Targretin: Uses, Dosage & Side Effects
Bexarotene 75 mg soft capsules – an oral rexinoid (selective RXR retinoid) for the treatment of skin manifestations of advanced cutaneous T-cell lymphoma (CTCL)
Targretin (bexarotene) is an orally administered anticancer medicine that belongs to a specialised class of retinoids called rexinoids. Unlike classical retinoids such as isotretinoin and acitretin, which act primarily on retinoic acid receptors (RARs), bexarotene selectively binds and activates retinoid X receptors (RXRs). This activation triggers a cascade of genetic signals that induces programmed cell death in malignant T lymphocytes, making Targretin a targeted treatment for cutaneous T-cell lymphoma (CTCL). It is indicated for the treatment of skin manifestations of advanced-stage CTCL in adult patients whose disease is refractory to at least one previous systemic therapy. Targretin is supplied as 75 mg soft capsules taken once daily with a fat-containing meal. Treatment requires a specialist in dermato-oncology or hematology and close laboratory monitoring because of characteristic effects on blood lipids, thyroid function, liver enzymes and blood counts, and because bexarotene is a highly teratogenic drug that must never be used during pregnancy.
Quick Facts: Targretin
Key Takeaways
- Targretin (bexarotene) is an oral rexinoid that selectively activates retinoid X receptors (RXRs) to induce apoptosis of malignant T lymphocytes in cutaneous T-cell lymphoma; the most common subtypes treated are mycosis fungoides and Sézary syndrome.
- It is indicated for adult patients with advanced-stage CTCL whose skin disease has not responded to at least one prior systemic therapy, and is typically used by specialists experienced in managing cutaneous lymphomas.
- The standard starting dose is 300 mg per square meter of body surface area per day, taken as a single oral dose with a fat-containing meal; doses are individualised based on response, lipid levels, thyroid function and tolerability.
- Nearly all patients develop hyperlipidaemia (very high triglycerides and cholesterol) and central hypothyroidism (from suppressed TSH) during treatment; routine lipid-lowering therapy and thyroid hormone replacement are commonly required alongside Targretin.
- Bexarotene is highly teratogenic and absolutely contraindicated in pregnancy; women of childbearing potential must use two reliable forms of contraception and have monthly pregnancy tests, and the drug must also be avoided during breastfeeding.
What Is Targretin and What Is It Used For?
The active substance in Targretin is bexarotene, a synthetic analogue of naturally occurring retinoids (vitamin A derivatives). Bexarotene is unique within the retinoid family because it binds selectively to a specific subset of retinoid receptors known as retinoid X receptors, or RXRs. For this reason, bexarotene and chemically similar compounds are often referred to as rexinoids. Classical retinoids used in dermatology, such as isotretinoin (for severe acne) and acitretin (for psoriasis), primarily act on a different receptor family called retinoic acid receptors (RARs). The RXR-selective profile of bexarotene translates into a distinct clinical activity and side-effect pattern that both oncologists and patients should understand.
Retinoid X receptors are nuclear transcription factors found inside the nucleus of almost every cell in the body. When bexarotene binds to an RXR, the activated receptor pairs with other nuclear receptors (including RARs, thyroid hormone receptors, vitamin D receptors and peroxisome proliferator-activated receptors) and regulates the expression of genes controlling cell growth, differentiation and apoptosis (programmed cell death). In malignant T lymphocytes of cutaneous T-cell lymphoma, RXR activation shifts the genetic program away from uncontrolled proliferation and towards maturation and controlled cell death. The clinical result is a reduction of skin lesions, improvement of itch and a slowing of disease progression.
Targretin is authorized by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA) and multiple other regulatory agencies worldwide. It is designated as an orphan medicinal product for cutaneous T-cell lymphoma, reflecting the rarity of this disease.
What Is Cutaneous T-Cell Lymphoma?
Cutaneous T-cell lymphoma (CTCL) is a group of rare non-Hodgkin lymphomas in which malignant T lymphocytes accumulate primarily in the skin. The two most common subtypes are mycosis fungoides (MF), characterised by progressive skin patches, plaques and eventually tumours, and Sézary syndrome, a leukaemic variant in which lymphoma cells are also found circulating in the blood. CTCL typically develops slowly over many years and is usually managed as a chronic disease rather than cured. Early-stage disease often responds well to skin-directed therapies such as topical steroids, phototherapy and topical chemotherapy. Advanced-stage disease with extensive skin involvement, tumours, lymph node spread or blood involvement usually requires systemic therapy.
