LENALIDOMIDE IS TAKEN DURING PREGNANCY, IT MAY CAUSE BIRTH DEFECTS OR DEATH TO AN UNBORN BABY.SHOULD BE ADVISED TO AVOID PREGNANCY WHILE TAKING REVLIMID(R) (lenalidomide).Special Prescribing Requirements BECAUSE OF THIS POTENTIAL TOXICITY AND TO AVOID FETAL EXPOSURE TO REVLIMID(R) (lenalidomide), REVLIMID(R) (lenalidomide) IS ONLY AVAILABLE UNDER A SPECIAL RESTRICTED DISTRIBUTION PROGRAM.IS CALLED "RevAssist(R)".THIS PROGRAM, ONLY PRESCRIBERS AND PHARMACISTS REGISTERED WITH THE PROGRAM CAN PRESCRIBE AND DISPENSE THE PRODUCT.ADDITION, REVLIMID(R) (lenalidomide) MUST ONLY BE DISPENSED TO PATIENTS WHO ARE REGISTERED AND MEET ALL THE CONDITIONS OF THE RevAssist(R) PROGRAM.PLEASE SEE THE FOLLOWING INFORMATION FOR PRESCRIBERS, FEMALE PATIENTS, AND MALE PATIENTS ABOUT THIS RESTRICTED DISTRIBUTION PROGRAM.RevAssist(R) PROGRAM DESCRIPTION Prescribers REVLIMID(R) (lenalidomide) can be prescribed only by licensed prescribers who are registered in the RevAssist(R) program and understand the potential risk of teratogenicity if lenalidomide is used during pregnancy.Effective contraception must be used by female patients of childbearing potential for at least 4 weeks before beginning REVLIMID(R) (lenalidomide) therapy, during REVLIMID(R) (lenalidomide) therapy, during dose interruptions and for 4 weeks following discontinuation of REVLIMID(R) (lenalidomide) therapy.Contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or because the patient has been postmenopausal naturally for at least 24 consecutive months.Reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is the chosen method.Of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed.Females who have not undergone a hysterectomy, have not had a bilateral oophorectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.Who have had menses at some time in the preceding 24 consecutive months) are considered to be females of childbearing potential.Before prescribing REVLIMID(R) (lenalidomide), females of childbearing potential should have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL).First test should be performed within 10-14 days, and the second test within 24 hours prior to prescribing REVLIMID(R) (lenalidomide).For REVLIMID(R) (lenalidomide) for a female of childbearing potential must not be issued by the prescriber until negative pregnancy tests have been verified by the prescriber.Male Patients: It is not known whether lenalidomide is present in the semen of patients receiving the drug.Males receiving REVLIMID(R) (lenalidomide) must always use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy.Once treatment has started and during dose interruptions, pregnancy testing for females of childbearing potential should occur weekly during the first 4 weeks of use, then pregnancy testing should be repeated every 4 weeks in females with regular menstrual cycles.Menstrual cycles are irregular, the pregnancy testing should occur every 2 weeks.And counseling should be performed if a patient misses her period or if there is any abnormality in her pregnancy test or in her menstrual bleeding.(lenalidomide) treatment must be discontinued during this evaluation.Pregnancy test results should be verified by the prescriber and the pharmacist prior to dispensing any prescription.If pregnancy does occur during REVLIMID(R) (lenalidomide) treatment, REVLIMID(R) (lenalidomide) must be discontinued immediately.Any suspected fetal exposure to REVLIMID(R) (lenalidomide) should be reported to the FDA via the MedWatch number at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.Patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.Female Patients REVLIMID(R) (lenalidomide) should be used in females of childbearing potential only when the patient MEETS ALL OF THE FOLLOWING CONDITIONS (i.She is unable to be pregnant while on lenalidomide therapy): she understands and can reliably carry out instructions.She is capable ofplying with the mandatory contraceptive measures, pregnancy testing, patient registration, and patient survey as described in the RevAssist(R) program.She has received and understands both oral and written warnings of the potential risks of taking lenalidomide during pregnancy and of exposing a fetus to the drug.She has received both oral and written warnings of the risk of possible contraception failure and of the need to use two reliable forms of contraception simultaneously, unless continuous abstinence from heterosexual sexual contact is the chosen method.Mature females