Vital Signs |
3.3.1) SUMMARY
A) WITH THERAPEUTIC USE 1) Fever and chills may occur with alemtuzumab therapy.
3.3.3) TEMPERATURE
A) WITH THERAPEUTIC USE 1) According to pooled data of two 2-year randomized active-controlled studies, fever and chills were reported in 29% and 9%, respectively, of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Heent |
3.4.3) EYES
A) WITH THERAPEUTIC USE 1) GRAVES' OPHTHALMOPATHY : During clinical trials, Graves' ophthalmopathy, with signs and symptoms of decreased vision, eye pain, and exophthalmos, was reported in 1% of patients treated with alemtuzumab, with 2 patients requiring surgical orbital decompression (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) RETINAL PIGMENT EPITHELIOPATHY: During clinical trials, retinal pigment epitheliopathy has been reported in 0.1% of patients treated with alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3.4.5) NOSE
A) WITH THERAPEUTIC USE 1) NASOPHARYNGITIS: According to pooled data of two 2-year randomized active-controlled studies, nasopharyngitis was reported in 25% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) SINUSITIS: According to pooled data of two 2-year randomized active-controlled studies, sinusitis was reported in 11% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3) EPISTAXIS: According to pooled data of two 2-year randomized active-controlled studies, epistaxis was reported in 5% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3.4.6) THROAT
A) WITH THERAPEUTIC USE 1) According to pooled data of two 2-year randomized active-controlled studies, oropharyngeal pain was reported in 11% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) TACHYCARDIA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, tachycardia was reported in 8% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) WITH POISONING/EXPOSURE a) Headache, rash, and hypotension or sinus tachycardia were reported in 2 patients with MS who inadvertently received alemtuzumab as a single infusion up to 60 mg (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) PERIPHERAL EDEMA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, peripheral edema was reported in 5% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) LOW BLOOD PRESSURE 1) WITH POISONING/EXPOSURE a) Headache, rash, and hypotension or sinus tachycardia were reported in 2 patients with MS who inadvertently received alemtuzumab as a single infusion up to 60 mg (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) CHEST DISCOMFORT 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, chest discomfort was reported in 7% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
E) CARDIOVASCULAR FINDING 1) WITH THERAPEUTIC USE a) During post-marketing surveillance, congestive heart failure, cardiomyopathy, and decreased ejection fraction were reported in non-MS patients treated with alemtuzumab and who were previously treated with potentially cardiotoxic agents (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Respiratory |
3.6.2) CLINICAL EFFECTS
A) DYSPNEA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, dyspnea was reported in 8% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) COUGH 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, cough was reported in 9% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) UPPER RESPIRATORY INFECTION 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, upper respiratory tract infection was reported in 16% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) PNEUMONITIS 1) WITH THERAPEUTIC USE a) During clinical trials, pneumonitis, including cases of hypersensitivity pneumonitis and pneumonitis with fibrosis, were reported in 6 of 1217 (0.5%) patients treated with alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Neurologic |
3.7.2) CLINICAL EFFECTS
A) HEADACHE 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, headaches were reported in 52% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) WITH POISONING/EXPOSURE a) Headache, rash, and hypotension or sinus tachycardia were reported in 2 patients with MS who inadvertently received alemtuzumab as a single infusion up to 60 mg (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) INSOMNIA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, insomnia was reported in 16% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) DIZZINESS 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, dizziness was reported in 10% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) PARESTHESIA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, paresthesia was reported in 10% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
E) ANXIETY 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, anxiety was reported in 7% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
F) FATIGUE 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, fatigue was reported in 18% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
G) GUILLAIN-BARRé SYNDROME 1) WITH THERAPEUTIC USE a) Guillain-Barre syndrome has been reported in patients treated for B-cell chronic lymphocytic leukemia during postmarketing use (Prod Info LEMTRADA(TM) intravenous injection, 2014).
