic lymphocytic leukaemia

Intravenous
Relapsing remitting multiple sclerosis

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.

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.

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.

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.

IV: C

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.

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.

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.

May interfere with diagnostic serum tests that utilise antibodies.

Description:
Mechanism of Action: 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.

Store between 2-8°C. Do not freeze. Protect from light.

Liệu pháp nhắm trúng đích

L04AG06 - alemtuzumab ; Belongs to the class of monoclonal antibodies. Used as immunosuppressants.

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.