who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months (i.Who have had menses at some time in the preceding 24 consecutive months), or had a bilateral oophorectomy are considered to be females of childbearing potential.She acknowledges, in writing, her understanding of these warnings and of the need for using two reliable methods of contraception for 4 weeks prior to beginning lenalidomide therapy, during lenalidomide therapy, during dose interruptions and for 4 weeks after discontinuation of lenalidomide therapy.She has had two negative pregnancy tests with a sensitivity of at least 50 mIU/mL, within 10-14 days and 24 hours prior to beginning therapy.If the patient is between 12 and 18 years of age, her parent or legal guardian must have read the educational materials and agreed to ensurepliance with the above.Patients REVLIMID(R)(lenalidomide) should be used in sexually active males when the PATIENT MEETS ALL OF THE FOLLOWING CONDITIONS: he understands and can reliably carry out instructions.He is capable ofplying with the mandatory contraceptive measures that are appropriate for men, patient registration, and patient survey as described in the RevAssist(R) program.He has received and understands both oral and written warnings of the potential risks of taking lenalidomide and exposing a fetus to the drug.He has received both oral and written warnings of the risk of possible contraception failure and that it is unknown whether lenalidomide is present in semen.Has been instructed that he must always use a latex condom during any sexual contact with females of childbearing potential, even if he has undergone a successful vasectomy.He acknowledges, in writing, his understanding of these warnings and of the need to use a latex condom during any sexual contact with females of childbearing potential, even if he has undergone a successful vasectomy.Of childbearing potential are considered to be sexually mature females who have not undergone a hysterectomy, have not had a bilateral oophorectomy or who have not been postmenopausal for at least 24 consecutive months (i.Who have had menses at any time in the preceding 24 consecutive months).If the patient is between 12 and 18 years of age, his parent or legal guardian must have read the educational materials and agreed to ensurepliance with the above.TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA) This drug is associated with significant neutropenia and thrombocytopenia.Percent of patients with del 5q myelodysplastic syndromes had to have a dose delay/reduction during the major study.Percent of patients had to have a second dose delay/reduction.3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study.On therapy for del 5q myelodysplastic syndromes should have theirplete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter.May require dose interruption and/or reduction.Use of blood product support and/or growth factors.) DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM This drug has demonstrated a significantly increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients with multiple myeloma who were treated with REVLIMID(R) (lenalidomide)bination therapy.And physicians are advised to be observant for the signs and symptoms of thromboembolism.Should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.Is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with REVLIMID(R) (lenalidomide) may lessen the potential for venous thromboembolic events.Decision to take prophylactic measures should be done carefully after an assessment of an individual patient's underlying risk factors.You can get the information about REVLIMID(R) (lenalidomide) and the RevAssist(R) program on the internet at www.Calling the manufacturer's toll free number 1-888-423-5436.REVLIMID(R)(lenalidomide), a thalidomide analogue, is an immunomodulatory agent with antiangiogenic and antineoplastic properties.Chemical name is 3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione and it has the following chemical structure: 3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione The empirical formula for lenalidomide is C13H13N3O3, and the gram molecular weight is 259.Lenalidomide is an off-white to pale-yellow solid powder.Is soluble in organic solvent/water mixtures, and buffered aqueous solvents.Is more soluble in organic solvents and low pH solutions.Was significantly lower in less acidic buffers, ranging from about 0.0.Lenalidomide has an asymmetric carbon atom and can exist as the optically active forms S(-) and R(+), and is produced