ASH News Daily 2013 - Day 3 - (Page B-15)
ASH News Daily
Monday, December 9, 2013
Page B-15
®
FocuS on traineeS
ASH Offers Wealth of Activities and Services to Trainees
T
he ASH annual meeting provides hematology trainees
with a variety of high-quality
educational, career-development,
and networking opportunities. To
help trainees make the most of their
meeting experience, the following
activities and services have been
identified as most relevant to the
unique interests of undergraduates,
medical and graduate students, residents, and fellows (MD and PhD).
These events are open only to
Associate members; Medical Student, Graduate Student, and Resident members; and non-members
or establish a causal relationship to drug exposure [see Warnings and
Precautions Section (5.5 to 5.8)].
Cases of hypothyroidism and hyperthyroidism have also been reported.
Optimal control of thyroid function is recommended before start of
treatment. Baseline and ongoing monitoring of thyroid function is
recommended.
7 DRUG INTERACTIONS
Results from human in vitro studies show that REVLIMID is neither
metabolized by nor inhibits or induces the cytochrome P450 pathway
suggesting that lenalidomide is not likely to cause or be subject to
P450-based metabolic drug interactions.
In vitro studies demonstrated that REVLIMID is not a substrate of human
breast cancer resistance protein (BCRP), multidrug resistance protein
(MRP) transporters MRP1, MRP2, or MRP3, organic anion transporters
(OAT) OAT1 and OAT3, organic anion transporting polypeptide 1B1
(OATP1B1 or OATP2), organic cation transporters (OCT) OCT1 and OCT2,
multidrug and toxin extrusion protein (MATE) MATE1, and organic cation
transporters novel (OCTN) OCTN1 and OCTN2.
In vitro, lenalidomide is a substrate, but is not an inhibitor of P-glycoprotein
(P-gp).
7.1 Digoxin
When digoxin was co-administered with multiple doses of REVLIMID
(10 mg/day) the digoxin Cmax and AUC0-∞ were increased by 14%. Periodic
monitoring of digoxin plasma levels, in accordance with clinical judgment
and based on standard clinical practice in patients receiving this
medication, is recommended during administration of REVLIMID.
7.2 Warfarin
Co-administration of multiple dose REVLIMID (10 mg) with single dose
warfarin (25 mg) had no effect on the pharmacokinetics of total
lenalidomide or R- and S-warfarin. Expected changes in laboratory
assessments of PT and INR were observed after warfarin administration,
but these changes were not affected by concomitant REVLIMID
administration. It is not known whether there is an interaction between
dexamethasone and warfarin. Close monitoring of PT and INR is
recommended in multiple myeloma patients taking concomitant warfarin.
7.3 Concomitant Therapies That May Increase the Risk of Thrombosis
Erythropoietic agents, or other agents that may increase the risk of
thrombosis, such as estrogen containing therapies, should be used with
caution in multiple myeloma patients receiving lenalidomide with
dexamethasone [see Warnings and Precautions (5.4)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category X [see Boxed Warnings and Contraindications (4.1)]
Risk Summary
REVLIMID can cause embryo-fetal harm when administered to a pregnant
female and is contraindicated during pregnancy. REVLIMID 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. 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 hazard
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.
Any suspected fetal exposure to REVLIMID must be reported to the
FDA via the MedWatch program at 1-800-332-1088 and also to Celgene
Corporation at 1-888-423-5436.
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.
Cosmos Communications
K
in training wearing blue trainee
meeting badges. To receive a blue
badge you must register as an Associate member or a non-member
in training.
Trainee Lounge
Trainees are invited to visit the
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.
8.3 Nursing mothers
It is not known whether this drug is excreted in human milk. Because many
drugs are excreted in human milk and because of the potential for adverse
reactions in nursing infants from lenalidomide, 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 below the age of 18 have not
been established.
8.5 Geriatric use
REVLIMID has been used in multiple myeloma (MM) clinical trials in
patients up to 86 years of age.
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 REVLIMID/dexamethasone and placebo/dexamethasone groups. Of the
353 patients who received REVLIMID/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 REVLIMID. No differences in
efficacy were observed between patients over 65 years of age and younger
patients.
REVLIMID has been used in del 5q MDS clinical trials in patients up to
95 years of age.
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 events (100%) was the same in patients over 65 years
of age as in younger patients, the frequency of serious adverse events 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 events 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.
REVLIMID has been used in a mantle cell lymphoma (MCL) clinical trial in
patients up to 83 years of age. 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 events 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 events was also similar in these 2 patient
groups (79% vs. 78%, respectively). The frequency of serious adverse
events 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.
8.6 Females of Reproductive Potential and Males
REVLIMID can cause fetal harm when administered during pregnancy [see
Use in Specific Populations (8.1)]. Females of reproductive potential must
avoid pregnancy 4 weeks before therapy, while taking REVLIMID, during
dose interruptions and for at least 4 weeks after completing therapy.
Females
Females of reproductive potential must commit either to abstain
continuously from heterosexual sexual intercourse or to use two 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
one additional effective contraceptive method - male latex or synthetic
condom, diaphragm or cervical cap. Contraception must begin 4 weeks
prior to initiating treatment with REVLIMID, during therapy, during dose
interruptions and continuing for 4 weeks following discontinuation of
REVLIMID 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.
Females of reproductive potential must have 2 negative pregnancy tests
before initiating REVLIMID. The first test should be performed within
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Trainee Lounge located in the Great
Hall Foyer of the Ernest N. Morial Convention Center. The lounge
provides a relaxing place for trainees to meet with colleagues, access
the Internet, and recharge with
»» TRAINEE EVENTS Page B-23
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ASH News Daily 2013 - Day 3
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