Drugs List

Therapeutic Indications

Uses

Leukaemia - acute promyelocytic

Contraindications

Breastfeeding
Hereditary fructose intolerance
Pregnancy

Precautions and Warnings

Children under 18 years
Females of childbearing potential
Predisposition to thromboembolic disease
Severe headache
Hepatic impairment
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains soya or soya derivative
Consult local policy on the safe use of oral anti-cancer drugs
Treatment to be administered under the supervision of a specialist
Exclude pregnancy prior to initiation of treatment
Monitor blood lipids before and during treatment
Ensure negative monthly pregnancy tests throughout treatment
Initiate chemotherapy immediately if leucocyte count increases rapidly
Monitor coagulation values
Monitor haematological parameters periodically
Monitor hepatic function
Monitor patients at risk for signs & symptoms of thromboembolism
Monitor serum calcium levels
Children may experience increased frequency of certain side effects
Consider interrupting treatment if pseudotumour cerebri occurs
If retinoic-acid syndrome occurs initiate treatment with dexamethasone
Risk of developing retinoic-acid syndrome
Consider interrupting treatment if moderate retinoic-acid syndrome occurs
Consider dose reduction in intractable headache in children
Advise patient not to take vitamin A or beta carotene supplements
Female: Contraception required during and for 1 month after treatment
If oral contraception appropriate use combined oestrogen-progestogen

There is a risk of thrombosis which may involve any organ system during the first month of treatment

The incidence of retinoic acid syndrome is diminished when full dose chemotherapy is added to the treatment regimen based on the white blood cell count. ( see Additional dosage )

If the patient presents any signs or symptoms of retinoic acid syndrome, treatment with dexamethasone (10 mg every 12 hours for up to a maximum of 3 days, or until resolution of the symptoms) should be given immediately.

Treatment with tretinoin should only be initiated in women of child bearing potential if the following conditions are met:
The patient should be informed of the hazards of pregnancy during treatment and for 1 month after treatment.
The patient is willing to comply with the mandatory effective contraceptive measures i.e. to use adequate contraception during treatment and for 1 month after.
Pregnancy tests must be performed at monthly intervals.

Pregnancy and Lactation

Pregnancy

Tretinoin is contraindicated during pregnancy.

Tretinoin is teratogenic. Tretinoin should only be used during pregnancy, or in women who might become pregnant during therapy, if the benefit outweighs the risk of foetal abnormalities, due to the severity of the patient's condition and the urgency of treatment.

If pregnancy does occur during treatment, or 1 month after the discontinuation of treatment, there is a high risk of malformation of the foetus (especially if given during the first trimester) regardless of the given dose or duration of treatment.

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

Tretinoin is contraindicated in breastfeeding.

The effect of concurrent therapies must also be considered.

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

Abdominal pain
Acute febrile dermatosis (Sweet's syndrome)
Acute respiratory distress
Alopecia
Anxiety
Arrhythmias
Asthma
Basophilia
Bone pain
Cerebrovascular accident
Cheilitis
Chest pain
Chills
Confusion
Conjunctivitis
Constipation
Decreased appetite
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspnoea
Erythema
Erythema nodosum
Fever
Flushing
Genital ulceration
Headache
Hearing disturbances
Hepatic failure
Hypercalcaemia
Hyperhidrosis
Hyperhistaminaemia
Hyperleukocytosis
Hypervitaminosis A
Hypotension
Increase in creatinine
Increase in plasma cholesterol
Increase in plasma triglyceride concentration
Increase in serum transaminases
Insomnia
Malaise
Multiorgan failure
Myocardial infarction
Myositis
Nasal dryness
Nausea
Necrotising fasciitis
Oedema
Pancreatitis
Paraesthesia
Pericardial effusion
Pleural effusion
Pruritus
Pseudotumour cerebri syndrome (mainly in children)
Pulmonary infiltrates
Raised intracranial pressure
Rash
Renal failure
Renal infarct
Respiratory failure
Retinoic acid syndrome
Thrombocytosis
Thromboembolism
Thrombosis
Vasculitis
Visual disturbances
Vomiting
Weight gain

Presentation

Capsules containing tretinoin

Drugs List

Therapeutic Indications

Uses

Leukaemia - acute promyelocytic

Dosage

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

The association of tretinoin with chemotherapy increases the duration of survival and reduces the risk of relapse compared to chemotherapy alone.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Breastfeeding
Hereditary fructose intolerance
Pregnancy

