Alemtuzumab - Drug Information 11-17-14

11/17/2014
Alemtuzumab: Drug information
Official reprint from UpToDate

www.uptodate.com 2014 UpToDate

Copyright 1978-2014 Lexicomp, Inc. All rights reserved.
(For additional information see "Alemtuzumab: Patient drug information")
For abbreviations and symbols that may be used in Lexicomp (show table)
ALERT: U.S. Boxed Warning

Bone marrow suppression (Campath):
Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and
autoimmune hemolytic anemia can occur in patients receiving alemtuzumab. Single doses of alemtuzumab
greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.
Infusion reactions (Campath):
Alemtuzumab administration can result in serious, including fatal, infusion reactions. Carefully monitor patients
during infusions and withhold alemtuzumab for Grade 3 or 4 infusion reactions. Gradually escalate
alemtuzumab to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or
more days.
Infections (Campath):
Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving
alemtuzumab. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus
infections.
Brand Names: Canada Lemtrada; MabCampath

Pharmacologic Category Antineoplastic Agent, Anti-CD52; Antineoplastic Agent, Monoclonal Antibody;
Monoclonal Antibody
Dosing: Adult Note: Dose escalation is required; usually accomplished in 3 to 7 days. Single doses >30
mg or cumulative doses >90 mg/week increase the incidence of pancytopenia. Pretreatment (with acetaminophen
500 to 1000 mg and diphenhydramine 50 mg) is recommended prior to the first dose, with dose escalations, and as
clinically indicated; IV hydrocortisone may be used for severe infusion-related reactions. Reinitiate with gradual
dose escalation if treatment is withheld 7 days. Alemtuzumab is associated with a moderate emetic potential in
the oncology setting; antiemetics may be recommended to prevent nausea and vomiting (Basch, 2011; Roila,
2010).
Dose escalation: Initial: 3 mg daily beginning on day 1; if tolerated (infusion reaction grade 2), increase to 10 mg
daily; if tolerated (infusion reaction grade 2), may increase to maintenance of 30 mg per dose 3 times weekly
if required for maintenance dose.
B-cell chronic lymphocytic leukemia (B-CLL): IV: Gradually escalate to a maintenance of 30 mg per dose 3
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times weekly on alternate days for a total duration of therapy of up to 12 weeks (Hillmen, 2007; Keating,
2002)
B-CLL (unlabeled route): SubQ: Initial: 3 mg on day 1; if tolerated 10 mg on day 3; if tolerated increase to 30
mg on day 5; maintenance: 30 mg per dose 3 times weekly for a maximum of 18 weeks (Lundin, 2002)
or 3 mg on day 1; if tolerated 10 mg on day 2; if tolerated 30 mg on day 3, followed by 30 mg per dose 3
times weekly for 4 to 12 weeks (Stilgenbauer, 2009)
Multiple sclerosis, relapsed-remitting (RRMS; unlabeled use in U.S.): Lemtrada [Canadian product]: IV: 12 mg
daily for 5 consecutive days (total 60 mg), followed 12 months later by 12 mg daily for 3 consecutive days
(total 36 mg); total duration of therapy: 24 months. Note: In some clinical trials patients received an additional
12 mg daily for 3 consecutive days 12 months later (total duration of 36 months) (CAMMS223, 2008; Coles,
2012). Premedicate with corticosteroids for initial 3 days of therapy (1 g of methylprednisolone was
administered in clinical trials). Antihistamines and/or antipyretics may also be given.
Autoimmune cytopenias, CLL-induced, refractory (unlabeled use): IV, SubQ: Gradually escalate to a
maintenance of 10 to 30 mg per dose 3 times weekly for 4 to 12 weeks (Karlsson, 2007; Osterborg, 2009)
Graft versus host disease (GVHD), acute, steroid refractory, treatment (unlabeled use): IV: 10 mg daily for 5
consecutive days, then 10 mg weekly on days 8, 15, and 22 if CR not achieved (Martinez, 2009) or 10 mg
weekly until symptom resolution (Schnitzler, 2009)
Renal transplant, induction (unlabeled use): IV: 30 mg as a single dose at the time of transplant (Hanaway,
2011)
Stem cell transplant (allogeneic) conditioning regimen (unlabeled use): IV: 20 mg daily for 5 days (in
combination with fludarabine and melphalan) beginning 8 days prior to transplant (Mead, 2010) or beginning 7
days prior to transplant (Van Besien, 2009)
T-cell prolymphocytic leukemia (T-PLL; unlabeled use): IV: Initial test dose 3 mg or 10 mg, followed by dose
escalation to 30 mg per dose 3 times weekly as tolerated until maximum response (Dearden, 2001) or Initial
dose: 3 mg day 1, if tolerated increase to 10 mg day 2, if tolerated increase to 30 mg on day 3 (days 1, 2, and
3 are consecutive days), followed by 30 mg per dose every Monday, Wednesday, Friday for a total of 4 to 12
weeks (Keating, 2002)
Dosing: Geriatric Refer to adult dosing.

