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Alemtuzumab: Drug information

Alemtuzumab: Drug information
(For additional information see "Alemtuzumab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
REMS Drugs COVID-19 Safety Alert March 2020

Due to challenges with completion of required laboratory testing or imaging studies for REMS drugs because of self-isolation or quarantine during the COVID-19 public health emergency, the FDA is recommending health care providers prescribing and/or dispensing REMS drugs consider whether there are compelling reasons or not to complete these requirements during this public health emergency and weigh with the patient the benefits and risks of continuing treatment in the absence of the laboratory testing and imaging studies. The FDA will not take action against sponsors and others during the public health emergency for failing to adhere to REMS requirements.

Further information may be found at https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-update-patient-access-certain-rems-drugs-during-covid-19.

ALERT: US 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 >30 mg or cumulative doses >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 days.

Infections (Campath):

Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving alemtuzumab. Administer prophylaxis against Pneumocystis jirovecii pneumonia and herpes virus infections.

Autoimmune effects (Lemtrada):

Alemtuzumab causes serious, sometimes fatal, autoimmune conditions, such as immune thrombocytopenia and anti-glomerular basement membrane disease. Monitor CBC with differential, serum creatinine levels, and urinalysis with urine cell counts before starting treatment and then at monthly intervals until 48 months after the last dose of alemtuzumab.

Infusion reactions (Lemtrada):

Alemtuzumab causes serious and life-threatening infusion reactions. Alemtuzumab must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for 2 hours after each infusion. Make patients aware that serious infusion reactions can also occur after the 2-hour monitoring period.

Malignancy (Lemtrada):

Alemtuzumab may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams.

REMS program (Lemtrada):

Because of the risk of autoimmunity, infusion reactions, and malignancies, Lemtrada is available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) Program. Call 1-855-676-6326 to enroll in the Lemtrada REMS program.

Stroke (Lemtrada):

Serious and life-threatening stroke (including ischemic and hemorrhagic stroke) has been reported within 3 days of alemtuzumab administration. Instruct patients to seek immediate medical attention if symptoms of stroke occur.

Brand Names: US
  • Campath;
  • Lemtrada
Brand Names: Canada
  • Lemtrada;
  • MabCampath
Pharmacologic Category
  • Antineoplastic Agent, Anti-CD52;
  • Antineoplastic Agent, Monoclonal Antibody;
  • Monoclonal Antibody
Dosing: Adult

Note: Alemtuzumab is associated with a moderate emetic potential in the oncology setting; antiemetics may be recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).

B-cell chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia (CLL): Campath, MabCampath [Canadian product]: IV: Gradually escalate to a maintenance of 30 mg per dose 3 times weekly on alternate days for a total duration of therapy of up to 12 weeks (Hillmen 2007; Keating 2002).

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 1,000 mg and diphenhydramine 50 mg) is recommended 30 minutes prior to the first dose, with dose escalations, and as clinically indicated; IV glucocorticoids may be used for severe infusion-related reactions. Administer antiviral prophylaxis (for herpetic viral infections) and Pneumocystis jirovecii pneumonia (PCP) prophylaxis; continue for at least 2 months after completion of alemtuzumab and until CD4+ lymphocyte count is ≥200/mm3. Reinitiate with gradual dose escalation if treatment is withheld ≥7 days.

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 (on alternate days) if required.

B-cell CLL (off-label route): Campath: 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 on alternate days 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 on alternate days for 4 to 12 weeks (Stilgenbauer 2009).

Multiple sclerosis, relapsing

Multiple sclerosis, relapsing:

Note: Safety: In high-risk populations or in countries with high tuberculosis burden, screen for latent infections (eg, hepatitis, tuberculosis) prior to initiating therapy. For patients who screen positive for latent infections, consult infectious disease or other appropriate specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]). Administer antiviral prophylaxis (for herpetic viral infections) beginning on the first day of treatment and continue for at least 2 months after completion of alemtuzumab or until CD4+ lymphocyte count is ≥200/mm3 (whichever occurs later). Premedication: Premedicate with corticosteroids (methylprednisolone 1 g or equivalent) immediately prior to alemtuzumab for the first 3 days of each treatment course. Antihistamines and/or antipyretics may also be considered.

Lemtrada: 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). Subsequent treatment courses of 12 mg daily for 3 consecutive days (total 36 mg) may be administered if necessary; courses should be administered no earlier than 12 months after the last dose of the prior treatment cycle.

Aplastic anemia, refractory

Aplastic anemia, refractory (off-label use): Campath:

IV: 10 mg daily for 10 days (as monotherapy); patients received a 1 mg test dose initially (Scheinberg 2012) or

SubQ: 3 mg day 1, 10 mg day 2, then 30 mg/day days 3, 4, and 5 (total dose: 103 mg over 5 consecutive days; in combination with cyclosporine) (Risitano 2009).

Autoimmune cytopenias, CLL-induced, refractory

Autoimmune cytopenias, CLL-induced, refractory (off-label use): Campath: 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, acute, steroid refractory, treatment

Graft versus host disease, acute, steroid refractory, treatment (off-label use): Campath: 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).