In the treatment hierarchy established by international guidelines (NCCN, EORTC), Targretin is considered a standard systemic option for advanced CTCL once simpler treatments have failed or become inadequate. Response rates in pivotal phase II/III trials ranged from approximately 45% in early-stage refractory CTCL to around 55% in patients with advanced disease, with time-to-response typically 8–12 weeks.
Approved Indication
Targretin is indicated for the treatment of skin manifestations of advanced-stage cutaneous T-cell lymphoma (CTCL) in adult patients who are refractory to at least one previous systemic treatment. Refractory, in this context, means the disease has not responded adequately, has progressed despite treatment, or has recurred after a response. The decision to initiate Targretin is made by a specialist in dermato-oncology or hematology with experience in cutaneous lymphoma management and access to multidisciplinary care. Targretin is not approved as first-line therapy for newly diagnosed CTCL, and its use in other malignancies or non-malignant skin conditions is not supported by regulatory approval.
How Bexarotene Works at the Molecular Level
Bexarotene is a ligand of all three RXR subtypes: RXR-alpha, RXR-beta and RXR-gamma. Once it enters a cell, bexarotene crosses the nuclear membrane and binds to these receptors. RXRs function as obligatory heterodimer partners for many other nuclear receptors, meaning they form pairs that jointly regulate gene expression. When bexarotene binds an RXR, the receptor complex recruits coactivator proteins and binds to specific DNA sequences called RXR response elements in the regulatory regions of target genes. This activates or represses transcription of genes involved in cell cycle control, apoptosis and immune signalling. In malignant T cells, this cascade leads to cell-cycle arrest, enhanced apoptosis and modulation of cytokine production.
The selectivity of bexarotene for RXRs (with more than 100-fold higher affinity for RXRs than for RARs) explains why it has a different side-effect profile from classical retinoids. However, RXRs also partner with the thyroid hormone receptor and the liver X receptor, which is why bexarotene produces characteristic changes in thyroid hormone regulation (central hypothyroidism through suppression of TSH) and in lipid metabolism (marked increases in triglycerides and cholesterol). These class effects are an integral part of the pharmacology of Targretin and are expected rather than idiosyncratic.
All rexinoids are retinoids, but not all retinoids are rexinoids. Classical retinoids (isotretinoin, tretinoin, acitretin, etretinate) act mainly on retinoic acid receptors (RARs). Rexinoids, of which bexarotene is the prototypical example, selectively activate retinoid X receptors (RXRs). Because RXRs pair with many other nuclear receptors, rexinoids have broad effects on lipid metabolism, thyroid signalling and immune function – effects that are both therapeutically useful in CTCL and responsible for most of the drug’s predictable side effects.
What Should You Know Before Taking Targretin?
Contraindications
There are several absolute contraindications to Targretin that must be reviewed carefully before any prescription is issued. Your specialist will confirm none of these apply to you before starting treatment.
- Pregnancy: Targretin is absolutely contraindicated in pregnancy. Bexarotene is highly teratogenic and is expected to cause severe birth defects based on mechanism of action and animal studies consistent with other retinoids.
- Women of childbearing potential without reliable contraception: Targretin must not be prescribed to any woman who could become pregnant unless she has been enrolled in a structured pregnancy-prevention programme and is using two complementary methods of contraception (see below).
- Breastfeeding: Bexarotene or its metabolites are likely to be excreted in breast milk and could harm a nursing infant. Breastfeeding must be discontinued before Targretin is initiated.
- Known hypersensitivity: Patients with a documented allergy to bexarotene, other retinoids, or any of the excipients (including soya-bean oil and sorbitol) must not take Targretin.
- Current or past history of pancreatitis: Because bexarotene markedly elevates triglycerides, it can trigger acute pancreatitis; prior pancreatitis is considered a contraindication in most prescribing information unless the precipitating cause has been definitively resolved.
- Uncontrolled hypercholesterolaemia or hypertriglyceridaemia: Patients whose blood lipids are already uncontrolled at baseline must have these corrected before bexarotene is started, as the drug will further elevate them.
- Uncontrolled hypothyroidism, hypervitaminosis A, or ongoing systemic infection: These conditions must be addressed before treatment begins.
- Hepatic insufficiency: Because bexarotene is almost exclusively cleared by the liver, significant liver impairment is a relative or absolute contraindication depending on severity.
Warnings and Precautions
Bexarotene is a powerful teratogen. Any pregnancy during or shortly after treatment may result in severe and often lethal birth defects. Women of childbearing potential must use two reliable forms of contraception (one highly effective method, such as a hormonal implant or intrauterine device, plus a barrier method such as a condom). Contraception must start at least one month before the first dose, continue throughout treatment, and continue for at least one month after the last dose. A negative pregnancy test is required within one week before treatment starts and must be repeated monthly during treatment. Report any suspected pregnancy immediately; Targretin must be stopped at once.
