Targretin
Targretin - General Information
Targretin (Targretin) is an oral antineoplastic agent indicated by the FDA for Cutaneous T cell lymphoma. It has been used off-label for lung cancer, breast cancer, and Kaposi's sarcoma. [Wikipedia]
Pharmacology of Targretin
Targretin is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Targretin is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Targretin selectively binds and activates retinoid X receptor subtypes (RXRa, RXRb, RXRg). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin Dy receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Targretin inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models.
Targretin for patients
Targretin Interactions
No formal studies to evaluate drug interactions with bexarotene have been conducted. Bexarotene oxidative metabolites appear to be formed by cytochrome P450 3A4.
On the basis of the metabolism of bexarotene by cytochrome P450 3A4, ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, and other inhibitors of cytochrome P450 3A4 would be expected to lead to an increase in plasma bexarotene concentrations. Furthermore, rifampin, phenytoin, phenobarbital, and other inducers of cytochrome P450 3A4 may cause a reduction in plasma bexarotene concentrations.
Concomitant administration of Targretin ® capsules and gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene, probably at least partially related to cytochrome P450 3A4 inhibition by gemfibrozil. Under similar conditions, bexarotene concentrations were not affected by concomitant atorvastatin administration. Concomitant administration of gemfibrozil with Targretin ® capsules is not recommended.
Targretin Contraindications
Targretin ® capsules are contraindicated in patients with a known hypersensitivity to bexarotene or other components of the product.
Pregnancy: Category X
Targretin ® (bexarotene) capsules may cause fetal harm when administered to a pregnant woman. Targretin ® capsules must not be given to a pregnant woman or a woman who intends to become pregnant. If a woman becomes pregnant while taking Targretin ® capsules, Targretin ® capsules must be stopped immediately and the woman given appropriate counseling.
Bexarotene caused malformations when administered orally to pregnant rats during days 7-17 of gestation. Developmental abnormalities included incomplete ossification at 4 mg/kg/day and cleft palate, depressed eye bulge/microphthalmia, and small ears at 16 mg/kg/day. The plasma AUC of bexarotene in rats at 4 mg/kg/day is approximately one third the AUC in humans at the recommended daily dose. At doses greater than 10 mg/kg/day, bexarotene caused developmental mortality. The no effect dose for fetal effects in rats was 1 mg/kg/day (producing an AUC approximately one sixth of the AUC at the recommended human daily dose).
Women of child-bearing potential should be advised to avoid becoming pregnant when Targretin ® capsules are used. The possibility that a woman of child-bearing potential is pregnant at the time therapy is instituted should be considered. A negative pregnancy test (e.g., serum beta-human chorionic gonadotropin, beta-HCG) with a sensitivity of at least 50 mlU/L should be obtained within one week prior to Targretin ® capsules therapy, and the pregnancy test must be repeated at monthly intervals while the patient remains on Targretin ® capsules. Effective contraception must be used for one month prior to the initiation of therapy, during therapy and for at least one month following discontinuation of therapy; it is recommended that two reliable forms of contraception be used simultaneously unless abstinence is the chosen method. Male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant must use condoms during sexual intercourse while taking Targretin ® capsules and for at least one month after the last dose of drug. Targretin ® capsules therapy should be initiated on the second or third day of a normal menstrual period. No more than a one month supply of Targretin ® capsules should be given to the patient so that the results of pregnancy testing can be assessed and counseling regarding avoidance of pregnancy and birth defects can be reinforced.
Additional information about Targretin
Targretin Indication: For the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy
Mechanism Of Action: The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Bexarotene
Synonyms: Not Available
Drug Category: Anticarcinogenic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Bexarotene: Targret; Targretin; Targretyn; Targrexin;
Absorption: Not Available
Toxicity (Overdose): Not Available
Protein Binding: >99%
Biotransformation: Not Available
Half Life: 7 hours
Dosage Forms of Targretin: Capsule Oral
Chemical IUPAC Name: 4-[1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)ethenyl]benzoic acid
Chemical Formula: C24H28O2
Bexarotene on Wikipedia: https://en.wikipedia.org/wiki/Bexarotene
Organisms Affected: Humans and other mammals
