MabCampath

How old is patient?
advertisement

MabCampath uses


WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES


WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES

See full prescribing information for complete boxed warning.

Warnings and Precautions, Acute Acalculous Cholecystitis (5.10) 10/2017
advertisement

1 INDICATIONS AND USAGE

MabCampath is indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of MabCampath should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage Information

The recommended dosage of MabCampath is 12 mg/day administered by intravenous infusion for 2 treatment courses:

2.2 Vaccinations

Patients should complete any necessary immunizations at least 6 weeks prior to treatment with MabCampath .

Prior to MabCampath treatment determine whether patients have a history of varicella or have been vaccinated for varicella zoster virus (VZV). If not, test the patient for antibodies to VZV and consider vaccination for those who are antibody-negative. Postpone treatment with MabCampath until 6 weeks after VZV vaccination.

2.3 Recommended Premedication and Concomitant Medication

Corticosteroids

Premedicate patients with high dose corticosteroids (1,000 mg methylprednisolone or equivalent) immediately prior to MabCampath infusion and for the first 3 days of each treatment course .

Herpes Prophylaxis

Administer anti-viral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with MabCampath or until the CD4+ lymphocyte count is ≥ 200 cells per microliter, whichever occurs later [see Warnings and Precautions (5.9)].

2.4 Preparation Instructions

Follow the steps below to prepare the diluted solution of MabCampath for intravenous infusion:


Prior to administration, protect diluted MabCampath solution from light and store for as long as 8 hours either at room temperature 15°C to 25°C or keep refrigerated at conditions 2°C to 8°C (36°F to 46°F).

2.5 Infusion Instructions

Infuse MabCampath over 4 hours starting within 8 hours after dilution. Extend the duration of the infusion if clinically indicated.

Administer MabCampath in a setting in which equipment and personnel to appropriately manage anaphylaxis or serious infusion reactions are available .

Do not add or simultaneously infuse other drug substances through the same intravenous line. Do not administer as an intravenous push or bolus.

Monitor vital signs before the infusion and periodically during the infusion. Provide appropriate symptomatic treatment for infusion reactions as needed. Consider immediate discontinuation of the intravenous infusion if severe infusion reactions occur.

Observe patients for infusion reactions during and for at least 2 hours after each MabCampath infusion. Consider longer periods of observation if clinically indicated. Inform patients that they should report symptoms that occur during and after each infusion because they may indicate a need for prompt medical intervention .

2.6 Laboratory Testing and Monitoring to Assess Safety

Conduct the following laboratory tests at baseline and at periodic intervals for 48 months following the last treatment course of MabCampath in order to monitor for early signs of potentially serious adverse effects:


Conduct baseline and yearly skin exams to monitor for melanoma .

advertisement

3 DOSAGE FORMS AND STRENGTHS

Injection: 12 mg/1.2 mL (10 mg/mL) in a single-use vial. MabCampath is a clear and colorless to slightly yellow solution that requires dilution prior to intravenous infusion.

Injection: 12 mg/1.2 mL (10 mg/mL) in a single-use vial. (3)

4 CONTRAINDICATIONS

MabCampath is contraindicated in patients who are infected with Human Immunodeficiency Virus (HIV) because MabCampath causes prolonged reductions of CD4+ lymphocyte counts.

Infection with Human Immunodeficiency Virus. (4)

5 WARNINGS AND PRECAUTIONS

5.1 Autoimmunity

Treatment with MabCampath can result in the formation of autoantibodies and increase the risk of serious autoimmune mediated conditions. In clinical studies, LEMTRADA-treated patients experienced thyroid disorders (34%), immune thrombocytopenia (2%), and glomerular nephropathies (0.3%) . Autoimmune hemolytic anemia and autoimmune pancytopenia , undifferentiated connective tissue disorders, and acquired hemophilia A (anti-Factor VIII antibodies) each occurred in 0.2% of patients. Rheumatoid arthritis, type I diabetes, vitiligo, and retinal pigment epitheliopathy occurred in 0.1% of patients.

During postmarketing use, additional autoimmune events including Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy have been reported in the treatment of patients with B-cell chronic lymphocytic leukemia (B-CLL), as well as other disorders, generally at higher and more frequent doses than recommended in MS. An oncology patient treated with MabCampath had fatal transfusion-associated graft-versus-host disease.

Autoantibodies may be transferred from the mother to the fetus during pregnancy. A case of transplacental transfer of anti-thyrotropin receptor antibodies resulting in neonatal Graves' disease occurred after MabCampath treatment in the mother .

MabCampath may increase the risk of other autoimmune conditions because of the broad range of autoantibody formation with MabCampath.

Monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts before starting treatment and then at monthly intervals for 48 months after the last dose of MabCampath to allow for early detection and treatment of autoimmune adverse reactions . After 48 months, testing should be performed based on clinical findings suggestive of autoimmunity.

MabCampath is available only through a restricted program under a REMS .

5.2 Infusion Reactions

MabCampath causes cytokine release syndrome resulting in infusion reactions, some of which may be serious and life threatening. In clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions. In some patients, infusion reactions were reported more than 24 hours after MabCampath infusion. Serious reactions occurred in 3% of patients and included anaphylaxis in 2 patients, angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia (including atrial fibrillation), transient neurologic symptoms, hypertension, headache, pyrexia, and rash. Other infusion reactions included nausea, urticaria, pruritus, insomnia, chills, flushing, fatigue, dyspnea, pulmonary infiltrates, dysgeusia, dyspepsia, dizziness, and pain. In clinical studies, 0.6% of patients with infusion reactions received epinephrine or atropine.

During postmarketing use, other serious and sometimes fatal infusion reactions included hypoxia, syncope, acute respiratory distress syndrome, respiratory arrest, myocardial infarction, acute cardiac insufficiency, and cardiac arrest have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses than recommended in MS.

Premedicate patients with corticosteroids immediately prior to MabCampath infusion for the first 3 days of each treatment course. In clinical studies, patients received 1,000 mg of methylprednisolone for the first 3 days of each MabCampath treatment course. Consider pretreatment with antihistamines and/or antipyretics prior to MabCampath administration. Infusion reactions may occur despite pretreatment.

Consider additional monitoring in patients with medical conditions which predispose them to cardiovascular or pulmonary compromise.

MabCampath can only be administered in certified healthcare settings that have on-site access to equipment and personnel trained to manage infusion reactions (including anaphylaxis and cardiac and respiratory emergencies).

MabCampath is available only through a restricted program under a REMS .

5.3 Malignancies

Thyroid Cancer

MabCampath may increase the risk of thyroid cancer. In controlled clinical studies, 3 of 919 (0.3%) LEMTRADA-treated patients developed thyroid cancer, compared to none in the interferon beta-1a-treated group. However, screening for thyroid cancer was performed more frequently in the LEMTRADA-treated group, because of the higher incidence of autoimmune thyroid disorders in those patients. Two additional cases of thyroid cancer in LEMTRADA-treated patients occurred in uncontrolled studies.

Patients and healthcare providers should monitor for symptoms of thyroid cancer including a new lump or swelling in the neck, pain in the front of the neck, persistent hoarseness or other voice changes, trouble swallowing or breathing, or a constant cough not due to an upper respiratory tract infection.

Melanoma

MabCampath may increase the risk of melanoma. In uncontrolled studies, 4 of 1486 (0.3%) LEMTRADA-treated patients developed melanoma or melanoma in situ. One of those patients had evidence of locally advanced disease.

Perform baseline and yearly skin examinations to monitor for melanoma in patients receiving MabCampath.

Lymphoproliferative Disorders and Lymphoma

Cases of lymphoproliferative disorders and lymphoma have occurred in LEMTRADA-treated patients with MS, including a MALT lymphoma, Castleman's Disease, and a fatality following treatment of non-Epstein Barr Virus-associated Burkitt's lymphoma. There are postmarketing reports of Epstein Barr Virus-associated lymphoproliferative disorders in non-MS patients.

Because MabCampath is an immunomodulatory therapy, caution should also be exercised in initiating MabCampath in patients with preexisting or ongoing malignancies.

MabCampath is available only through a restricted program under a REMS .

5.4 MabCampath REMS Program

MabCampath is available only through a restricted program under a REMS called the MabCampath REMS Program because of the risks of autoimmunity, infusion reactions, and malignancies .

Notable requirements of the MabCampath REMS Program include the following:


Further information, including a list of qualified healthcare facilities, is available at 1-855-676-6326.

5.5 Immune Thrombocytopenia

Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated patients in clinical studies in MS.

In a controlled clinical study in patients with MS, one LEMTRADA-treated patient developed ITP that went unrecognized prior to the implementation of monthly blood monitoring requirements, and died from intracerebral hemorrhage. Nadir platelet counts ≤20,000 cells per microliter as a result of ITP occurred in 2% of all LEMTRADA-treated patients in clinical studies in MS. Anti-platelet antibodies did not precede ITP onset. ITP has been diagnosed more than 3 years after the last MabCampath dose.