Beyond the risk of teratogenicity, several other laboratory and clinical parameters require close monitoring before and during Targretin therapy. Your doctor will arrange baseline blood tests and schedule repeat testing throughout treatment.
- Hyperlipidaemia: Bexarotene very commonly raises fasting triglycerides (often into the severe range, above 4.5 mmol/L or 400 mg/dL) and total cholesterol. Fasting lipid profiles should be checked at baseline, weekly for the first 2–4 weeks, then at least monthly. Lipid-lowering therapy (typically fenofibrate, omega-3 fatty acids, statins, or a combination) is frequently required. Gemfibrozil must not be used for this purpose (see drug interactions).
- Hypothyroidism: Bexarotene suppresses pituitary TSH, leading to central hypothyroidism in about 40% of patients. Thyroid function (TSH and free T4) should be measured at baseline and then every 1–2 months initially. Levothyroxine replacement is often started early in treatment and adjusted based on symptoms and free T4 levels (TSH is not a reliable marker under bexarotene therapy).
- Hepatotoxicity: Elevations of liver transaminases (AST, ALT) and alkaline phosphatase are common. Liver function tests should be checked at baseline, weekly for the first month, then at 1-, 2- and 3-month intervals.
- Leukopenia and neutropenia: Reversible decreases in white blood cell count, particularly neutrophils, may occur. Full blood counts should be monitored throughout treatment.
- Cataracts: Cataracts have been reported with long-term retinoid therapy, including bexarotene. Patients with visual changes should have an ophthalmological assessment.
- Pancreatitis: Severe hypertriglyceridaemia can precipitate acute pancreatitis. Treatment must be stopped immediately if triglycerides rise above approximately 9 mmol/L (800 mg/dL) despite lipid-lowering therapy, or if symptoms of pancreatitis develop (severe abdominal pain radiating to the back, vomiting).
- Photosensitivity: As with other retinoids, the skin may become more sensitive to sunlight. Patients should minimise sun exposure, use sunscreen and protective clothing.
- Diabetes mellitus: Bexarotene may enhance the effect of insulin and oral antidiabetic drugs, sometimes causing hypoglycaemia. Blood glucose should be monitored closely in diabetic patients, and dose adjustments of antidiabetic medications may be needed.
Pregnancy and Breastfeeding
Pregnancy must be avoided at all costs during Targretin therapy and for at least one month after the last dose. Bexarotene is a retinoid, and the retinoid class has consistently been shown to cause severe human teratogenicity, including characteristic craniofacial, cardiovascular, thymic and central nervous system malformations. Because bexarotene blood levels can persist for weeks after treatment stops, the post-treatment contraception requirement is strict.
Women of childbearing potential (essentially any woman who has not been postmenopausal for at least one year, has not undergone surgical sterilisation, or is not otherwise permanently infertile) must:
- Use two reliable methods of contraception simultaneously, one highly effective (hormonal contraception, copper or hormonal IUD, implant, vasectomised partner) and one barrier method (male condom, diaphragm).
- Start contraception at least one month before the first Targretin dose.
- Continue contraception throughout treatment.
- Continue contraception for at least one month after the last dose.
- Have a negative serum or urine pregnancy test within one week before starting treatment.
- Repeat pregnancy testing every month during treatment and one month after the last dose.
- Report any missed periods, contraceptive failure or suspected pregnancy immediately.
Male patients taking Targretin must use condoms during intercourse with pregnant women or with women of childbearing potential, because traces of bexarotene may be present in semen. This requirement continues throughout treatment and for at least one month after the last dose.
Breastfeeding is contraindicated during Targretin treatment. It is not known whether bexarotene is excreted in human breast milk, but because of its lipophilicity and the predicted risk to the infant, breastfeeding must not be performed while taking this medicine.
Use in Children and Adolescents
Targretin is indicated for adult patients only. The safety and efficacy of bexarotene in children and adolescents below 18 years of age have not been established, and it is not recommended for use in this age group. CTCL is rare in children, and any pediatric case should be managed in a specialised centre.
Use in Elderly Patients
Older adults can respond well to Targretin but may be more susceptible to hypothyroidism, hyperlipidaemia and cataract formation. The usual adult dose applies, but more frequent monitoring and gentler dose titration are often appropriate. Baseline assessment of cardiovascular risk, renal function and concomitant medications is particularly important in this population.
Driving and Operating Machinery
Targretin has no direct effect on the ability to drive or use machines. However, patients sometimes experience fatigue, dizziness, headache or visual changes (including cataracts after long-term treatment), all of which can impair the ability to drive safely. Patients experiencing such symptoms should refrain from driving and using machinery and inform their physician.
