Drugs List

Therapeutic Indications

Uses

Treatment of skin symptoms of advanced stage cutaneous T-cell lymphoma

Treatment of skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL) refractory to at least one systemic treatment.

Contraindications

Children under 18 years
Hypervitaminosis A
Systemic infection
Breastfeeding
Hepatic impairment
Hereditary fructose intolerance
History of pancreatitis
Pregnancy
Uncontrolled hypercholesterolaemia
Uncontrolled hypertriglyceridaemia
Uncontrolled thyroid disorder

Precautions and Warnings

Females of childbearing potential
History of high alcohol intake
Biliary tract disorder
Depression
Diabetes mellitus
History of depression
Hyperlipidaemia
Porphyria
Renal impairment
Uncontrolled diabetes mellitus

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Ensure negative pregnancy test in week preceding initiation of treatment
Monitor blood lipids before and during treatment
Monitor haemoglobin prior to initiating therapy and periodically thereafter
Monitor thyroid function prior to and periodically during treatment
Perform liver function tests before commencing therapy and during therapy
Initiate antilipaemic therapy if fasting triglycerides raised
Monitor blood counts weekly for 1 month, then monthly thereafter
Monitor patient for signs and symptoms of depression
Advise eye examination if visual disturbance occurs:Lens opacities reported
Advise patient to report any new or worsening depression/suicidal ideation
Risk of pancreatitis
Discontinue if ALT level exceeds 3 times the upper limit of normal
Discontinue if AST level exceeds 3 times the upper limit of normal
Discontinue treatment if total bilirubin >3 times upper limit of normal
Reduce dose or discontinue if fasting triglycerides raised
Advise patient to limit vitamin A supplements to less than 15,000 IU/day
Advise patient grapefruit products may increase plasma level
Female: Two reliable methods of contraception should be used simultaneously
Female:Contraception required before & until at least 1 month after therapy
Male: Use barrier contraception during and for 1 month after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
Patients should not donate blood for transfusion during treatment

Fasting blood lipid determinations (triglycerides and cholesterol) should be performed before bexarotene therapy is initiated and at weekly intervals until the lipid response to bexarotene is established, which usually occurs within 2 to 4 weeks, and then monthly. Fasting triglycerides should be normal or normalised with appropriate intervention prior to bexarotene therapy. Every attempt should be made to maintain triglyceride levels below 4.52 mmol/l. If fasting triglycerides are elevated or become elevated during treatment, institution of antilipaemic therapy is recommended, and if necessary, dose reductions or treatment discontinuation. Elevations of serum cholesterol should be managed according to current medical practice, however concomitant administration of gemfibrozil with bexarotene in NOT recommended.

Baseline liver function tests (LFTs) should be obtained, and LFTs should be carefully monitored weekly during the first month and then monthly thereafter. Consideration should be given to a suspension or discontinuation of bexarotene if test results reach greater than three times the upper limit of normal values for AST, ALT or bilirubin.

Baseline thyroid function tests should be obtained and then monitored at least monthly during treatment and as indicated by the emergence of symptoms consistent with hypothyroidism. Patients with symptomatic hypothyroidism on bexarotene therapy have been treated with thyroid hormone supplements with resolution of symptoms.

Caution should be exercised when administering bexarotene in patients using insulin, agents enhancing insulin secretion (e.g. sulfonylureas), or insulin-sensitisers (e.g. thiazolidinediones). Based on the known mechanism of action, bexarotene may potentially enhance the action of these agents, resulting in hypoglycaemia.

Use in Porphyria

Some sources suggest bexarotene is unsuitable for use in porphyria as it is probably porphyrinogenic.

Pregnancy and Lactation

Pregnancy

Bexarotene is contraindicated in pregnancy.

At the time of writing there is no adequate data from the use of bexarotene in pregnant women. Studies in animals have shown have shown reproductive toxicity.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Bexarotene is contraindicated in breastfeeding.

