LENALIDOMIDE capsule

Χώρα: Ηνωμένες Πολιτείες

Γλώσσα: Αγγλικά

Πηγή: NLM (National Library of Medicine)

Δραστική ουσία:

LENALIDOMIDE (UNII: F0P408N6V4) (LENALIDOMIDE - UNII:F0P408N6V4)

Διαθέσιμο από:

Teva Pharmaceuticals, Inc.

Οδός χορήγησης:

ORAL

Τρόπος διάθεσης:

PRESCRIPTION DRUG

Θεραπευτικές ενδείξεις:

Lenalidomide capsules in combination with dexamethasone are indicated for the treatment of adult patients with multiple myeloma (MM). Lenalidomide capsules are indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. Lenalidomide capsules are indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. Lenalidomide capsules are not indicated and are not recommended for the treatment of patients with CLL outside of controlled clinical trials [see Warnings and Precautions (5.5)] . Lenalidomide capsules can cause fetal harm when administered to a pregnant female. Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis. This effect was seen at all doses tested. Due to the results of this developmental monkey study, and lenalidomide’s structural similarities to thalidomide, a known human teratogen, lenalidomide is contraindicated in females who are pregnant [see Boxed Warning] . If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus [see Warnings and Precautions (5.1, 5.2), Use in Special Populations (8.1, 8.3)] . Lenalidomide capsules are contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide [see Warnings and Precautions (5.9, 5.15)] . Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to lenalidomide capsules during pregnancy as well as female partners of male patients who are exposed to lenalidomide capsules. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to lenalidomide capsules to the FDA via the MedWatch program at 1-800-FDA-1088 and also to the REMS Call Center at 1‐888‐423‐5436. Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1)] and findings from animal studies [see Data] , lenalidomide can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy [see Boxed Warning, Contraindications (4.1), and Use in Specific Populations (5.1)] . Lenalidomide is a thalidomide analogue. Thalidomide is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Alimentary tract, urinary tract, and genital malformations have also been documented and mortality at or shortly after birth has been reported in about 40% of infants. Lenalidomide caused thalidomide-type limb defects in monkey offspring. Lenalidomide crossed the placenta after administration to pregnant rabbits and pregnant rats [see Data] . If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to lenalidomide capsules to the FDA via the MedWatch program at 1-800-FDA-1088 and also to the REMS Call Center at 1‐888‐423‐5436. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal data In an embryo-fetal developmental toxicity study in monkeys, teratogenicity, including thalidomide-like limb defects, occurred in offspring when pregnant monkeys received oral lenalidomide during organogenesis. Exposure (AUC) in monkeys at the lowest dose was 0.17 times the human exposure at the maximum recommended human dose (MRHD) of 25 mg. Similar studies in pregnant rabbits and rats at 20 times and 200 times the MRHD respectively, produced embryo lethality in rabbits and no adverse reproductive effects in rats. In a pre- and post-natal development study in rats, animals received lenalidomide from organogenesis through lactation. The study revealed a few adverse effects on the offspring of female rats treated with lenalidomide at doses up to 500 mg/kg (approximately 200 times the human dose of 25 mg based on body surface area). The male offspring exhibited slightly delayed sexual maturation and the female offspring had slightly lower body weight gains during gestation when bred to male offspring. As with thalidomide, the rat model may not adequately address the full spectrum of potential human embryo-fetal developmental effects for lenalidomide. Following daily oral administration of lenalidomide from Gestation Day 7 through Gestation Day 20 in pregnant rabbits, fetal plasma lenalidomide concentrations were approximately 20% to 40% of the maternal Cmax . Following a single oral dose to pregnant rats, lenalidomide was detected in fetal plasma and tissues; concentrations of radioactivity in fetal tissues were generally lower than those in maternal tissues. These data indicated that lenalidomide crossed the placenta. Risk Summary There is no information regarding the presence of lenalidomide in human milk, the effects of lenalidomide capsules on the breastfed child, or the effects of lenalidomide on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children from lenalidomide capsules, advise women not to breastfeed during treatment with lenalidomide capsules. Pregnancy Testing Lenalidomide capsules can cause fetal harm when administered during pregnancy [see Use in Specific Populations (8.1)] . Verify the pregnancy status of females of reproductive potential prior to initiating lenalidomide capsules therapy and during therapy. Advise females of reproductive potential that they must avoid pregnancy 4 weeks before therapy, while taking lenalidomide capsules, during dose interruptions and for at least 4 weeks after completing therapy. Females of reproductive potential must have 2 negative pregnancy tests before initiating lenalidomide capsules. The first test should be performed within 10 to 14 days, and the second test within 24 hours prior to prescribing lenalidomide capsules. Once treatment has started and during dose interruptions, pregnancy testing for females of reproductive 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. If menstrual cycles are irregular, the pregnancy testing should occur every 2 weeks. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in her menstrual bleeding. Lenalidomide treatment must be discontinued during this evaluation. Contraception Females Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously: one highly effective form of contraception – tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or implants), or partner’s vasectomy, and 1 additional effective contraceptive method – male latex or synthetic condom, diaphragm, or cervical cap. Contraception must begin 4 weeks prior to initiating treatment with lenalidomide capsules, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of lenalidomide therapy. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy. Females of reproductive potential should be referred to a qualified provider of contraceptive methods, if needed. Males Lenalidomide is present in the semen of males who take lenalidomide capsules. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide capsules and for up to 4 weeks after discontinuing lenalidomide capsules, even if they have undergone a successful vasectomy. Male patients taking lenalidomide capsules must not donate sperm and for up to 4 weeks after discontinuing lenalidomide capsules. Safety and effectiveness have not been established in pediatric patients. MM In Combination : Overall, of the 1613 patients in the NDMM study who received study treatment, 94% (1521/1613) were 65 years of age or older, while 35% (561/1613) were over 75 years of age. The percentage of patients over age 75 was similar between study arms (Rd Continuous: 33%; Rd18: 34%; MPT: 33%). Overall, across all treatment arms, the frequency in most of the adverse reaction categories (eg, all adverse reactions, grade 3/4 adverse reactions, serious adverse reactions) was higher in older (> 75 years of age) than in younger (≤ 75 years of age) subjects. Grade 3 or 4 adverse reactions in the General Disorders and Administration Site Conditions body system were consistently reported at a higher frequency (with a difference of at least 5%) in older subjects than in younger subjects across all treatment arms. Grade 3 or 4 adverse reactions in the Infections and Infestations, Cardiac Disorders (including cardiac failure and congestive cardiac failure), Skin and Subcutaneous Tissue Disorders, and Renal and Urinary Disorders (including renal failure) body systems were also reported slightly, but consistently, more frequently (<5% difference), in older subjects than in younger subjects across all treatment arms. For other body systems (e.g., Blood and Lymphatic System Disorders, Infections and Infestations, Cardiac Disorders, Vascular Disorders), there was a less consistent trend for increased frequency of grade 3/4 adverse reactions in older vs younger subjects across all treatment arms Serious adverse reactions were generally reported at a higher frequency in the older subjects than in the younger subjects across all treatment arms. MM After At Least One Prior Therapy : Of the 703 MM patients who received study treatment in Studies 1 and 2, 45% were age 65 or over while 12% of patients were age 75 and over. The percentage of patients age 65 or over was not significantly different between the lenalidomide/dexamethasone and placebo/dexamethasone groups. Of the 353 patients who received lenalidomide/dexamethasone, 46% were age 65 and over. In both studies, patients > 65 years of age were more likely than patients ≤ 65 years of age to experience DVT, pulmonary embolism, atrial fibrillation, and renal failure following use of lenalidomide capsules. No differences in efficacy were observed between patients over 65 years of age and younger patients. Of the 148 patients with del 5q MDS enrolled in the major study, 38% were age 65 and over, while 33% were age 75 and over. Although the overall frequency of adverse reactions (100%) was the same in patients over 65 years of age as in younger patients, the frequency of serious adverse reactions was higher in patients over 65 years of age than in younger patients (54% vs. 33%). A greater proportion of patients over 65 years of age discontinued from the clinical studies because of adverse reactions than the proportion of younger patients (27% vs.16%). No differences in efficacy were observed between patients over 65 years of age and younger patients. Of the 134 patients with MCL enrolled in the MCL trial, 63% were age 65 and over, while 22% of patients were age 75 and over. The overall frequency of adverse reactions was similar in patients over 65 years of age and in younger patients (98% vs. 100%). The overall incidence of grade 3 and 4 adverse reactions was also similar in these 2 patient groups (79% vs. 78%, respectively). The frequency of serious adverse reactions was higher in patients over 65 years of age than in younger patients (55% vs. 41%). No differences in efficacy were observed between patients over 65 years of age and younger patients. Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function. Adjust the starting dose of lenalidomide capsules based on the creatinine clearance value and for patients on dialysis [see Dosage and Administration (2.6)] .