Hematopoietic stem cell transplant conditioning regimen

Hematopoietic stem cell transplant (allogeneic) conditioning regimen (off-label use): Campath: 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).

Hemophagocytic lymphohistiocytosis, refractory

Hemophagocytic lymphohistiocytosis, refractory (off-label use): Campath: IV, SubQ: Note: The optimal dose and duration of therapy is not known. Median dose: 1 mg/kg (range 0.1 to 8.9 mg/kg; maximum initial dose: 3 mg) divided over a median of 4 days (range 2 to 10 days); refer to article for further information (Marsh 2013).

Mycosis fungoides/Sézary syndrome, advanced

Mycosis fungoides/Sézary syndrome, advanced (off-label use): Campath: IV: Initial: 3 mg, increase to 10 mg and then to 30 mg as soon as infusion-related reactions were tolerated; Maintenance: 30 mg 3 times weekly for up to 12 weeks, or until complete remission is achieved or disease progression is noted; for dosing interruptions >7 days due to toxicity, reinitiate at 3 or 10 mg (Lundin 2003).

Solid organ transplantation

Solid organ transplantation: Campath:

Heart transplant, induction (off-label use): IV: 30 mg once intra-operatively at the time of transplant followed by minimized maintenance immunosuppression (Teuteberg 2010).

Lung transplant, induction (off-label use): IV, SubQ: 30 mg once either immediately before allograft reperfusion or immediately following transplant; followed by minimized maintenance immunosuppression (Jaksch 2014; Shyu 2011; Whited 2015).

Renal transplant, induction (off-label use): IV: 30 mg as a single dose at the time of transplant (immediately following reperfusion) followed by a second 30 mg dose 24 hours later (the second dose was omitted in patients >60 years of age); followed by minimized maintenance immunosuppression (Haynes 2014).

Renal transplant, steroid resistant cellular rejection (off-label use): IV, SubQ: 15 to 30 mg/dose SubQ on 2 subsequent days (van den Hoogen 2013) or 30 mg/dose IV over 2 to 4 hours for 1 to 2 doses (Basu 2005).

T-cell large granular lymphocytic leukemia

T-cell large granular lymphocytic leukemia (off-label use): Campath: IV: 10 mg daily for 10 days; patients received a 1 mg test dose initially (Dumitriu 2016).

T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia (off-label use): Campath: 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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Pediatric

Aplastic anemia, refractory (off-label use): Campath:

Children ≥2 years of age and Adolescents (<50 kg): IV: 0.2 mg/kg/dose (maximum: 10 mg/dose) for 10 days (as monotherapy); patients received a 1 mg test dose initially (Scheinberg 2012)

Children ≥2 years of age and Adolescents (≥50 kg): IV: 10 mg daily for 10 days (as monotherapy); patients received a 1 mg test dose initially (Scheinberg 2012)

Hemophagocytic lymphohistiocytosis, refractory (off-label use): Infants, Children, and Adolescents: Campath: IV, SubQ: Note: The optimal dose and duration of therapy is not known. Median dose: 1 mg/kg (range 0.1 to 8.9 mg/kg; maximum initial dose: 3 mg) divided over a median of 4 days (range 2 to 10 days); refer to article for further information (Marsh 2013)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: There are no pediatric-specific recommendations; the presented dosing adjustments are based on experience in adult patients. Refer to specific protocol for management in pediatric patients if available.

Nonhematologic toxicity:

Treatment of B-CLL: Campath, MabCampath [Canadian product]:

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

Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab

Hematologic toxicity (severe neutropenia or thrombocytopenia, not autoimmune): Treatment of B-CLL: Campath, MabCampath [Canadian product]:

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 by ≥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.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

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 (ASBMT [Bubalo 2014]).

Dosing: Adjustment for Toxicity: Adult

Dosage adjustment for nonhematologic toxicity:

Treatment of B-CLL: Campath, MabCampath [Canadian product]:

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

Autoimmune anemia or autoimmune thrombocytopenia: Discontinue alemtuzumab

Treatment of MS: Lemtrada:

Adult-onset Still disease: Discontinue alemtuzumab if alternate etiology cannot be established.

Serious infusion reaction: Consider immediate discontinuation

Dosage adjustment for hematologic toxicity (severe neutropenia or thrombocytopenia, not autoimmune): Treatment of B-CLL: Campath, MabCampath [Canadian product]:

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 by ≥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.

Hemophagocytic lymphohistiocytosis: Discontinue alemtuzumab if alternate etiology of signs/symptoms cannot be established.

Thrombotic thrombocytopenic purpura: Discontinue alemtuzumab if thrombotic thrombocytopenic purpura is confirmed or if alternate etiology of signs/symptoms cannot be established.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Campath: 30 mg/mL (1 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]

Lemtrada: 12 mg/1.2 mL (1.2 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Lemtrada: 12 mg/1.2 mL (1.2 mL) [contains edetate (edta) disodium dihydrate, mouse (murine) and/or hamster protein, polysorbate 80]

MabCampath: 30 mg/mL (1 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]

Prescribing and Access Restrictions

Campath is no longer commercially available in the United States; a restricted distribution program will allow access for appropriate patients. Information on necessary documentation and requirements is available from Clinigen Direct (1-877-768-4303) or https://www.clinigengroup.com/direct/en-gb/contact-us/#address-13.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Lemtrada: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/103948s5185lbl.pdf#page=30

Administration: Adult

IV: Campath or MabCampath [Canadian product]: Administer by IV infusion over 2 hours. Premedicate with diphenhydramine 50 mg and acetaminophen 500 to 1,000 mg 30 minutes before each infusion. IV glucocorticoids have 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. May be given through peripheral IV.