Symptoms of ITP include easy bruising, petechiae, spontaneous mucocutaneous bleeding (e.g., epistaxis, hemoptysis), and heavier than normal or irregular menstrual bleeding. Hemoptysis may also be indicative of anti-glomerular basement membrane (GBM) disease , and an appropriate differential diagnosis has to be undertaken. Remind the patient to remain vigilant for symptoms they may experience and to seek immediate medical help if they have any concerns.

Obtain complete blood counts (CBCs) with differential prior to initiation of treatment and at monthly intervals thereafter until 48 months after the last infusion . After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP is suspected, a complete blood count should be obtained immediately. If ITP onset is confirmed, promptly initiate appropriate medical intervention.

5.6 Glomerular Nephropathies

Glomerular nephropathies occurred in 0.3% of LEMTRADA-treated patients in MS clinical studies. There were 3 cases of membranous glomerulonephritis and 2 cases of anti-glomerular basement membrane disease. There are published and postmarketing cases of MS patients treated with MabCampath who developed anti-GBM disease and subsequently developed end-stage renal disease requiring renal transplantation. Cases of anti-GBM disease have been diagnosed up to 40 months after the last dose of MabCampath. Urgent evaluation and treatment is required because anti-GBM disease can lead to renal failure requiring dialysis or transplantation and can be life-threatening if left untreated.

Clinical manifestations of nephropathy may include elevated serum creatinine levels, hematuria, or proteinuria. Alveolar hemorrhage manifested as hemoptysis is a common component of anti-GBM disease but did not occur in clinical studies.

Obtain serum creatinine levels and urinalysis with cell counts prior to initiation of treatment and at monthly intervals thereafter until 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of nephropathies.

If clinically significant changes from baseline in serum creatinine, unexplained hematuria, or proteinuria are observed, perform further evaluation for nephropathies. Early detection and treatment of nephropathies may decrease the risk of poor outcomes.

5.7 Thyroid Disorders

Autoimmune thyroid disorders occurred in 34% of LEMTRADA-treated patients in clinical studies. Newly diagnosed thyroid disorders occurred throughout the uncontrolled clinical study follow-up period, more than 7 years after the first MabCampath dose. Autoimmune thyroid disorders included Graves' disease, hyperthyroidism and hypothyroidism. Graves' ophthalmopathy with decreased vision, eye pain, and exophthalmos occurred in 1% of LEMTRADA-treated patients. Two patients required surgical orbital decompression. Serious thyroid events occurred in about 2% of LEMTRADA-treated patients in clinical studies and included cardiac and psychiatric events associated with thyroid disease. Of all LEMTRADA-treated patients, 3% underwent thyroidectomy.

Thyroid disease poses special risks in women who are pregnant .

Obtain thyroid function tests, such as TSH levels, prior to initiation of treatment and every 3 months thereafter until 48 months after the last infusion. Continue to test thyroid function after 48 months if clinically indicated.

In patients with ongoing thyroid disorder, MabCampath should be administered only if the potential benefit justifies the potential risks.

5.8 Other Autoimmune Cytopenias

Autoimmune cytopenias such as neutropenia, hemolytic anemia (0.2%), and pancytopenia (0.2%) occurred in LEMTRADA-treated patients in clinical studies in MS. In cases of autoimmune hemolytic anemia, patients tested positive for direct antiglobulin antibodies, and nadir hemoglobin levels ranged from 2.9-8.6 g/dL. Symptoms of autoimmune hemolytic anemia include weakness, chest pain, jaundice, dark urine, and tachycardia. One LEMTRADA-treated patient with autoimmune pancytopenia died from sepsis.

During postmarketing use, additional autoimmune cytopenias including fatal autoimmune hemolytic anemia and aplastic anemia have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses than recommended in MS.

Use CBC results to monitor for cytopenias. Prompt medical intervention is indicated if a cytopenia is confirmed.

5.9 Infections

Infections occurred in 71% of LEMTRADA-treated patients compared to 53% of patients treated with interferon beta-1a in controlled clinical studies in MS up to 2 years in duration. Infections that occurred more often in LEMTRADA-treated patients than interferon beta-1a patients included nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, herpetic infections, influenza, and bronchitis. Serious infections occurred in 3% of patients treated with MabCampath as compared to 1% of patients treated with interferon beta-1a. Serious infections in the MabCampath group included: appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infection.

Do not administer live viral vaccines following a course of MabCampath. Patients treated with MabCampath have altered immunity and may be at increased risk of infection following administration of live viral vaccines.

Consider delaying MabCampath administration in patients with active infection until the infection is fully controlled.

Concomitant use of MabCampath with antineoplastic or immunosuppressive therapies could increase the risk of immunosuppression.

