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Alemtuzumab

Class: Antineoplastic Agents
ATC Class: L01XC04
VA Class: AN900
Chemical Name: Disulfide with human-rat monoclonal CAMPATH-1H light chain, anti-(human CD52 (antigen)) (human-rat monoclonal CAMPATH-1H, γ1-chain), immunoglobulin G1 dimer
CAS Number: 216503-57-0
Brands: Campath, Lemtrada

Warning(s)

  • Risk of Cytopenias with Alemtuzumab (Campath) in Patients with B-cell Chronic Lymphocytic Leukemia (B-CLL)
  • Risk of serious, sometimes fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia (ITP), and autoimmune hemolytic anemia.1 (See Hematologic Effects under Cautions.)

    Do not administer single doses >30 mg or cumulative weekly doses >90 mg, since these dosages have been associated with an increased incidence of pancytopenia.1 (See Dosage under Dosage and Administration.)

  • Risk of Infections with Alemtuzumab (Campath) in Patients with B-CLL
  • Risk of serious, sometimes fatal, bacterial, viral, fungal, and protozoan infections.1 (See Infectious Complications under Cautions.)

  • Administer prophylaxis against Pneumocystis jiroveci (formerly P. carinii) pneumonia and herpes virus infections.1 (See Anti-infective Prophylaxis under Dosage and Administration.)

  • Risk of Autoimmune Conditions with Alemtuzumab (Lemtrada) in Patients with Relapsing-remitting Multiple Sclerosis (RRMS)
  • Risk of serious, sometimes fatal, autoimmune disorders such as ITP and anti-glomerular basement membrane disease.a (See Hematologic Effects, and see Glomerular Nephropathy, and also see Thyroid Disorders under Cautions.)

  • Perform CBCs with differential, Scr, and urinalysis with cell counts at periodic intervals for at least 48 months after completion of therapy.a (See Therapy Monitoring under Cautions.)

  • Risk of Malignancies with Alemtuzumab (Lemtrada) in Patients with RRMS
  • Risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders.a (See Malignancy under Cautions.)

  • Perform baseline and annual skin examinations.a

  • Infusion Reactions
  • Risk of serious, potentially fatal, infusion reactions.1 a (See Infusion Reactions under Cautions.)

  • Patients with B-CLL: Carefully monitor during infusions and withhold therapy for grade 3 or 4 infusion reactions; gradually titrate dosage during initiation of therapy and after interruption of therapy for ≥7 days.1 (See Dosage under Dosage and Administration.)

  • Patients with RRMS: Administer in a setting with appropriate personnel and equipment available to manage serious infusion reactions, including anaphylaxis.a Monitor patients for ≥2 hours after each infusion.a

  • Restricted Distribution Program for Alemtuzumab (Lemtrada)
  • Because of the risks of autoimmunity, infusion reactions, and malignancies, alemtuzumab (Lemtrada) for the treatment of RRMS is available only through the Lemtrada REMS Program.a (See Restricted Distribution Programs under Dosage and Administration.)

REMS:

FDA approved a REMS for alemtuzumab to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of alemtuzumab and consists of the following: communication plan, elements to assure safe use, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center (). (Also see Restricted Distribution Programs under Dosage and Administration.)

Introduction

Antineoplastic and immunomodulatory agent; recombinant DNA-derived humanized anti-CD52 monoclonal antibody.1 a

Uses for Alemtuzumab

Chronic Lymphocytic Leukemia (CLL)

First-line therapy of B-CLL.1 6 31 Comparative efficacy and safety of alemtuzumab versus fludarabine as initial therapy for B-CLL not established.3

Treatment of B-CLL in patients who have been treated with alkylating agents and who have not responded adequately to fludarabine therapy (designated an orphan drug by FDA for this use).1 6 7 8

Has been used in combination with fludarabine for the second-line treatment of relapsed or refractory B-CLL.30 40

Multiple Sclerosis (MS)

Management of relapsing forms of MS (e.g., RRMS).a b c d

Because of potentially life-threatening adverse effects (e.g., autoimmunity, infusion reactions, malignancy), generally reserved for patients with inadequate response to ≥2 MS drugs.a (See Cautions.)

Alemtuzumab Dosage and Administration

General

Restricted Distribution Programs

  • Campath Distribution Program
  • As of September 2012, alemtuzumab (Campath) is no longer commercially available in the US, but may be obtained through the Campath Distribution Program for patients who require continued access to the drug.37

    Additional information available at 877-422-6728.37

  • Lemtrada REMS Program
  • Alemtuzumab (Lemtrada) is available only through a restricted distribution program called the Lemtrada REMS program.a e Clinicians, pharmacies, healthcare facilities (e.g., infusion sites), and patients must be enrolled and meet all conditions of the program before they can prescribe, dispense, administer, and receive the drug.a

    Additional information available at 855-676-6326 or .a

Premedication and Patient Monitoring

  • Patients with B-CLL
  • 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.1 (See Infusion Reactions under Cautions.)