Infusion times may have varied in studies for off-label uses; refer to specific reference citations.

Lemtrada: Administer by IV infusion over 4 hours (beginning within 8 hours after dilution); do not administer by IV push or IV bolus. May extend the infusion duration if clinically indicated. Do not infuse other medications through the same IV line. Premedicate with corticosteroids (methylprednisolone 1,000 mg or equivalent) for first 3 days of each treatment course. Administer in a setting with personnel and equipment appropriate to manage infusion reactions. Monitor vital signs prior to and periodically during the infusion. Infusion reactions should be managed symptomatically; consider discontinuing immediately for severe infusion reaction. Observe for at least 2 hours after each infusion, longer if clinically indicated.

SubQ: Campath: SubQ (off-label 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 1,000 mg 30 minutes before dose. The subQ route should NOT be used for the treatment of T-PLL (Deardon 2011).

Alemtuzumab is associated with a moderate emetic potential in adults in the oncology setting; antiemetics may be recommended to prevent nausea and vomiting (ASCO [Hesketh 2020; MASCC/ESMO [Roila 2016]).

Administration: Pediatric

IV: Campath: Dilute prior to administration; begin administration within 8 hours of dilution; administer by IV infusion over 2 hours (Scheinberg 2012); do not give as an IV push or bolus injection. Compatible in polyvinylchloride (PVC) or polyethylene lined administration sets. Premedication with diphenhydramine and acetaminophen 30 minutes prior to infusion is recommended to help with infusion reaction. IV glucocorticoids have been effective in decreasing severe infusion-related events.

SubQ: Hemophagocytic lymphocytosis: Campath: Limited data available for subcutaneous administration (Lundin 2002; Marsh 2013; Stilgenbauer 2009). In adults, target dose was divided into 2 injection sites of 1.5 mL each (Lundin 2002). Premedicate with diphenhydramine and acetaminophen 30 minutes before dose.

Use: Labeled Indications

B-cell chronic lymphocytic leukemia: Campath or MabCampath [Canadian product]: Treatment (as a single agent) of B-cell chronic lymphocytic leukemia.

Multiple sclerosis, relapsing: Lemtrada: Treatment of relapsing-remitting and active secondary progressive multiple sclerosis (MS); generally reserved for patients who have had an inadequate response to ≥2 medications indicated for the treatment of MS.

Limitations of use: Alemtuzumab is not recommended for use in patients with clinically isolated syndrome due to its safety profile.

Use: Off-Label: Adult

Acute graft-versus-host disease (steroid refractory) (treatment); Aplastic anemia, refractory; Autoimmune hemolytic anemia, chronic lymphocytic leukemia–induced; Hematopoietic stem cell transplant (allogeneic) conditioning regimen and/or graft-versus-host disease prophylaxis; Hemophagocytic lymphohistiocytosis, refractory; Mycosis fungoides/Sézary syndrome (advanced); Solid organ transplantation: Heart transplant (induction); Solid organ transplantation: Lung transplant (induction); Solid organ transplantation: Renal transplant (induction); Solid organ transplantation: Renal transplant (steroid-resistant cellular rejection); T-cell large granular lymphocytic leukemia; T-cell prolymphocytic leukemia

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.

Other safety concerns:

Duplicate therapy issues: Campath and MabCampath contain alemtuzumab, which is the same ingredient contained in Lemtrada; patients receiving Lemtrada should not be treated with Campath or MabCampath.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

Multiple sclerosis:

>10%:

Dermatologic: Pruritus (14%), skin rash (53%), urticaria (16%)

Endocrine & metabolic: Thyroid disease (13% to 37%)

Gastrointestinal: Diarrhea (12%), nausea (21%)

Genitourinary: Urinary tract infection (19%)

Hematologic & oncologic: Lymphocytopenia (100%)

Hypersensitivity: Infusion-related reaction (92%; severe infusion-related reaction: 3%)

Immunologic: Antibody development (neutralizing: 5% to 94%; anti-alemtuzumab: 29% to 83%; no significant effect on drug efficacy)

Infection: Fungal infection (12% to 13%; including oral candidiasis, vulvovaginal candidiasis), herpes virus infection (16%), infection (71%; serious infection: 3%)

Nervous system: Fatigue (18%), headache (52%), insomnia (16%)

Neuromuscular & skeletal: Arthralgia (12%), back pain (12%), limb pain (12%)

Respiratory: Nasopharyngitis (25%), oropharyngeal pain (11%), sinusitis (11%), upper respiratory tract infection (16%)

Miscellaneous: Fever (29%)

1% to 10%:

Cardiovascular: Chest discomfort (7%), flushing (10%), peripheral edema (5%), tachycardia (8%)