Herpes Viral Infections

In controlled clinical studies, 16% of LEMTRADA-treated patients developed a herpes viral infection compared to 3% of interferon beta-1a patients. These events included oral herpes (8.8%), herpes zoster (4.2%), herpes simplex (1.8%), and genital herpes (1.3%). Serious herpetic infections in LEMTRADA-treated patients included primary varicella (0.1%), herpes zoster (0.2%), and herpes meningitis (0.1%). Administer antiviral agents for herpetic prophylaxis at appropriate suppressive dosing regimens. Administer antiviral prophylaxis for herpetic viral infections starting on the first day of each treatment course and continue for a minimum of two months following treatment with MabCampath or until the CD4+ lymphocyte count is ≥ 200 cells per microliter, whichever occurs later [see Dosage and Administration (2.3)].

Human Papilloma Virus

Cervical human papilloma virus (HPV) infection, including cervical dysplasia, occurred in 2% of LEMTRADA-treated patients. Annual HPV screening is recommended for female patients.

Tuberculosis

Tuberculosis occurred in patients treated with MabCampath and interferon beta-1a in controlled clinical studies. Active and latent tuberculosis cases occurred in 0.3% of LEMTRADA-treated patients, most often in endemic regions. Perform tuberculosis screening according to local guidelines prior to initiation of MabCampath. For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with MabCampath.

Fungal Infections

Fungal infections, especially oral and vaginal candidiasis, occurred more commonly in LEMTRADA-treated patients (12%) than in patients treated with interferon beta-1a (3%) in controlled clinical studies in MS.

Listeria Infections

Listeria meningitis has been reported in LEMTRADA-treated patients. Cases of listeria meningitis occurred within 1 month of MabCampath dosing. The duration of increased risk for listeria meningitis is unclear. Patients should avoid or adequately heat foods that are potential sources of Listeria monocytogenes.

Infections in Non-MS Patients

During postmarketing use, serious and sometimes fatal viral, bacterial, protozoan, and fungal infections, including some due to reactivation of latent infections, have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses than recommended in MS.

Hepatitis

No data are available on the association of MabCampath with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) reactivation because patients with evidence of active or chronic infections were excluded from the clinical studies. Consider screening patients at high risk of HBV and/or HCV infection before initiation of MabCampath and exercise caution in prescribing MabCampath to patients identified as carriers of HBV and/or HCV as these patients may be at risk of irreversible liver damage relative to a potential virus reactivation as a consequence of their pre-existing status.

5.10 Acute Acalculous Cholecystitis

MabCampath may increase the risk of acute acalculous cholecystitis. In controlled clinical studies, 0.2% of LEMTRADA-treated MS patients developed acute acalculous cholecystitis, compared to 0% of patients treated with interferon beta-1a. During postmarketing use, additional cases of acute acalculous cholecystitis have been reported in LEMTRADA-treated patients. Time to onset of symptoms ranged from less than 24 hours to 2 months after MabCampath infusion. Typical risk or predisposing factors such as concurrent critical illness were often not reported. Abnormal ultrasound or computed tomography was used to support the diagnosis of acute acalculous cholecystitis in some cases. Some patients were treated conservatively with antibiotics and recovered without surgical intervention, whereas others underwent cholecystectomy.

Symptoms of acute acalculous cholecystitis include abdominal pain, abdominal tenderness, fever, nausea, and vomiting. Leukocytosis and abnormal liver enzymes are also commonly observed. Acute acalculous cholecystitis is a condition that is associated with high morbidity and mortality rates if not diagnosed early and treated. If acute acalculous cholecystitis is suspected, evaluate and treat promptly.

5.11 Pneumonitis

In clinical studies, 6 of 1217 LEMTRADA-treated patients had pneumonitis of varying severity. Cases of hypersensitivity pneumonitis and pneumonitis with fibrosis occurred in clinical studies. Patients should be advised to report symptoms of pneumonitis, which include shortness of breath, cough, wheezing, chest pain or tightness, and hemoptysis.

5.12 Drug Products with Same Active Ingredient

MabCampath contains the same active ingredient (alemtuzumab) found in CAMPATH®. If MabCampath is considered for use in a patient who has previously received CAMPATH, exercise increased vigilance for additive and long-lasting effects on the immune system.

advertisement

6 ADVERSE REACTIONS

The following serious adverse reactions are described below and elsewhere in the labeling:


Most common adverse reactions (incidence ≥ 10% and > interferon beta-1a): rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-800-745-4447 (option 2) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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.

In controlled clinical trials (Study 1 and Study 2), a total of 811 patients with relapsing forms of MS received MabCampath. A total of 811 patients received 1 course of therapy, and 789 patients received a second course of therapy at 12 months. The overall follow-up in the controlled trials was equivalent to 1622 patient years, with an additional 3411 person-years of follow-up in an open-label extension study. The population was 18-55 years of age, 65% were female, and 92% were Caucasian.

