targretin

bexarotene

(beks-air-oh-teen) ,

Targretin

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: retinoids
Pregnancy Category: X

Indications

Oral—Treatment of cutaneous T-cell lymphoma (cutaneous manifestations) in patients who have failed at least one previous systemic therapy.Topical—Treatment of cutaneous T-cell lymphoma (cutaneous manifestations) in Stage IA or IB patients who have refractory/persistent lesions and have not responded to or tolerated other treatments.

Action

Binds and inactivates selected retinoid X receptors (RXRs) that are ultimately responsible for cellular differentiation and proliferation. Inhibits growth of some tumor cell lines including lines of hematopoetic and squamous cell origin.

Therapeutic effects

Decreased spread of cutaneous T-cell lymphoma.

Pharmacokinetics

Absorption: Well absorbed following oral administration, absorption is enhance by a fat-containing meal. Some systemic absorption follows topical application.
Distribution: Unknown.
Protein Binding: >99%.
Metabolism and Excretion: Mostly metabolized by the liver, mainly by the CYP3A4 enzyme system; some metabolites may be pharmacologically active. Excreted almost entirely via hepatobiliary elimination, <1% excreted in urine.
Half-life: 7 hr.

Time/action profile (improvement in lesions)

ROUTEONSETPEAKDURATION
PO, Topwithin 4 wk†unknownunknown
† Some responses took longer.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent use of gemfibrozil; Obstetric: Pregnancy (may cause fetal harm); Lactation: Avoid breastfeeding.
Use Cautiously in: Hepatic impairment (may ↓ elimination); Renal impairment (may alter protein binding); Diabetic patients (concurrent use with some antidiabetics may increase the risk of hypoglycemia); Patients with child-bearing potential/male patients with partners who have child-bearing potential; Geriatric: Elderly patients may be more sensitive to drug effects; Pediatric: Safe and effective use in pediatric patients has not been established.

Adverse Reactions/Side Effects

Oral

Central nervous system

  • headache (most frequent)
  • weakness (most frequent)
  • insomnia

Ear, Eye, Nose, Throat

  • new/worsening cataracts (most frequent)

Cardiovascular

  • peripheral edema (most frequent)

Gastrointestinal

  • pancreatitis (life-threatening)
  • abdominal pain (most frequent)
  • nausea (most frequent)
  • anorexia
  • diarrhea
  • liver function abnormalities
  • vomiting

Dermatologic

  • dry skin (most frequent)
  • rash (most frequent)
  • alopecia
  • exfoliative dermatitis
  • photosensitivity

Endocrinologic

  • hyperlipidemia (most frequent)
  • hypercholesterolemia
  • hypothyroidism (most frequent)

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)

Miscellaneous

  • flu-like syndrome
Topical

Central nervous system

  • headache (most frequent)

Cardiovascular

  • edema

Dermatologic

  • pain (most frequent)
  • pruritus (most frequent)
  • skin disorder (most frequent)
  • rash (most frequent)

Endocrinologic

  • hyperlipidemia

Hematologic

  • leukopenia

Miscellaneous

  • lymphadenopathy

Interactions

Drug-Drug interaction

Interactions are noted for oral use, but may occur with topical use especially with high dose/prolonged treatment.↑ levels and risk of toxicity with gemfibrozil ; concurrent use not recommended.Combination regimen of paclitaxel and carboplatin ↑ levels.May act as an inducer of the CYP3A4 enzyme system; may ↓ levels and effectiveness of substrates of the CYP3A4 system including atorvastatin, tamoxifen, paclitaxel, and hormonal contraceptives.Vitamin A may ↑ risk of toxicity (limit supplementation to <15,000 IU/day).Concurrent use of insulin, sulfonylureas, or thiazolidinediones in diabetic patients may ↑ risk of hypoglycemia.Topical—Concurrent use with DEET (N,N-diethyl-m-toluamide)-containing insect repellents may ↑ risk of DEET toxicity and should be avoided.

Route/Dosage

Oral (Adults) 300 mg/m2 once daily; dosage to be adjusted based on tolerance/toxicity.
Topical (Adults) Apply once every other day for 1 wk, increase at weekly interval to once daily, then twice daily, then 3 times daily and finally four times daily as tolerated, continued as long as benefit is derived.

Availability

Capsules: 75 mg
Topical gel: 1.0% (contains dehydrated alcohol and propylene glycol in 60 gram tubes

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of pancreatitis.
  • Assess for visual difficulties. May cause cataracts.
  • Lab Test Considerations: Monitor fasting blood lipid levels prior to therapy, weekly until lipid response is established (usually 2–4 wks), every 8 wks thereafter. May cause hyperlipemia and hypercholesterolemia. Maintain triglyceride levels <400 mg/dL during therapy. If fasting triglyceride levels are elevated or become elevated during therapy, institute antilipemic therapy. May require ↓ dose or stopping bexarotene.
    • Monitor liver function tests prior to therapy and after 1, 2, and 4 wks of therapy. If stable, monitor every 8 wks thereafter. May cause ↑AST, ALT, and serum bilirubin. May require interruption or discontinuation of therapy if levels are > 3 times the upper limit of normal.
    • Monitor thyroid function tests at baseline and periodically during therapy. Consider thyroid replacement if levels ↓.
    • Monitor WBC with differential at baseline and periodically during therapy. May cause leukopenia in the range of 1000 to <3000 WBC/mm3. Onset is usually 4–8 wks. Usually resolves within 30 days with dose ↓ or discontinuation of therapy.
    • Obtain a pregnancy test with a sensitivity of at least 50 mIU/L within 1 wk of starting bexarotene and monthly during therapy.

