bexarotene

High Alert

PO: Cutaneous T-cell lymphoma (cutaneous manifestations) in patients who have failed at least one previous systemic therapy.
Topical 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 that are ultimately responsible for cellular differentiation and proliferation. Inhibits growth of some tumor cell lines, including lines of hematopoietic and squamous cell origin.

Therapeutic effects:

Decreased spread of cutaneous T-cell lymphoma.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration; absorption is enhanced by a fat-containing meal. Some systemic absorption follows topical application.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Mostly metabolized by the liver, primarily by the CYP3A4 isoenzyme; 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)

ROUTE	ONSET	PEAK	DURATION
PO, Top	within 4 wk‡	unknown	unknown

‡Some responses took longer.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
Hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be more sensitive to drug effects.

Adv. Reactions/Side Effects ⬆ ⬇

Oral

CV: peripheral edema

Derm: dry skin, rash, alopecia, exfoliative dermatitis, photosensitivity

EENT: new/worsening cataracts

Endo: hyperlipidemia, hypothyroidism, hypercholesterolemia

GI: abdominal pain, nausea, ↑liver enzymes, anorexia, diarrhea, PANCREATITIS, vomiting

Hemat: anemia, leukopenia

Neuro: headache, weakness, insomnia

Misc: flu-like syndrome

Topical

CV: edema

Derm: pruritus, skin disorder, rash

Endo: hyperlipidemia

Hemat: leukopenia

Misc: lymphadenopathy

Interactions ⬆ ⬇

Drug-drug:

Interactions are noted for oral use but may occur with topical use, especially with high dose/prolonged treatment.
Gemfibrozil may ↑ levels and risk of toxicity; concurrent use not recommended.
Combination regimen of paclitaxel and carboplatin may ↑ levels and risk of toxicity.
May ↓ levels and effectiveness of CYP3A4 substrates, including atorvastatin, tamoxifen, paclitaxel, and hormonal contraceptives.
Vitamin A may ↑ risk of toxicity (limit supplementation to <15,000 units/day).
Insulin, sulfonylureas, or thiazolidinediones may ↑ risk of hypoglycemia in patients with diabetes.
Topical: May ↑ risk of toxicity of DEET (N,N-diethyl-m-toluamide)-containing insect repellents; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 300 mg/m² once daily; dosage to be adjusted based on tolerance/toxicity.
(Adults ): Apply once every other day for 1 wk; ↑ at weekly interval to once daily, then twice daily, then 3 times daily, and finally 4 times daily as tolerated; continue as long as benefit is derived.

Availability ⬆ ⬇

(Generic available)

Capsules: 75 mg
Topical gel: 1% (contains dehydrated alcohol and propylene glycol)

Assessment ⬆ ⬇

Monitor for signs and symptoms of pancreatitis.
Assess for visual difficulties. May cause cataracts.

Lab Test Considerations:

Obtain a pregnancy test with a sensitivity of at least 50 mIU/L within 1 wk of starting bexarotene and monthly during therapy.
- Monitor fasting lipid levels prior to therapy, weekly until lipid response is established (usually 2–4 wk), and every 8 wk thereafter. May cause hyperlipidemia. Maintain triglyceride levels <400 mg/dL during therapy. If fasting triglyceride levels are ↑ or become ↑ during therapy, start lipid-lowering therapy. May require ↓ dose or stopping bexarotene.
- Monitor liver function tests prior to therapy and after 1, 2, and 4 wk of therapy. If stable, monitor every 8 wk thereafter. May ↑ AST, ALT, and serum bilirubin. If levels are > 3 times the upper limit of normal, may require interruption or discontinuation of therapy.
- 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 wk. Usually resolves within 30 days with dose ↓ or discontinuation of therapy.

Implementation ⬆ ⬇

PO: Administer all capsules at once, once a day with or immediately following a meal. DNC: Swallow capsules whole; do not chew or dissolve in liquid or in mouth.
Topical Initiate therapy with gel on 2nd or 3rd 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 provider. Do not use capsules after expiration date.
Advise patient to notify health care provider immediately if signs and symptoms of pancreatitis (persistent nausea, vomiting, abdominal or back pain) occur.
Caution patient to wear protective clothing and avoid sunlight and artificial ultraviolet light to prevent photosensitivity reactions.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications, especially vitamin A.
Rep: May cause fetal harm. 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 one being condom, diaphragm, cervical cap, IUD, or spermicide. Patients should not breastfeed during therapy. Male patients whose partner is pregnant or capable of becoming pregnant must use a condom during and for ≥1 mo after completion of therapy.
Explain need for regular blood tests to patient.
Topical Advise patient to avoid showering, bathing, or swimming for ≥3 hr 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 provider if they become troublesome.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