H) ASTHENIA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, asthenia was reported in 5% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
I) CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY 1) WITH THERAPEUTIC USE a) Chronic inflammatory demyelinating polyradiculoneuropathy has been reported in patients treated for B-cell chronic lymphocytic leukemia during postmarketing use (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) NAUSEA AND VOMITING 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, nausea and vomiting were reported in 21% and 10%, respectively, of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) DIARRHEA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, diarrhea was reported in 12% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) ABDOMINAL PAIN 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, abdominal pain was reported in 10% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) INDIGESTION 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, dyspepsia was reported in 8% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
E) TASTE SENSE ALTERED 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, dysgeusia was reported in 8% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Genitourinary |
3.10.2) CLINICAL EFFECTS
A) URINARY TRACT INFECTIOUS DISEASE 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, urinary tract infection was reported in 19% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) BLOOD IN URINE 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, blood in urine was reported in 8% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) GLOMERULAR DISEASE 1) WITH THERAPEUTIC USE a) During MS clinical trials, glomerular nephropathies occurred in 0.3% of patients treated with alemtuzumab, with 3 cases of membranous glomerulonephritis and 2 cases of anti-glomerular basement membrane (anti-GBM) disease. During post-marketing surveillance, there were cases of alemtuzumab-treated patients who developed anti-GBM disease and subsequently developed end stage renal disease that necessitated renal transplantation. Diagnosis of anti-GBM disease has occurred up to 40 months after the last dose of alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Hematologic |
3.13.2) CLINICAL EFFECTS
A) LYMPHOCYTOPENIA 1) WITH THERAPEUTIC USE a) In clinical trials, 99.9% of patients treated with alemtuzumab developed lymphopenia, with the lowest lymphocyte counts occurring approximately 1 month following each treatment course. Following the first and second alemtuzumab treatment course, mean lymphocyte counts were 0.25 x 10(9)/L (range 0.02 to 2.3 x 10(9)/L) and 0.32 x 10(9)/L (range 0.02 to 1.81 x 10(9)/L), respectively. By 6 months and 12 months after each course, the total lymphocyte counts increased to the lower limit of normal in 40% and 80%, respectively, of patients (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) AUTOIMMUNE THROMBOCYTOPENIA 1) WITH THERAPEUTIC USE a) During MS clinical trials, immune thrombocytopenia (ITP) was reported in 2% of patients treated with alemtuzumab. Nadir platelet counts were 20,000 cells/mcL or less. Signs and symptoms of ITP may include easy bruising, petechiae, spontaneous mucocutaneous bleeding (eg, epistaxis, hemoptysis), and irregular menstrual bleeding. In some cases, ITP has been diagnosed greater than 3 years after the last alemtuzumab dose (Prod Info LEMTRADA(TM) intravenous injection, 2014).
b) One patient, treated with alemtuzumab during a clinical trial, developed ITP that was not recognized until monthly hematologic monitoring was implemented, and the patient died from intracerebral hemorrhage (Prod Info LEMTRADA(TM) intravenous injection, 2014).
c) Severe idiopathic thrombocytopenic purpura (ITP) has occurred in 3 patients in a multiple sclerosis (MS) clinical study. Two of the patients had received a 5 day course of alemtuzumab 24 milligrams (mg)/day which was followed a year later by a 3-day course of 24 mg/day. In both patients, approximately 7 to 11 months after the second treatment, ecchymoses developed. One of these patients also developed ataxia followed by obtundation and death from intracranial hemorrhage. Antiplatelet antibodies were detected in this patient and petechiae had been observed 1 month prior to the development of neurological symptoms. The third patient received a 5-day course of alemtuzumab 12 mg/day, then 12 and 24 months later, a 3-day course of 12 mg/day. Although platelet count was 81,000 cells/microliter (mcL) after receiving the third cycle of alemtuzumab, subsequently, petechiae developed and the platelet count fell to 1000 cells/mcL (FDA alert for healthcare professionals: Alemtuzumab, November 2005).
|
Dermatologic |
3.14.2) CLINICAL EFFECTS
A) ERUPTION 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, rash was reported in 53% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) WITH POISONING/EXPOSURE a) Headache, rash, and hypotension or sinus tachycardia were reported in 2 patients with MS who inadvertently received alemtuzumab as a single infusion up to 60 mg (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) URTICARIA 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, urticaria and pruritus were reported in 16% and 14%, respectively, of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) FLUSHING 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, flushing and erythema were reported in 10% and 5%, respectively, of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) DERMATITIS 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, dermatitis was reported in 8% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
E) VITILIGO 1) WITH THERAPEUTIC USE a) During clinical trials, vitiligo has been reported in 0.1% of patients treated with alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) MUSCLE PAIN 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, muscular weakness and myalgias were reported in 7% and 6%, respectively, of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) SPASM 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, muscle spasms were reported in 6% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) JOINT PAIN 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, arthralgias were reported in 12% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) BACKACHE 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, back pain was reported in 12% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
E) PAIN IN LIMB 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, pain in extremity was reported in 12% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
F) NECK PAIN 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, neck pain was reported in 5% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Endocrine |
3.16.2) CLINICAL EFFECTS
A) DISORDER OF THYROID GLAND 1) WITH THERAPEUTIC USE a) During MS clinical trials, Autoimmune thyroid disorders, including Graves' disease, hyperthyroidism, and hypothyroidism, were reported in 34% of patients treated with alemtuzumab. Approximately 2% of patients experienced serious thyroid events, including cardiac and psychiatric events associated with thyroid disease (Prod Info LEMTRADA(TM) intravenous injection, 2014).
