Alemtuzumab (Antineoplastic) (Monograph)

Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

Antineoplastic and immunomodulatory agent; recombinant DNA-derived humanized anti-CD52 monoclonal antibody.

Uses for Alemtuzumab (Antineoplastic)

Chronic Lymphocytic Leukemia

Used as a single agent for treatment of B-cell chronic lymphocytic leukemia (B-CLL); has been used in both previously untreated and previously treated patients (i.e., patients who have been treated with alkylating agents and who have not responded adequately to fludarabine therapy).

As of September 2012, alemtuzumab (Campath) no longer is commercially available in the US, but may be obtained through the Campath Distribution Program for patients who require continued access to the drug. Additional information about the Campath Distribution program is available at 877-422-6728.

Alemtuzumab (Antineoplastic) Dosage and Administration

General

Pretreatment Screening

• Pregnancy testing recommended for females of reproductive potential prior to initiating therapy.

Patient Monitoring

• Obtain CBCs at weekly intervals during therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia occurs. Assess CD4+ counts after treatment until recovery to ≥200/mm³.

• Monitor patients for manifestations of infusion reactions (e.g., rigors, fever, bronchospasm, chills, nausea, vomiting, rash, urticaria, dyspnea, hypotension).

• Routinely monitor patients for CMV infection during treatment and for at least 2 months following completion of therapy.

• Monitor for signs and symptoms of Epstein-Barr virus infection.

Premedication and Prophylaxis

• To minimize risk of IV infusion-related reactions, administer diphenhydramine hydrochloride 50 mg and acetaminophen 500–1000 mg 30 minutes prior to first alemtuzumab infusion and when dosage is escalated.

• To minimize risk of injection site reactions, administer an antihistamine and acetaminophen prior to sub-Q^{† [off-label]} injections (e.g., 30 minutes before administration); in one study, premedication was gradually withdrawn following resolution of any injection-related reactions.

• To minimize risk of serious opportunistic infections, administer prophylactic anti-infectives upon initiation of alemtuzumab and continue for at least 2 months after completion of therapy or until CD4⁺ count ≥200/mm³ (whichever occurs later).

• Administer co-trimoxazole (sulfamethoxazole 800 mg and trimethoprim 160 mg per dose) twice daily 3 times weekly (or equivalent) for PCP prophylaxis.

• Administer famciclovir 250 mg twice daily (or equivalent) for prophylaxis of herpes virus infection.

Administration

Administer by IV infusion. Do not administer by rapid IV injection (e.g., IV push or bolus). For treatment of B-CLL,also has been administered by sub-Q injection^{† [off-label]}.

Do not mix with any other drug or administer any other drug simultaneously in the same IV line.

Vials are for single use only and do not contain a preservative.

Must be diluted prior to IV infusion.

Do not shake vial prior to use.

Use strict aseptic technique.

Compatible with polyvinylchloride (PVC) bags and PVC or polyethylene-lined PVC administration sets.

Dilution

Use a 1 mL syringe calibrated in increments of 0.01 mL when preparing a 3-mg dose or a 10-mg dose; for a 30-mg dose, use a 1 or 3 mL syringe calibrated in increments of 0.1 mL.

To prepare a 3-mg dose, withdraw 0.1 mL of alemtuzumab concentrate from a vial containing 30 mg in 1 mL of drug, and add to 100 mL of 0.9% sodium chloride or 5% dextrose injection.

To prepare a 10-mg dose, withdraw 0.33 mL of alemtuzumab concentrate from a vial containing 30 mg in 1 mL of drug, and add to 100 mL of 0.9% sodium chloride or 5% dextrose injection.

To prepare a 30-mg dose, withdraw 1 mL of alemtuzumab concentrate from a vial containing 30 mg in 1 mL of drug, and add to 100 mL of 0.9% sodium chloride or 5% dextrose injection.

Discard any unused portion after withdrawal of dose.

Gently invert infusion bag to mix solution.

Rate of Administration

Administer IV infusion over 2 hours.

Dosage

Adults

B-CLL

IV

Gradual titration to the recommended maximum single dose of 30 mg administered 3 times weekly on alternate days (e.g., Monday, Wednesday, Friday) is required during initiation of therapy and if therapy is interrupted for ≥7 days. In most patients, escalation to the 30 mg dose can be accomplished in 3–7 days.