Precautions and Warnings

Children under 18 years
Females of childbearing potential
Predisposition to thromboembolic disease
Severe headache
Hepatic impairment
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Contains soya or soya derivative
Consult local policy on the safe use of oral anti-cancer drugs
Treatment to be administered under the supervision of a specialist
Exclude pregnancy prior to initiation of treatment
Monitor blood lipids before and during treatment
Ensure negative monthly pregnancy tests throughout treatment
Initiate chemotherapy immediately if leucocyte count increases rapidly
Monitor coagulation values
Monitor haematological parameters periodically
Monitor hepatic function
Monitor patients at risk for signs & symptoms of thromboembolism
Monitor serum calcium levels
Children may experience increased frequency of certain side effects
Consider interrupting treatment if pseudotumour cerebri occurs
If retinoic-acid syndrome occurs initiate treatment with dexamethasone
Risk of developing retinoic-acid syndrome
Consider interrupting treatment if moderate retinoic-acid syndrome occurs
Consider dose reduction in intractable headache in children
Advise patient not to take vitamin A or beta carotene supplements
Female: Contraception required during and for 1 month after treatment
If oral contraception appropriate use combined oestrogen-progestogen

There is a risk of thrombosis which may involve any organ system during the first month of treatment

The incidence of retinoic acid syndrome is diminished when full dose chemotherapy is added to the treatment regimen based on the white blood cell count. ( see Additional dosage )

If the patient presents any signs or symptoms of retinoic acid syndrome, treatment with dexamethasone (10 mg every 12 hours for up to a maximum of 3 days, or until resolution of the symptoms) should be given immediately.

Treatment with tretinoin should only be initiated in women of child bearing potential if the following conditions are met:
The patient should be informed of the hazards of pregnancy during treatment and for 1 month after treatment.
The patient is willing to comply with the mandatory effective contraceptive measures i.e. to use adequate contraception during treatment and for 1 month after.
Pregnancy tests must be performed at monthly intervals.

Pregnancy and Lactation

Pregnancy

Tretinoin is contraindicated during pregnancy.

Tretinoin is teratogenic. Tretinoin should only be used during pregnancy, or in women who might become pregnant during therapy, if the benefit outweighs the risk of foetal abnormalities, due to the severity of the patient's condition and the urgency of treatment.

If pregnancy does occur during treatment, or 1 month after the discontinuation of treatment, there is a high risk of malformation of the foetus (especially if given during the first trimester) regardless of the given dose or duration of treatment.

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

Tretinoin is contraindicated in breastfeeding.

The effect of concurrent therapies must also be considered.

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

Abdominal pain
Acute febrile dermatosis (Sweet's syndrome)
Acute respiratory distress
Alopecia
Anxiety
Arrhythmias
Asthma
Basophilia
Bone pain
Cerebrovascular accident
Cheilitis
Chest pain
Chills
Confusion
Conjunctivitis
Constipation
Decreased appetite
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspnoea
Erythema
Erythema nodosum
Fever
Flushing
Genital ulceration
Headache
Hearing disturbances
Hepatic failure
Hypercalcaemia
Hyperhidrosis
Hyperhistaminaemia
Hyperleukocytosis
Hypervitaminosis A
Hypotension
Increase in creatinine
Increase in plasma cholesterol
Increase in plasma triglyceride concentration
Increase in serum transaminases
Insomnia
Malaise
Multiorgan failure
Myocardial infarction
Myositis
Nasal dryness
Nausea
Necrotising fasciitis
Oedema
Pancreatitis
Paraesthesia
Pericardial effusion
Pleural effusion
Pruritus
Pseudotumour cerebri syndrome (mainly in children)
Pulmonary infiltrates
Raised intracranial pressure
Rash
Renal failure
Renal infarct
Respiratory failure
Retinoic acid syndrome
Thrombocytosis
Thromboembolism
Thrombosis
Vasculitis
Visual disturbances
Vomiting
Weight gain

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: April 2014

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 https://www.medicinescomplete.com [Accessed on 15 April 2014].

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com [Accessed on 15 April 2014].

Summary of Product Characteristics: Vesanoid 10mg soft capsules. Intrapharm Laboratories Limited. Revised November 2013