  • Monitor patients carefully during or shortly after infusion for manifestations of infusion reactions (e.g., rigors, fever, bronchospasm, chills, nausea, vomiting, rash, urticaria, dyspnea, hypotension).1

  • To minimize risk of injection site reactions, administer an antihistamine and acetaminophen prior to sub-Q injections (e.g., 30 minutes before administration);34 35 36 in one study, premedication was gradually withdrawn following resolution of any injection-related reactions.34

  • Patients with RRMS
  • To minimize risk of IV infusion-related reactions, administer a high-dose corticosteroid (e.g., methylprednisolone 1 g or equivalent) immediately prior to alemtuzumab infusion for the first 3 days of each treatment course.a (See Infusion Reactions under Cautions.) May also consider premedication with antihistamines and/or antipyretics.a

  • Monitor patients carefully for infusion reactions during and for ≥2 hours after each infusion.a Monitor vital signs prior to and periodically during each infusion.a

  • Administer in a setting with appropriate personnel and equipment to manage serious infusion reactions.a

  • Perform appropriate laboratory tests (e.g., CBC with differential, Scr, urinalysis, thyroid function tests) and clinical evaluations (e.g., dermatologic examinations) prior to, during, and following treatment.a (See Therapy Monitoring under Cautions.)

Vaccinations

  • Patients with RRMS
  • Complete any necessary immunizations ≥6 weeks prior to initiating therapy.a

  • Prior to alemtuzumab therapy, test patients without a history of varicella infection or vaccination for antibodies to varicella zoster virus; consider vaccination of antibody-negative patients and postpone alemtuzumab therapy until 6 weeks after vaccination.a

Anti-infective Prophylaxis

  • Patients with B-CLL
  • To minimize risk of serious opportunistic infections, give prophylactic anti-infectives upon initiation of alemtuzumab and continue for 2 months after completion of therapy or until CD4+ T-cell count ≥200/mm3 (whichever occurs later).1 (See Infectious Complications under Cautions.)

  • Administer co-trimoxazole (sulfamethoxazole 800 mg and trimethoprim 160 mg per dose) twice daily 3 times weekly (or equivalent) for prophylaxis of Pneumocystis jiroveci (formerly P. carinii) pneumonia.1

  • Administer famciclovir 250 mg twice daily (or equivalent) for prophylaxis of herpes virus infection.1

  • Patients with RRMS
  • Administer antiviral prophylaxis for herpes virus infection; initiate prophylactic regimen on the first day of each alemtuzumab course and continue for at least 2 months after completion of the course or until CD4+ T-cell counts ≥200/mm3 (whichever occurs later).a

Administration

Administer by IV infusion.1 a For treatment of B-CLL, also has been administered by sub-Q injection.34 35 36

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 a Do not administer by rapid IV injection (e.g., IV push or bolus).1 a

Do not mix with any other drug or administer any other drug simultaneously in the same IV line.1 a

Vials are for single use only and do not contain a preservative.1 a

Must be diluted prior to IV infusion.1 a

Do not shake vial prior to use.1 5

Use strict aseptic technique.1

Campath

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.1

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.1

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.1

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.1

Discard drug vial, including any unused portion, after withdrawal of dose.1

Gently invert infusion bag to mix solution.1

Lemtrada

Withdraw 1.2 mL of alemtuzumab concentrate from a vial containing 12 mg in 1.2 mL of drug, and add to 100 mL of 0.9% sodium chloride or 5% dextrose injection.a

Gently invert bag to mix solution.a

Rate of Administration

Campath: Administer IV infusion over 2 hours for treatment of B-CLL.1

Lemtrada: Administer IV infusion over 4 hours (or longer if clinically indicated) for treatment of RRMS.a

Dosage

Adults

B-CLL

Gradual titration to the recommended maintenance dosage is required during initiation of therapy and after interruption of therapy for ≥7 days.1 In most patients, escalation to maintenance dosage can be accomplished in 3–7 days.1

IV

Initially, 3 mg daily.1 4 When infusion-related toxicities are ≤grade 2, increase dosage to 10 mg daily.1 4 Continue at this dosage until infusion-related toxicities are ≤grade 2, and then increase to a maintenance dosage of 30 mg 3 times weekly on alternate days (i.e., Monday, Wednesday, Friday).1 4 Total duration of therapy, including initial dosage and dosage escalation, is 12 weeks.1

Sub-Q

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.34 35 36 If local skin erythema or edema occurred, dosage escalation phase was prolonged to 1 or 2 weeks.34 36 (See Injection Site Reactions under Cautions.)

