Drug information of Alemtuzumab

Alemtuzumab


Alemtuzumab is used to treat chronic B-cell lymphocytic leukemia.

Mechanism of effect

Recombinant monoclonal antibody against CD52 (lymphocyte antigen); promotes antibody-dependent lysis

Pharmacodynamic

Alemtuzumab is used to treat leukemia by exploiting antibody mediated lysis of CD52 presenting cells. The CD52 antigen is a cell surface protein found on essentially all B and T lymphocytes, a majority of monocytes, macrophages and most granulocytes. The CD52 antigen is not present on erythrocytes or hematopoetic stem cells. In leukemia there is an excess of B and T cells, so Campath permits selective reduction of lymphocyte populations.

Pharmacokinetics

Distribution

Vd: IV: Campath: 0.18 L/kg (range: 0.1 to 0.4 L/kg); Lemtrada: 14.1 L

Metabolism

Campath: Clearance decreases with repeated dosing (due to loss of CD52 receptors in periphery), resulting in a sevenfold increase in AUC after 12 weeks of therapy.

Half-Life Elimination

IV: Campath: 11 hours (following first 30 mg dose; range: 2 to 32 hours); 6 days (following the last 30 mg dose; range: 1 to 14 days); Lemtrada: ~2 weeks

Drug indications

Multiple sclerosis

-B-cell chronic lymphocytic leukemia

-Multiple Sclerosis

Dosage

Chronic Lymphocytic Leukemia (Campath)

Indicated as a single agent for treatment of B-cell chronic lymphocytic leukemia (B-CLL)

Gradually escalate to maximum recommended single dose of 30 mg (typically over 3-7 days)

Escalation is required at initiation of dosing or if dose is held ≥7 days during treatment

Escalation strategy

  • Administer 3 mg IV qDay until infusion reactions are Grade ≤2, THEN
  • Administer 10 mg IV qDay until infusion reactions are Grade ≤2, THEN
  • Administer 30 mg IV 3x/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

  

Multiple Sclerosis (Lemtrada)

Indicated for relapsing forms of multiple sclerosis (MS); owing to its safety profile, reserve for patients who have an inadequate response to ≥2 other drugs for MS

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

 

Drug contraindications

Infection , Hypersensitivity to this drug , history of myocardial infarction

Hypersensitivity to alemtuzumab or any component of the formulation; HIV infection; active or latent tuberculosis; severe active infections; active malignancies; concurrent anticoagulant, antineoplastic, or immunosuppressive therapy; history of progressive multifocal leukoencephalopathy (PML); history of stroke and arterial dissection of cervicocephalic arteries infections; uncontrolled hypertension; history of arterial dissection of the cervicocephalic arteries; history of stroke; history of angina or myocardial infarction; known coagulopathy.

Side effects

Sinusitis , Infection , Insomnia , Diarrhea , Headache , edema , thyroid dysfunction , vertigo , urticaria , Urinary tract infection , fever , infusion reactions , fungal infection , pneumonia , itching , sweating , Sore mouth , tiredness , Abdominal pain , Rash , Back pain , Herpes Simplex , tachycardia

 (Campath)

Rigors --Fever -Neutropenia -Anemia –Thrombocytopenia-Nausea -Vomiting -Rash -Fatigue -Dyspnea -Cough -Headache -Pruritus -Sepsis -Skeletal pain -Diarrhea -Anorexia -Excessive sweating -Pneumonia -Dysthesias -Stomatitis -Asthenia -Edema -Dizziness -Abdominal pain -Herpes simplex -Hypertension -Myalgias -Tachycardia, SVT - Chest/back pain -Dyspepsia -Insomnia -Bronchospasm -Constipation -Depression -Epistaxis -Moniliasis -Pancytopenia -Somnolence

 (Lemtrada)