Important Information About Ingredients
Targretin soft capsules contain polyethylene glycol, polysorbate 20, povidone, butylated hydroxyanisole and butylated hydroxytoluene in the drug core, with the capsule shell made of gelatin, sorbitol solution, glycerol and titanium dioxide. Patients with hereditary fructose intolerance should consult their doctor before taking Targretin because of its sorbitol content. The capsules are not suitable for patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption when such excipients are present, so the full patient information leaflet for the specific product received should be consulted.
How Does Targretin Interact with Other Drugs?
Bexarotene is cleared primarily by the hepatic cytochrome P450 enzyme CYP3A4, and bexarotene itself is also a CYP3A4 inducer. This combination creates two categories of interaction: drugs that change bexarotene blood levels (and therefore toxicity or effectiveness) and drugs whose levels are changed by bexarotene (increasing or reducing their effect). It is essential that patients tell their oncologist about every medicine, supplement, herbal product and vitamin they take, including over-the-counter items such as antacids and herbal teas.
Some interactions are clinically significant enough that the combinations are avoided altogether; others require only careful monitoring. Your treating physician will perform a structured medication review before each dose adjustment.
Major Interactions
| Interacting Drug / Substance | Effect | Clinical Significance |
|---|---|---|
| Gemfibrozil (fibrate, lipid-lowering drug) | Markedly increased bexarotene plasma concentrations; paradoxically increases triglycerides rather than lowering them | Contraindicated – must not be used concomitantly; use fenofibrate instead for triglyceride management |
| Ketoconazole, itraconazole, voriconazole, posaconazole (azole antifungals, strong CYP3A4 inhibitors) | Increased bexarotene levels, greater risk of lipid, thyroid and liver toxicity | Avoid combination; if unavoidable, reduce bexarotene dose and intensify monitoring |
| Erythromycin, clarithromycin (macrolide antibiotics) | Inhibition of CYP3A4 increases bexarotene exposure | Avoid; substitute with alternatives such as azithromycin (weaker CYP3A4 effect) when appropriate |
| Grapefruit juice and grapefruit-containing products | Inhibits intestinal CYP3A4; raises bexarotene blood levels unpredictably | Avoid throughout treatment |
| Rifampicin, rifabutin (antibiotics), carbamazepine, phenytoin, phenobarbital (antiepileptics) | Strong CYP3A4 induction decreases bexarotene plasma levels and may reduce efficacy | Avoid if possible; consider alternative agents and closely follow response to CTCL therapy |
| St John’s wort (Hypericum perforatum, herbal supplement) | Strong CYP3A4 inducer; reduces bexarotene levels | Must be discontinued before starting Targretin |
| Vitamin A and beta-carotene supplements (>15,000 IU/day) | Additive retinoid toxicity (mucocutaneous effects, hepatotoxicity, hyperlipidaemia, teratogenicity) | Avoid high-dose vitamin A supplementation; standard multivitamins generally acceptable |
Minor Interactions and Additional Considerations
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Tamoxifen (breast cancer therapy) | Bexarotene induces CYP3A4, reducing tamoxifen active-metabolite levels | Avoid combination where possible; monitor for reduced antitumour effect |
| Combined oral contraceptives | CYP3A4 induction by bexarotene may reduce contraceptive hormone levels and effectiveness | Hormonal contraception alone is insufficient; always combine with a barrier method |
| Insulin and oral antidiabetic drugs (sulfonylureas, meglitinides) | Enhanced glucose-lowering effect; hypoglycaemia risk | Monitor blood glucose closely in diabetic patients; antidiabetic doses may need reduction |
| Atorvastatin, simvastatin and other CYP3A4-metabolised statins | Reduced statin levels via CYP3A4 induction | Consider pravastatin or rosuvastatin if statin therapy is needed; monitor lipid response |
| Warfarin, direct oral anticoagulants (DOACs) | Possible reduction in anticoagulant effect due to CYP3A4 induction | Monitor INR (warfarin) or consider DOAC selection carefully; adjust as required |
| Tetracyclines and systemic retinoids (other retinoids) | Increased risk of benign intracranial hypertension (pseudotumor cerebri) | Avoid combination; report severe headaches or visual changes immediately |
| Vaccines (live attenuated) | Possible reduced response and theoretical infection risk due to immunomodulation | Avoid live vaccines during treatment; inactivated vaccines generally safe |
As the interaction profile of bexarotene is complex, always involve your pharmacist when starting or stopping any other medicine. Community pharmacists can cross-check your full medication list against current interaction databases and alert your oncologist about any new risks.