Some experts recommend that sub-Q therapy be given for at least 12 weeks.36 In a clinical trial in previously untreated patients, the drug was administered up to 18 weeks;34 in another clinical trial in previously treated patients, total duration of therapy was up to 12 weeks.35

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Withhold therapy during serious adverse reactions until resolution of toxicity.1 Discontinuance of therapy may be necessary.1

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).1

No dosage modifications recommended for lymphopenia.1

Dosage Adjustments for Hematologic Toxicities

Hematologic Measurements

Comments

For first occurrence of ANC <250/mm3 and/or platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC ≥500/mm3 and platelets ≥50,000/mm3, resume therapy at maintenance dosage (i.e., 30 mg 3 times weekly)1

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg daily and then to 30 mg 3 times weekly as tolerated1

For second occurrence of ANC <250/mm3 and/or platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC ≥500/mm3 and platelets ≥50,000/mm3,1 resume therapy at 10 mg 3 times weekly;5 higher dosages not recommended1 5

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg daily and then to 30 mg 3 times weekly as tolerated.1

For third occurrence of ANC <250/mm3 and/or platelets ≤25,000/mm3

Discontinue alemtuzumab permanently1

For first occurrence of a decrease of ANC and/or platelets by ≥50% from baseline value in patients initiating therapy with a baseline ANC ≤250/mm3 and/or baseline platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC and/or platelets return to baseline values, resume therapy at maintenance dosage (i.e., 30 mg 3 times weekly)1 5

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg daily and then to 30 mg 3 times weekly as tolerated1

For second occurrence of a decrease of ANC and/or platelets by ≥50% from baseline value in patients initiating therapy with ANC of ≤250/mm3 and/or platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC and/or platelets return to baseline values, resume therapy at 10 mg 3 times weekly1

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg 3 times weekly as tolerated1

For third occurrence of a decrease of ANC and/or platelets by ≥50% from baseline value in patients initiating therapy with ANC <250/mm3 and/or platelets ≤25,000/mm3

Discontinue alemtuzumab permanently1

Infusion Reactions

Withhold therapy in patients experiencing grade 3 or 4 infusion reactions.1

Infectious Complications

If serious infection occurs, temporarily discontinue therapy; may reinitiate therapy following resolution of infection.1

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).1

RRMS
IV

Dosage regimen consists of 2 treatment courses: Initial treatment course of 12 mg daily for 5 consecutive days (total dose of 60 mg), followed 12 months later by a second treatment course of 12 mg daily for 3 consecutive days (total dose of 36 mg).a

Prescribing Limits

Adults

B-CLL
IV

Maximum 30 mg (as single dose) or 90 mg (as cumulative weekly dose); maximum 12 weeks total duration of therapy, including initial dosage and dosage escalation.1 (See Boxed Warning and see Hematologic Effects under Cautions.)

Special Populations

No special population dosage recommendations at this time.1 a

Cautions for Alemtuzumab

Contraindications

  • Campath: None.1

  • Lemtrada: HIV infection.a

Warnings/Precautions

Warnings

Hematologic Effects

Risk of severe (sometimes fatal) cytopenias, including autoimmune anemia, thrombocytopenia, neutropenia, pancytopenia, and prolonged myelosuppression.1 5 a (See Boxed Warning.)

Hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have occurred in patients receiving recommended dosages for B-CLL.1 Increased incidence of pancytopenia with higher than recommended dosages (i.e., single doses >30 mg or cumulative weekly doses >90 mg).1

Severe, sometimes fatal, ITP reported in patients with RRMS.a In some cases, diagnosed more than 3 years after discontinuance of alemtuzumab.a Manifestations include easy bruising, petechiae, spontaneous mucocutaneous bleeding (e.g., epistaxis, hemoptysis), and heavier than normal or irregular menstrual bleeding.a If ITP suspected, obtain CBC immediately; if confirmed, promptly initiate appropriate treatment.a

Hemolytic anemia also reported in patients with RRMS.a Manifestations include weakness, chest pain, jaundice, dark urine, and tachycardia.a

In patients with RRMS, obtain CBC with differential prior to initiation of therapy and monthly thereafter for at least 48 months after completion of therapy.a (See Therapy Monitoring under Cautions.) If a cytopenia is confirmed, promptly initiate appropriate treatment.a