Most Common Adverse Reactions

In clinical trials, the most common adverse reactions with MabCampath (in at least 10% of patients and more frequently than in interferon beta-1a) were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.

Table 1 lists adverse reactions occurring in ≥5% of LEMTRADA-treated patients in Study 1 and 2 and at the same or at a higher rate than interferon beta-1a.

MabCampath

(N=811)

%

interferon beta-1a 44 mcg

(N=389)

%

Rash 53 6
Headache 52 23
Pyrexia 29 9
Nasopharyngitis 25 19
Nausea 21 9
Urinary tract infection 19 8
Fatigue 18 13
Insomnia 16 15
Upper respiratory tract infection 16 13
Herpes viral infection 16 3
Urticaria 16 2
Pruritus 14 2
Thyroid gland disorders 13 3
Fungal infection 13 4
Arthralgia 12 9
Pain in extremity 12 9
Back pain 12 8
Diarrhea 12 6
Sinusitis 11 8
Oropharyngeal pain 11 5
Paresthesia 10 8
Dizziness 10 5
Abdominal pain 10 5
Flushing 10 4
Vomiting 10 3
Cough 9 4
Chills 9 3
Dysgeusia 8 7
Influenza 8 6
Dermatitis 8 5
Dyspepsia 8 4
Blood in urine 8 3
Dyspnea 8 1
Tachycardia 8 1
Anxiety 7 6
Muscular weakness 7 6
Bronchitis 7 4
Chest discomfort 7 2
Muscle spasms 6 5
Myalgia 6 5
Decrease in CD4 lymphocytes 6 2
Decrease in CD8 lymphocytes 6 2
Asthenia 5 4
Decrease in T-lymphocyte count 5 3
Erythema 5 2
Peripheral edema 5 2
Epistaxis 5 2
Neck Pain 5 2
Abnormal uterine bleeding 5 1

6.2 Lymphopenia

Nearly all patients treated with MabCampath in MS clinical trials experienced lymphopenia. The lowest lymphocyte counts occurred approximately by 1 month after each course of treatment. The mean lymphocyte count at 1 month after MabCampath treatment was 0.25 × 109 L (range 0.02-2.30 × 109 L) and 0.32 (0.02-1.81 × 109 L) for treatment courses 1 and 2, respectively. Total lymphocyte counts increased to reach the lower limit of normal in approximately 40% of patients by 6 months after each MabCampath treatment course and approximately 80% of patients by 12 months after each course .

6.3 Suicidal Behavior or Ideation

In clinical studies, 0.6% of patients in both the MabCampath and interferon beta-1a groups had events of attempted suicide or suicidal ideation. There were no completed suicides in either clinical study treatment group. Suicidal behavior or ideation occurred in patients with or without a history of a psychiatric or thyroid disorder. Advise patients to report immediately any symptoms of depression or suicidal ideation to the prescribing physician.

6.4 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. Using an enzyme-linked immunosorbent assay and a competitive binding assay, anti-alemtuzumab binding antibodies were detected in 62%, 67%, and 29% of LEMTRADA-treated patients, at months 1, 3, 12 (Course 1) as well as 83%, 83%, and 75% of LEMTRADA-treated patients at months 13, 15, and 24 (Course 2). Samples that tested positive for binding antibodies were further evaluated for evidence of in vitro inhibition using a flow cytometry assay. Neutralizing antibodies were detected in 87%, 46%, and 5% of positive binding antibody patients at months 1, 3, 12 (Course 1) as well as 94%, 88%, and 42% of positive binding antibody patients at months 13, 15, and 24 (Course 2). Anti-alemtuzumab antibodies were associated with decreased MabCampath concentration during Course 2 but not Course 1. There was no evidence from clinical trials that the presence of binding or inhibitory anti-alemtuzumab antibodies had a significant effect on clinical outcomes, total lymphocyte count, or adverse events.

The incidence of antibodies is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including inhibitory antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to MabCampath with the incidence of antibodies to other products may be misleading.

6.5 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of MabCampath. 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 drug exposure.

Postmarketing Experience with MabCampath

Gastrointestinal System Disorders: Acute acalculous cholecystitis.

Postmarketing Experience with CAMPATH

CAMPATH is approved for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) and is generally administered at higher and more frequent doses (e.g., 30 mg) than recommended in the treatment of MS.

