Alemtuzumab: Difference between revisions

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Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg Campath intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2 – 1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed in TABLE 1 that occurred at an incidence rate of > 5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm.
Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg Campath intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2 – 1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed in TABLE 1 that occurred at an incidence rate of > 5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm.
|postmarketing=The following adverse reactions were identified during post-approval use of Campath. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Campath exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors:
|postmarketing=The following adverse reactions were identified during post-approval use of Campath. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Campath exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors:
* Seriousness of the reaction
* Seriousness of the reaction,
* Reported frequency of the reaction, or
* Reported frequency of the reaction, or  
* Strength of causal connection to Campath.
* Strength of causal connection to Campath


====Fatal infusion reactions====
====Fatal infusion reactions====
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Optic neuropathy
Optic neuropathy
|drugInteractions=No formal drug interaction studies have been performed with Campath.
|drugInteractions=No formal drug interaction studies have been performed with Campath.
|FDAPregCat=C
|useInPregnancyFDA=Animal reproduction studies have not been conducted with Campath. IgG antibodies, such as Campath, can cross the placental barrier. It is not known whether Campath can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Campath should be given to a pregnant woman only if clearly needed.
|AUSPregCat=B2
|useInNursing=Excretion of Campath in human breast milk has not been studied; it is not known whether this drug is excreted in human milk. IgG antibodies, such as Campath, can be excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Campath, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the elimination half-life of Campath and the importance of the drug to the mother.
|useInPed=Safety and effectiveness have not been established in pediatric patients.
|useInGeri=Of 147 previously untreated B-CLL patients treated with Campath, 35% were ≥ age 65 and 4% were ≥ age 75. Of 149 previously treated patients with B-CLL, 44% were ≥ 65 years of age and 10% were ≥ 75 years of age. Clinical studies of Campath did not include sufficient number of subjects age 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
|administration=Intravenous
|overdose=Across all clinical experience, the reported maximum single dose received was 90 mg. Bone marrow aplasia, infections, or severe infusions reactions occurred in patients who received a dose higher than recommended.
One patient received an 80 mg dose by IV infusion and experienced acute bronchospasm, cough, and dyspnea, followed by anuria and death. Another patient received two 90 mg doses by IV infusion one day apart during the second week of treatment and experienced a rapid onset of bone marrow aplasia.
There is no known specific antidote for Campath overdosage. Treatment consists of drug discontinuation and supportive therapy.
|alcohol=Alcohol-Alemtuzumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=Alcohol-Alemtuzumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
}}
}}
{{drugbox-mab
| image = Alemtuzumab Fab 1CE1.png
| source = Human
| target = CD52 | CAS_number = | ATC_prefix = L01 | ATC_suffix = XC04 | ATC_supplemental = | PubChem = | DrugBank = BTD00109 | C=6468 | H=10066 | N=1732 | O=2005 | S=40 | molecular_weight = 145453.8 g/mol | bioavailability = | protein_bound = | metabolism = | elimination_half-life = ~288 hrs | pregnancy_AU=B2 | legal_status = | routes_of_administration = }}
{{SI}}

Revision as of 16:05, 16 January 2015

Alemtuzumab
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]

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Black Box Warning

WARNING: CYTOPENIAS, INFUSION REACTIONS, AND INFECTIONS
See full prescribing information for complete Boxed Warning.
Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.

Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for Grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days.

Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections.

Overview

Alemtuzumab is a monoclonal antibody that is FDA approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). There is a Black Box Warning for this drug as shown here. Common adverse reactions include cytopenias, infusion reactions, cytomegalovirus (CMV) and other infections, nausea, emesis, diarrhea, and insomnia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Alemtuzumab is indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL).

Dosage

  • Gradually escalate to the maximum recommended single dose of 30 mg.
  • Escalation Strategy:
  • Administer 3 mg daily until infusion reactions are ≤ grade 2.
  • Then administer 10 mg daily until infusion reactions are ≤ grade 2.
  • Then administer 30 mg/day three times per week on alternate days (e.g., Mon-Wed-Fri).
  • The total duration of therapy, including dose escalation, is 12 weeks.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Alemtuzumab in adult patients.

Non–Guideline-Supported Use

  • Autoimmune disease - Cytopenia
  • Malignant tumor of lymphoid hemopoietic and related tissue
  • Relapsed or refractory primary cutaneous T-cell lymphoma
  • Prophylaxis of renal transplant rejection
  • T-cell prolymphocytic leukemia

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Alemtuzumab FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Alemtuzumab in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Alemtuzumab in pediatric patients.

Contraindications

None

Warnings

WARNING: CYTOPENIAS, INFUSION REACTIONS, AND INFECTIONS
See full prescribing information for complete Boxed Warning.
Cytopenias: Serious, including fatal, pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia can occur in patients receiving Campath. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.