Potential Nursing Diagnoses

Impaired skin integrity (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Triglycerides should be normal or normalized with medication prior to starting bexarotene.
  • Oral: Administer all capsules at once, once a day with or immediately following a meal. Swallow capsules whole; do not chew or dissolve in liquid or in mouth.
  • Topical: Initiate therapy with gel on second or third day of a normal menstrual period. Apply generous amount of gel to cover entire lesion. Allow gel to dry for 5–10 min before covering with clothing. If applied after shower or bath, wait 20 min before application. Do not apply gel to normal skin or mucosal surfaces. Do not cover with occlusive dressings. Wash hands following application. Do not use gel after the expiration date.

Patient/Family Teaching

  • Instruct patient to take or apply bexarotene as directed. Take missed doses as soon as remembered unless close to time for next dose; do not double doses.
  • Advise patient to avoid touching broken or leaking capsules and notify pharmacist. If contents get on skin, immediately wash area with soap and water and notify health care professional. Do not use capsules after expiration date.
  • Advise patient to notify health care professional immediately if signs and symptoms of pancreatitis (persistent nausea, vomiting and abdominal or back pain) occur.
  • Caution patient to wear protective clothing and avoid sunlight and artificial ultraviolet light to prevent phototoxocity reactions.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially vitamin A.
  • Caution patient that bexarotene is teratogenic and should be avoided during pregnancy. Pregnancy tests will be taken before starting and monthly during therapy. Effective contraception must be used 1 mo before beginning therapy, during, and 1 mo following therapy. Two forms of contraception are recommended with at least 1 being condom, diaphragm, cervical cap, IUD, or spermacide. Patients should not breastfeed during therapy. Male patients whose partner is pregnant or capable of becoming pregnant should discuss precautions with health care professional.
  • Explain need for regular blood tests to patient.
  • Topical: Advise patient to avoid showering, bathing, or swimming for at least 3 hrs after application. Avoid insect repellent containing DEET or other products containing DEET during therapy. Keep gel away from flame; contains alcohol.
  • Inform patient that redness, itching, burning, irritation, and scaling at application area may occur; notify health care professional if they become troublesome.

Evaluation/Desired Outcomes

  • Decrease in lesions of cutaneous T-cell lymphoma.

tar·gre·tin

(tar'gre-tin),
A novel synthetic retinoid analog that binds to members of the RXR subclass of receptors; of low toxicity, it induces apoptosis in a variety of tumor cell types.

bexarotene

A retinoid that binds to retinoid X receptors, upregulating their activity by either removing negative transcription control or by facilitating transcription. It is FDA-approved for treating cutaneous T cell lymphoma, and has been used off label for lung and breast cancer, and Kaposi sarcoma.
Adverse effects Similar to hypervitaminosis A—headache, nausea, vomiting, lip inflammation, mucous-membrane dryness, joint pain, scaly skin, hyperlipidaemia
References in periodicals archive ?
Mylan CEO Heather Bresch commented: "Mylan's launch of the first and only generic Targretin is another example of our commitment to expand access to high quality, more affordable medicines.
The drug, also known as Targretin, was approved by the US Food and Drug Administration in 1999 for treating a type of skin cancer known as refractory cutaneous T-cell lymphoma.
Tokyo, Japan, Sept 8, 2006 - (JCN) - Eisai has announced that it signed a product acquisition agreement with California-based Ligand Pharmaceuticals for exclusive global rights for their four oncology-related products, ONTAK (denileukin diftitox), Targretin (bexarotene) capsules, Targretin (bexarotene) gel 1% and Panretin (alitretinoin) gel 0.
If approved in Europe, ONZAR will join Targretin(R) capsules and Panretin(R) gel, which were launched this quarter, and Targretin gel, whose MAA is under review, as we bring our U.
Based upon available information, Banner believes that it is the first applicant to file an ANDA for Targretin containing a Paragraph IV certification under the provisions of the Hatch-Waxman Act, and expects to qualify for 180 days of generic marketing exclusivity upon FDA approval.
Bexarotene is the generic version of TARGRETIN, which 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.
Food and Drug Administration has granted marketing approval for Targretin (bexarotene) capsules with once daily oral administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy.
Previous research demonstrated that Targretin is equally as effective as tamoxifen at preventing the emergence of breast cancer tumors in this animal model, which was designed to test prevention.
Gross margin for the first quarter 2006 compared to the same 2005 period was positively impacted by a 7% AVINZA price increase effective April 1, 2005; a 7% price increase for the Company's oncology products effective January 1, 2005; and a 4% and 5% price increase for ONTAK and Targretin, respectively, effective July 1, 2005.
Targretin is the first in a new class of oral diabetes therapies.