Dermatologic: Dermatitis (8%), erythema of skin (5%)

Gastrointestinal: Abdominal pain (10%), appendicitis (≤3%), dysgeusia (8%), dyspepsia (8%), gastroenteritis (≤3%), oral herpes simplex infection (9%), tooth infection (≤3%), vomiting (10%)

Genitourinary: Abnormal uterine bleeding (5%), genital herpes simplex (1%), microscopic hematuria (8%)

Hematologic & oncologic: Decreased CD-4 cell count (6%), decreased CD-8 cell counts (6%), decreased T cell lymphocytes (5%), immune thrombocytopenia (2%)

Hypersensitivity: Angioedema (≤3%)

Infection: Herpes simplex infection (2%), herpes zoster infection (4%), human papilloma virus infection (2%), influenza (8%)

Nervous system: Anxiety (7%), asthenia (5%), chills (9%), dizziness (10%), myasthenia (7%), paresthesia (10%)

Neuromuscular & skeletal: Muscle spasm (6%), myalgia (6%), neck pain (5%)

Ophthalmic: Graves ophthalmopathy (2%)

Respiratory: Bronchitis (7%), cough (9%), dyspnea (8%), epistaxis (5%), pneumonia (≤3%)

<1%:

Dermatologic: Malignant melanoma, vitiligo

Endocrine & metabolic: Malignant neoplasm of thyroid, type 1 diabetes mellitus

Hematologic & oncologic: Acquired blood coagulation disorder (hemophilia A [anti-Factor VIII antibodies]), hemolytic anemia (including autoimmune hemolytic anemia), neutropenia, pancytopenia

Hypersensitivity: Anaphylactic shock, anaphylaxis

Immunologic: Anti-GBM disease

Infection: Varicella zoster infection

Nervous system: Meningitis (herpes), suicidal ideation, suicidal tendencies

Neuromuscular & skeletal: Connective tissue disease (undifferentiated), rheumatoid arthritis

Ophthalmic: Retinal pigment changes (epitheliopathy)

Renal: Membranous glomerulonephritis

Respiratory: Pneumonitis (including with fibrosis), tuberculosis

Frequency not defined:

Endocrine & metabolic: Goiter, Graves disease, hyperthyroidism, hypothyroidism, thyroiditis

Nervous system: Pain

Respiratory: Hypersensitivity pneumonitis

B-cell chronic lymphocytic leukemia:

>10%:

Cardiovascular: Cardiac arrhythmia (14%), hypertension (14%), hypotension (16%)

Dermatologic: Skin rash (13%), urticaria (16%)

Hematologic & oncologic: Anemia (76%; grades 3/4: 12% to 38%), lymphocytopenia (97%; grades 3/4: 97%), neutropenia (77%; grades 3/4: 42% to 64%), thrombocytopenia (71%; grades 3/4: 13% to 52%)

Hypersensitivity: Infusion-related reaction (more frequently seen in the first week of treatment)

Infection: CMV viremia (55%), cytomegalovirus disease (6% to 16%), infection (50% to 74%)

Nervous system: Chills (53%), headache (14%)

Respiratory: Dyspnea (14%)

Miscellaneous: Fever (69%)

1% to 10%:

Cardiovascular: Tachycardia (10%)

Dermatologic: Erythema of skin (4%)

Gastrointestinal: Anorexia (>5%), diarrhea (10%), nausea (>5%), stomatitis (>5%), vomiting (>5%)

Hematologic & oncologic: Autoimmune thrombocytopenia (2%), febrile neutropenia (grades ≥3: 5% to 10%)

Immunologic: Antibody development (2% to 8%; neutralizing: 2%)

Infection: Sepsis (grades ≥3: 3% to 10%)

Nervous system: Anxiety (8%), dysesthesia (>5%), fatigue (>5%), insomnia (10%), tremor (3%)

Neuromuscular & skeletal: Musculoskeletal pain (>5%)

Respiratory: Bronchospasm (>5%)

Frequency not defined: Gastrointestinal: Abdominal pain

Postmarketing (all indications):

Cardiovascular: Acute myocardial infarction, cardiac insufficiency (acute), cardiomyopathy, coronary artery dissection (cervicocephalic arterial dissection [vertebral, carotid]), heart failure, ischemic heart disease, reduced ejection fraction, syncope, vasculitis

Gastrointestinal: Cholecystitis (calculous and acalculous)

Hematologic & oncologic: Aplastic anemia, bone marrow aplasia, bone marrow depression (prolonged), hemophagocytic lymphohistiocytosis, lymphoproliferative disorder, malignant lymphoma, pure red cell aplasia, thrombotic thrombocytopenic purpura, tumor lysis syndrome

Hepatic: Autoimmune hepatitis, viral hepatitis

Hypersensitivity: Serum sickness

Immunologic: Autoimmune disease (Adult Onset Still’s Disease), Epstein-Barr-associated lymphoproliferative disorder, Goodpasture syndrome, graft-versus-host disease (transfusion associated), sarcoidosis

Infection: Epstein-Barr infection, listeriosis (including gastroenteritis, encephalitis, sepsis), opportunistic infection (including aspergillosis, coccidioidomycosis, histoplasmosis, nocardiosis)