Infusion Reactions: Campath administration can result in serious, including fatal, infusion reactions. Carefully monitor patients during infusions and withhold Campath for Grade 3 or 4 infusion reactions. Gradually escalate Campath to the recommended dose at the initiation of therapy and after interruption of therapy for 7 or more days.

Infections: Serious, including fatal, bacterial, viral, fungal, and protozoan infections can occur in patients receiving Campath. Administer prophylaxis against Pneumocystis jiroveci pneumonia (PCP) and herpes virus infections.

Cytopenias

Severe, including fatal, autoimmune anemia and thrombocytopenia, and prolonged myelosuppression have been reported in patients receiving Campath.

In addition, hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have been reported after treatment with Campath at the recommended dose. Single doses of Campath greater than 30 mg or cumulative doses greater than 90 mg per week increase the incidence of pancytopenia.

Withhold Campath for severe cytopenias (except lymphopenia). Discontinue for autoimmune cytopenias or recurrent/persistent severe cytopenias (except lymphopenia). No data exist on the safety of Campath resumption in patients with autoimmune cytopenias or marrow aplasia.

Infusion Reactions

Adverse reactions occurring during or shortly after Campath infusion include pyrexia, chills/rigors, nausea, hypotension, urticaria, dyspnea, rash, emesis, and bronchospasm. In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Monitor for the signs and symptoms listed above and withhold infusion for Grade 3 or 4 infusion reactions.

The following serious, including fatal, infusion reactions have been identified in post-marketing reports: syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock.

Initiate Campath according to the recommended dose-escalation scheme. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, meperidine) for infusion reactions as needed. If therapy is interrupted for 7 or more days, reinstitute Campath with gradual dose escalation.

Immunosuppression/Infections

Campath treatment results in severe and prolonged lymphopenia with a concomitant increased incidence of opportunistic infections. Administer PCP and herpes viral prophylaxis during Campath therapy and for a minimum of 2 months after completion of Campath or until the CD4+ count is ≥ 200 cells/µL, whichever occurs later. Prophylaxis does not eliminate these infections.

Routinely monitor patients for CMV infection during Campath treatment and for at least 2 months following completion of treatment. Withhold Campath for serious infections and during antiviral treatment for CMV infection or confirmed CMV viremia (defined as polymerase chain reaction (PCR) positive CMV in ≥ 2 consecutive samples obtained 1 week apart) [see ADVERSE REACTIONS (6.1)]. Initiate therapeutic ganciclovir (or equivalent) for CMV infection or confirmed CMV viremia.

Administer only irradiated blood products to avoid transfusion associated Graft versus Host Disease (TAGVHD), unless emergent circumstances dictate immediate transfusion.

In patients receiving Campath as initial therapy, recovery of CD4+ counts to ≥ 200 cells/µL occurred by 6 months post-treatment; however at 2 months post-treatment, the median was 183 cells/µL. In previously treated patients receiving Campath, the median time to recovery of CD4+ counts to ≥ 200 cells/µL was 2 months; however, full recovery (to baseline) of CD4+ and CD8+ counts may take more than 12 months.

Laboratory Monitoring

Obtain complete blood counts (CBC) at weekly intervals during Campath therapy and more frequently if worsening anemia, neutropenia, or thrombocytopenia occurs. Assess CD4+ counts after treatment until recovery to ≥ 200 cells/µL.

Immunization

The safety of immunization with live viral vaccines following Campath therapy has not been studied. Do not administer live viral vaccines to patients who have recently received Campath. The ability to generate an immune response to any vaccine following Campath therapy has not been studied.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data below reflect exposure to Campath in 296 patients with CLL of whom 147 were previously untreated and 149 received at least 2 prior chemotherapy regimens. The median duration of exposure was 11.7 weeks for previously untreated patients and 8 weeks for previously treated patients.

Lymphopenia: Severe lymphopenia and a rapid and sustained decrease in lymphocyte subsets occurred in previously untreated and previously treated patients following administration of Campath. In previously untreated patients, the median CD4+ was 0 cells/μL at one month after treatment and 238 cells/μL [25-75% interquartile range 115 to 418 cells/μL at 6 months post-treatment.

Neutropenia: In previously untreated patients, the incidence of Grade 3 or 4 neutropenia was 42% with a median time to onset of 31 days and a median duration of 37 days. In previously treated patients, the incidence of Grade 3 or 4 neutropenia was 64% with a median duration of 28 days. Ten percent of previously untreated patients and 17% of previously treated patients received granulocyte colony stimulating factors.

Anemia: In previously untreated patients, the incidence of Grade 3 or 4 anemia was 12% with a median time to onset of 31 days and a median duration of 8 days. In previously treated patients, the incidence of Grade 3 or 4 anemia was 38%. Seventeen percent of previously untreated patients and 66% of previously treated patients received either erythropoiesis stimulating agents, transfusions or both.