Cardiac Disorders: Congestive heart failure, cardiomyopathy, and decreased ejection fraction in non-MS patients previously treated with potentially cardiotoxic agents.

advertisement

8 USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm.

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. MabCampath was embryolethal in pregnant huCD52 transgenic mice when administered during organogenesis. Auto-antibodies may develop after administration of MabCampath. Placental transfer of anti-thyroid antibodies resulting in neonatal Graves' disease has been reported. MabCampath should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal Data

When MabCampath was administered to pregnant huCD52 transgenic mice during organogenesis (gestation days [GD] 6-10 or GD 11-15) at doses of 3 or 10 mg/kg IV, no teratogenic effects were observed. However, there was an increase in embryolethality (increased post-implantation loss and the number of dams with all fetuses dead or resorbed) in pregnant animals dosed during GD 11-15.

In a separate study in pregnant huCD52 transgenic mice, administration of MabCampath during organogenesis (GD 6-10 or GD 11-15) at doses of 3 or 10 mg/kg/IV, decreases in B lymphocytes and T-lymphocyte populations were observed in the offspring at both doses tested. The effects of MabCampath, administered during organogenesis, on postnatal development have not been adequately assessed.

Clinical Considerations

To avoid in utero exposure to MabCampath, women of child bearing potential should use effective contraceptive measures when receiving a course of treatment with MabCampath and for 4 months following that course of treatment.

MabCampath induces persistent thyroid disorders . Untreated hypothyroidism in pregnant women increases the risk for miscarriage and may have effects on the fetus including mental retardation and dwarfism. In mothers with Graves' disease, maternal thyroid stimulating hormone receptor antibodies can be transferred to a developing fetus and can cause neonatal Graves' disease. In a patient who developed Graves' disease after treatment with MabCampath, placental transfer of anti-thyrotropin receptor antibodies resulted in neonatal Graves' Disease with thyroid storm in her infant who was born 1 year after MabCampath dosing .

8.3 Nursing Mothers

MabCampath was detected in the milk of lactating mice administered 10 mg/kg MabCampath on Days 8 through 12 postpartum. Serum levels of MabCampath were similar in lactating mice and offspring on Day 13 postpartum, and were associated with evidence of pharmacological activity in the offspring.

It is not known whether MabCampath is 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 MabCampath, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients less than 17 years of age have not been established. Use of MabCampath is not recommended in pediatric patients due to the risks of autoimmunity, infusion reactions, and because it may increase the risk of malignancies (thyroid, melanoma, lymphoproliferative disorders, and lymphoma) .

8.5 Geriatric Use

Clinical studies of MabCampath did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

10 OVERDOSAGE

Two MS patients experienced serious reactions (headache, rash, and either hypotension or sinus tachycardia) after a single accidental infusion up to 60 mg of MabCampath. Doses of MabCampath greater than those recommended may increase the intensity and/or duration of infusion reactions or its immune effects. There is no known antidote for MabCampath overdosage.

11 DESCRIPTION

MabCampath (alemtuzumab) is a recombinant humanized IgG1 kappa monoclonal antibody directed against the cell surface glycoprotein, CD52. MabCampath has an approximate molecular weight of 150 kD. MabCampath is produced in mammalian cell (Chinese hamster ovary) suspension culture in a nutrient medium containing neomycin. Neomycin is not detectable in the final product. MabCampath is a sterile, clear and colorless to slightly yellow, solution (pH 7.2±0.2) for infusion.

Each 1 mL of solution contains MabCampath 10 mg, dibasic sodium phosphate (1.15 mg), disodium edetate dihydrate (0.0187 mg), polysorbate 80 (0.1 mg), potassium chloride (0.2 mg), potassium dihydrogen phosphate (0.2 mg), sodium chloride (8 mg), and water for injection.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The precise mechanism by which MabCampath exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD52, a cell surface antigen present on T and B lymphocytes, and on natural killer cells, monocytes, and macrophages. Following cell surface binding to T and B lymphocytes, MabCampath results in antibody-dependent cellular cytolysis and complement-mediated lysis.

12.2 Pharmacodynamics

Effects of MabCampath on the Lymphocyte Population

MabCampath depletes circulating T and B lymphocytes after each treatment course. In clinical trials, the lowest cell counts occurred 1 month after a course of treatment at the time of the first post-treatment blood count. Lymphocyte counts then increased over time: B cell counts usually recovered within 6 months; T cell counts increased more slowly and usually remained below baseline 12 months after treatment. Approximately 60% of patients had total lymphocyte counts below the lower limit of normal 6 months after each treatment course and 20% had counts below the lower limit of normal after 12 months.

Reconstitution of the lymphocyte population varies for the different lymphocyte subtypes. At Month 1 in clinical trials, the mean CD4+ lymphocyte count was 40 cells per microliter, and, at Month 12, 270 cells per microliter. At 30 months, approximately half of patients had CD4+ lymphocyte counts that remained below the lower limit of normal.

