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The safety of Targretin® gel has been assessed in clinical studies of 117 patients with CTCL who received Targretin® gel for up to 172 weeks. In the multicenter open-label study, 50 patients with CTCL received Targretin® gel for up to 98 weeks. The mean duration of therapy for these 50 patients was 199 days. The most common adverse events reported with an incidence at the application site of at least 10% in patients with CTCL were rash, pruritus, skin disorder, and pain.
Adverse events leading to dose reduction or study drug discontinuation in at least two patients were rash, contact dermatitis, and pruritus.
Of the 49 patients (98%) who experienced any adverse event, most experienced events categorized as mild (9 patients, 18%) or moderate (27 patients, 54%). There were 12 patients (24%) who experienced at least one moderately severe adverse event. The most common moderately severe events were rash (7 patients, 14%) and pruritus (3 patients, 6%). Only one patient (2%) experienced a severe adverse event (rash).
In the patients with CTCL receiving Targretin® gel, adverse events reported regardless of relationship to study drug at an incidence of 5% are presented in Table 1.
A similar safety profile for Targretin® gel was demonstrated in the Phase I-II program. For the 67 patients enrolled in the Phase I-II program, the mean duration of treatment was 436 days (range 12-1203 days). As in the multicenter study, the most common adverse events regardless of relationship to study drug in the Phase I-II program were rash (78%), pain (40%), and pruritus (40%).
Table 1: Incidence of All Adverse Events* and Application
Site Adverse Events with Incidence ≥ 5% for All Application Frequencies of
Targretin® Gel in the Multicenter CTCL Study
|COSTART 5 Body System/Preferred Term||All Adverse Events
N = 50
|Application Site Adverse Events
N = 50
|Skin and Appendages|
|Contact Dermatitis1||7 (14)||4 (8)|
|Exfoliative Dermatitis||3 (6)||0|
|Pruritus2||18 (36)||9 (18)|
|Rash3||36 (72)||28 (56)|
|Maculopapular Rash||3 (6)||0|
|Skin Disorder (NOS)4||13 (26)||9 (18)|
|Body as a Whole|
|Pain||15 (30)||9 (18)|
|Peripheral Edema||3 (6)||0|
|Hemic and Lymphatic|
|WBC Abnormal||3 (6)||0|
|Metabolic and Nutritional|
|Paresthesia||3 (6)||3 (6)|
|Cough Increased||3 (6)||0|
|* Regardless of association with treatment
Includes Investigator terms such as:
1 Contact dermatitis, irritant contact dermatitis, irritant dermatitis
2 Pruritus, itching, itching of lesion
3 Erythema, scaling, irritation, redness, rash, dermatitis
4 Skin inflammation, excoriation, sticky or tacky sensation of skin; NOS = Not Otherwise Specified
Read the Targretin Gel (bexarotene gel) Side Effects Center for a complete guide to possible side effects
Patients who are applying Targretin® gel should not concurrently use products that contain DEET (N,N-diethyl-m-toluamide), a common component of insect repellent products. An animal toxicology study showed increased DEET toxicity when DEET was included as part of the formulation.
No formal studies to evaluate drug interactions with bexarotene have been conducted. Bexarotene oxidative metabolites appear to be formed through cytochrome P450 3A4.
On the basis of the metabolism of bexarotene by cytochrome P450 3A4, concomitant ketoconazole, itraconazole, erythromycin and grapefruit juice could increase bexarotene plasma concentrations. Similarly, based on data that gemfibrozil increases bexarotene concentrations following oral bexarotene administration, concomitant gemfibrozil could increase bexarotene plasma concentrations. However, due to the low systemic exposure to bexarotene after low to moderately intense gel regimens (see CLINICAL PHARMACOLOGY), increases that occur are unlikely to be of sufficient magnitude to result in adverse effects.
No drug interaction data are available on concomitant administration of Targretin® gel and other CTCL therapies.
No formal studies have been conducted with Targretin® gel in patients with renal insufficiency. Urinary elimination of bexarotene and its known metabolites is a minor excretory pathway for bexarotene ( < 1% of an orally administered dose), but because renal insufficiency can result in significant protein binding changes, and bexarotene is > 99% protein bound, pharmacokinetics may be altered in patients with renal insufficiency.
No specific studies have been conducted with Targretin® gel in patients with hepatic insufficiency. Because less than 1% of the dose of oral bexarotene is excreted in the urine unchanged and there is in vitro evidence of extensive hepatic contribution to bexarotene elimination, hepatic impairment would be expected to lead to greatly decreased clearance.
Bexarotene is highly bound ( > 99%) to plasma proteins. The plasma proteins to which bexarotene binds have not been elucidated, and the ability of bexarotene to displace drugs bound to plasma proteins and the ability of drugs to displace bexarotene binding have not been studied.
Read the Targretin Gel Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/2/2011
Additional Targretin Gel Information
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