bexarotene

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/Excretion: Mostly metabolized by the liver, mainly 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;
Concurrent use of gemfibrozil;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Hepatic impairment;
Renal 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.
↑levels and risk of toxicity with gemfibrozil; concurrent use not recommended.
Combination regimen of paclitaxel and carboplatin↑ levels.
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).
Concurrent use of insulin, sulfonylureas, or thiazolidinediones in patients with 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 ⬆ ⬇

PO (Adults ): 300 mg/m² once daily; dosage to be adjusted based on tolerance/toxicity.
(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 4 times daily as tolerated; continued 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:

Monitor fasting blood 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 elevated or become elevated during therapy, institute 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 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 wk. 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.

Implementation ⬆ ⬇

Triglycerides should be normal or normalized with medication prior to starting bexarotene.
PO: 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.
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 photosensitivity 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.
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 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 must use a condom during and for at least 1 mo after completion of therapy and should discuss precautions with health care professional.
Explain need for regular blood tests to patient.
Advise patient to avoid showering, bathing, or swimming for at least 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 professional if they become troublesome.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