In patients with B-CLL, withhold therapy if severe cytopenia (except lymphopenia) occurs.1 (See Dosage under Dosage and Administration.) Discontinue therapy permanently in patients who develop autoimmune hematologic toxicity (i.e., autoimmune anemia or thrombocytopenia) or recurrent or persistent severe cytopenias (except lymphopenia).1 Safety of reinitiating alemtuzumab in patients with autoimmune cytopenia or bone marrow aplasia not established.1

Glomerular Nephropathy

Autoimmune renal conditions, such as membranous glomerulonephritis and anti-glomerular basement membrane disease, reported in patients receiving alemtuzumab for treatment of RRMS.a (See Boxed Warning.) In some cases, occurred up to 40 months after discontinuance of the drug.a Anti-glomerular basement membrane disease can result in end-stage renal disease requiring dialysis or transplantation.a Clinical manifestations of nephropathy may include elevated Scr, hematuria, proteinuria, and alveolar hemoptysis.a

In patients with RRMS, perform Scr and urinalysis with cell counts prior to initiation of therapy and monthly thereafter for at least 48 months after completion of therapy.a (See Therapy Monitoring under Cautions.) If clinically important changes in Scr, unexplained hematuria, or proteinuria occur, further evaluate for possible nephropathy.a

Thyroid Disorders

Autoimmune thyroid disorders (e.g., Graves' disease, hyperthyroidism, hypothyroidism) reported in approximately 34% of alemtuzumab-treated patients in MS clinical studies.a In some cases, delayed onset (more than 7 years after initiation of therapy) observed.a

In patients with RRMS, perform thyroid function tests prior to initiation of therapy and every 3 months thereafter for at least 48 months after completion of therapy.a (See Therapy Monitoring under Cautions.)

Use in patients with preexisting thyroid disorders only if potential benefits outweigh potential risks.a

Infusion Reactions

Risk of serious, sometimes fatal, infusion reactions, including anaphylaxis, angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia, atrial fibrillation, transient neurologic symptoms, hypertension, headache, pyrexia, and rash.1 a (See Boxed Warning.) Other possible manifestations may include nausea, vomiting, rash, urticaria, pruritus, insomnia, chills, flushing, fatigue, dyspnea, pulmonary infiltrates, dysgeusia, dyspepsia, dizziness, rigors, fever, or pain.1 a In some cases, infusion reactions occurred more than 24 hours after the drug was administered.a

Administer appropriate premedications (e.g., corticosteroids, antihistamines, antipyretics).1 a

In patients with B-CLL, monitor closely for infusion-related reactions during and shortly after infusion; withhold therapy if a grade 3 or 4 infusion reaction occurs.1 Initiate medical management (e.g., glucocorticoids, epinephrine, meperidine) as clinically indicated.1

In patients with RRMS, administer only in a setting with appropriate equipment and personnel to manage serious infusion reactions, including anaphylaxis.a Monitor for infusion reactions during and for at least 2 hours after each infusion.a (See Advice to Patients.)

Acute systemic injection-related reactions, including fever and chills/rigors, also reported with sub-Q injection of alemtuzumab, but appear to be more common with IV infusion.34 35 36

Malignancy

Malignancies, including thyroid cancer, melanoma, lymphoproliferative disorders, and lymphoma (e.g., mucosa-associated lymphoid tissue [MALT] lymphoma, Castleman's disease, fatal non-Epstein-Barr virus-associated Burkitt lymphoma, Epstein-Barr virus-associated lymphoproliferative disorders) have occurred.a (See Boxed Warning.)

Caution advised when initiating therapy in patients with history of or ongoing malignancy.a

Monitor for symptoms of thyroid cancer and perform dermatologic evaluations.a (See Advice to Patients.)

Infectious Complications

Risk of serious (sometimes fatal) opportunistic bacterial, viral, fungal, or protozoan infections resulting from severe and profound lymphopenia.1 a Reported infections have included herpes infection, CMV infection, cervical human papillomavirus (HPV) infection, tuberculosis, and listeria meningitis.1 a

In patients with B-CLL, administer prophylactic anti-infectives against Pneumocystis jiroveci (formerly Pneumocystis carinii) and herpes virus infections during alemtuzumab therapy and for at least 2 months after the last dose is administered.1 3 4 (See Anti-infective Prophylaxis under Dosage and Administration.)

In patients with RRMS, administer antiviral prophylaxis for herpes infection during and for at least 2 months after a course of alemtuzumab.a (See Anti-infective Prophylaxis under Dosage and Administration.)