What Is the Correct Dosage of Targretin?
Targretin is taken orally as 75 mg soft capsules. The dose is individualised based on body surface area (BSA), calculated from height and weight. The standard starting dose is 300 mg per square meter per day, given as a single daily dose. For most adults this corresponds to 4–6 capsules per day, taken at the same time with food.
Capsules must be swallowed whole with a glass of water. They should not be crushed, chewed or opened, both to preserve stability and to protect the person handling them (retinoids can be absorbed through the skin). Ideally, the dose is taken with a meal that contains some fat, because fat substantially increases bexarotene absorption. Consistency from day to day is important; taking the dose at very different times of day or on an empty stomach on some days can produce erratic blood levels.
Adults (Starting Dose)
Standard Starting Dose – CTCL Refractory to Prior Systemic Therapy
Dose: 300 mg/m² body surface area per day, rounded to the nearest 75 mg capsule.
Schedule: Once daily, taken with a meal (preferably containing fat).
Typical adult dose: Approximately 300–450 mg per day (4–6 capsules) for most adults with BSA between 1.5 and 2.0 m².
Duration: Treatment continues as long as there is clinical benefit and acceptable tolerability. Responses are usually seen by 8–16 weeks; treatment may be maintained for many months or years in responders.
Dose Reductions for Side Effects
If the 300 mg/m²/day starting dose is not tolerated (most commonly because of severe hyperlipidaemia, liver toxicity or unmanageable hypothyroidism), your specialist will step down in defined increments:
Step 1: 200 mg/m²/day
First reduction if 300 mg/m²/day is not tolerated. Reassess after 2–4 weeks.
Step 2: 100 mg/m²/day
Second reduction if 200 mg/m²/day is still not tolerated. Many patients can continue treatment at this reduced dose with adequate supportive therapy.
Step 3: Temporary or Permanent Discontinuation
If 100 mg/m²/day is not tolerated, treatment must be temporarily suspended and laboratory values allowed to recover. Restarting may be possible at a lower dose, or treatment may need to be discontinued permanently.
Dose Increases
If the patient responds partially or not at all at 300 mg/m²/day after at least 8 weeks and tolerability has been good (no significant laboratory abnormalities), a dose increase to 400 mg/m²/day may be considered by the specialist. Careful monitoring is required because higher doses are associated with more frequent hyperlipidaemia, hepatotoxicity and hypothyroidism. Doses above 400 mg/m²/day are not recommended outside of specialist oversight.
Children
Targretin is indicated for adult patients only. Safety and efficacy of bexarotene in children and adolescents below 18 years of age have not been established. It is not recommended for use in the pediatric population.
Elderly
No specific dose adjustment based on age alone is required. Older adults often start at the standard 300 mg/m²/day, but careful assessment for hypothyroidism, cataracts, cardiovascular comorbidity and polypharmacy is particularly important in this group. A slower titration and more frequent laboratory checks may be appropriate.
Hepatic and Renal Impairment
Bexarotene is extensively metabolised by the liver. In patients with hepatic impairment, drug exposure is increased and the risk of toxicity is higher. Targretin is generally avoided in significant liver disease; if used, starting at a reduced dose with close monitoring is essential. The drug is not significantly cleared by the kidneys, so standard dose adjustment based on creatinine clearance is not required; however, patients with severe renal impairment have not been extensively studied and caution is warranted.
Supportive Therapy During Targretin
Most patients require concomitant medications from the outset of treatment or soon after, particularly:
- A fibrate (usually fenofibrate) or omega-3 fatty acids to manage hypertriglyceridaemia. Gemfibrozil is contraindicated.
- A statin for elevated LDL cholesterol in selected patients; pravastatin and rosuvastatin are less affected by CYP3A4 induction.
- Levothyroxine for central hypothyroidism. Because bexarotene suppresses TSH, dose adjustments are guided by free T4 and symptoms, not TSH levels.
- Topical emollients and sunscreen to manage skin dryness and photosensitivity.
Missed Dose
If you forget to take a dose of Targretin, take it as soon as you remember, provided there are still several hours until the next scheduled dose. If it is almost time for the next dose, skip the missed dose and take only the next dose as usual. Do not take a double dose to make up for a missed one. If you miss several doses in a row, contact your specialist for advice before restarting.
Overdose
Clinical experience with bexarotene overdose is limited. Doses up to 1,000 mg/m²/day have been administered in clinical trials without acute toxicity, but chronic overdose would be expected to cause severe hypertriglyceridaemia, pancreatitis, hepatotoxicity and marked hypothyroidism. There is no specific antidote for bexarotene. Management of overdose consists of discontinuing the drug, supportive care (including aggressive management of lipids), and monitoring of liver function, thyroid function, blood counts and blood glucose. Haemodialysis is unlikely to be effective because of the high protein binding of bexarotene. If an overdose is suspected, contact your healthcare provider or poison control centre immediately.
