(ay lem TU zoo mab)
- Anti-CD52 Monoclonal Antibody
- Humanized IgG1 Anti-CD52 Monoclonal Antibody
- MoAb CD52
- Monoclonal Antibody Campath-1H
- Monoclonal Antibody CD52
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 disodium dihydrate, mouse (murine) and/or hamster protein, polysorbate 80]
Lemtrada: 12 mg/1.2 mL (1.2 mL) [contains edetate disodium dihydrate, mouse (murine) and/or hamster protein, polysorbate 80]
Brand Names: U.S.
- Antineoplastic Agent, Anti-CD52
- Antineoplastic Agent, Monoclonal Antibody
- Monoclonal Antibody
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.
Vd: IV: Campath: 0.18 L/kg (range: 0.1 to 0.4 L/kg); Lemtrada: 14.1 L
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.
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
Use: Labeled Indications
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, relapsing: Lemtrada: Treatment of patients with relapsing forms of multiple sclerosis (MS), generally reserved for patients who have had an inadequate response to 2 or more medications indicated for the treatment of MS.
Off Label Uses
Acute graft-versus-host disease (steroid refractory) (treatment)
Data from a limited number of patients in two studies (one phase II and one retrospective) suggest that alemtuzumab may be beneficial for the treatment of steroid refractory acute graft-versus-host disease (aGVHD) [Martinez 2009], [Schnitzler 2009]. Additional data may be necessary to further define the role of alemtuzumab in this condition.
Autoimmune hemolytic anemia, chronic lymphocytic leukemia (CLL)-induced
Data from a limited number of patients and clinical experience suggests alemtuzumab may be beneficial for the treatment of CLL-induced autoimmune hemolytic anemias [Karlsson 2007], [ Osterborg 2009]. Additional data may be necessary to further define the role of alemtuzumab in this condition.
B-cell chronic lymphocytic leukemia (B-CLL) (subcutaneous [off-label route])
Data from two phase II open-label clinical trials support the subcutaneous use of alemtuzumab in the treatment of B-CLL [Lundin 2002], [ Stilgenbauer 2009].
Solid organ transplantation: Heart transplant (induction)
Data from a single center retrospective review suggests that alemtuzumab may be beneficial for prevention of rejection in heart transplant recipients when used in combination with decreased maintenance immunosuppression [Teuteberg 2010]. Additional data may be necessary to further define the role of alemtuzumab in this condition.
Solid organ transplantation: Lung transplant (induction)
A retrospective analysis of data obtained from the United Network for Organ Sharing (UNOS) registry supports the use of alemtuzumab as induction therapy in patients receiving double lung transplants [Furuya 2016]. Data from other studies also support the use of alemtuzumab in the prevention of rejection in lung transplant recipients when followed by decreased maintenance immunosuppression [Jaksch 2014], [Shyu 2011], [Whited 2015]. Additional data may be necessary to further define the role of alemtuzumab in this condition.
Solid organ transplantation: Renal transplant (induction)
Data from a large, prospective, multicenter randomized study supports the use of alemtuzumab as induction therapy (followed by reduced maintenance immunosuppression) in the prevention of renal transplant rejection [Haynes 2014].
Solid organ transplantation: Renal transplant (steroid-resistant cellular rejection)
Data from small retrospective reviews support the use of alemtuzumab for treatment of acute steroid-resistant cellular rejection after renal transplant [Basu 2005], [van den Hoogen 2013]
Stem cell transplant (allogeneic) conditioning regimen and/or graft-versus-host disease prophylaxis
Data from two studies support the use of alemtuzumab in conditioning regimens for allogeneic stem cell transplantation to reduce the incidence of acute and/or chronic graft-versus-host disease (GVHD) [Mead 2010 ], [Van Biesen 2009]. Additional trials may be necessary to further define the role of alemtuzumab in this setting.