Monitor patients closely for CMV infection during and for at least 2 months following completion of therapy.1

Screen for HPV annually in women.a

Screen and treat (if necessary) patients for tuberculosis prior to alemtuzumab therapy.a

Avoid or adequately heat foods that are potential sources of Listeria monocytogenes.a

Although no data available regarding specific risk with alemtuzumab, potential exists for reactivation of viral hepatitis; consider screening patients at high risk of HBV or HCV infection prior to initiation of alemtuzumab therapy and use caution in those identified as carriers of the viruses.a

In patients with active infection, consider delay in alemtuzumab therapy until infection is controlled.a If serious infection occurs, temporarily withhold therapy until infection resolves.1

Other Warnings/Precautions

Therapy Monitoring

In patients with B-CLL, monitor CBCs and platelet counts weekly during therapy;1 more frequent monitoring may be required in patients with worsening anemia, neutropenia, or thrombocytopenia.1 Following completion of alemtuzumab therapy, monitor CD4+ T-cell counts until levels return to ≥200/mm3.1 (See Boxed Warning.)

In patients with RRMS, perform tests for CBCs with differential, Scr, and urinalysis with cell counts prior to initiation of therapy and monthly thereafter for at least 48 months after the last dose is administered.a After 48 months, perform such testing based on clinical findings suggestive of possible adverse effects of the drug.a (See Boxed Warning.)

In patients with RRMS, obtain thyroid function tests (e.g., TSH concentrations) prior to initiation of therapy and every 3 months thereafter for at least 48 months after the last dose is administered.a Continue thyroid testing after 48 months if clinically indicated.a (See Thyroid Disorders under Cautions.)

In patients with RRMS, obtain baseline and annual dermatologic examinations to monitor for melanoma.a (See Boxed Warning.)

Pneumonitis

Pneumonitis, including hypersensitivity pneumonitis and pneumonitis with fibrosis, reported in patients receiving alemtuzumab for RRMS.a Manifestations include dyspnea, cough, wheezing, chest pain or tightness, and hemoptysis.a

Other Alemtuzumab Preparations

Alemtuzumab (Lemtrada) for treatment of RRMS contains same active ingredient as alemtuzumab (Campath) for treatment of B-CLL; increased monitoring for additive, long-term effects may be necessary in patients currently receiving Lemtrada who have previously received Campath.a

Suicidality

In clinical studies in patients with RRMS, attempted suicide or suicidal ideation reported in both alemtuzumab and interferon beta-1a treatment groups.a Advise patients to report any symptoms of depression or suicidal ideation to their clinician.a

Immunosuppression

Risk of severe and profound lymphopenia, which may increase the potential for transfusion-associated graft versus host disease.1 2 Administer only irradiated blood products unless immediate transfusion is required because of emergency.1

Immunogenicity

Potential for immunogenicity with use of all therapeutic proteins including alemtuzumab.1 Development of antibodies (including neutralizing antibodies) to alemtuzumab reported; however, clinically important effects not observed.1 a

Immunization

Avoid immunization with live virus vaccines in patients who have recently received alemtuzumab (safety not established).1 a Complete any necessary immunizations ≥6 weeks prior to initiating therapy.a

Injection Site Reactions

Risk of localized skin and injection site reactions (e.g., erythema, edema, pruritus, pain) with sub-Q administration in patients receiving the drug for B-CLL, especially during first 1–2 weeks of therapy; may occur more frequently in previously untreated patients.34 35 36

Specific Populations

Pregnancy

Category C.1 a

No adequate and well-controlled studies in pregnant women; however, embryolethality demonstrated in animals.a Use during pregnancy only if potential benefits justify potential risk to fetus.a Contraceptive measures recommended.1 a (See Advice to Patients.)

Alemtuzumab may induce autoimmune thyroid disorders, which can increase the risk of complications in pregnant women and developing fetuses.a (See Thyroid Disorders under Cautions)

Placental transfer of anti-thyrotropin receptor antibodies may occur in pregnant women who develop Graves' disease following alemtuzumab therapy; at least one case of neonatal Graves' disease with thyroid storm reported as a result of such placental transfer.a

Lactation

Not known whether alemtuzumab is distributed into milk;1 a discontinue nursing or the drug.1 a

Pediatric Use

Safety and efficacy not established.1 5 a

Use not recommended in pediatric patients because of potentially serious adverse effects associated with the drug (e.g., autoimmunity, infusion reactions, malignancies).a

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 a

Hepatic Impairment

Pharmacokinetics not evaluated.1 Safety and efficacy not established.5

Renal Impairment

Pharmacokinetics not evaluated.1 Safety and efficacy not established.5

Common Adverse Effects

Patients with B-CLL: Infusion reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea),1 cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia),1 infections (e.g., CMV viremia, CMV infection, other infections),1 adverse GI effects (nausea, vomiting, diarrhea, abdominal pain),1 adverse neurologic effects (insomnia, anxiety).1