b) According to pooled data of two 2-year randomized active-controlled studies, thyroid gland disorders were reported in 13% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) DIABETES MELLITUS 1) WITH THERAPEUTIC USE a) During clinical trials, type I diabetes has been reported in 0.1% of patients treated with alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Immunologic |
3.19.2) CLINICAL EFFECTS
A) INFECTIOUS DISEASE 1) WITH THERAPEUTIC USE a) During 2-year controlled MS clinical trials, infections, including nasopharyngitis, urinary tract infections, upper respiratory tract infections, sinusitis, herpetic infections, influenza, and bronchitis, were reported in 71% of patients treated with alemtuzumab, with 3% of patients experiencing serious infections, including appendicitis, gastroenteritis, pneumonia, herpes zoster, and tooth infections (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) COMPLICATION OF INFUSION 1) WITH THERAPEUTIC USE a) During clinical trials, infusion reactions were reported in 92% of patients treated with alemtuzumab, with serious reactions occurring in 3% of patients. In some instances, infusion reactions were reported more than 24 hours after alemtuzumab infusion. Signs and symptoms included anaphylaxis (in 2 patients), angioedema, bronchospasm, hypotension, chest pain, bradycardia, tachycardia, atrial fibrillation, transient neurologic symptoms, hypertension, nausea, headache, pyrexia, chills, rash, urticaria, pruritus, insomnia, flushing, fatigue, dyspnea, pulmonary infiltrates, dysgeusia, dyspepsia, dizziness, and pain (Prod Info LEMTRADA(TM) intravenous injection, 2014).
b) Infusion reactions, with fatalities, have been reported in patients receiving alemtuzumab for treatment of B-cell chronic lymphocytic leukemia and other disorders, at higher and more frequent doses than what is normally recommended for treatment of patients with MS. Signs and symptoms in these patients included hypoxia, syncope, acute respiratory distress syndrome, respiratory arrest, myocardial infarction, acute cardiac insufficiency, and cardiac arrest (Prod Info LEMTRADA(TM) intravenous injection, 2014).
C) MYCOSIS 1) WITH THERAPEUTIC USE a) According to pooled data of two 2-year randomized active-controlled studies, fungal infections were reported in 13% of 811 patients with relapsing-remitting multiple sclerosis who received alemtuzumab at a dose of 12 mg, as an IV infusion, once daily for 5 days, followed, 12 months later, by an IV infusion of 12 mg once daily for 3 days (Prod Info LEMTRADA(TM) intravenous injection, 2014).
D) RHEUMATOID ARTHRITIS 1) WITH THERAPEUTIC USE a) During clinical trials, rheumatoid arthritis was reported in 0.1% of patients treated with alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
E) ANAPHYLAXIS 1) WITH THERAPEUTIC USE a) Anaphylaxis has been reported as an infusion complication in patients treated with alemtuzumab during clinical trials (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Summary Of Exposure |
A) USES: Alemtuzumab is approved for the treatment of relapsing forms of multiple sclerosis (MS) in patients who were not adequately responding to two or more drugs indicated for the treatment of MS.
B) PHARMACOLOGY: Alemtuzumab is a recombinant monoclonal antibody that causes antibody-dependent cellular cytolysis, complement-mediated lysis, and depletes circulating T and B lymphocytes by binding to CD52, on the surface of B and T lymphocytes, monocytes, macrophages, and natural killer cells.
C) EPIDEMIOLOGY: Overdose is rare.
D) WITH THERAPEUTIC USE
1) COMMON: The most commonly reported adverse reactions, with an incidence of at least 10% during clinical trials, were rash, headache, pyrexia, nausea, infections (ie, nasopharyngitis, urinary tract infection, upper respiratory tract infection, sinusitis, herpetic infections, influenza, and bronchitis), lymphopenia, fatigue, insomnia, urticaria, pruritus, thyroid gland disorders, arthralgia, extremity pain, back pain, diarrhea, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.
2) INFREQUENT: Adverse reactions that have been reported less frequently include cough, chills, dysgeusia, immune thrombocytopenia, dermatitis, dyspepsia, hematuria, dyspnea, tachycardia, anxiety, muscular weakness, chest discomfort, muscle spasms, myalgia, asthenia, erythema, peripheral edema, epistaxis, neck pain, and abnormal uterine bleeding.
3) RARE: Glomerular nephropathies, pneumonitis, and autoimmune cytopenias, including neutropenia, hemolytic anemia, and pancytopenia, have been rarely reported.