T-cell prolymphocytic leukemia (T-PLL)
Data from two studies support the use of alemtuzumab in the treatment of T-cell prolymphocytic leukemia [Deardon 2001], [Keating 2002].
US labeling: Lemtrada is contraindicated in patients infected with HIV (due to prolonged reduction in CD4+ lymphocytes). There are no contraindications listed in the manufacturer's Campath labeling.
Lemtrada: 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: 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)
Note: Alemtuzumab is associated with a moderate emetic potential in the oncology setting; antiemetics may be recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016).
B-cell chronic lymphocytic leukemia (B-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-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: 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); total duration of therapy: 24 months.
Note: Premedicate with corticosteroids (methylprednisolone 1,000 mg or equivalent) immediately prior to alemtuzumab for the first 3 days of each treatment course. Antihistamines and/or antipyretics may also be considered. 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). 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).
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 (GVHD), 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)
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). Additional data may be necessary to further define the role of alemtuzumab in this condition.
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). Additional data may be necessary to further define the role of alemtuzumab in this condition.
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). Additional data may be necessary to further define the role of alemtuzumab in this condition.
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)
T-cell prolymphocytic leukemia (T-PLL; 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)
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Dosing: Adjustment for Toxicity
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: 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 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.
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).
Campath MabCampath [Canadian product]: Dilute appropriate dose for infusion in 100 mL NS or D5W. Compatible in polyvinylchloride (PVC) bags. Gently invert the bag to mix the solution. Do not shake prior to use.
Lemtrada: Withdraw 12 mg (1.2 mL) from vial and add to 100 mL bag of NS or D5W. Gently invert the bag to mix the solution.
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. 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.
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 1000 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 (Hesketh 2017; Roila 2016).
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.
Campath: Prior to dilution in NS or D5W, store intact (30 mg/1 mL) vials at 2°C to 8°C (36°F to 46°F); do not freeze (if accidentally frozen, thaw in refrigerator prior to administration). Do not shake; protect from light. Following dilution, store at room temperature or refrigerate; protect from light; use within 8 hours. Discard unused portion in the vial.
Lemtrada: Prior to dilution in NS or D5W, store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake; protect from light. Following dilution, store at room temperature or refrigerate; use within 8 hours.
MabCampath [Canadian product]: Prior to dilution in NS or D5W, store vials at 2°C to 8°C (36°F to 46°F). Do not freeze (discard vial if frozen). Do not shake. Protect from light. Following dilution, store at room temperature or refrigerate; use within 8 hours.
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). 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. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
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. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). 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. Avoid combination
May interfere with diagnostic serum tests that utilize antibodies.
Central nervous system: Headache (44% to 52%), fatigue (8% to 21%), insomnia (11% to 17%), paresthesia (10% to 12%)
Dermatologic: Skin rash (43% to 53%), urticaria (15% to 17%), pruritus (13% to 17%)
Endocrine & metabolic: Thyroid disease (13% to 34%)
Gastrointestinal: Nausea (16% to 22%), diarrhea (12%), oral candidiasis (3% to 12%)
Genitourinary: Urinary tract infection (18% to 19%), vulvovaginal candidiasis (3% to 12%)
Hematologic & oncologic: Lymphocytopenia (6% to 100%)
Immunologic: Antibody development (8% to 85%; no effect on drug efficacy; anti-alemtuzumab: 2%)