as a racemic mixture with a net optical rotation of zero.Is available in 5 mg, 10 mg, 15 mg and 25 mg capsules for oral administration.Capsule contains lenalidomide as the active ingredient and the following inactive ingredients: lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.5 mg and 25 mg capsule shell contains gelatin, titanium dioxide and black ink.10 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink.15 mg capsule shell contains gelatin, FD the median time to the first dose reduction or interruption was 21 days (mean, 35.2-253 days), and the median duration of the first dose interruption was 22 days (mean, 28.Range, 2-265 days).Second dose reduction or interruption due to adverse events was required in 50 (33.The 148 patients.Median interval between the first and second dose reduction or interruption was 51 days (mean, 59.15-205 days) and the median duration of the second dose interruption was 21 days (mean, 26 days; range, 2-148 days).Colony-stimulating factors were permitted for patients who developed neutropenia or fever in association with neutropenia.MYELOMA Two randomized studies (Studies 1 and 2) were conducted to evaluate the efficacy and safety of REVLIMID(R) (lenalidomide).Multicenter, multinational, double-blind, placebo-controlled studiespared REVLIMID(R) (lenalidomide) plus oral pulse high-dose dexamethasone therapy to dexamethasone therapy alone, in patients with multiple myeloma who had received at least one prior treatment.In both studies, patients in the REVLIMID(R) (lenalidomide)/dexamethasone group took 25 mg of REVLIMID(R) (lenalidomide) orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28вЂ'day cycle.Placebo/dexamethasone group took 1 placebo capsule on Days 1 to 28 of each 28вЂ'day cycle.In both treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28вЂ'day cycle for the first 4 cycles of therapy.The dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 of each 28вЂ'day cycle after the first 4 cycles of therapy.Both studies, treatment was to continue until disease progression.In both studies, dose adjustments were allowed based on clinical and laboratory findings.Dose reductions to 15 mg daily, 10 mg daily and 5 mg daily were allowed for toxicity.) Table 2 summarizes the baseline patient and disease characteristics in the two studies.Both studies, baseline demographic and disease-related characteristics wereparable between the REVLIMID(R) (lenalidomide)/dexamethasone and placebo/dexamethasone groups.Table 2 Baseline Demographic and Disease-Related Characteristics - Studies 1 and 2 Study 1 Study 2 REVLIMID/Dex N=170Placebo/Dex N=171REVLIMID/Dex N=176Placebo/Dex N=175 Patient Characteristics Age (years) Median 64 62 63 64 Min,Max 36,86 37, 85 33, 84 40, 82 Sex Male 102 (60%) 101 (59%) 104 (59%) 103 (59%) Female 68 (40%) 70 (41%) 72 (41%) 72 (41%) Race/Ethnicity White 134 (79%) 143 (84%) 172 (98%) 175 (100%) Other 36 (21%) 28 (16%) 4 (2%) 0 (0%) ECOG Performance Status 0-1 151 (89%) 163 (95%) 150 (85%) 144 (82%) Disease Characteristics Baseline Multiple Myeloma Stage (Durie-Salmon) I 2% 2% 6% 5% II 31% 31% 28% 33% III 67% 67% 65% 63% Baseline Creatinine (mg/dL) Median 1.0.Min,Max 0.5, 2.2.2.B2-microglobulin (mg/L) Median 3.3.Min,Max 1.15.14.25.Number of Prior Therapies No.Prior Antimyeloma Therapies 1 38% 37% 32% 33% 2 62% 63% 68% 67% Types of Prior Therapies Stem Cell Transplantation 60% 60% 56% 54% Thalidomide 42% 46% 30% 38% Dexamethasone 80% 70% 66% 69% Bortezomib 11% 12% 5% 4% Melphalan 34% 31% 56% 52% Doxorubicin 55% 52% 56% 57% The primary efficacy endpoint in both studies was time to progression (TTP).Was defined as the time from randomization to the first occurrence of progressive disease or death due to progressive disease.Preplanned interim analyses of both studies showed that thebination of REVLIMID(R) (lenalidomide)/dexamethasone was significantly superior to dexamethasone alone for TTP.Studies were unblinded to allow patients in the placebo/dexamethasone group to receive treatment with the REVLIMID(R) (lenalidomide)/dexamethasonebination.Table 3 summarizes TTP and response rates based on the best response assessments for Studies 1 and 2.Table 3: Summary of Efficacy Analysis Studies 1 and 2 1 NE, Not estimable due to short follow-up.2 Hazard Ratio of Revlimid/Dexamethasone to Placebo/Dexamethasone 3 The p-value is based on a one-tailed unstratified log rank test.Read more Maternal obesity at conception programs obesity in the offspring
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