Dosing: Renal Impairment There are no dosage adjustments provided in the manufacturers labeling
(has not been studied).
Dosing: Hepatic Impairment There are no dosage adjustments provided in the manufacturers labeling
(has not been studied).
Dosing: Obesity American Society for Blood and Marrow Transplantation (ASBMT) practice guideline
committee position statement on chemotherapy dosing in obesity: Utilize a flat dose based on the regimen
selected for hematopoietic stem cell transplant conditioning in adults (Bubalo, 2014).
Dosing: Adjustment for Toxicity

Dosage adjustment for nonhematologic toxicity: Treatment of B-CLL:
Note: If treatment is withheld 7 days, reinitiate at 3 mg with re-escalation to 10 mg and then 30 mg.
Grade 3 or 4 infusion reaction: Withhold infusion
Serious infection or other serious adverse reaction: Withhold alemtuzumab until resolution
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Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab

Dosage adjustment for hematologic toxicity (severe neutropenia or thrombocytopenia, not autoimmune):
Treatment of B-CLL:
Note: If treatment is withheld 7 days, reinitiate at 3 mg with re-escalation to 10 mg and then 30 mg.
ANC <250/mm3 and/or platelet count 25,000/mm3:
First occurrence: Withhold treatment; resume at 30 mg per dose when ANC 500/mm3 and platelet count
50,000/mm3
Second occurrence: Withhold treatment; resume at 10 mg per dose when ANC 500/mm3 and platelet
count 50,000/mm3
Third occurrence: Discontinue alemtuzumab.
Patients with a baseline ANC 250/mm3 and/or a baseline platelet count 25,000/mm3 at initiation of therapy:
If ANC and/or platelet counts decrease to 50% of the baseline value:
First occurrence: Withhold treatment; resume at 30 mg per dose upon return to baseline values
Second occurrence: Withhold treatment; resume at 10 mg per dose upon return to baseline values
Third occurrence: Discontinue alemtuzumab.
Dosage Forms: Canada Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.
Injection, solution [preservative free]:
MabCampath: 30 mg/mL (1 mL) [contains edetate disodium, polysorbate 80]
Injection, solution [preservative free]:
Lemtrada: 10 mg/mL (1.2 mL) [contains edetate disodium, polysorbate 80]
Generic Equivalent Available: U.S. Yes

Prescribing and Access Restrictions As of September 4, 2012, alemtuzumab (Campath) is no
longer commercially available in the United States (or Europe); a restricted distribution program will allow access
(free of charge) for appropriate patients. Information on necessary documentation and requirements is available at
Campath Distribution Program (1-877-422-6728) or Genzyme Medical Information (1-800-745-4447, option 2).
Administration
Campath or MabCampath [Canadian product]: Administer by IV infusion over 2 hours. Premedicate with
diphenhydramine 50 mg and acetaminophen 500 to 1000 mg 30 minutes before each infusion. Hydrocortisone
(IV) has been effective in decreasing severe infusion-related events. Start anti-infective prophylaxis. Other
drugs should not be added to or simultaneously infused through the same IV line. Do not give IV push or
bolus. Compatible in polyvinylchloride (PVC) or polyethylene lined administration sets or low protein binding
filters.
Campath: SubQ (unlabeled route): SubQ administration has been studied (Lundin, 2002; Stilgenbauer, 2009); an
increased rate of injection site reactions has been observed, with only rare incidences of chills or infusion-like
reactions typically observed with IV infusion. A longer dose escalation time (1 to 2 weeks) may be needed
due to injection site reactions (Lundin, 2002). Premedicate with diphenhydramine 50 mg and acetaminophen
500 to 1000 mg 30 minutes before dose. The subQ route should NOT be used for the treatment of T-PLL
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(Deardon, 2011).
Alemtuzumab is associated with a moderate emetic potential in the oncology setting; antiemetics may be
recommended to prevent nausea and vomiting (Basch, 2011; Roila, 2010).
Lemtrada [Canadian product]: Administer by IV infusion over 4 hours; do not administer by IV push or IV bolus.
Premedicate with corticosteroids for initial 3 days of each treatment course (1000 mg of methylprednisolone
was administered in clinical trials). Antihistamines and/or antipyretics may also be considered.
Compatibility Stable in D5W, NS. Medications should not be added to the solution or simultaneously
infused through the same IV line.
Use
B-cell chronic lymphocytic leukemia: Campath or MabCampath [Canadian product]: Treatment (as a single
agent) of B-cell chronic lymphocytic leukemia (B-CLL)
Multiple sclerosis: Lemtrada [Canadian product]: Management of patients with relapsing remitting multiple
sclerosis (RRMS), who have had an inadequate response to interferon beta or other disease-modifying
treatment.
Use - Unlabeled Conditioning regimen in stem cell transplant; prophylaxis of graft-versus-host disease
(GVHD); treatment of steroid-refractory GVHD; treatment of T-cell prolymphocytic leukemia; treatment of
autoimmune hemolytic anemia (CLL-induced); immunosuppressant in solid organ transplant (induction and steroidrefractory rejection); treatment of relapsed-remitting multiple sclerosis
Medication Safety Issues

High alert medication:
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug
classes which have a heightened risk of causing significant patient harm when used in error.
Adverse Reactions Significant