Infusion reactions, all -Infections, -Rash -Headache -Pyrexia -Nasopharyngitis -Nausea -Urinary tract infection -Fatigue -Insomnia -Upper respiratory tract infection -Herpes viral infection -Urticaria -Pruritus -Thyroid gland disorders -Fungal infection -Arthralgia -Pain in extremity -Back pain -Diarrhea -Sinusitis -Oropharyngeal pain -Paresthesia -Dizziness -Abdominal pain -Flushing -Vomiting -Cough -Chills -Dysgeusia -Influenza -Dermatitis -Dyspepsia -Blood in urine -Dyspnea -Tachycardia -Anxiety -Muscular weakness -Bronchitis -Chest discomfort -Muscle spasm -Myalgia -Decreased CD4 and CD8 lymphocytes -Asthenia -Infusion reactions, serious -Infections, serious -Immune thrombocytopenia -HPV infection -Pneumonitis -Glomerular nephropathies -Thyroid cancer -Melanoma -Active/latent tuberculosis -Hemolytic anemia -Pancytopenia -Neutropenia

poliovirus vaccine, smallpox vaccine

Alerts

-Serious infusion reactions, including fatal reactions, can occur

-May cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders

-Perform baseline and yearly skin exams

-Serious cytopenias, including fatal pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia, can occur

-Serious infections, including fatal bacterial, viral, fungal, and protozoan infections, reported

-Serious, sometimes fatal, autoimmune conditions (eg, immune thrombocytopenia, antiglomerular basement membrane disease) may occur

-Serious and life-threatening stroke (eg, ischemic, hemorrhagic stroke) reported within 3 days of administration

-Leukoencephalopathy (PML) reported; withhold therapy immediately for symptoms suggestive of PML

-Safety of immunization with live viral vaccines has not been studied; do not administer live viral vaccines to patients who have recently therapy

-Hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia reported after treatment

-Serious infusion reactions (pyrexia, chills/rigors, nausea, hypotension, urticaria, dyspnea, rash, emesis, bronchospasm) reported

-Autoimmune hepatitis causing clinically significant liver injury, including acute liver failure requiring transplant, reported

-May increase risk of acute acalculous cholecystitis;

Points of recommendation

-Withhold therapy during serious infection or other serious adverse reactions until resolution

-Discontinue therapy for autoimmune anemia or autoimmune thrombocytopenia

-No dosage adjustment necessary for lymphopenia

-Delay between doses (≥7 days): Initiate therapy at 3 mg; escalate to 10 mg, and then to 30 mg as tolerated

-ANC <250 cells/mcL and/or platelet count ≤25,000 cells/mcL

  • First occurrence: Withhold therapy, resume at 30 mg when ANC ≥500 cells/mcL and platelet count ≥50,000 cells/mcL
  • Second occurrence: Withhold therapy, resume at 10 mg when ANC ≥500 cells/mcL and platelet count ≥50,000 cells/mcL
  • Third occurrence: Discontinue therapy

-Before initiating

  • 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
  • Perform tuberculosis screening according to local guidelines
  • Instruct to avoid potential sources of Listeria monocytogenes (see Cautions)

-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

-Administer in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions

-Monitor during infusions and for 2 hr after each infusion, withhold drug for Grade 3 or 4 infusion reactions

-Gradually escalate drug to recommended dose at initiation of therapy and after interruption of therapy for ≥7 days

-Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections

-Advise to seek immediate medical attention if symptoms of stroke occur

-may recommend antiemetics to prevent nausea and vomiting

Pregnancy level

Consult a physician before using

There are no adequate data on the developmental risk associated with the use of this drug in pregnant women. It was embryolethal in animal studies when administered during organogenesis. Autoantibodies may develop after administration. Placental transfer of antithyroid antibodies resulting in neonatal Graves' disease has been reported.

Breast feeding warning

No information is available on the use of this drug during breastfeeding. Because it is a large protein molecule, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant GI tract. Until more data become available, this drug should be used with caution or avoided during breastfeeding, especially while nursing a newborn or preterm infant.

Drug forms

: Campath, Lemtrada

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