It is not known whether bexarotene is excreted in human milk however the molecular weight is low enough that excretion should be expected, a risk to neonates cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agitation
Albuminuria
Allergic reaction
Altered hormone levels
Anaemia
Anxiety
Arrhythmias
Asthenia
Ataxia
Blood dyscrasias
Breast enlargement
Cellulitis
Changes in gonadotrophic luteinizing hormone levels
Cheilitis
Chills
Cholecystitis
Coagulation disorders
Congestive cardiac failure
Creatine phosphokinase increased
Deafness
Decrease in high density lipoprotein (HDL)
Dehydration
Depression
Dizziness
Electrolyte disturbances
Elevated amylase levels
Elevated serum lipase
Epistaxis
Exfoliative dermatitis
Eye disorder
Fever
Gait abnormality
Gastro-intestinal symptoms
Gingivitis
Gout
Haemorrhage
Hair disorder
Headache
Hepatic disorders
Hypaesthesia
Hyperaesthesia
Hyperbilirubinaemia
Hyperlipidaemia
Hypertension
Hyperthyroidism
Hypertonia
Hyperuricaemia
Hypolipaemia
Hypoproteinaemia
Hypothyroidism
Hypovolaemia
Impaired renal function
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Infections
Influenza-like syndrome
Jaundice
Laryngismus
Leucopenia
Lymphadenopathy
Lymphoma-like disorder
Malaise
Migraine
Mood changes
Mouth ulcers
Mucous membrane disorder
Musculoskeletal disturbances
Nail disorders
Neoplasms
Nystagmus
Oedema
Oral moniliasis
Pain
Pallor
Pancreatitis
Paraesthesia
Peripheral neuritis
Peripheral vascular disorders
Photosensitivity
Pruritus
Purpura
Rash
Respiratory disorders
Rhinitis
Serous drainage
Serum creatinine increased
Sexual dysfunction
Skin disorder
Sleep disturbances
Stomatitis
Stupor
Subdural haematoma
Sweating
Taste disturbances
Tinnitus
Urinary tract disorders
Vascular disorders
Vertigo
Weight changes

Presentation

Oral formulations of bexarotene

Drugs List

Therapeutic Indications

Uses

Treatment of skin symptoms of advanced stage cutaneous T-cell lymphoma

Treatment of skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL) refractory to at least one systemic treatment.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Hypervitaminosis A
Systemic infection
Breastfeeding
Hepatic impairment
Hereditary fructose intolerance
History of pancreatitis
Pregnancy
Uncontrolled hypercholesterolaemia
Uncontrolled hypertriglyceridaemia
Uncontrolled thyroid disorder

Precautions and Warnings

Females of childbearing potential
History of high alcohol intake
Biliary tract disorder
Depression
Diabetes mellitus
History of depression
Hyperlipidaemia
Porphyria
Renal impairment
Uncontrolled diabetes mellitus

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Ensure negative pregnancy test in week preceding initiation of treatment
Monitor blood lipids before and during treatment
Monitor haemoglobin prior to initiating therapy and periodically thereafter
Monitor thyroid function prior to and periodically during treatment
Perform liver function tests before commencing therapy and during therapy
Initiate antilipaemic therapy if fasting triglycerides raised
Monitor blood counts weekly for 1 month, then monthly thereafter
Monitor patient for signs and symptoms of depression
Advise eye examination if visual disturbance occurs:Lens opacities reported
Advise patient to report any new or worsening depression/suicidal ideation
Risk of pancreatitis
Discontinue if ALT level exceeds 3 times the upper limit of normal
Discontinue if AST level exceeds 3 times the upper limit of normal
Discontinue treatment if total bilirubin >3 times upper limit of normal
Reduce dose or discontinue if fasting triglycerides raised
Advise patient to limit vitamin A supplements to less than 15,000 IU/day
Advise patient grapefruit products may increase plasma level
Female: Two reliable methods of contraception should be used simultaneously
Female:Contraception required before & until at least 1 month after therapy
Male: Use barrier contraception during and for 1 month after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
Patients should not donate blood for transfusion during treatment

Fasting blood lipid determinations (triglycerides and cholesterol) should be performed before bexarotene therapy is initiated and at weekly intervals until the lipid response to bexarotene is established, which usually occurs within 2 to 4 weeks, and then monthly. Fasting triglycerides should be normal or normalised with appropriate intervention prior to bexarotene therapy. Every attempt should be made to maintain triglyceride levels below 4.52 mmol/l. If fasting triglycerides are elevated or become elevated during treatment, institution of antilipaemic therapy is recommended, and if necessary, dose reductions or treatment discontinuation. Elevations of serum cholesterol should be managed according to current medical practice, however concomitant administration of gemfibrozil with bexarotene in NOT recommended.

