In an embryofetal developmental toxicity study in monkeys, teratogenicity, including thalidomide-like limb defects, occurred in offspring when pregnant monkeys received oral lenalidomide during organogenesis at doses approximately 0.17 times the maximum recommended human dose (MRHD) of 25 mg, based on body surface area. Similar studies in pregnant rabbits and rats at 20 times and 200 times the MRHD respectively, produced embryolethality in rabbits and no adverse reproductive effects in rats. In another study, pregnant rats received lenalidomide from organogenesis through lactation, some delay in sexual maturation occurred in male offspring. As with thalidomide, the rat model may not adequately address the full spectrum of potential human embryofetal developmental effects for lenalidomide.

Females of childbearing potential must use effective means of contraception for 28 days before therapy, during lenalidomide therapy and dose interruptions, and for 28 days following discontinuation of lenalidomide therapy, or continually abstain from reproductive heterosexual sexual intercourse. Because of the increased risk of VTE in patients with multiple myeloma taking lenalidomide and dexamethasone, and to a lesser extent patients with MDS taking lenalidomide monotherapy, and because there is an increased risk of VTE in patients taking combined oral contraceptive pills, physicians should discuss the risk/benefit of contraceptive methods with their patients.

8.3Nursing 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.

8.4Pediatric Use
Safety and effectiveness in pediatric patients below the age of 18 have not been established.

8.5Geriatric 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 great