Infection: Infection (71%), herpes virus infection (16%), fungal infection (12% to 13%)
Local: Infusion related reaction (92%)
Neuromuscular & skeletal: Arthralgia (12% to 13%), limb pain (13%), back pain (12%)
Respiratory: Nasopharyngitis (24% to 25%), upper respiratory tract infection (15% to 16%), oropharyngeal pain (11%), sinusitis (11%)
Miscellaneous: Fever (26% to 30%)
1% to 10%:
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 (9% to 10%), dizziness (10%), anxiety (7%), 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%), abdominal pain (5% to 10%), oral herpes (9%), dyspepsia (6% to 9%), dysgeusia (8%), gastroenteritis (4%), upper abdominal pain (4%), abdominal distention (2%), oral mucosa ulcer (1%)
Genitourinary: Occult blood in urine (4% to 8%), uterine hemorrhage (5%), 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%), decreased CD-4 cell count (5% to 6%), decreased CD-8 cell counts (5% to 6%), decreased absolute lymphocyte count (4% to 5%), decreased T cell lymphocytes (4%), reduction of B-cells (4%), abnormal white blood cell differential (lymphocyte percentage decreased: 3%; lymphocyte percentage increased: 2%), immune thrombocytopenia (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%), human papilloma virus infection (2%)
Local: Catheter pain (1%), infusion related reaction
Neuromuscular & skeletal: Myalgia (6% to 7%), myasthenia (7%), muscle spasm (6%), weakness (5% to 6%), neck pain (5%), joint sprain (2%), joint swelling (2%), musculoskeletal chest pain (2%)
Ophthalmic: Blurred vision (5%), conjunctivitis (2%), Graves ophthalmopathy (1%)
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, antithyroid 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, connective tissue disease (undifferentiated), decreased hematocrit, decreased hemoglobin, decreased monocytes, decreased neutrophils, dehydration, depression, desquamation, eosinopenia, eosinophilia, Epstein-Barr-associated lymphoproliferative disorder, Epstein-Barr infection, esophagitis, furuncle, gastroesophageal reflux disease, gastrointestinal disease, gingival hemorrhage, glycosuria, graft versus host disease (transfusion associated), Guillain-Barre syndrome, hemiparesis, hemophilia A (acquired [anti-Factor VIII antibodies]), hyperemia, hypersensitivity reaction, increased monocytes, infusion site reaction, labyrinthitis, leukocytosis, lymphoproliferative disorder, maculopapular rash, major hemorrhage, malignant lymphoma, malignant melanoma, malignant neoplasm of thyroid, membranous glomerulonephritis, memory impairment, meningitis due to listeria monocytogenes, meningitis (herpes), migraine, mucosal inflammation, multiple sclerosis, muscle spasticity, natural killer cell count increased, neutropenia, night sweats, onychomycosis, optic neuropathy, ostealgia, ovarian cyst, pancytopenia, papule, peripheral neuropathy, photophobia, pleurisy, pneumonia, pneumonitis, positive direct Coombs test, postherpetic neuralgia, progressive multifocal leukoencephalopathy, protozoal infection, psychomotor agitation, pyelonephritis, reactivation of disease, reduced ejection fraction, restless leg syndrome, retinal pigment changes (epitheliopathy), rheumatoid arthritis, serum sickness, skin hyperpigmentation, skin lesion, streptococcal pharyngitis, subacute thyroiditis, suicidal ideation, suicidal tendencies, syncope, tachypnea, thrombocytopenia, tongue discoloration, tonsillitis, tooth abscess, tracheobronchitis, tuberculosis, tumor lysis syndrome, type 1 diabetes mellitus, upper airway symptoms (cough syndrome), urethritis, urinary incontinence, varicella, viral infection, vitiligo, voice disorder, weight gain, weight loss
Concerns related to adverse effects:
• Autoimmune effects: [US Boxed Warning (Lemtrada)]: Alemtuzumab causes serious, sometimes fatal, autoimmune conditions, such as immune thrombocytopenia and antiglomerular basement membrane disease, in patients receiving alemtuzumab for the treatment of multiple sclerosis (MS). Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals for 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. Monitor for nephropathy symptoms (eg, elevated serum creatinine, hematuria, proteinuria). Alveolar hemorrhage manifesting as hemoptysis may be present in antiglomerular basement membrane disease. Glomerular nephropathies require urgent evaluation; may lead to renal failure if not treated. Prompt intervention is necessary for autoimmune cytopenias. Immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura), thyroid disorders, autoimmune hemolytic anemia, autoimmune pancytopenia, undifferentiated connective tissue disorders, acquired hemophilia A, rheumatoid arthritis, type 1 diabetes, 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.