Cardiac Electrophysiology

In a study of 53 MS patients, MabCampath 12 mg per day for 5 days caused no changes in the QTc interval greater than 20 ms. An average 22 to 26 beats-per-minute increase in heart rate was observed for at least 2 hours after the first but not subsequent infusions.

12.3 Pharmacokinetics

The pharmacokinetics of MabCampath were evaluated in a total of 148 patients with relapsing forms of MS who received 12 mg/day on 5 consecutive days, followed by 12 mg/day on 3 consecutive days 12 months following the first treatment course.

Absorption

Serum concentrations increased with each consecutive dose within a treatment course, with the highest observed concentrations occurring following the last infusion of a treatment course. The mean maximum concentration was 3014 ng/mL on Day 5 of the first treatment course, and 2276 ng/mL on Day 3 of the second treatment course.

Distribution

MabCampath is largely confined to the blood and interstitial space with a central volume of distribution of 14.1 L.

Elimination

The elimination half-life was approximately 2 weeks and was comparable between courses. The serum concentrations were generally undetectable (< 60 ng/mL) within approximately 30 days following each treatment course.

Specific Populations

Age, race, or gender had no effect on the pharmacokinetics of MabCampath.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to assess the carcinogenic or genotoxic potential of MabCampath have not been conducted.

When MabCampath (3 or 10 mg/kg IV) was administered to huCD52 transgenic male mice on 5 consecutive days prior to cohabitation with untreated wild-type females, no effect on fertility or reproductive performance was observed. However, adverse effects on sperm parameters (including abnormal morphology [detached /no head] and reduced total count and motility) were observed at both doses tested.

When MabCampath (3 or 10 mg/kg IV) was administered to huCD52 transgenic female mice for 5 consecutive days prior to cohabitation with untreated wild-type males, there was a decrease in the average number of corpora lutea and implantation sites and an increase in post-implantation loss, resulting in fewer viable embryos at the higher dose tested.

14 CLINICAL STUDIES

The efficacy of MabCampath was demonstrated in two studies (Study 1 and 2) that evaluated MabCampath 12 mg in patients with relapsing-remitting multiple sclerosis (RRMS). MabCampath was administered by intravenous infusion once daily over a 5-day course, followed one year later by intravenous infusion once daily over a 3-day course. Both studies included patients who had experienced at least 2 relapses during the 2 years prior to trial entry and at least 1 relapse during the year prior to trial entry. Neurological examinations were performed every 12 weeks and at the time of suspected relapse. Magnetic resonance imaging (MRI) evaluations were performed annually.

Study 1

Study 1 was a 2 year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. Patients entering Study 1 had Expanded Disability Status Scale (EDSS) scores of 5 or less and had to have experienced at least one relapse while on interferon beta or glatiramer acetate therapy.

Patients were randomized to receive MabCampath (n=426) or interferon beta-1a (n=202). At baseline, the mean age was 35 years, the mean disease duration was 4.5 years, and the mean EDSS score was 2.7.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression. Confirmed disability progression was defined as at least a 1 point increase above baseline EDSS (1.5 point increase for patients with baseline EDSS of 0) sustained for 6 months. The MRI outcome measure was the change in T2 lesion volume.

The annualized relapse rate was significantly lower in patients treated with MabCampath than in patients who received interferon beta-1a. Time to onset of 6-month confirmed disability progression was significantly delayed with MabCampath treatment compared to interferon beta-1a. There was no significant difference between the treatment groups for the change in T2 lesion volume. The results of Study 1 are shown in Table 2 and Figure 1.

MabCampath

(N=426)

interferon beta-1a 44 mcg

(N=202)

p-value
Clinical Outcomes
Annualized relapse rate

Relative reduction

0.26

49%

0.52 <0.0001
Proportion of patients with disability progression at Year 2

Relative risk reduction

13%

42%

21% 0.0084
Percent of patients remaining relapse-free at Year 2 65% 47% <0.0001
MRI Outcomes
Percent change in T2 lesion volume from baseline -1.3 -1.2 0.14
Figure 1: Time to 6-month Confirmed Disability Progression (Study 1)

Figure 1

Study 2

Study 2 was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. Patients entering Study 2 had EDSS scores of 3 or less and no prior treatment for multiple sclerosis.

Patients were randomized to receive MabCampath (n=376) or interferon beta-1a (n=187). At baseline, the mean age was 33 years, the mean disease duration was 2 years, and the mean EDSS score was 2.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression, as defined in Study 1. The MRI outcome measure was the change in T2 lesion volume.