>10%:
Central nervous system: Headache (44% to 52%), fatigue (8% to 21%), insomnia (11% to 17%), paresthesia
(12%)
Dermatologic: Skin rash (43% to 48%), urticaria (15% to 17%), pruritus (13% to 17%)
Gastrointestinal: Nausea (16% to 22%), diarrhea (12%), oral candidiasis (3% to 12%)
Genitourinary: Urinary tract infection (18%), vulvovaginal candidiasis (3% to 12%)
Immunologic: Antibody development (85%; no effect on drug efficacy)
Neuromuscular & skeletal: Arthralgia (13%), limb pain (13%), back pain (12%)
Respiratory: Nasopharyngitis (24%), upper respiratory tract infection (15%), oropharyngeal pain (11%),
sinusitis (11%)
Miscellaneous: Fever (26% to 30%)
1% to 10%:
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Cardiovascular: Flushing (10%), chest discomfort (7% to 8%), tachycardia (6% to 8%), peripheral edema
(5%), palpitations (4%), bradycardia (3%), hypotension (3%), chest pain (2%), cold extremities (1%)
Central nervous system: Chills (10%), dizziness (10%), pain (5% to 7%), vertigo (4%), equilibrium disturbance
(3%), hyperthermia (3%), increased body temperature (3%), drowsiness (2%), facial hypoesthesia (2%),
hypertonia (2%)
Dermatologic: Skin rash (generalized; 7% to 8%), erythema (6%), acne vulgaris (3%), allergic dermatitis (3%),
alopecia (3%), erythematous rash (3%), hyperhidrosis (3%), pruritic rash (3%), papular rash (2%), pruritus
(generalized; 2%), skin blister (1%), xeroderma (1%)
Endocrine & metabolic: Hypothyroidism (5%), hypermenorrhea (4%), hyperthyroidism (4%), chronic
lymphocytic thyroiditis (2%), Graves' disease (2%), thyroid stimulating hormone suppression (2%), goiter
(1%)
Gastrointestinal: Vomiting (10%), oral herpes (9%), dyspepsia (6% to 9%), abdominal pain (5%),
gastroenteritis (4%), upper abdominal pain (4%), abdominal distention (2%), oral mucosa ulcer (1%)
Genitourinary: Occult blood in urine (4%), hematuria (3%), cystitis (2%), fungal vaginosis (2%), increase in
urinary protein (2%), irregular menses (2%), proteinuria (2%), abnormal urinalysis (1%), herpes genitalis
(1%), vaginal hemorrhage (1%)
Hematologic & oncologic: Bruise (10%), lymphocytopenia (6%), decreased CD-4 cell count (5%), decreased
CD-8 cell counts (5%), decreased absolute lymphocyte count (4%), decreased T cell lymphocytes (4%),
reduction of B-cells (4%), abnormal white blood cell differential (lymphocyte percentage decreased: 3%;
lymphocyte percentage increased: 2%), nonthrombocytopenic purpura (2%), hematoma (1%), petechia
(1%)
Hypersensitivity: Cytokine release syndrome (2%)
Infection: Influenza (8%), herpes zoster (4%), bacterial infection (3%), herpes simplex infection (2%)
Local: Catheter pain (1%)
Neuromuscular & skeletal: Myalgia (7%), weakness (6%), neck pain (5%), joint sprain (2%), joint swelling
(2%), musculoskeletal chest pain (2%)
Ophthalmic: Blurred vision (5%), conjunctivitis (2%)
Otic: Otalgia (3%), otic infection (3%)
Respiratory: Cough (9%), dyspnea (8% to 9%), bronchitis (7%), epistaxis (5%), pharyngitis (4%), rhinitis (4%),
sinus congestion (3%), nasal congestion (2%), wheezing (2%), bronchospasm (1%)
<1% (Limited to important or life-threatening): Abnormal hepatic function tests, acquired blood coagulation disorder,
allodynia, altered blood pressure, amenorrhea, anemia, anti-GBM disease, anti-thyroid antibody positive,
aphthous stomatitis, asthma, ataxia, atrial fibrillation, autoimmune hemolytic anemia, autoimmune
thrombocytopenia, bacterial vaginosis, candidiasis, cardiac failure, cellulitis, cervical dysplasia, cervicitis,
chronic inflammatory demyelinating polyradiculoneuropathy, decreased hematocrit, decreased hemoglobin,
decreased monocytes, decreased neutrophils, dehydration, depression, dermatitis, desquamation,
eosinopenia, eosinophilia, Epstein-Barr-associated lymphoproliferative disorder, esophagitis, fungal infection,
furuncle, gastroesophageal reflux disease, gastrointestinal disease, gingival hemorrhage, glycosuria, graft
versus host disease (transfusion associated), Guillain-Barre syndrome, hemiparesis, human papilloma virus
infection, hyperemia, hypersensitivity reaction, immune thrombocytopenia, increased monocytes, infusion site
reaction, labyrinthitis, leukocytosis, maculopapular rash, major hemorrhage, memory impairment, migraine,
mucosal inflammation, multiple sclerosis, muscle spasticity, natural killer cell count increased, neutropenia,
night sweats, onychomycosis, ostealgia, ovarian cyst, papule, peripheral neuropathy, photophobia, pleurisy,
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pneumonia, positive direct Coombs test, postherpetic neuralgia, protozoal infection, psychomotor agitation,
pyelonephritis, reactivation of disease, reduced ejection fraction, restless leg syndrome, skin
hyperpigmentation, skin lesion, streptococcal pharyngitis, subacute thyroiditis, syncope, tachypnea,
thrombocytopenia, thyroid disease, tongue discoloration, tonsillitis, tooth abscess, tracheobronchitis, upper
airway symptoms (cough syndrome), urethritis, urinary incontinence, urinary urgency, varicella, viral infection,
voice disorder, weight gain, weight loss
Contraindications
Campath: There are no contraindications listed in the manufacturer's labeling.
Lemtrada [Canadian product]: Hypersensitivity to alemtuzumab or any component of the formulation; HIV
infection; active or latent tuberculosis; severe active infections; active malignancies; concurrent antineoplastic
or immunosuppressive therapy; history of progressive multifocal leukoencephalopathy (PML)
MabCampath [Canadian product): Known Type 1 hypersensitivity or anaphylactic reactions to alemtuzumab or any
component of the formulation; active infections; underlying immunodeficiency (eg, seropositive for HIV);
active secondary malignancies; current or history of progressive multifocal leukoencephalopathy (PML)
Warnings/Precautions
Concerns related to adverse effects:
Bone marrow suppression: Campath: [U.S. Boxed Warning]: Serious and fatal cytopenias (including
pancytopenia, bone marrow hypoplasia, autoimmune hemolytic anemia, and autoimmune
idiopathic thrombocytopenia) have occurred. Single doses >30 mg or cumulative weekly doses
>90 mg are associated with an increased incidence of pancytopenia. Severe prolonged
myelosuppression, hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and bone marrow
hypoplasia have also been reported with use at the normal dose for the treatment of B-CLL. Discontinue
for serious hematologic or other serious toxicity (except lymphopenia) until the event resolves.
Permanently discontinue if autoimmune anemia or autoimmune thrombocytopenia occurs. Patients