Manufacturer's recommended dose escalation strategy is as follows:

Administer 3 mg daily until infusion-related reactions are ≤grade 2, then increase dosage to 10 mg daily. Continue at this dosage until infusion-related reactions are ≤grade 2, and then increase to 30 mg 3 times weekly on alternate days (e.g., Monday, Wednesday, Friday). Total duration of therapy, including initial dose escalation, is 12 weeks.

Single doses >30 mg or cumulative weekly doses >90 mg increase the incidence of pancytopenia.

Sub-Q† [off-label]

In some clinical trials, dose was escalated from an initial dosage of 3 mg daily to a maintenance dosage of 30 mg 3 times weekly. If local skin erythema or edema occurred, dosage escalation phase was prolonged to 1 or 2 weeks.

Some experts recommend that sub-Q therapy be given for at least 12 weeks. In a clinical trial in previously untreated patients, the drug was administered up to 18 weeks; in another clinical trial in previously treated patients, total duration of therapy was up to 12 weeks.

Local reactions, including erythema, edema, pruritus, and pain, have been reported, generally during the first 1–2 weeks of therapy, in patients receiving sub-Q^{† [off-label]} therapy. Some experts state that if symptomatic local reactions occur during dosage escalation, the escalation period may be prolonged to up to 2 weeks.

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Hematologic Toxicities

Adjust dosage and/or temporarily discontinue therapy if severe cytopenias (except lymphopenia) occur; permanently discontinue drug in patients with evidence of autoimmune hematologic toxicity (i.e., autoimmune anemia or thrombocytopenia). See Table 1 for adjustments for hematologic toxicities.

No dosage modifications recommended for lymphopenia.

Infusion Reactions

Withhold therapy in patients experiencing grade 3 or 4 infusion reactions.

Infectious Complications

If serious infection occurs, temporarily discontinue therapy; may reinitiate therapy following resolution of infection.

Withhold therapy during antiviral therapy for CMV infection or confirmed CMV viremia (defined as positive for CMV according to PCR in ≥2 consecutive samples obtained ≥1 week apart) and initiate anti-infective therapy (ganciclovir or equivalent).

Special Populations

Hepatic Impairment

Manufacturer makes no dosage adjustment recommendations.

Renal Impairment

Manufacturer makes no dosage adjustment recommendations.

Geriatric Patients

Manufacturer makes no dosage adjustment recommendations.

Cautions for Alemtuzumab (Antineoplastic)

Contraindications

• None.

Warnings/Precautions

Warnings

Cytopenias

Risk of severe (sometimes fatal) cytopenias, including autoimmune anemia, thrombocytopenia, neutropenia, pancytopenia, and prolonged myelosuppression. (See Boxed Warning.)

Hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have occurred in patients receiving recommended dosages for B-CLL. Increased incidence of pancytopenia with higher than recommended dosages (i.e., single doses >30 mg or cumulative weekly doses >90 mg).

Withhold therapy if severe cytopenia (except lymphopenia) occurs. Discontinue therapy in patients who develop autoimmune hematologic toxicity (i.e., autoimmune anemia or thrombocytopenia) or recurrent or persistent severe cytopenias (except lymphopenia). Safety of reinitiating alemtuzumab in patients with autoimmune cytopenia or bone marrow aplasia not established.

Infusion-related Reactions

Risk of serious syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock. (See Boxed Warning.) Other possible manifestations may include rigors, fever, bronchospasm, chills, nausea, vomiting, rash, urticaria, dyspnea, and hypotension.

In some cases, infusion reactions may occur more frequently during first week of therapy..

Monitor patients closely for infusion-related reactions during and shortly after infusion; withhold therapy if a grade 3 or 4 infusion reaction occurs. Initiate medical management (e.g., glucocorticoids, epinephrine, meperidine) as clinically indicated.

Immunosuppression/Infectious Complications

Risk of serious (sometimes fatal) opportunistic bacterial, viral, fungal, or protozoan infections resulting from severe and profound lymphopenia. (See Boxed Warning.)

Administer prophylactic anti-infectives against PCP and herpes virus infections during alemtuzumab therapy and for at least 2 months after the last dose is administered or until CD4+ count is ≥200 cells/mm³ (whichever occurs later)

Monitor patients closely for CMV infection during and for at least 2 months following completion of therapy. Withhold therapy for serious infections and during antiviral treatment for CMV infection or confirmed CMV viremia (defined as polymerase chain reaction [PCR] positive CMV in ≥2 consecutive samples obtained 1 week apart). Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia.

Monitor for signs and symptoms of Epstein-Barr virus infection.

If serious infection occurs, temporarily withhold therapy until infection resolves.