Thrombocytopenia: In previously untreated patients, the incidence of Grade 3 or 4 thrombocytopenia was 14% with a median time to onset of 9 days and a median duration of 14 days. In previously treated patients, the incidence of Grade 3 or 4 thrombocytopenia was 52% with a median duration of 21 days. Autoimmune thrombocytopenia was reported in 2% of previously treated patients with one fatality.

Infusion reactions: Infusion reactions, which included pyrexia, chills, hypotension, urticaria, and dyspnea, were common. Grade 3 and 4 pyrexia and/or chills occurred in approximately 10% of previously untreated patients and in approximately 35% of previously treated patients. The occurrence of infusion reactions was greatest during the initial week of treatment and decreased with subsequent doses of Campath. All patients were pretreated with antipyretics and antihistamines; additionally, 43% of previously untreated patients received glucocorticoid pre-treatment.

Infections: In the study of previously untreated patients, patients were tested weekly for CMV using a PCR assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy. CMV infection occurred in 16% (23/147) of previously untreated patients; approximately one-third of these infections were serious or life threatening. In studies of previously treated patients in which routine CMV surveillance was not required, CMV infection was documented in 6% (9/149) of patients; nearly all of these infections were serious or life threatening.

Other infections were reported in approximately 50% of patients across all studies. Grade 3 - 5 sepsis ranged from 3% to 10% across studies and was higher in previously treated patients. Grade 3 - 4 febrile neutropenia ranged from 5 to 10% across studies and was higher in previously treated patients. Infection-related fatalities occurred in 2% of previously untreated patients and 16% of previously treated patients. There were 198 episodes of other infection in 109 previously untreated patients; 16% were bacterial, 7% were fungal, 4% were other viral, and in 73%, the organism was not identified.

Cardiac: Cardiac dysrhythmias occurred in approximately 14% of previously untreated patients. The majority were tachycardias and were temporally associated with infusion; dysrhythmias were Grade 3 or 4 in 1% of patients.

Previously Untreated Patients

TABLE 1 contains selected adverse reactions observed in 294 patients randomized (1:1) to receive Campath or chlorambucil as first line therapy for B-CLL. Campath was administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks. The median duration of therapy was 11.7 weeks with a median weekly dose of 82 mg (25-75% interquartile range: 69 mg – 90 mg).

Previously Treated Patients

Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg Campath intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2 – 1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed in TABLE 1 that occurred at an incidence rate of > 5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm.

Postmarketing Experience

The following adverse reactions were identified during post-approval use of Campath. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Campath exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors:

  • Seriousness of the reaction,
  • Reported frequency of the reaction, or
  • Strength of causal connection to Campath

Fatal infusion reactions

syncope, pulmonary infiltrates, acute respiratory distress syndrome (ARDS), respiratory arrest, cardiac arrhythmias, myocardial infarction, acute cardiac insufficiency, cardiac arrest, angioedema, and anaphylactoid shock.

Cardiovascular

Congestive heart failure,cardiomyopathy, decreased ejection fraction (some patients had been previously treated with cardiotoxic agents).

Immune disorders

Goodpasture's syndrome, Graves' disease, aplastic anemia, Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, serum sickness, fatal transfusion associated Graft versus Host Disease.

Infections

Epstein-Barr Virus (EBV) including EBV-associated lymphoproliferative disorder, progressive multifocal leukoencephalopathy (PML), re-activation of latent viruses.

Metabolic

Tumor lysis syndrome

Neurologic

Optic neuropathy

Drug Interactions

No formal drug interaction studies have been performed with Campath.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Alemtuzumab in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Alemtuzumab in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Alemtuzumab during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Alemtuzumab in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Alemtuzumab in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Alemtuzumab in geriatric settings.

Gender

There is no FDA guidance on the use of Alemtuzumab with respect to specific gender populations.

Race

There is no FDA guidance on the use of Alemtuzumab with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Alemtuzumab in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Alemtuzumab in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Alemtuzumab in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Alemtuzumab in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Alemtuzumab Administration in the drug label.

Monitoring

There is limited information regarding Alemtuzumab Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Alemtuzumab and IV administrations.

Overdosage

There is limited information regarding Alemtuzumab overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Alemtuzumab Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Alemtuzumab Mechanism of Action in the drug label.

Structure

There is limited information regarding Alemtuzumab Structure in the drug label.

Pharmacodynamics

There is limited information regarding Alemtuzumab Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Alemtuzumab Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Alemtuzumab Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Alemtuzumab Clinical Studies in the drug label.

How Supplied

There is limited information regarding Alemtuzumab How Supplied in the drug label.

Storage

There is limited information regarding Alemtuzumab Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Alemtuzumab |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Alemtuzumab |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Alemtuzumab Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Alemtuzumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Alemtuzumab Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Alemtuzumab Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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