receiving blood products should only receive irradiated blood products due to the potential for transfusionassociated GVHD during lymphopenia.
Gastrointestinal toxicity: Alemtuzumab is associated with a moderate emetic potential in the oncology
setting; antiemetics may be recommended to prevent nausea and vomiting (Basch, 2011; Roila, 2010).
Infections: Campath: [U.S. Boxed Warning]: Serious and potentially fatal infections (bacterial, viral,
fungal, and protozoan) have been reported. Administer prophylactic medications against PCP
pneumonia and herpes viral infections during treatment and for at least 2 months following last dose
or until CD4+ counts are 200 cells/L (whichever is later). Severe and prolonged lymphopenia may
occur; CD4+ counts usually return to 200 cells/L within 2-6 months; however, CD4+ and CD8+
lymphocyte counts may not return to baseline levels for more than 1 year. Withhold treatment during
serious infections; may be reinitiated upon resolution of infection. Monitor for CMV infection (during and
for at least 2 months after completion of therapy); initiate appropriate antiviral treatment and withhold
alemtuzumab for CMV infection or confirmed CMV viremia (withhold alemtuzumab during CMV antiviral
treatment). Lemtrada [Canadian product] labeling recommends initiating herpes prophylactic therapy on
the first day of treatment and continuing for at least 1 month after each treatment course. Consider
delaying Lemtrada treatment in patients with active infection until infection is controlled.
Infusion reactions: Campath: [U.S. Boxed Warning]: Serious and potentially fatal infusion-related
reactions may occur; monitor for infusion reaction; withhold treatment for grade 3 or 4 infusion
reactions. Gradual escalation to the recommended maintenance dose is required at initiation and
with treatment interruptions (for 7 days) to minimize infusion-related reactions. Infusion reaction
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symptoms may include acute respiratory distress syndrome, anaphylactic shock, angioedema,
bronchospasm, cardiac arrest, cardiac arrhythmias, chills, dyspnea, fever, hypotension, myocardial
infarction, pulmonary infiltrates, rash, rigors, syncope, or urticaria. The incidence of infusion reaction is
highest during the first week of treatment. Premedicate with acetaminophen and an oral antihistamine.
Medications for the treatment of reactions should be available for immediate use. Use caution and
carefully monitor blood pressure in patients with ischemic heart disease and patients on antihypertensive
therapy. Reinitiate with gradual dose escalation if treatment is withheld 7 days. Similar infusion
reactions have been observed with use in the treatment of RMMS; premedication with corticosteroids for
initial 3 days of each treatment course is recommended. Antihistamines and/or antipyretics may also be
considered. Lemtrada [Canadian product] labeling recommends obtaining an ECG prior to each treatment
course. Observe for infusion-related reactions; advise patients to monitor for signs/symptoms of infusion
reaction, particularly during the 24 hours following infusion.
Malignancy: Malignant neoplasm (eg, breast, thyroid, basal cell carcinoma) has been observed (rarely) in
patients receiving treatment for RRMS. Use of Lemtrada [Canadian product] in patients with active
malignancies is contraindicated; use caution if initiating treatment in patients with preexisting malignancy.
Progressive multifocal leukoencephalopathy (PML): Has been reported with use (rarely); withhold therapy
immediately for signs/symptoms suggestive of PML. Use of Lemtrada [Canadian product] and
MabCampath [Canadian product] is contraindicated in patients with a history of PML.
Thyroid dysfunction: In a trial evaluating alemtuzumab versus interferon beta-1a in patients with multiple
sclerosis, thyroid dysfunction occurred more frequently in patients taking alemtuzumab (34% versus
6.5%) (Daniels, 2014). The incidence of the first episode of thyroid dysfunction increased annually the
first 3 years (year 1: 4.6%; year 2: 13.3%; year 3: 16.1%) then gradually decreased thereafter. Among
patients with alemtuzumab-related thyroid dysfunction, Graves hyperthyroidism occurred most
commonly (23%), followed by hypothyroidism and subacute thyroiditis (7% and 4%, respectively).
Thyroid dysfunction (thyroiditis, Graves disease) has also been reported with alemtuzumab use for the
treatment of other conditions. TSH monitoring is recommended; monitor TSH at baseline and every 2 to 3
months during alemtuzumab treatment (Hamnvik, 2011).
Disease-related concerns:
Autoimmune disorders: Use with caution in patients with autoimmune disorders. Immune thrombocytopenia
(ITP) or idiopathic thrombocytopenic purpura has been reported in six patients receiving alemtuzumab for
the treatment of relapsed-remitting multiple sclerosis; some cases were severe, with one fatality (Cuker,
2011). The median time to onset was 24.5 months from initial alemtuzumab exposure and 10.5 months
from the last dose. Nephropathy (eg, antiglomerular basement membrane disease) has also been
observed; monitor for signs/symptoms of nephropathy (eg, hematuria, proteinuria, significant change in
serum creatinine).
Concurrent drug therapy issues:
Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment,
additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more
detailed information.
Special populations:
HBV or HCV infected patients: Use of Lemtrada [Canadian product] has not been studied in patients
infected with HBV or HCV; consider screening patients at increased risk of infection prior to initiating
Lemtrada treatment. Use with caution in HBV or HCV carriers; patients may be at risk for viral
reactivation.
Other warnings/precautions:
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Appropriate use: Lemtrada [Canadian product] is not recommended for use in patients with inactive disease
or who are stable on other treatment. Patients should commit to at least 48 months of follow-up after the
last infusion.
Immunizations: Patients should not be immunized with live, viral vaccines during or recently after treatment.
The ability to respond to any vaccine following therapy is unknown. Testing for antibodies to varicella
zoster virus (VZV) is recommended prior to initiation of Lemtrada [Canadian product] if history of
chickenpox or VZV vaccination status is unknown. Completion of required immunizations at least 6
weeks prior to initiating Lemtrada [Canadian product] is recommended.
Metabolism/Transport Effects None known.