Baseline liver function tests (LFTs) should be obtained, and LFTs should be carefully monitored weekly during the first month and then monthly thereafter. Consideration should be given to a suspension or discontinuation of bexarotene if test results reach greater than three times the upper limit of normal values for AST, ALT or bilirubin.

Baseline thyroid function tests should be obtained and then monitored at least monthly during treatment and as indicated by the emergence of symptoms consistent with hypothyroidism. Patients with symptomatic hypothyroidism on bexarotene therapy have been treated with thyroid hormone supplements with resolution of symptoms.

Caution should be exercised when administering bexarotene in patients using insulin, agents enhancing insulin secretion (e.g. sulfonylureas), or insulin-sensitisers (e.g. thiazolidinediones). Based on the known mechanism of action, bexarotene may potentially enhance the action of these agents, resulting in hypoglycaemia.

Use in Porphyria

Some sources suggest bexarotene is unsuitable for use in porphyria as it is probably porphyrinogenic.

Pregnancy and Lactation

Pregnancy

Bexarotene is contraindicated in pregnancy.

At the time of writing there is no adequate data from the use of bexarotene in pregnant women. Studies in animals have shown have shown reproductive toxicity.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Bexarotene is contraindicated in breastfeeding.

It is not known whether bexarotene is excreted in human milk however the molecular weight is low enough that excretion should be expected, a risk to neonates cannot be excluded.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agitation
Albuminuria
Allergic reaction
Altered hormone levels
Anaemia
Anxiety
Arrhythmias
Asthenia
Ataxia
Blood dyscrasias
Breast enlargement
Cellulitis
Changes in gonadotrophic luteinizing hormone levels
Cheilitis
Chills
Cholecystitis
Coagulation disorders
Congestive cardiac failure
Creatine phosphokinase increased
Deafness
Decrease in high density lipoprotein (HDL)
Dehydration
Depression
Dizziness
Electrolyte disturbances
Elevated amylase levels
Elevated serum lipase
Epistaxis
Exfoliative dermatitis
Eye disorder
Fever
Gait abnormality
Gastro-intestinal symptoms
Gingivitis
Gout
Haemorrhage
Hair disorder
Headache
Hepatic disorders
Hypaesthesia
Hyperaesthesia
Hyperbilirubinaemia
Hyperlipidaemia
Hypertension
Hyperthyroidism
Hypertonia
Hyperuricaemia
Hypolipaemia
Hypoproteinaemia
Hypothyroidism
Hypovolaemia
Impaired renal function
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Infections
Influenza-like syndrome
Jaundice
Laryngismus
Leucopenia
Lymphadenopathy
Lymphoma-like disorder
Malaise
Migraine
Mood changes
Mouth ulcers
Mucous membrane disorder
Musculoskeletal disturbances
Nail disorders
Neoplasms
Nystagmus
Oedema
Oral moniliasis
Pain
Pallor
Pancreatitis
Paraesthesia
Peripheral neuritis
Peripheral vascular disorders
Photosensitivity
Pruritus
Purpura
Rash
Respiratory disorders
Rhinitis
Serous drainage
Serum creatinine increased
Sexual dysfunction
Skin disorder
Sleep disturbances
Stomatitis
Stupor
Subdural haematoma
Sweating
Taste disturbances
Tinnitus
Urinary tract disorders
Vascular disorders
Vertigo
Weight changes

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2015

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 3 July 2015.

Summary of Product Characteristics: Targretin tablets. Eisai Ltd. Revised March 2018.

Napos. The drug database for acute porphyria.
Available at https://www.drugs-porphyria.org/languages/UnitedKingdom/s1.php?l=gbr
Bexarotene Last revised: 14 June 2010.
Last accessed: 3 July 2015.