Nervous system: Cerebrovascular accident, chronic inflammatory demyelinating polyneuropathy, encephalitis (autoimmune), Guillain-Barre syndrome, hemorrhagic stroke, ischemic stroke, meningitis due to Listeria monocytogenes, progressive multifocal leukoencephalopathy

Ophthalmic: Optic neuropathy

Respiratory: Acute respiratory distress syndrome, apnea, pneumonia due to Pneumocystis jirovecii, pulmonary alveolar hemorrhage, pulmonary infiltrates

Miscellaneous: Reactivation of disease

Contraindications

US labeling: Hypersensitivity (eg, anaphylactic reactions) to alemtuzumab or any component of the formulation; HIV infection (due to prolonged reduction in CD4+ lymphocytes); active infection. There are no contraindications listed in the manufacturer's Campath labeling.

Canadian labeling:

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

MabCampath: 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 PML.

Warnings/Precautions

Concerns related to adverse effects:

• Adult-onset Still disease: Rare cases of adult-onset Still disease have been reported in patients receiving alemtuzumab for multiple sclerosis. Promptly evaluate patients with signs and symptoms (eg, fever, arthritis, rash, leukocytosis in the absence of infections, malignancies, or other rheumatic conditions) suggestive of adult-onset Still disease.

• Autoimmune effects: [US Boxed Warning (Lemtrada)]: Alemtuzumab causes serious, sometimes fatal, autoimmune conditions, such as immune thrombocytopenia and antiglomerular basement membrane (anti-GBM) disease, in patients receiving alemtuzumab for the treatment of multiple sclerosis (MS). Monitor CBC with differential, serum creatinine levels, and urinalysis with urine cell counts before starting treatment and then at monthly intervals until 48 months after the last dose of alemtuzumab. Monitor for symptoms of immune thrombocytopenia (easy bruising, petechiae, spontaneous mucocutaneous bleeding, heavy menstrual bleeding) in patients receiving alemtuzumab for MS. Glomerular nephropathies, including anti-GBM disease, have been reported up to 40 months after the last dose. Monitor for nephropathy symptoms (dyspnea, edema, elevated serum creatinine, change in urine color, decreased urine output, fatigue, hematuria, hemoptysis, proteinuria). Glomerular nephropathies require urgent evaluation; may lead to end-stage renal disease requiring dialysis or renal transplantation if not treated. Urine dipstick results of ≥1+ protein warrant assessment of urine protein to creatinine ratio. Perform further evaluation for nephropathies if urine protein to creatinine ratio >200 mg/g, increase in serum creatinine >30%, or unexplained hematuria. Alveolar hemorrhage manifesting as hemoptysis has been reported with anti-GBM disease. Prompt intervention is necessary for increased serum creatinine with hematuria, signs of pulmonary involvement of anti-GBM disease (eg, hemoptysis, exertional dyspnea), or autoimmune cytopenias. Immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura), thrombotic thrombocytopenic purpura (TTP), thyroid disorders, autoimmune encephalitis, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune pancytopenia, undifferentiated connective tissue disorders, acquired hemophilia A, rheumatoid arthritis, type 1 diabetes, vasculitis, vitiligo, and retinal pigment epitheliopathy have been reported in patients receiving alemtuzumab for MS. Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy have been reported in patients receiving alemtuzumab for other uses. Alemtuzumab may increase the risk for other autoimmune conditions.

• Autoimmune encephalitis: Autoimmune encephalitis, including signs and symptoms of altered mental status, subacute onset of memory impairment, neurological findings, psychiatric symptoms, and seizures, has been reported. Discontinue therapy if autoimmune encephalitis is suspected or confirmed by the presence of neural autoantibodies.

• Bone marrow suppression: [US Boxed Warning (Campath)]: 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-cell chronic lymphocytic leukemia (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 transfusion-associated graft-versus-host disease during lymphopenia.

• Cholecystitis: In a clinical trial of patients with MS, an increased risk of acute acalculous cholecystitis was observed in patients receiving alemtuzumab versus interferon beta-1a; additional postmarketing cases have also been reported. Symptom onset ranged from <24 hours to 2 months after alemtuzumab infusion. Some patients recovered without surgical intervention (and received antibiotics); some patients underwent cholecystectomy. Monitor closely (acute acalculous cholecystitis is associated with high morbidity and mortality); symptoms may include abdominal pain/tenderness, fever, nausea, vomiting, leukocytosis, and abnormal liver enzymes. Evaluate and treat promptly if acute acalculous cholecystitis is suspected or diagnosed.

• Hemophagocytic lymphohistiocytosis: Hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune system reaction, has been reported with alemtuzumab use and is associated with high mortality rates if not treated early; it is characterized by clinical signs and symptoms of extreme systemic inflammation. Symptoms may include fever, rash, hepatosplenomegaly, lymphadenopathy, neurologic symptoms, cytopenias, elevated serum ferritin, hypertriglyceridemia, and liver function and coagulation abnormalities. Symptoms of HLH have been reported to occur up to 33 months following initiation of treatment.