Drug Interactions
(For additional information: Launch Lexi-Interact Drug Interactions Program)
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Risk X: Avoid
combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk
for agranulocytosis may be increased. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk
C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious
infections may be increased. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for
agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for
hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants.
Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow
suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of
concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy
modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management:
Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic
drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent
immunosuppressants. Risk X: Avoid combination
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Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk
C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial
infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live).
Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines
should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Pregnancy Risk Factor C (show table)

Pregnancy Implications Human IgG is known to cross the placental barrier; therefore, alemtuzumab
may also cross the barrier and cause fetal B- and T-lymphocyte depletion. Use during pregnancy only if the benefit
to the mother outweighs the potential risk to the fetus. Effective contraception is recommended during and for at
least 6 months after treatment for women of childbearing potential and men of reproductive potential. Lemtrada
[Canadian product] labeling recommends avoiding use in pregnant women and that women of childbearing potential
should use effective contraception during therapy and for 4 months after completing treatment course.
Lactation Excretion in breast milk unknown/not recommended

Breast-Feeding Considerations Human IgG is excreted in breast milk; therefore, alemtuzumab may
also be excreted in milk. Due to the potential for serious adverse reactions in the nursing infant, the decision to
discontinue alemtuzumab or to discontinue breast-feeding should take into account the importance of treatment to
the mother and the half-life of alemtuzumab. The Canadian labeling recommends discontinuing nursing during
treatment and for at least 3 months (MabCampath) or 4 months (Lemtrada) after completing treatment course.
Monitoring Parameters Vital signs; carefully monitor BP especially in patients with ischemic heart
disease or on antihypertensive medications; CBC with differential and platelets (weekly, more frequent if
worsening); signs and symptoms of infection; CD4+ lymphocyte counts (after treatment until recovery); CMV
antigen (routinely during and for 2 months after treatment). Monitor closely for infusion reactions (including
hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash); consider TSH at baseline and
then every 2 to 3 months during alemtuzumab treatment (Hamnvik, 2011).
Lemtrada [Canadian product] labeling recommendations: Monitor closely for infusion reactions for 2 hours after
each infusion; CBC with differential prior to initiation then monthly until 48 months after last infusion; serum
creatinine prior to initiation then monthly until 48 months after last infusion or at any time during therapy if clinically
indicated; urinalysis with urine cell counts (prior to initiation then monthly); signs/symptoms of infection; TSH at
baseline and every 3 months until 48 months after last infusion or at any time during therapy if clinically indicated;
ECG prior to each treatment course; annual HPV screening; signs/symptoms of PML.
International Brand Names Campath (PE, UY); Lemtrada (AU, CZ, DE, DK, EE, GB, SE); Lemttrada
(NO); MabCampath (AU, CY, FR, GB, HN, ID, IL, KP, MT, MY, NO, RU, SE, SG, SK, TH, TR, ZA);
Mabcampath (JO); Remniq (AU)
Mechanism of Action Binds to CD52, a nonmodulating antigen present on the surface of B and T
lymphocytes, a majority of monocytes, macrophages, NK cells, and a subpopulation of granulocytes. After binding
to CD52+ cells, an antibody-dependent lysis of malignant cells occurs. In multiple sclerosis, alemtuzumab
immunomodulatory effects may include alteration in the number, proportions, and properties of some lymphocyte
subsets following treatment.
Pharmacodynamics and Pharmacokinetics