Targretin must be prescribed and monitored by a specialist experienced in the systemic treatment of cutaneous T-cell lymphoma. Do not adjust the dose, take additional medicines or stop treatment without discussing with your specialist team. Safe use of Targretin depends on disciplined laboratory monitoring and prompt recognition of treatment-emergent side effects.
What Are the Side Effects of Targretin?
Like other retinoids, Targretin causes a characteristic pattern of side effects that is highly predictable and largely dose-dependent. With appropriate supportive therapy and dose adjustments, the majority of patients can continue treatment safely for extended periods. The side effects below are organized by frequency category based on pivotal clinical trials and post-marketing surveillance. Frequency categories follow the Medical Dictionary for Regulatory Activities (MedDRA) conventions used in EMA product information.
Reporting side effects promptly to your specialist team is essential. Many of these effects are manageable when addressed early but can become serious if ignored. Laboratory monitoring is designed to catch problems before they become clinically apparent.
Very Common
May affect more than 1 in 10 people
- Hyperlipidaemia – elevated triglycerides (very common, often severe) and elevated total / LDL cholesterol; reduced HDL cholesterol
- Central hypothyroidism – reduced TSH and free T4; symptoms may include fatigue, cold intolerance, dry skin, constipation, weight gain
- Headache (often in the first weeks of therapy)
- Asthenia (weakness), fatigue
- Rash, pruritus (itching), skin dryness (xerosis) and peeling
- Exfoliative dermatitis on the palms and soles
- Leukopenia, particularly neutropenia (reversible)
- Elevated liver transaminases (ALT, AST) and alkaline phosphatase
- Nausea, vomiting, diarrhoea
- Abdominal pain, anorexia
- Dry lips, cheilitis
- Insomnia
Common
May affect up to 1 in 10 people
- Anaemia, thrombocytopenia (reduced platelets)
- Pancreatitis (acute, often triglyceride-driven)
- Cholestasis, elevated bilirubin
- Oedema (peripheral swelling)
- Hair loss (alopecia), alterations in hair texture
- Nail disorders (brittle nails, paronychia, nail shedding)
- Skin infections (bacterial, fungal, including folliculitis)
- Cellulitis, herpes simplex reactivation
- Eye disorders: dry eyes, conjunctivitis, blurred vision, cataracts (after long-term use)
- Ear disorders: hearing impairment, tinnitus
- Arthralgia, myalgia, back pain
- Dizziness, paraesthesia, taste disturbance
- Depression, anxiety
- Chills, fever
- Increased blood creatine kinase, LDH
Uncommon
May affect up to 1 in 100 people
- Agranulocytosis, pancytopenia, coagulation disorders
- Hyperthyroidism or thyroid storm-like presentation (rare due to TSH suppression)
- Severe hepatotoxicity with cirrhosis reported in rare cases of prolonged exposure
- Benign intracranial hypertension (pseudotumor cerebri) – severe headache, vision changes, papilloedema
- Dehydration and electrolyte disturbances
- Acute renal impairment secondary to dehydration or metabolic derangement
- Hypersensitivity reactions (angioedema, urticaria, severe rash)
- Photosensitivity reactions
- Cystic acne
- Accentuation of pre-existing diabetes mellitus or new-onset hypoglycaemia when combined with insulin/sulfonylureas
- Menstrual irregularities
- Hair colour changes, hypertrichosis
Rare
May affect up to 1 in 1,000 people
- Severe hepatitis including hepatic failure
- Cardiac events including angina, myocardial infarction (in predisposed patients)
- Deep vein thrombosis, pulmonary embolism
- Cerebrovascular events
- Severe ocular complications including retinal disturbance
- Hyperuricaemia and gout flare
Very Rare
May affect up to 1 in 10,000 people
- Stevens-Johnson syndrome and toxic epidermal necrolysis (severe, life-threatening skin reactions)
- DRESS syndrome (drug reaction with eosinophilia and systemic symptoms)
- Severe autoimmune thyroid phenomena
Not Known
Frequency cannot be estimated from available data
- Long-term effects on bone density (hyperostosis, skeletal hyperostosis reported with other retinoids)
- Mood changes including suicidal ideation (reported with the retinoid class)
It is important to report any suspected side effects to your healthcare provider. Reporting helps regulatory authorities continuously monitor the benefit-risk balance of medicines. You can also report side effects directly to your national pharmacovigilance agency (e.g., the FDA MedWatch program in the United States, the Yellow Card scheme in the United Kingdom, or the EMA EudraVigilance system in the European Union). Bexarotene-related hyperlipidaemia, hypothyroidism and hepatotoxicity are all listed as important identified risks in the EU Risk Management Plan and should be reported whenever they occur.