Patients with RRMS: Rash,a headache,a pyrexia,a nasopharyngitis,a nausea,a urinary tract infection,a fatigue,a insomnia,a upper respiratory tract infection,a herpes virus infection,a urticaria,a pruritus,a thyroid disorders,a fungal infection,a arthralgia,a extremity pain,a back pain,a diarrhea,a sinusitis,a oropharyngeal pain,a paresthesia,a dizziness,a abdominal pain,a flushing,a vomiting.a

Interactions for Alemtuzumab

No formal drug interaction studies to date.1 5

Vaccines

Do not administer live vaccines to patients who have recently received a course of alemtuzumab therapy.a

Specific Drugs

Drug

Interaction

Comments

Antineoplastic agents

Potential for increased immunosuppression and risk of infectiona

Immunosuppressive agents

Potential for increased immunosuppression and risk of infectiona

Alemtuzumab Pharmacokinetics

Absorption

Bioavailability

In patients with RRMS, serum concentrations of alemtuzumab increase with each consecutive dose within a treatment course.a

Distribution

Extent

Not known whether alemtuzumab crosses the placenta or is distributed into milk;1 however, human IgG crosses the placenta and is distributed into milk.1

Elimination

Elimination Route

Likely metabolized by proteolytic degradation to small peptides and amino acids.4

Clearance decreases with repeated administration secondary to decreased receptor-mediated clearance (i.e., loss of CD52 receptors in periphery); AUC increases substantially (sevenfold) after 12 weeks of IV dosing in B-CLL patients receiving recommended dosages.1

Half-life

Patients with B-CLL: 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.1

Patients with RRMS: Half-life is approximately 2 weeks.a Serum alemtuzumab concentrations generally undetectable within 30 days after each treatment course.a

Stability

Storage

Parenteral

Concentrate for IV infusion (Campath)

2–8°C.1 Do not freeze; if accidentally frozen, thaw at 2–8°C before administration.1 Protect from direct sunlight.1

Following dilution, may store at 15–30°C or under refrigeration (2–8°C); use within 8 hours.1 5 Protect from light.1

Concentrate for IV infusion (Lemtrada)

2–8°C in original carton; protect from light.a Do not freeze or shake.a

Following dilution, may store at room temperature (15–30°C) or under refrigeration (2–8°C) for up to 8 hours; protect from light.a

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

No incompatibilities observed between alemtuzumab solution and PVC bags, PVC or polyethylene-lined PVC administration sets.1

Parenteral

Solution Compatibility

Compatible1

Dextrose 5% in water

Sodium chloride 0.9%

Actions

  • An IgG1 kappa immunoglobulin containing human framework (i.e., variable and constant regions) and murine complementarity-determining regions.1 3 a

  • 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),1 2 a triggering a host immune response causing lysis of normal and leukemic cells.1 5 a

  • Mechanism of cell lysis is thought to involve complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.1 2

  • Although exact mechanism in MS not fully elucidated, the depletion and repopulation of B and T cells is thought to result in the drug's immunomodulatory effects.a d

Advice to Patients

  • Importance of advising patients receiving alemtuzumab (Lemtrada) for treatment of RRMS to read the manufacturer's patient information (medication guide) prior to each treatment course.a

  • Advise patients that alemtuzumab (Lemtrada) is available only through a restricted distribution program called the Lemtrada REMS Program.a Inform patients of the requirements of the program and provide them with information on how to locate a certified infusion site.a Advise patients to read the Lemtrada REMS educational materials and to carry the Patient Safety Information Card with them in case of an emergency.a

  • Risk of hematologic toxicity.1 a Importance of patients immediately informing clinician if signs or symptoms of cytopenias (bleeding, easy bruising, petechiae or purpura, pallor, weakness, or fatigue) occur.1

  • Risk of autoimmune diseases such as ITP and anti-glomerular basement membrane disease.a Importance of patients immediately informing clinician if any manifestations of potential autoimmunity (e.g., bleeding, easy bruising, petechiae, purpura, hematuria, edema, jaundice, hemoptysis) occur.a Importance of informing patients receiving alemtuzumab (Lemtrada) for treatment of RRMS that monthly monitoring of blood cell counts and urine tests is required during and for at least 48 months after completion of therapy.a

  • Risk of infusion-related reactions.1 a Importance of patients immediately informing clinician if any infusion-related reaction (e.g., swelling of the mouth or throat, difficulty breathing, weakness, abnormal heart rate, chest pain, rash) occurs.a Importance of informing patients receiving alemtuzumab (Lemtrada) that they will need to be monitored at the healthcare facility (e.g., infusion center) for at least 2 hours after each infusion.a Advise patients that infusion-related reactions may still occur after the 2-hour monitoring period.a