Distribution: Vd: IV: 0.18 L/kg (range: 0.1-0.4 L/kg)
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Metabolism: 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: 11 hours (following first 30 mg dose; range: 2-32 hours); 6 days (following the last 30 mg
dose; range: 1-14 days)
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REFERENCES
1. Basch E, Prestrud AA, Hesketh PJ, et al; American Society of Clinical Oncology. Antiemetics: American Society of Clinical
Oncology clinical practice guideline update. J Clin Oncol. 2011;29(31):4189-4198. [PubMed 21947834]
2. Basu A, Ramkumar M, Tan HP, et al, Reversal of Acute Cellular Rejection After Renal Transplantation With Campath-1H,
Transplant Proc, 2005, 37(2):923-6. [PubMed 15848576]
3. Berger JR and Houff S, Opportunistic Infections and Other Risks With Newer Multiple Sclerosis Therapies, Ann Neurol, 2009,
65(4):367-77. [PubMed 19399841]
4. Bubalo J, Carpenter PA, Majhail N, et al. Conditioning chemotherapy dose adjustment in obese patients: a review and position
statement by the American Society for Blood and Marrow Transplantation practice guideline committee. Biol Blood Marrow
Transplant. 2014;20(5):600-616. [PubMed 24462742]
5. CAMMS223 Trial Investigators: Coles AJ, Compston DA, Selmaj KW, et al, Alemtuzumab vs Interferon Beta-1a in Early
Multiple \Sclerosis, N Engl J Med, 2008, 359(17):1786-801. [PubMed 18946064]
6. Campath (alemtuzumab) [prescribing information]. Cambridge, MA: Genzyme Corporation; August 2009.
7. Ciancio G, Burke GW, Gaynor JJ, et al, A Randomized Trial of Three Renal Transplant Induction Antibodies: Early
Comparison of Tacrolimus, Mycophenolate Mofetil, and Steroid Dosing, and Newer Immune-Monitoring, Transplantation,
2005, 80(4):457-65. [PubMed 16123718]
8. Coles AJ, Fox E, Vladic A, et al, Alemtuzumab More Effective Than Interferon -1a at 5-Year Follow-Up of CAMMS223
Clinical Trial, Neurology, 2012, 78(14):1069-78. [PubMed 22442431]
9. Cuker A, Coles AJ, Sullivan H, et al, A Distinctive Form of Immune Thrombocytopenia in a Phase 2 Study of Alemtuzumab
for the Treatment of Relapsing-Remitting Multiple Sclerosis, Blood, 2011, 118(24):6299-305. [PubMed 21960587]
10. Daniels GH, Vladic A, Brinar V, et al. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsingremitting multiple sclerosis. J Clin Endocrinol Metab. 2014;99(1):80-89. [PubMed 24170099]
11. Dearden CE, Johnson R, Pettengell R, et al, Guidelines for the Management of Mature T-Cell and NK-Cell Neoplasms
(Excluding Cutaneous T-Cell Lymphoma), Br J Haematol, 2011, 153(4):451-85. [PubMed 21480860]
12. Dearden CE, Matutes E, Cazin B, et al, High Remission Rate in T-Cell Prolymphocytic Leukemia With CAMPATH-1H,
Blood, 2001, 98(6):1721-6. [PubMed 11535503]
13. Dupuis LL, Boodhan S, Holdsworth M, et al; Pediatric Oncology Group of Ontario. Guideline for the prevention of acute nausea
and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013;60(7):1073-1082.
[PubMed 23512831]
14. Dupuis LL, Boodhan S, Sung L, et al; Pediatric Oncology Group of Ontario. Guideline for the classification of the acute
emetogenic potential of antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2011;57(2):191-198.
[PubMed 21465637]
15. 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, 2003, 103(8):2920-4. [PubMed
15070664]
16. Farney A, Sundberg A, Moore P, et al, A Randomized Trial of Alemtuzumab vs Anti-Thymocyte Globulin Induction in Renal
and Pancreas Transplantation, Clin Transplant, 2008, 22(1):41-9. [PubMed 18217904]
17. Ferrajoli A, O'Brien SM, Cortes JE, et al, Phase II Study of Alemtuzumab in Chronic Lymphoproliferative Disorders, Cancer,
2003, 98(4):773-8. [PubMed 12910522]