How Should Targretin Be Stored?
Although Targretin is taken at home, it is a cytotoxic medicine and should be handled with the same care as other anticancer drugs. Correct storage preserves potency and avoids accidental exposure of children, pets or household members.
- Temperature: Store below 30°C (86°F). The bottle does not need to be refrigerated. Do not freeze.
- Light and moisture: Keep capsules in the original container with the cap tightly closed. Avoid storing in bathrooms or kitchens where humidity is high.
- Child safety: Keep the bottle out of reach of children and pets at all times. The child-resistant cap must be replaced firmly after each dose.
- Expiry date: Do not use Targretin after the expiry date printed on the carton and bottle label. The expiry date refers to the last day of that month.
- Appearance: Capsules that have leaked, discoloured, become sticky or shown any other change in appearance should not be used. Return them to the pharmacy.
- Travel: Carry capsules in the original labelled container when travelling, together with the prescription. Do not leave the bottle in a hot vehicle.
Disposal
Targretin is classified as a cytotoxic product. Unused capsules, empty bottles and any spilled material must not be disposed of via household waste or wastewater. Return unused medicine to your pharmacy for incineration in accordance with local cytotoxic-drug disposal regulations. If a capsule breaks or its contents spill, wear disposable gloves, collect the material with absorbent paper and seal it in a plastic bag before returning to the pharmacy. Wash hands thoroughly afterwards.
What Does Targretin Contain?
Knowing the exact composition of Targretin is important for patients with specific allergies, intolerances or dietary requirements.
- Active substance: Bexarotene 75 mg per soft capsule.
- Inactive ingredients (capsule fill): Polyethylene glycol 400, polysorbate 20, povidone, butylated hydroxyanisole (E320) and butylated hydroxytoluene (E321) as antioxidants.
- Capsule shell: Gelatin, sorbitol (sorbitan) solution, glycerol, titanium dioxide (E171), purified water.
- Printing ink: Pharmaceutical-grade printing ink (exact composition varies by regional product).
Appearance: Targretin is supplied as off-white to yellowish oval soft capsules printed with identification markings (for example “Targretin” on one side). Each capsule contains a clear yellow liquid.
Pack sizes: Typically supplied in high-density polyethylene (HDPE) bottles containing 100 capsules. Pack sizes may vary between countries.
Marketing authorisation holder:
- European Union: Eisai Europe Ltd., Mosquito Way, Hatfield, Hertfordshire, United Kingdom.
- United States: Bausch Health (Valeant Pharmaceuticals), Laval, Quebec, Canada (distributed in the US).
The marketing authorisation holder and the manufacturing site may change over time. The most up-to-date information is available on the patient information leaflet enclosed in the product package and on the EMA (EPAR) or FDA (Drugs@FDA) websites.
Notes for Specific Populations
- Patients with sorbitol intolerance: The capsule shell contains sorbitol, which can cause symptoms in patients with hereditary fructose intolerance.
- Vegetarians/vegans: The gelatin capsule shell is of animal origin; alternative formulations are not currently available.
- Soya allergy: Some retinoid formulations contain soya-bean oil; always verify the current package insert for the specific product received.
Frequently Asked Questions About Targretin
Most patients begin to notice improvement in skin lesions, erythema and itch within 4–8 weeks of starting Targretin at 300 mg/m²/day. Objective, measurable responses in clinical trials typically occurred by 8–16 weeks. Because CTCL is a chronic disease, treatment response should be assessed over months, not days. If there is no meaningful improvement by week 12, your specialist may consider a dose increase (if tolerated) or a change in therapy. Some patients experience slow, cumulative improvement that continues throughout the first year of treatment.
Targretin has highly predictable but serious effects on lipid metabolism, thyroid function, liver enzymes and blood counts. Frequent monitoring allows your specialist to detect problems early, before they become clinically dangerous. Typical testing includes a fasting lipid panel, thyroid function tests (TSH and free T4), liver function tests and a complete blood count at baseline, weekly for the first month, then at roughly monthly intervals. Extra pregnancy tests every month are mandatory in women of childbearing potential. These tests are the single most important safety tool during Targretin treatment – skipping them is never appropriate.
