Revlimid (Celgene)
Revlimid (Celgene) - General Information
Revlimid (Celgene) (initially known as CC-5013 and marketed as Revlimid® by Celgene) is a derivative of thalidomide introduced in 2004. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic modality, but has also shown efficacy in the hematological disorders known as the myelodysplastic syndromes. [Wikipedia]
Pharmacology of Revlimid (Celgene)
Revlimid (Celgene), a thalidomide analogue, is an immunomodulatory agent possessing immunomodulatory and antiangiogenic properties. Revlimid (Celgene) inhibits the secretion of pro-inflammatory cytokines and increases the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Revlimid (Celgene) inhibits cell proliferation with varying effectiveness (IC50s) in some but not all cell lines. Revlimid (Celgene) is effective in inhibiting growth of Namalwa cells (a human B cell lymphoma cell line with a deletion of one chromosome 5) but is much less effective in inhibiting growth of KG-1 cells (human myeloblastic cell line, also with a deletion of one chromosome 5) and other cell lines without chromosome 5 deletions.
Revlimid (Celgene) for patients
Patients should be counseled on lenalidomide’s potential risk of teratogenicity due to its structural similarity to thalidomide. Under the RevAssist SM program, patients may only acquire a prescription for REVLIMID® (lenalidomide) therapy through a controlled distribution program through contracted pharmacies. Female patients of childbearing potential will be educated and counseled on the requirements of the RevAssist SM program and the precautions to be taken to preclude fetal exposure to REVLIMID® (lenalidomide). Patients should become familiar with the REVLIMID® RevAssistSM educational materials, Patient Medication Guide, and direct any questions to their physician or pharmacist prior to starting REVLIMID® (lenalidomide) therapy.
Revlimid (Celgene) Interactions
Results from human in vitro metabolism studies and nonclinical studies show that REVLIMID® (lenalidomide) 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 man.
Co-administration of multiple doses of 10 mg of lenalidomide had no effect on the single dose pharmacokinetics of R- and S- warfarin. Co-administration of single 25-mg dose warfarin had no effect on the pharmacokinetics of total lenalidomide. Expected changes in laboratory assessments of PT and INR were observed after warfarin administration, but these changes were not affected by concomitant lenalidomide administration.
Revlimid (Celgene) Contraindications
Pregnancy: Category X
Due to its structural similarities to thalidomide, a known human teratogen, lenalidomide is contraindicated in pregnant women and women capable of becoming pregnant. When there is no alternative, females of childbearing potential may be treated with lenalidomide provided adequate precautions are taken to avoid pregnancy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, including at least one highly effective method (e.g., IUD, hormonal contraception, tubal ligation, or partner’s vasectomy) and one additional effective method (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to initiating treatment with REVLIMID® (lenalidomide), during therapy with REVLIMID® (lenalidomide), during therapy delay, and continuing for 4 weeks following discontinuation of REVLIMID® (lenalidomide) therapy. If hormonal or IUD contraception is medically contraindicated, two other effective or highly effective methods may be used.
Females of childbearing potential being treated with REVLIMID® (lenalidomide) should have pregnancy testing (sensitivity of at least 50 mIU/mL). The first test should be performed within 10-14 days and the second test within 24 hours prior to beginning REVLIMID® (lenalidomide) therapy and then weekly during the first month of REVLIMID® (lenalidomide), then monthly thereafter in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in menstrual bleeding. If pregnancy occurs, REVLIMID® (lenalidomide) must be immediately discontinued. Under these conditions, the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.
REVLIMID® (lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components.
Additional information about Revlimid (Celgene)
Revlimid (Celgene) Indication: For the treatment of patients with transfusion-dependent anemia due to low- or intermediate- risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.
Mechanism Of Action: The mechanism of action of lenalidomide remains to be fully characterized, however it has been demonstrated that lenalidomide inhibits the expression of cyclooxygenase-2 (COX-2), but not COX-1, in vitro.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Lenalidomide
Synonyms: CDC 501; CC-5013; IMiD3
Drug Category: Antineoplastic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Lenalidomide: Revimid; Revlimid (Celgene); Revlimid;
Absorption: Rapidly absorbed following oral administration, with maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose. Co-administration with food does not alter the extent of absorption (AUC) but does reduce the maximal plasma concentration (Cmax) by 36%. The pharmacokinetic disposition of lenalidomide is linear.
Toxicity (Overdose): The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions.
Protein Binding: 30%
Biotransformation: The metabolic profile of lenalidomide in humans has not been studied. In healthy volunteers, approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion. The process exceeds the glomerular filtration rate and therefore is partially or entirely active.
Half Life: 3 hours
Dosage Forms of Revlimid (Celgene): Not Available
Chemical IUPAC Name: 3-(7-amino-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
Chemical Formula: C13H13N3O3
Lenalidomide on Wikipedia: https://en.wikipedia.org/wiki/Lenalidomide
Organisms Affected: Humans and other mammals