• Hemophilia: Acquired hemophilia A (anti-factor VIII antibodies) has been reported. Symptoms have included spontaneous subcutaneous hematomas and extensive bruising; epistaxis, GI bleeding, hematuria, and other types of bleeding may also occur. Coagulopathy panel including aPTT should be obtained if acquired hemophilia is suspected. Patients should seek medical attention for signs and symptoms of acquired hemophilia A.

• Hepatitis: Autoimmune hepatitis causing clinically significant liver injury, including acute liver failure requiring transplant, has been reported; monitor serum transaminases and total bilirubin prior to initiation of therapy, then periodically until 48 months after the last infusion or at any time during therapy. Monitor for clinical signs/symptoms of hepatic dysfunction (unexplained nausea, vomiting, abdominal pain, anorexia, fatigue, jaundice, and/or dark urine); if reported, promptly obtain serum transaminases and total bilirubin; may require treatment interruption or discontinuation.

• Infections: [US Boxed Warning (Campath)]: Serious and potentially fatal infections (bacterial, viral, fungal, and protozoan) have been reported. Administer prophylactic medications against Pneumocystis jirovecii pneumonia (PCP) and herpes viral infections during treatment and for at least 2 months following last dose or until CD4+ counts are ≥200 cells/mm3 (whichever is later). Severe and prolonged lymphopenia may occur; CD4+ counts usually return to ≥200 cells/mm3 within 2 to 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 cytomegalovirus (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). For patients being treated for MS, initiate antiviral prophylaxis (for herpetic viral infections) beginning on the first day of treatment and continue for at least 2 months or until CD4+ lymphocyte count is ≥200/mm3. In clinical trials for MS, infections seen more commonly in alemtuzumab-treated patients included nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, herpetic infections, influenza, and bronchitis; serious cases of appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection also occurred. Serious (sometimes fatal) opportunistic infections have been reported, including aspergillosis, coccidioidomycosis, histoplasmosis, PCP, nocardiosis, Epstein-Barr virus, and CMV. Listeria monocytogenes infections (encephalitis, gastroenteritis, meningitis, sepsis), including fatal cases of Listeria meningoencephalitis have been reported; Listeria infections have developed as early as 3 days post treatment and up to 8 months after the last dose for MS. The duration of increased risk for Listeria infections after treatment is unknown. Patients should initiate Listeria precautions prior to starting treatment, which include avoiding or adequately heating foods that may potentially carry this bacteria (eg, deli meat, dairy products made with unpasteurized milk, soft cheeses, or undercooked meat, seafood, or poultry). The incubation period for Listeria monocytogenes ranges from 3 to 70 days; signs/symptoms of invasive listeriosis generally start within 1 month of exposure. Symptoms of Listeria infection include fever, chills, diarrhea, nausea, vomiting, headache, pains in joints and muscles, neck stiffness, difficulty walking, mental status changes, coma, and other neurologic changes. Treatment (eg, with anti-infectives) may not adequately prevent Listeria infection-related morbidity/mortality. Epstein-Barr virus (EBV), including severe and fatal EBV-associated hepatitis, has been reported; monitor for signs and symptoms of EBV infection. Consider delaying treatment in patients with any active infection or EBV reactivation until infection is controlled. In high-risk populations or in countries with high tuberculosis burden, screen for latent infections (eg, hepatitis, tuberculosis) prior to initiating therapy. For patients who screen positive for latent infections, consult infectious disease or other specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]). Patients should be screened for human papilloma virus as clinically necessary.

• Infusion reactions: [US Boxed Warning]: Serious and potentially fatal infusion-related reactions may occur; monitor for infusion reaction; carefully monitor during infusion; withhold treatment for serious or grade 3 or 4 infusion reactions. For B-CLL, gradual escalation to the recommended maintenance dose is required at initiation and with treatment interruptions (for ≥7 days) to minimize infusion-related reactions. For MS, must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reaction; monitor for 2 hours after each infusion; inform patients that serious infusion reactions may also occur after the 2-hour monitoring period. In patients treated for B-CLL, infusion reaction symptoms may include acute respiratory distress syndrome, anaphylactic/anaphylactoid 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 B-CLL 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. For B-CLL, reinitiate with gradual dose escalation if treatment is withheld ≥7 days. Similar infusion reactions, as well as pulmonary alveolar hemorrhage, myocardial ischemia, myocardial infarction, cervicocephalic (eg, vertebral, carotid) arterial dissection, and life-threatening stroke (including ischemic and hemorrhagic stroke), have been observed with use in the treatment of multiple sclerosis; most cases occurred within 1 to 3 days. Cases of severe (including fatal) neutropenia have also been reported within 2 months of infusion; may resolve with granulocyte colony-stimulating factor treatment. Mild to moderate decreases in platelet counts at infusion initiation have been reported; may resolve without treatment. Premedication with corticosteroids for initial 3 days of each treatment course is recommended. Antihistamines and/or antipyretics may also be considered. Consider additional monitoring in patients with existing cardiovascular or respiratory compromise. Observe for infusion-related reactions; advise patients to monitor for signs/symptoms of infusion reaction, particularly during the 48 hours following infusion.