Yes – these are classic symptoms of central hypothyroidism caused by bexarotene’s suppression of pituitary TSH. Up to 40% of patients develop biochemical hypothyroidism, often within the first 1–2 weeks of treatment. Symptoms include cold intolerance, fatigue, constipation, dry skin, weight gain and slowed thinking. Your specialist will often start you on levothyroxine replacement based on symptoms and free T4 levels, because TSH cannot be used as a target under bexarotene therapy. With appropriate levothyroxine dosing, most patients feel substantially better. Tell your doctor about any new fatigue, feeling cold or other thyroid-like symptoms.
Moderate alcohol is not strictly forbidden, but regular or heavy alcohol consumption is not recommended during Targretin therapy. Alcohol adds to the effects of bexarotene on liver enzymes, worsens hypertriglyceridaemia and can increase the risk of pancreatitis when triglycerides are high. Patients with a history of heavy drinking or with already elevated liver enzymes should avoid alcohol entirely. If you choose to drink occasionally, keep intake low (for example up to one standard drink occasionally), never on days when you feel unwell, and discuss with your specialist at each monitoring visit.
Hair loss (alopecia) occurs in a significant minority of patients on Targretin, but it is less common than with traditional cytotoxic chemotherapy. When it happens, it is usually a diffuse thinning rather than the complete hair loss seen with drugs like paclitaxel. Hair texture changes (curlier, drier) are also reported. In almost all cases, hair regrows once treatment is stopped or reduced. Using gentle shampoos, avoiding heat styling and taking care with chemical treatments can help protect hair during therapy. Discuss any significant hair loss with your team; sometimes a dose reduction helps.
This is one of the most important interaction questions. Gemfibrozil must not be combined with Targretin – this combination raises bexarotene blood levels dramatically and paradoxically worsens triglyceride control. Instead, fenofibrate is the preferred fibrate for managing Targretin-induced hypertriglyceridaemia, often together with omega-3 fatty acids (2–4 g per day of marine omega-3s). Pravastatin or rosuvastatin are the preferred statins because they are less affected by bexarotene’s induction of CYP3A4 (which can reduce the effectiveness of simvastatin and atorvastatin). Always review your lipid-lowering regimen with your specialist team at every visit.
Cutaneous T-cell lymphoma, particularly mycosis fungoides and Sézary syndrome, is generally managed as a chronic disease rather than cured by any systemic therapy currently available. Targretin can produce durable skin responses – ranging from partial improvement to complete disappearance of visible lesions – and can significantly improve quality of life, itch and cosmetic appearance. However, the disease usually recurs if Targretin is stopped, and some patients need lifelong systemic therapy rotating through different agents. The aim of treatment is to control the disease, minimise symptoms, preserve quality of life and prevent progression to more advanced stages. New targeted therapies and combinations continue to emerge, and your specialist will tailor a long-term plan with you.
References
- European Medicines Agency (EMA). Targretin (bexarotene) – Summary of Product Characteristics (SmPC) and European Public Assessment Report (EPAR). Last updated 2025. Available at: ema.europa.eu/en/medicines/human/EPAR/targretin
- U.S. Food and Drug Administration (FDA). Targretin (bexarotene) Capsules – Prescribing Information. Last updated 2024.
- Duvic M, Hymes K, Heald P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. Journal of Clinical Oncology. 2001;19(9):2456-2471. doi:10.1200/JCO.2001.19.9.2456
- Duvic M, Martin AG, Kim Y, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Archives of Dermatology. 2001;137(5):581-593.
- Talpur R, Ward S, Apisarnthanarax N, Breuer-McHam J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. Journal of the American Academy of Dermatology. 2002;47(5):672-684. doi:10.1067/mjd.2002.124607
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Primary Cutaneous Lymphomas. Version 2025.
- Willemze R, Hodak E, Zinzani PL, et al. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2018;29(Suppl 4):iv30-iv40. doi:10.1093/annonc/mdy133
- Trautinger F, Eder J, Assaf C, et al. European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides / Sézary syndrome – Update 2017. European Journal of Cancer. 2017;77:57-74. doi:10.1016/j.ejca.2017.02.027
- Assaf C, Bagot M, Dummer R, et al. Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma: an expert opinion. British Journal of Dermatology. 2006;155(2):261-266. doi:10.1111/j.1365-2133.2006.07329.x
- Sherman SI, Gopal J, Haugen BR, et al. Central hypothyroidism associated with retinoid X receptor-selective ligands. New England Journal of Medicine. 1999;340(14):1075-1079. doi:10.1056/NEJM199904083401404
- Boehm MF, Zhang L, Badea BA, et al. Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. Journal of Medicinal Chemistry. 1994;37(18):2930-2941. doi:10.1021/jm00044a014
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization.
- British National Formulary (BNF). Bexarotene monograph. London: BMJ Group and Pharmaceutical Press; 2025.
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