18. Hale G, Rebello P, Brettman LR, et al, Blood Concentrations of Alemtuzumab and Antiglobulin Responses in Patients With
Chronic Lymphocytic Leukemia Following Intravenous or Subcutaneous Routes of Administration, Blood, 2004, 104(4):948-55.
[PubMed 15090452]
19. Hamnvik OP, Larsen PR, and Marqusee E, Thyroid Dysfunction From Antineoplastic Agents, J Natl Cancer Inst, 2011,
103(21):1572-87. [PubMed 22010182]
20. Hanaway MJ, Woodle ES, Mulgaonkar S, et al, Alemtuzumab Induction In Renal Transplantation, N Engl J Med, 2011,
364(20):1909-19. [PubMed 21591943]
http://www.uptodate.com.ezproxy.pacific.edu/contents/alemtuzumab-drug-information?topicKey=DRUG_GEN%2F8725&elapsedTimeMs=2&source=searc
10/12
11/17/2014
21. Hillmen P, Skotnicki A, Robak T, et al, Alemtuzumab Compared With Chlorambucil as First-Line Therapy for Chronic
Lymphocytic Leukemia, J Clin Oncol, 2007, 25(35):5616-23. [PubMed 17984186]
22. Kanda J, Lopez RD, and Rizzieri DA, "Alemtuzumab for the Prevention and Treatment of Graft-Versus-Host Disease," Int J
Hematol, 2011, 93(5):586-93. [PubMed 21369856]
23. Karlsson C, Hansson L, Celsing F, et al, Treatment of Severe Refractory Autoimmune Hemolytic Anemia in B-Cell Chronic
Lymphocytic Leukemia With Alemtuzumab (Humanized CD52 Monoclonal Antibody), Leukemia, 2007, 21(3):511-4. [PubMed
17215854]
24. Keating MJ, Cazin B, Coutr 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(1):205-13. [PubMed 11773171]
25. 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(10):3554-61. [PubMed 11986207]
26. Kennedy B and Hillmen P, Immunological Effects and Safe Administration of Alemtuzumab (MabCampath) in Advanced BcLL, Med Oncol, 2002, 19(Suppl):49-55.
27. Lemtrada (alemtuzumab) [product monograph]. Mississauga, Ontario, Canada: Genzyme Canada; December 2013.
28. Lepretre S, Aurran T, Mah B, et al, Excess Mortality After Treatment With Fludarabine and Cyclophosphamide in
Combination With Alemtuzumab in Previously Untreated Patients With Chronic Lymphocytic Leukemia in a Randomized
Phase 3 Trial," Blood, 2012, 119(22):5104-10. [PubMed 22337714]
29. Lundin J, Hagberg H, Repp R, et al, Phase 2 Study of Alemtuzumab (Anti-CD52 Monoclonal Antibody) in Patients With
Advanced Mycosis Fungoides/Szary Syndrome, Blood, 2003, 101(11):4267-72. [PubMed 12543862]
30. Lundin J, Kimby E, Bjorkholm 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(3):768-73. [PubMed 12130484]
31. 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(10):3257-63. [PubMed 9779699]
32. MabCampath (alemtuzumab) [product monograph]. Mississauga, Ontario, Canada: Genzyme Canada; March 2010.
33. Magliocca JF and Knechtle SJ, The Evolving Role of Alemtuzumab (Campath-1H) for Immunosuppressive Therapy in Organ
Transplantation, Transpl Int, 2006, 19(9):705-14. [PubMed 16918530]
34. Marcos A, Eghtesad B, Fung JJ, et al, Use of Alemtuzumab and Tacrolimus Monotherapy for Cadaveric Liver Transplantation:
With Particular Reference to Hepatitis C Virus, Transplantation, 2004, 78(7):966-71. [PubMed 15480160]
35. Margreiter R, Klempnauer J, Neuhaus P, et al, Alemtuzumab (Campath-1H) and Tacrolimus Monotherapy After Renal
Transplantation: Results of a Prospective Randomized Trial, Am J Transplant, 2008, 8(7):1480-5. [PubMed 18510632]
36. Martinez C, Solano C, Ferr C, et al, Alemtuzumab as Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease:
Results From a Phase II Study, Biol Blood Marrow Transplant, 2009, 15(5):639-42. [PubMed 19361757]
37. Mead AJ, Thomson KJ, Morris EC, et al, HLA-Mismatched Unrelated Donors are a Viable Alternate Graft Source for
Allogeneic Transplantation Following Alemtuzumab-Based Reduced-Intensity Conditioning, Blood, 2010, 115(25):5147-53.