The annualized relapse rate was significantly lower in patients treated with MabCampath than in patients who received interferon beta-1a. There was no significant difference between the treatment groups for the time to confirmed disability progression and for the primary MRI endpoint (change in T2 lesion volume). The results for Study 2 are shown in Table 3.

MabCampath interferon beta-1a 44 mcg p-value
(N=376) (N=187)
Clinical Outcomes
Annualized relapse rate

Relative reduction

0.18

55%

0.39 <0.0001
Proportion of patients with disability progression at Year 2

Relative risk reduction

8%

30%

11% 0.22
Percent of patients remaining relapse-free at Year 2 78% 59% <0.0001
MRI Outcomes
Percent change in T2 lesion volume from baseline -9.3 -6.5 0.31

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Each MabCampath carton contains 1 single-use vial that delivers 12 mg/1.2 mL (10 mg/mL). The vial stopper is not made with natural rubber latex.

MabCampath is a sterile, clear and colorless to slightly yellow solution for infusion, containing no antimicrobial preservatives.

16.2 Storage and Handling

Store MabCampath vials at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Store in original carton to protect from light.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Autoimmunity


Infusion Reactions


Malignancies


MabCampath REMS Program


Infections


Acute Acalculous Cholecystitis


Pneumonitis


Concomitant Use of Campath


Manufactured and distributed by:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

US License Number: 1596

MabCampath and CAMPATH are registered trademarks of Genzyme Corporation.© 2017 Genzyme Corporation.

MEDICATION GUIDE

MabCampath® (lem-TRA-da)

(alemtuzumab)

Injection for intravenous infusion

Read this Medication Guide before you start receiving MabCampath and before you begin each treatment course. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about MabCampath?

MabCampath can cause serious side effects, including:


You should have your skin checked before you start receiving MabCampath and each year while you are receiving treatment to monitor symptoms of skin cancer.


What is MabCampath?

MabCampath is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS). Because of its risks, MabCampath is generally used in people who have tried 2 or more MS medicines that have not worked well enough. It is not known if MabCampath is safe and effective for use in children under 17 years of age.

Who should not receive MabCampath?

Do not receive MabCampath if you are infected with human immunodeficiency virus (HIV).

What should I tell my healthcare provider before receiving MabCampath?

Before receiving MabCampath, tell your healthcare provider if you:


Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

MabCampath and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take medicines that increase your chance of getting infections, including medicines used to treat cancer or to control your immune system.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How will I receive MabCampath?


What are the possible side effects of MabCampath?

MabCampath may cause serious side effects including:


The most common side effects of MabCampath include:

  • rash
  • headache
  • thyroid problems
  • fever
  • swelling of your nose and throat (nasopharyngitis)
  • nausea
  • urinary tract infection
  • feeling tired
  • trouble sleeping
  • upper respiratory tract infection
  • herpes viral infection
  • hives
  • itching
  • fungal infection
  • joint pain
  • pain in your arms or legs
  • back pain
  • diarrhea
  • sinus infection
  • mouth pain or sore throat
  • tingling sensation
  • dizziness
  • stomach pain
  • sudden redness in face, neck, or chest
  • vomiting

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of MabCampath. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

General information about the safe and effective use of MabCampath.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use MabCampath for a condition for which it was not prescribed. Do not give MabCampath to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about MabCampath. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about MabCampath that is written for health professionals.

For more information, go to www. LemtradaREMS.com or call Sanofi Genzyme at 1-855-676-6326.

What are the ingredients in MabCampath?

Active ingredient: MabCampath

Inactive ingredients: sodium chloride, dibasic sodium phosphate, potassium chloride, potassium dihydrogen phosphate, polysorbate 80, disodium edetate dihydrate, and water for injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured and distributed by:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

US License Number: 1596

MabCampath and CAMPATH are registered trademarks of Genzyme Corporation.

©2017 Genzyme Corporation. All rights reserved.

Revised: 10/2017

MabCampath pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


MabCampath available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


MabCampath destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


MabCampath Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


MabCampath pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."LEMTRADA (ALEMTUZUMAB) INJECTION, SOLUTION, CONCENTRATE [GENZYME CORPORATION]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "Alemtuzumab". https://pubchem.ncbi.nlm.nih.gov/su... (accessed August 28, 2018).
  3. "Alemtuzumab - DrugBank". http://www.drugbank.ca/drugs/DB0008... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming MabCampath?

Depending on the reaction of the MabCampath after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider MabCampath not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is MabCampath addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on MabCampath, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of MabCampath consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 18 here

The information was verified by Dr. Rachana Salvi, MD Pharmacology

© 2002 - 2022 "sdrugs.com". All Rights Reserved