  • Risk of malignancies such as thyroid cancer and melanoma.a Advise patients to report any symptoms of thyroid cancer such as a new lump or swelling in the neck, pain in the front of the neck, persistent hoarseness or other voice changes, difficulty swallowing or breathing, or constant cough not due to upper respiratory tract infection.a Importance of annual skin examinations in patients receiving alemtuzumab (Lemtrada) to monitor for melanoma.a

  • Risk of infections.1 a Importance of taking prophylactic anti-infectives as prescribed.1 a Importance of advising patients to immediately contact their clinician if they develop any signs or symptoms of infection (e.g., fever, swollen glands).1 a Importance of advising patients to avoid or adequately heat foods that are potential sources of Listeria monocytogenes.a

  • Risk of thyroid disorders (e.g., hyperthyroidism, hypothyroidism).a Importance of advising patients to inform their clinician if they experience any manifestations of a potential thyroid disorder (e.g., unexplained weight loss or gain, rapid heart rate or palpitations, eye swelling, constipation, feeling cold).a

  • Advise patients that irradiation of blood products is required in the event that transfusions are necessary.1

  • Importance of patients completing any necessary vaccinations at least 6 weeks prior to the start of alemtuzumab therapy and to consult with their clinician prior to receiving any vaccination after recent use of alemtuzumab.a Advise patients that they should not be immunized with live viral vaccines if they have recently received alemtuzumab.1 a

  • Risk of pneumonitis; advise patients to report any symptoms such as shortness of breath, cough, wheezing, chest pain or tightness, or hemoptysis.a

  • Advise patients that alemtuzumab (Lemtrada) for the treatment of RRMS contains the same active ingredient as alemtuzumab (Campath) for the treatment of B-CLL; patients receiving Lemtrada should inform their clinician if they have previously received Campath.a

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 a Advise women of childbearing potential of the need for effective contraception during and for 4 months after a course of alemtuzumab (Lemtrada) therapy for treatment for MS.a Advise women of childbearing potential and men receiving alemtuzumab (Campath) to use effective contraceptive methods during therapy and for at least 6 months following completion of therapy.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1 a

  • Importance of informing patients of other important precautionary information.1 a (See Cautions.)

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.

Distribution of alemtuzumab is restricted.1 37 (See Restricted Distribution Programs under Dosage and Administration.)

Alemtuzumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion

10 mg/mL (12 mg)

Lemtrada

Genzyme

30 mg/mL

Campath

Genzyzme

AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions January 27, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Genzyme. Campath (alemtuzumab) prescribing information. Cambridge, MA; 2014 Sep.

2. Flynn JM, Byrd JC. Campath-1H monoclonal antibody therapy. Curr Opin Oncol. 2000; 12:574-81. [PubMed 11085457]

3. Food and Drug Administration. Oncologic drugs advisory committee sixty-sixth meeting. Bethesda, MD; December 2000. From FDA web site.

4. Keating MJ, Flinn I, Jain V et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002; 99:3554-61. [IDIS 483673] [PubMed 11986207]

5. Berlex Laboratories, Richmond, CA: Personal communication.

6. Chronic lymphocytic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 May 16.

7. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; [May 5, 2003]. From FDA web site.

8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]

9. Food and Drug Administration. MedWatch—Safety-related drug labeling changes: Campath (alemtuzumab) [May 2004]. From FDA web site.

10. Rai KR, Freter CE, Mercier RJ et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002; 20:3891-7. [IDIS 492956] [PubMed 12228210]

11. Adult non-Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 Jun 06.

12. Lenihan DJ, Alencar AJ, Yang D et al. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sezary syndrome. Blood. 2004; 104:655-8. [IDIS 520055] [PubMed 15073032]

13. Enblad G, Hagberg H, Erlanson M et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood. 2004; 103:2920-4. [IDIS 515482] [PubMed 15070664]

14. Kennedy GA, Seymour JF, Wolf M et al. Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol. 2003; 71:250-6. [PubMed 12950233]

15. Lundin J, Hagberg H, Repp R et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood. 2003; 101:4267-72. [IDIS 500361] [PubMed 12543862]

16. Uppenkamp M, Engert A, Diehl V et al. Monoclonal antibody therapy with CAMPATH-1H in patients with relapsed high- and low-grade non-Hodgkin’s lymphomas: a multicenter phase I/II study. Ann Hematol. 2002; 81:26-32. [PubMed 11807632]