• 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-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 GVHD during lymphopenia.
• Cholecystitis: In a clinical trial of MS patients, 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 less than 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.
• Gastrointestinal toxicity: Alemtuzumab is associated with a moderate emetic potential in adults in the oncology setting; antiemetics may be recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016).
• Infections: [US Boxed Warning (Campath)]: 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/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 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. Consider delaying treatment in patients with active infection until infection is controlled. Patients should be screened for human papilloma virus (HPV) and tuberculosis 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-cell chronic lymphocytic leukemia (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 multiple sclerosis, 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. Infusion reactions have been reported more than 24 hours after infusion. 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 have been observed with use in the treatment of multiple sclerosis; 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 24 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 (PML): Has been reported with use (rarely); withhold therapy immediately for signs/symptoms suggestive of PML.
• 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) has also been reported with alemtuzumab use for the treatment of other conditions. For B-CLL treatment, 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.
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.
• HBV or HCV infected patients: Alemtuzumab has not been studied in MS patients infected with HBV or HCV; consider screening patients at increased risk of infection prior to initiating treatment. Use with caution in HBV or HCV carriers; patients may be at risk for viral reactivation.
• Appropriate use: Alemtuzumab is not recommended for use in MS 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.
• 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: 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 if history of chickenpox or VZV vaccination status is unknown. When using for the treatment of multiple sclerosis, complete necessary immunizations at least 6 weeks prior to initiating alemtuzumab. Determine if patient has a history varicella or vaccination for VZV; if not, test for VZV antibodies and consider vaccinations for antibody-negative patients; 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.
Campath: 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); consider 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;
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; 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 longer or at any time during therapy if clinically indicated; observe for at least 2 hours after each infusion, longer if clinically indicated; ECG prior to each treatment course; annual HPV screening; signs/symptoms of PML; baseline and annual skin exams (for melanoma).
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. 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 (Campath) after treatment for women and men of reproductive potential or 4 months (Lemtrada) after a treatment course for women of reproductive potential.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience anxiety, back pain, painful extremities, neck pain, flushing, nausea, vomiting. diarrhea, muscle pain, joint pain, abdominal pain, rhinitis, pharyngitis, lack of appetite, muscle spasms, muscle weakness, change in taste, or insomnia. Have patient report immediately to prescriber signs of gallbladder problems (pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; jaundice; or fever with chills); bloating; severe nausea or vomiting), signs of infusion reactions (chest pain, passing out, abnormal heartbeat, hives, difficulty breathing, swelling of face or mouth, chest tightness, wheezing, change in taste, chills, dizziness, flushing, nausea, insomnia, fatigue),signs of infection, signs of progressive multifocal leukoencephalopathy (confusion, depression, memory impairment, behavioral changes, change in strength on one side is greater than the other, difficulty speaking, change in balance, or vision changes), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), shortness of breath, severe loss of strength and energy, swollen glands, severe dizziness, passing out, thrush, severe headache, bradycardia, angina, tachycardia, burning or numbness feeling, vision changes, abnormal heartbeat, abnormal sweating, signs of tumor lysis syndrome (tachycardia or abnormal heartbeat; any passing out; urinary retention; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish), signs of thyroid problems (change in weight without trying, anxiety, feeling restless, feeling very weak, hair thinning, depression, neck swelling, difficulty focusing, inability handling heat or cold, menstrual changes, tremors, or sweating), signs of thyroid cancer (new lump or swelling in the neck, pain in the front of the neck, persistent cough, persistent change in voice like hoarseness, or difficulty swallowing or breathing), mole changes, depression, night sweats, suicidal ideation, swelling of arms or legs, or skin growths (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
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