• Malignancy: [US Boxed Warning (Lemtrada)]: Alemtuzumab may cause an increased risk of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams. Other malignant neoplasm (breast cancer or basal cell carcinoma) has been observed (rarely) in patients receiving treatment for MS. Use caution if initiating treatment in patients with preexisting or ongoing malignancies.

• Pneumonitis: Pneumonitis (hypersensitivity or fibrosis) has been reported. Monitor for symptoms (dyspnea, cough, wheezing, hemoptysis, chest pain/tightness).

• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML) was diagnosed in a patient 2 months after the second alemtuzumab course for the treatment of MS. PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus and usually leads to death or severe disability. PML typically only occurs in patients who are immunocompromised; however, the patient who developed PML while taking alemtuzumab had no identifiable systemic medical condition resulting in immunosuppression, had not received other MS medications for >1 year, was not taking any concomitant immunomodulatory or immunosuppressant medications, and had not previously been treated with natalizumab. At the first sign or symptom suggestive of PML, perform a diagnostic evaluation and withhold therapy; symptoms progress over days to weeks and may include progressive weakness on one side of the body or clumsiness of limbs, vision disturbances, and mental status changes. Cases of PML have been diagnosed based on MRI findings and the detection of JC virus DNA in the cerebrospinal fluid without specific PML signs/symptoms. Monitoring with brain MRI for signs that may be consistent with PML may be beneficial and allow for an early diagnosis of PML.

• Stroke and cervicocephalic arterial dissection (Lemtrada): [US Boxed Warning (Lemtrada)]: Serious and life-threatening stroke (including ischemic and hemorrhagic stroke) has been reported within 3 days of Lemtrada administration. Instruct patients to seek immediate medical attention if symptoms of a stroke occur. Most cases of stroke occurred within 1 day of administration; cases of cervicocephalic (eg, vertebral, carotid) arterial dissection involving multiple arteries occurred within 3 days. Educate patients to seek immediate medical care if symptoms of stroke and cervicocephalic arterial dissection occur.

• Thrombotic thrombocytopenic purpura: TTP has been reported, and cases may include thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, fever, and kidney impairment.

• Thyroid disorders: Autoimmune thyroid disorders occurred in over one-third of patients receiving alemtuzumab for MS. In a trial evaluating alemtuzumab versus interferon beta-1a in patients with MS, 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, goiter) has also been reported with alemtuzumab use for the treatment of other conditions. For B-CLL treatment, thyroid-stimulating hormone (TSH) monitoring is recommended; monitor TSH at baseline and every 2 to 3 months during alemtuzumab treatment (Hamnvik 2011). For MS, monitor TSH at baseline and every 3 months until 48 months after last infusion or longer or at any time during therapy if clinically indicated or in case of pregnancy.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: Alemtuzumab is not recommended for use in patients with MS 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.

• Duplicate therapy: If considering Lemtrada treatment for use in a patient who has previously received Campath/MabCampath, consider the additive and long-lasting immune system effects.

• Immunizations: In the oncology setting, patients should not be immunized with live, viral vaccines during or recently after treatment. When using for the treatment of multiple sclerosis (MS), complete necessary immunizations at least 6 weeks prior to initiating alemtuzumab. Avoid live-attenuated vaccines in patients who currently receive or have recently discontinued alemtuzumab for MS; consider using live-attenuated vaccines only if risk of infection is high and killed vaccines are unavailable (AAN [Farez 2019]). 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 alemtuzumab for non-oncology purposes if history of chickenpox or VZV vaccination status is unknown; consider vaccinations for antibody-negative patients and postpone alemtuzumab treatment for 6 weeks following VZV vaccination.

• REMS Program: [US Boxed Warning (Lemtrada)]: Due to the risk of autoimmunity, infusion reactions, and malignancies, alemtuzumab is available only through restricted distribution under a Risk Evaluation Mitigation Strategy (REMS) Program when used for the treatment of MS. Contact 1-855-676-6326 to enroll in the Lemtrada REMS program. Prescribers and pharmacies must be certified with the REMS program, and patients and healthcare facilities must be enrolled and comply with ongoing monitoring.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Anticoagulants: Alemtuzumab may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA vaccine at least 28 days after the primary vaccine dose. Patients should also receive 2 booster doses of mRNA vaccine - one 2 months after the 2nd (additional) dose and another 4 months after the first booster dose. Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups based on the brand of mRNA vaccine received. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Ozanimod: Alemtuzumab may enhance the immunosuppressive effect of Ozanimod. Risk X: Avoid combination

Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Ponesimod: May enhance the immunosuppressive effect of Alemtuzumab. Risk X: Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Evaluate pregnancy status prior to using Campath in patients who may become pregnant.

Patients who could become pregnant should use effective contraception during therapy and for at least 3 months after the last dose of Campath. Patients who could become pregnant should use effective contraception during therapy and for 4 months after the last dose of Lemtrada.

In general, disease-modifying therapies for multiple sclerosis are stopped prior to a planned pregnancy except in females at high risk of multiple sclerosis activity (AAN [Rae-Grant 2018]). Consider use of agents other than alemtuzumab for patients at high risk of disease reactivation who are planning to become pregnant. Delaying pregnancy is recommended for patients with persistent high disease activity; however, use of alemtuzumab may be an alternative option in these patients if the last infusion is at least 4 months prior to conception (ECTRIMS/EAN [Montalban 2018]).