[PubMed 20371745]
38. 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(4):1567-74. [PubMed 9193354]
39. Osterborg A, Fassas AS, Anagnostopoulos A, et al, Humanifed CD52 Monoclonal Antibody Campath-1H as First-Line
Treatment in Chronic Lymphocytic Leukaemia, Br J Haematol, 1996, 93(1):151-3. [PubMed 8611450]
40. Osterborg A, Karlsson C, and Lundin J, Alemtuzumab to Treat Refractory Autoimmune Hemolytic Anemia or
Thrombocytopenia in Chronic Lymphocytic Leukemia, Curr Hematol Malig Rep, 2009, 4(1):47-53. [PubMed 20425438]
41. Pawson R, Dyer MJ, Barge R, et al, Treatment of T-Cell Prolymphocytic Leukemia With Human CD52 Antibody, J Clin
Oncol, 1997, 15(7):2667-72. [PubMed 9215839]
42. 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(18):3891-7. [PubMed 12228210]
43. Roila F, Herrstedt J, Aapro M, et al; ESMO/MASCC Guidelines Working Group. Guideline update for MASCC and ESMO in
the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference.
Ann Oncol. 2010;21(suppl 5):v232-v243. [PubMed 20555089]
44. Scheinberg P, Nunez O, Weinstein B, et al, Activity of Alemtuzumab Monotherapy in Treatment-Naive, Relapsed, and
Refractory Severe Acquired Aplastic Anemia, Blood, 2012, 119(2):345-54. [PubMed 22067384]
45. Schnitzler M, Hasskerl J, Egger M, et al, Successful Treatment of Severe Acute Intestinal Graft-Versus-Host Resistant to
Systemic and Topical Steroids With Alemtuzumab, Biol Blood Marrow Transplant, 2009, 15(8):910-18. [PubMed 19589480]
46. Schweighofer CD, Ritgen M, Eichhorst BF, et al, Consolidation With Alemtuzumab Improves Progression-Free Survival in
Patients With Chronic Lymphocytic Leukaemia (CLL) in First Remission: Long-Term Follow-Up of a Randomized Phase III
11/12
11/17/2014
Trial of the German CLL Study Group (GCLLSG), Br J Haematol, 2009, 144(1):95-8. [PubMed 19016732]
47. 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(24):3994-4001. [PubMed 19597025]
48. Treon SP, Soumerai JD, Hunter ZR, et al, Long-Term Follow-Up of Symptomatic Patients With Lymphoplasmacytic
Lymphoma/Waldenstrm Macroglobulinemia Treated With the Anti-CD52 Monoclonal Antibody Alemtuzumab, Blood, 2011,
118(2):276-81. [PubMed 21566092]
49. van Besien K, Artz A, Smith S, et al, Fludarabine, Melphalan, and Alemtuzumab Conditioning in Adults With Standard-Risk
Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome, J Clin Oncol, 2005, 23(24):5728-38. [PubMed 16009946]
50. van Besien K, Kunavakkam R, Rondon G, et al, Fludarabine-Melphalan Conditioning for AML and MDS: Alemtuzumab
Reduces Acute and Chronic GVHD Without Affecting Long-term Outcomes, Biol Blood Marrow Transplant, 2009, 15(5):610-7.
[PubMed 19361753]
51. Vo AA, Wechsler EA, Wang J, et al, Analysis of Subcutaneous (SQ) Alemtuzumab Induction Therapy in Highly Sensitized
Patients Desensitized With IVIG and Rituximab, Am J Transplant, 2008, 8(1):144-9. [PubMed 17973966]
52. Willis F, Marsh JC, Bevan DH, et al, The Effect of Treatment With Campath-1H in Patients With Autoimmune Cytopenias, Br
J Haematol, 2001, 114(4):891-8. [PubMed 11564082]
53. Wolff D, Schleuning M, von Harsdorf S, et al, Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line
Treatment of Chronic Graft-Versus-Host Disease, Biol Blood Marrow Transplant, 2011, 17(1):1-17. [PubMed 20685255]
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Alemtuzumab: Drug information

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Alemtuzumab: Drug information

ALERT: U.S. Boxed Warning

Brand Names: Canada Lemtrada; MabCampath

Alemtuzumab: Drug information

Dosing: Geriatric Refer to adult dosing.

Dosing: Adjustment for Toxicity

Alemtuzumab: Drug information

Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab

Generic Equivalent Available: U.S. Yes

Alemtuzumab: Drug information

Medication Safety Issues

Adverse Reactions Significant

Alemtuzumab: Drug information

Alemtuzumab: Drug information

Alemtuzumab: Drug information

Alemtuzumab: Drug information

Metabolism/Transport Effects None known.

Alemtuzumab: Drug information

Pregnancy Risk Factor C (show table)

Lactation Excretion in breast milk unknown/not recommended

Pharmacodynamics and Pharmacokinetics

Alemtuzumab: Drug information

Alemtuzumab: Drug information

Allogeneic Transplantation Following Alemtuzumab-Based Reduced-Intensity Conditioning, Blood, 2010, 115(25):5147-53.

Alemtuzumab: Drug information

Topic 8725 Version 95.0

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