17. Khorana A, Bunn P, McLaughlin P et al. A phase II multicenter study of CAMPATH-1H antibody in previously treated patients with nonbulky non-Hodgkin’s lymphoma. Leuk Lymphoma. 2001; 41:77-87. [PubMed 11342359]

18. Lundin J, Osterborg A, Brittinger G et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin’s Lymphoma. J Clin Oncol. 1998; 16:3257-63. [IDIS 414051] [PubMed 9779699]

19. Tang SC, Hewitt K, Reis MD et al. Immunosuppressive toxicity of CAMPATH1H monoclonal antibody in the treatment of patients with recurrent low grade lymphoma. Leuk Lymphoma. 1996; 24:93-101. [PubMed 9049965]

20. Osterborg A, Dyer MJ, Bunjes D et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol. 1997; 15:1567-74. [IDIS 383720] [PubMed 9193354]

21. Lundin J, Kennedy B, Dearden C et al. No cardiac toxicity associated with alemtuzumab therapy for mycosis fungoides/Sezary syndrome. Blood. 2005; 105:4148-9. [IDIS 535479] [PubMed 15867423]

22. Damaj G, Rubio MT, Audard V et al. Severe cardiac toxicity after monoclonal antibody therapy. Eur J Haematol. 2002; 68:324. [PubMed 12144543]

23. Herbert KE, Prince HM, Westerman DA. Pure red-cell aplasia due to parvovirus B19 infection in a patient treated with alemtuzumab. Blood. 2003; 101:1654. [IDIS 498239] [PubMed 12560244]

24. Crowley B, Woodcock B. Red cell aplasia due to parvovirus b19 in a patient treated with alemtuzumab. Br J Haematol. 2002; 119:279-80. [PubMed 12358942]

25. Pawson R, Dyer MJ, Barge R et al. Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. J Clin Oncol. 1997; 15:2667-72. [IDIS 392532] [PubMed 9215839]

26. Dearden CE, Matutes E, Cazin B et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood. 2001; 98:1721-6. [IDIS 469299] [PubMed 11535503]

27. Keating MJ, Cazin B, Coutre S et al. Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. J Clin Oncol. 2002; 20:205-13. [IDIS 475048] [PubMed 11773171]

28. Dearden CE, Matutes E, Cazin B et al. Very high response rates in previously untreated T-cell prolymphocytic leukaemia patients receiving alemtuzumab (Campath-1H) therapy. Blood. 2003; 102:644a.

29. Polman CH, Uitdehaag BM. New and emerging treatment options for multiple sclerosis. Lancet Neurol. 2003; 2:563-6. [PubMed 12941579]

30. Genzyme Corporation. Fludara plus alemtuzumab (Campath, MabCampath) vs Fludara alone in B-cell chronic lymphocytic leukemia (B-CLL) patients. National Cancer Institute: Clinical Trials (database). Protocol ID: CAM-314. Last accessed: 810/2008.

31. Hillmen P, Skotnicki AB, Robak T et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007; 25:5616-23. [PubMed 17984186]

32. FDA Alert: Alemtuzumab (marketed as Campath). Food and Drug Administration; 2005 Nov 30.(AHFS DI 2007rev: p.10, yellow)

33. Rai KR, Peterson BL, Appelbaum FR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000; 343:1750-7. [IDIS 456744] [PubMed 11114313]

34. Lundin J, Kimby E, Björkholm M et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2002; 100:768-73. [PubMed 12130484]

35. Stilgenbauer S, Zenz T, Winkler D et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009; 27:3994-4001. [PubMed 19597025]

36. Osterborg A, Foà R, Bezares RF et al. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Leukemia. 2009; 23:1980-8. [PubMed 19626051]

37. Genzyme Corporation. US Campath Distribution Program. From product web site. Accessed 2015 July 28.

40. Elter T, Gercheva-Kyuchukova L, Pylylpenko H et al. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol. 2011; 12:1204-13. [PubMed 21992852]

a. Genzyme Corporation. Lemtrada (alemtuzumab) injection for intravenous use prescribing information. Cambridge, MA; 2014 Nov.

b. Coles AJ, Twyman CL, Arnold DL et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012; 380:1829-39. [PubMed 23122650]

c. Cohen JA, Coles AJ, Arnold DL et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012; 380:1819-28. [PubMed 23122652]

d. Garnock-Jones KP. Alemtuzumab: a review of its use in patients with relapsing multiple sclerosis. Drugs. 2014; 74:489-504. [PubMed 24604792]

e. Lemtrada risk evaluation and mitigation strategy (REMS). From FDA website. Accessed 2015 May 19.

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