Patients requiring alemtuzumab for multiple sclerosis and desiring pregnancy should have thyroid function testing prior conception and be euthyroid before attempting to become pregnant (Decallonne 2018; Hammerstad 2021).

Pregnancy Considerations

Alemtuzumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Outcome data following use of alemtuzumab in pregnant patients with multiple sclerosis are available (Alroughani 2016; Oh 2020; Tuohy 2015; Valeria 2021).

Alemtuzumab administration may result in the formation of autoantibodies, which may cross the placenta. A case report describes the development of maternal Graves disease following alemtuzumab therapy with placental transfer of anti-thyroid antibodies resulting in neonatal Graves disease. The patient became pregnant 8 months after a third dose of alemtuzumab for the treatment of multiple sclerosis. Maternal thyrotropin receptor stimulating antibodies (TRAb) were slightly elevated at conception and increased significantly during pregnancy. TRAb levels were also significantly elevated in the infant at birth. Symptoms of thyrotoxicosis were observed at 10 days of age in the newborn; thyroid function tests returned to normal after 3 weeks of treatment and normal growth and development were reported at 3 months of age (Hammerstad 2022). Thyroid disorders induced by alemtuzumab therapy may cause adverse maternal and fetal events.

In general, disease-modifying therapies for multiple sclerosis are not initiated during pregnancy, except in patients at high risk of multiple sclerosis activity (AAN [Rae-Grant 2018]).

Data collection to monitor pregnancy and infant outcomes following exposure to alemtuzumab is ongoing. Health care providers are encouraged to enroll patients exposed to alemtuzumab during pregnancy in the pregnancy exposure registry (1-800-745-4447, option 2).

Breastfeeding Considerations

It is not known if alemtuzumab is present in breast milk.

Alemtuzumab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

According to the manufacturer, the decision to breastfeed during Lemtrada therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, benefits of treatment to the mother, and the long half-life of alemtuzumab. Other sources do not recommend breastfeeding during therapy (Dobson 2019; Fragoso 2018). Due to the potential for adverse reactions, including reduced lymphocyte counts in a breastfed child, the manufacturer does not recommend breastfeeding during Campath therapy or for at least 3 months after the last Campath dose.

Monitoring Parameters

Campath: CBC with differential and platelets (weekly, more frequent if worsening); signs and symptoms of infection; CD4+ lymphocyte counts (after treatment until recovery); cytomegalovirus antigen (routinely during and for 2 months after treatment); consider thyroid-stimulating hormone (TSH) at baseline and then every 2 to 3 months during alemtuzumab treatment (Hamnvik 2011). Monitor closely for infusion reactions (including hypotension, rigors, fever, shortness of breath, bronchospasm, chills, and/or rash); vital signs (prior to and during infusion); carefully monitor BP, especially in patients with ischemic heart disease or on antihypertensive medications. The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up. Evaluate pregnancy status prior to use in patients who may become pregnant.

Lemtrada: 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; serum transaminases and total bilirubin prior to initiation then periodically until 48 months after the last infusion or at any time during therapy if clinically indicated; urinalysis with urine cell counts prior to initiation then monthly until 48 months after last infusion (urine dipstick results of ≥1+ protein warrant assessment of urine protein to creatinine ratio); urine protein to creatinine ratio at baseline and then as clinically indicated (evaluate further for nephropathies if urine protein to creatinine ratio >200 mg/g, increase in serum creatinine >30%, or unexplained hematuria); ECG at baseline; TSH at baseline and every 3 months until 48 months after last infusion or longer or at any time during therapy if clinically indicated or in case of pregnancy; coagulopathy panel, including aPTT, in patients presenting with signs of acquired hemophilia A. Observe for at least 2 hours after each infusion, longer if clinically indicated. Monitor for signs/symptoms of infection; annual human papillomavirus screening; latent infection screening (eg, hepatitis, tuberculosis) in high-risk populations or in countries with high tuberculosis burden (baseline); signs/symptoms of progressive multifocal leukoencephalopathy and hemophagocytic lymphohistiocytosis; signs/symptoms of thrombotic thrombocytopenic purpura; signs and symptoms of autoimmune encephalitis; baseline and annual skin exams (for melanoma).

Mechanism of Action

Alemtuzumab 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.

Pharmacokinetics

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

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

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

Pricing: US

Solution (Lemtrada Intravenous)

12 mg/1.2 mL (per mL): $27,072.11

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Campath (CZ, PE, RU, UY);
  • Lemtrada (AT, AU, BE, BH, BR, CH, CZ, DE, DK, EE, ES, FI, GB, GR, HK, HR, HU, IE, IL, KR, LB, LT, LU, LV, MT, MY, NL, NO, PL, RO, SE, SG, SI, TH, TW);
  • MabCampath (AU, CY, GB, HN, ID, JP, KR, MY, SG, TH, TR);
  • Mabcampath (CR, DO, GT, JO, NI, SV);
  • Remniq (AU)


For country abbreviations used in Lexicomp (show table)
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