Περίληψη προϊόντος:

Lenalidomide capsules are available as follows: 2.5 mg – Each size 4 capsule with white cap and body printed with “NAT” on cap and “2.5mg” on body in black ink contains 2.5 mg of lenalidomide. 2.5 mg bottles of 28 (NDC 0480-1241-28) 20 mg – Each size 2 capsule with green cap and blue body printed with “NAT” on cap and “20 mg” on body in black ink contains 20 mg of lenalidomide. 20 mg bottles of 21 (NDC 0480-1245-21) Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Care should be exercised in the handling of lenalidomide capsules. Lenalidomide capsules should not be opened or broken. If powder from lenalidomide capsules contacts the skin, wash the skin immediately and thoroughly with soap and water. If lenalidomide contacts the mucous membranes, flush thoroughly with water. Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published.1 Dispense no more than a 28-day supply.

Καθεστώς αδειοδότησης:

Abbreviated New Drug Application

Φύλλο οδηγιών χρήσης

Teva Pharmaceuticals, Inc.
----------
MEDICATION GUIDE
LENALIDOMIDE (len" a lid' oh mide) Capsules
What is the most important information I should know about
lenalidomide capsules?
Before you begin taking lenalidomide capsules, you must read and agree
to all of the instructions in the
Lenalidomide REMS program. Before prescribing lenalidomide capsules,
your healthcare provider will
explain the Lenalidomide REMS program to you and have you sign the
Patient-Physician Agreement
Form.
Lenalidomide capsules may cause serious side effects including:
•
Possible birth defects (deformed babies) or death of an unborn baby.
Females who are pregnant or
who plan to become pregnant must not take lenalidomide capsules.
Lenalidomide is similar to the medicine thalidomide. We know
thalidomide can cause severe
life-threatening birth defects. Lenalidomide capsules have not been
tested in pregnant females.
Lenalidomide capsules have harmed unborn animals in animal testing.
Females must not get pregnant:
•
For at least 4 weeks before starting lenalidomide capsules
•
While taking lenalidomide capsules
•
During any breaks (interruptions) in your treatment with lenalidomide
capsules
•
For at least 4 weeks after stopping lenalidomide capsules
Females who can become pregnant:
•
Will have pregnancy tests weekly for 4 weeks, then every 4 weeks if
your menstrual cycle is
regular, or every 2 weeks if your menstrual cycle is irregular.
•
If you miss your period or have unusual bleeding, you will need to
have a pregnancy test and
receive counseling.
•
Must agree to use two acceptable forms of birth control at the same
time, for at least 4 weeks
before, while taking, during any breaks (interruptions) in your
treatment, and for at least 4 weeks
after stopping lenalidomide capsules.
•
Talk with your healthcare provider to find out about options for
acceptable forms of birth control
that you may use to prevent pregnancy before, during, and after
treatment with lenalidomide
capsules.
•
If you had unprotected sex or if you think y

Αρχείο Π.Χ.Π.

LENALIDOMIDE- LENALIDOMIDE CAPSULE
TEVA PHARMACEUTICALS, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LENALIDOMIDE CAPSULES
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
LENALIDOMIDE CAPSULES.
LENALIDOMIDE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2005
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, AND VENOUS AND
ARTERIAL THROMBOEMBOLISM
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
EMBRYO-FETAL TOXICITY
LENALIDOMIDE, A THALIDOMIDE ANALOGUE, CAUSED LIMB ABNORMALITIES IN A
DEVELOPMENTAL MONKEY STUDY SIMILAR TO BIRTH DEFECTS CAUSED BY
THALIDOMIDE IN
HUMANS. IF LENALIDOMIDE IS USED DURING PREGNANCY, IT MAY CAUSE BIRTH
DEFECTS OR
EMBRYO-FETAL DEATH.
PREGNANCY MUST BE EXCLUDED BEFORE START OF TREATMENT. PREVENT
PREGNANCY DURING
TREATMENT BY THE USE OF TWO RELIABLE METHODS OF CONTRACEPTION (5.1).
LENALIDOMIDE CAPSULES ARE AVAILABLE ONLY THROUGH A RESTRICTED
DISTRIBUTION
PROGRAM, CALLED THE LENALIDOMIDE REMS PROGRAM (5.2, 17).
HEMATOLOGIC TOXICITY. LENALIDOMIDE CAPSULES CAN CAUSE SIGNIFICANT
NEUTROPENIA
AND THROMBOCYTOPENIA (5.3).
VENOUS AND ARTERIAL THROMBOEMBOLISM
SIGNIFICANTLY INCREASED RISK OF DEEP VEIN THROMBOSIS (DVT) AND
PULMONARY EMBOLISM
(PE), AS WELL AS RISK OF MYOCARDIAL INFARCTION AND STROKE IN PATIENTS
WITH MULTIPLE
MYELOMA RECEIVING LENALIDOMIDE CAPSULES WITH DEXAMETHASONE.
ANTI-THROMBOTIC
PROPHYLAXIS IS RECOMMENDED (5.4).
RECENT MAJOR CHANGES
Warnings and Precautions (5.1, 5.2)
8/2021
Warnings and Precautions (5.1, 5.11) 5/2022
INDICATIONS AND USAGE
Lenalidomide is a thalidomide analogue indicated for the treatment of
adult patients with:
Multiple myeloma (MM), in combination with dexamethasone (1.1).
Transfusion-dependent anemia due to low- or intermediate-1-risk
myelodysplastic syndromes (MDS)
associated with a deletion 5q abnormality with or without additional
cytogenetic abnormalities (1.2).
Mantle cell lymphoma (MCL) whose disease has relapsed or progressed
after two prior therapies,