E) WITH POISONING/EXPOSURE
1) Headache, rash, and hypotension or sinus tachycardia were reported in 2 patients with MS who inadvertently received alemtuzumab as a single infusion up to 60 mg . In general, overdose effects are anticipated to be an extension of adverse effects following therapeutic administration.
|
Reproductive |
3.20.1) SUMMARY
A) Alemtuzumab is classified as FDA pregnancy category C. There are no adequate and well-controlled studies of alemtuzumab in pregnant women. Although there was no evidence of teratogenicity in animal studies with IV doses of 3 or 10 mg/kg in pregnant huCD52 transgenic mice during organogenesis, increased embryolethality occurred and decreased B- and T-lymphocytes were observed in mice offspring. Antithyroid antibodies, which may develop with alemtuzumab use, have been reported to cross the placenta and result in neonatal Graves disease.
3.20.3) EFFECTS IN PREGNANCY
A) PREGNANCY CATEGORY 1) Alemtuzumab is classified as FDA pregnancy category C (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) Auto-antibodies may develop with alemtuzumab use. Antithyroid antibodies have been reported to cross the placenta and subsequently neonatal Graves disease has developed. Therefore, it is recommended that alemtuzumab be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. It is also recommended that women of childbearing potential use effective contraception during treatment and for 4 months post-therapy to avoid in utero exposure (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) ANIMAL STUDIES 1) In animal studies, alemtuzumab IV doses of 3 or 10 mg/kg in pregnant huCD52 transgenic mice during organogenesis (gestation days (GD) 6 to 10 or GD 11 to 15) resulted in no teratogenic effects; however, increased embryolethality (increased post-implantation loss and the number of dams, with all dead or resorbed fetuses) occurred with dosing during GD 11 to 15. In another study of pregnant huCD52 transgenic mice, IV doses of 3 or 10 mg/kg during organogenesis (GD 6 to 10 or GD 11 to 15) resulted in decreased B- and T-lymphocytes in the offspring (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3.20.4) EFFECTS DURING BREAST-FEEDING
A) BREAST MILK 1) It is unknown whether alemtuzumab is excreted in human milk. Because many drugs are excreted in human milk and the potential for serious adverse effects exists in nursing infants, it is recommended to either discontinue nursing or the drug, giving consideration to the importance of the drug to the mother (Prod Info LEMTRADA(TM) intravenous injection, 2014).
B) ANIMAL STUDIES 1) Alemtuzumab is excreted in the milk of lactating mice at a similar level to the maternal serum level and results in pharmacological activity (decreased lymphocyte counts) in the offspring (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3.20.5) FERTILITY
A) ANIMAL STUDIES 1) In animal studies, alemtuzumab IV doses of 3 or 10 mg/kg in male and female huCD52 transgenic mice for 5 consecutive days prior to cohabitation with untreated wild-type mice of the opposite sex resulted in no effects on fertility or reproductive performance in the males; however, adverse effects on sperm morphology (detached or no head) and reduced sperm count and motility occurred at both doses tested. In females, decreased number of corpora lutea and implantation sites and increased post-implantation losses occurred with the 10-mg/kg dose (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Carcinogenicity |
3.21.2) SUMMARY/HUMAN
A) Lymphoma, melanoma, and thyroid cancer have been reported in patients treated with alemtuzumab during clinical trials.
3.21.3) HUMAN STUDIES
A) CARCINOMA 1) Lymphoproliferative disorders and lymphoma were reported in multiple sclerosis patients treated with alemtuzumab. Reports included cases of MALT lymphoma, Castleman's Disease, and non-Epstein-Barr Virus-associated Burkitt's lymphoma. There have been postmarketing reports of non-Epstein-Barr Virus-associated lymphoproliferative disorders in non-multiple sclerosis patients (Prod Info LEMTRADA(TM) intravenous injection, 2014).
2) Melanoma was reported in 0.3% of patients administered alemtuzumab (n=1486) during uncontrolled clinical trials. Patients developed melanoma or melanoma in situ. Locally advanced disease was reported in one of these patients (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3) Thyroid cancer was reported in 0.3% of patients administered alemtuzumab (n=919) during controlled clinical trials. There were no reports of thyroid cancer in patients in the interferon beta-1a treatment group; however, thyroid cancer screenings were more frequently performed in the alemtuzumab treatment group. Thyroid cancer was reported in 2 additional patients during uncontrolled clinical trials (Prod Info LEMTRADA(TM) intravenous injection, 2014).
3.21.4) ANIMAL STUDIES
A) LACK OF INFORMATION 1) No long term studies in animals have been performed to establish the carcinogenic potential of alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|
Genotoxicity |
A) No long term studies in animals have been performed to establish the genotoxic potential of alemtuzumab (Prod Info LEMTRADA(TM) intravenous injection, 2014).
|