Severe and prolonged lymphopenia may increase the potential for tranfusion-associated graft versus host disease (TA-GVHD). Administer only irradiated blood products unless immediate transfusion is required.

Other Warnings and Precautions

Immunization

Safety of immunization with live viral vaccines following alemtuzumab therapy not studied.

Do not administer live viral vaccines to patients or infants born to patients receiving the drug.

Immunogenicity

Potential for immunogenicity with use of all therapeutic proteins including alemtuzumab. Development of antibodies (including neutralizing antibodies) to alemtuzumab reported.

Specific Populations

Pregnancy

No adequate data in pregnant women; however, may cause fetal harm. Embryolethality demonstrated in animal studies.

Advise women of potential risk to fetus.

Infants born to pregnant women treated with alemtuzumab may be at increased risk for infections.

Lactation

Distributed into milk in animals; not known whether distributed into human milk. Effects of the drug on nursing infant or on milk production not known.

Because of the potential for serious adverse reactions, advise lactating women not to breastfeed during treatment and for at least 3 months following the last dose.

Females and Males of Reproductive Potential

May cause fetal harm. Pregnancy testing recommended for females of reproductive potential prior to initiating therapy.

Advise female patients of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.

May impair fertility in females and males of reproductive potential; reversibility of this effect not known.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Pharmacokinetics not evaluated. Safety and efficacy not established.

Renal Impairment

Pharmacokinetics not evaluated. Safety and efficacy not established.

Common Adverse Effects

Common adverse reactions: infusion reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), infections (e.g., CMV viremia, CMV infection, other infections), adverse GI effects (nausea, vomiting, diarrhea, abdominal pain), adverse neurologic effects (insomnia, anxiety).

Drug Interactions

No formal drug interaction studies to date.

Live Vaccines

Because of the immunosuppressive effects of alemtuzumab, live virus vaccines should not be administered following a course of alemtuzumab therapy.

Alemtuzumab (Antineoplastic) Pharmacokinetics

Absorption

Bioavailability

After 12 weeks of dosing, a 7-fold increase in mean AUC is observed.

Distribution

Extent

Not known whether distributes into human milk.

Crosses the placenta.

Elimination

Elimination Route

Clearance decreases with repeated administration secondary to decreased receptor-mediated clearance (i.e., loss of CD52 receptors in periphery); AUC increases substantially (7-fold) after 12 weeks of IV dosing in B-CLL patients receiving recommended dosages.

Half-life

Mean half-life is 11 hours (range: 2–32 hours) following the first 30-mg IV dose; mean half-life is 6 days (range: 1–14 days) following the last 30-mg IV dose.

Stability

Storage

Parenteral

Injection Concentrate for IV Infusion

2–8°C. Do not freeze; if accidentally frozen, thaw at 2–8°C before administration. Protect from direct sunlight.

Following dilution, may store at 15–30°C or under refrigeration (2–8°C); use within 8 hours. Protect from light.

Actions

• Recombinant DNA-derived humanized anti-CD52 monoclonal antibody.

• Binds specifically to antigen CD52 (expressed on the surface of B and T cells; most monocytes, macrophages, and natural killer cells; and a subpopulation of granulocytes), triggering a host immune response causing lysis of normal and leukemic cells.

• Mechanism of cell lysis is thought to involve complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

Advice to Patients

• Advise patients to report any signs or symptoms of cytopenias such as bleeding, easy bruising, petechiae or purpura, pallor, weakness, or fatigue.

• Advise patients of the signs and symptoms of infusion-related reactions and of the need to take premedications as prescribed.

• Advise patients to immediately report symptoms of infection (e.g., pyrexia) and to takeprophylactic anti-infectives for PCP (trimethoprim/sulfamethoxazole DS or equivalent)and herpes virus (famciclovir or equivalent) as prescribed.

• Advise patients that they should not be immunized with live viral vaccines if they have recently been treated with alemtuzumab. Advise females with infants exposed to the drug in utero to inform the pediatrician of the exposure.

• Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy.

• Advise female patients of reproductive potential to use effective contraception during treatment with alemtuzumab and for 3 months after the final dose.

• Advise females not to breastfeed during treatment with alemtuzumab and for 3 months after the final dose.

• Advise females and males of reproductive potential that alemtuzumab may impair fertility.

• Advise patients on signs and symptoms of glomerular nephropathies that may occur months to years after receiving alemtuzumab.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Alemtuzumab (Campath) is available only through the Campath Distribution Program.

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