Drugs List

Therapeutic Indications

Uses

Benign prostatic hyperplasia
Hypertension

Unlicensed Uses

Dysfunctional voiding of urine

Contraindications

Children under 6 years
Anuria
Breastfeeding
Chronic urinary tract infections - if treating benign prostatic hyperplasia
History of gastrointestinal obstruction
History of gastrointestinal stenosis
History of oesophageal obstruction
History of postural hypotension
Pregnancy
Urolithiasis - if treating benign prostatic hyperplasia

Precautions and Warnings

Children aged 6 to 18 years
Cardiac failure
Hepatic impairment
Hypotension - if treating benign prostatic hyperplasia
Left ventricular failure with low filling pressure
Pulmonary oedema

Advise ability to drive/operate machinery may be affected by side effects
Benign prostatic hyperplasia: Exclude prostate carcinoma before treatment
Advise patient that postural hypotension may occur
Intraoperative Floppy Iris Syndrome has been reported in cataract surgery
May affect urine test results
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effects may be potentiated by alcohol
Advise patients that empty tablet/capsule may be observed in stools

Use with care in patients with diabetic autonomic neuropathy.

Abnormally short transient times through the gastrointestinal tract (e.g. following surgical resection) could result in incomplete absorption. The clinical significance, given the long half life of doxazosin, is unclear.

Pregnancy and Lactation

Pregnancy

Doxazosin is contraindicated for use during pregnancy.

In animal studies doxazosin crosses the placenta. Doxazosin has demonstrated no teratogenic effects in animal testing, but at extremely high doses (300 times the maximum recommended human dose) reduced foetal survival was observed. Briggs (2011) states that reduced foetal survival has been observed in rabbits at 20 times therapeutic dose and delayed postnatal development in rat pups at 8 times the therapeutic dose during perinatal and postnatal periods.

As there are no adequate or well-controlled studies in pregnant women, the safety of doxazosin during pregnancy has not been established. Schaefer (2007) comments that inadvertent use of the doxazosin is no reason for termination of pregnancy or for invasive procedures.

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

Doxazosin is contraindicated during breastfeeding.

Animal studies have shown that doxazosin accumulates via a possible concentration mechanism in breast milk to 20 times that of the maternal blood plasma.

Although no human reports to date are catalogued, presence and accumulation in human milk should be anticipated due to the animal study outcomes. The manufacturers recommend to stop breastfeeding when treatment with doxazosin is necessary and advice from LactMed, via TOXNET states that an alternative drug may be preferred especially whilst nursing a newborn or preterm infant. Information on LactMed also states that the pharmacological similar drug prazosin does not affect serum prolactin concentration in patients with hypertension. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Schaefer (2007) comments that doxazosin should not be taken during breastfeeding. If treatment has begun weaning is not necessary, however therapy should be changed to an antihypertensive of choice, including an acceptable calcium antagonist or, if really indicated, an ACE inhibitor with a low transfer dosage via breast milk. Hale recommends doxazosin is used with extreme caution and no paediatrics concerns have been reported via the milk.

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
Abnormal ejaculation
Abnormal liver function tests
Agitation
Allergic reaction
Alopecia
Angina pectoris
Anorexia
Anxiety
Arrhythmias
Arthralgia
Asthenia
Back pain
Blurred vision
Bradycardia
Bronchitis
Bronchospasm
Cerebrovascular disorders
Chest pain
Cholestasis
Constipation
Cough
Cystitis
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Dysuria
Epistaxis
Fatigue
Flatulence
Flushing
Gastro-enteritis
Gastrointestinal obstruction
Gout
Gynaecomastia
Haematuria
Headache
Hepatitis
Hypoaesthesia
Hypotension
Impotence
Increased appetite
Influenza-like symptoms
Intraoperative floppy iris syndrome
Jaundice
Leucopenia
Malaise
Micturition disorders
Muscle cramps
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Nervousness
Nocturia
Oedema
Pain
Palpitations
Paraesthesia
Peripheral oedema
Polyuria
Postural hypotension
Priapism
Pruritus
Purpura
Rash
Respiratory tract infection
Rhinitis
Sleep disturbances
Somnolence
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Tremor
Urinary incontinence
Urinary tract infections
Urticaria
Vertigo
Vomiting
Weight changes

Presentation

Modified release formulations of doxazosin.

Drugs List

Therapeutic Indications

Uses

Benign prostatic hyperplasia
Hypertension

Unlicensed Uses

Dysfunctional voiding of urine

Dosage

Adults

Children

Patients with Renal Impairment

Contraindications

Children under 6 years
Anuria
Breastfeeding
Chronic urinary tract infections - if treating benign prostatic hyperplasia
History of gastrointestinal obstruction
History of gastrointestinal stenosis
History of oesophageal obstruction
History of postural hypotension
Pregnancy
Urolithiasis - if treating benign prostatic hyperplasia

Precautions and Warnings

Children aged 6 to 18 years
Cardiac failure
Hepatic impairment
Hypotension - if treating benign prostatic hyperplasia
Left ventricular failure with low filling pressure
Pulmonary oedema

Advise ability to drive/operate machinery may be affected by side effects
Benign prostatic hyperplasia: Exclude prostate carcinoma before treatment
Advise patient that postural hypotension may occur
Intraoperative Floppy Iris Syndrome has been reported in cataract surgery
May affect urine test results
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effects may be potentiated by alcohol
Advise patients that empty tablet/capsule may be observed in stools

Use with care in patients with diabetic autonomic neuropathy.

Abnormally short transient times through the gastrointestinal tract (e.g. following surgical resection) could result in incomplete absorption. The clinical significance, given the long half life of doxazosin, is unclear.

Pregnancy and Lactation

Pregnancy

Doxazosin is contraindicated for use during pregnancy.

In animal studies doxazosin crosses the placenta. Doxazosin has demonstrated no teratogenic effects in animal testing, but at extremely high doses (300 times the maximum recommended human dose) reduced foetal survival was observed. Briggs (2011) states that reduced foetal survival has been observed in rabbits at 20 times therapeutic dose and delayed postnatal development in rat pups at 8 times the therapeutic dose during perinatal and postnatal periods.

As there are no adequate or well-controlled studies in pregnant women, the safety of doxazosin during pregnancy has not been established. Schaefer (2007) comments that inadvertent use of the doxazosin is no reason for termination of pregnancy or for invasive procedures.

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

Doxazosin is contraindicated during breastfeeding.

Animal studies have shown that doxazosin accumulates via a possible concentration mechanism in breast milk to 20 times that of the maternal blood plasma.

Although no human reports to date are catalogued, presence and accumulation in human milk should be anticipated due to the animal study outcomes. The manufacturers recommend to stop breastfeeding when treatment with doxazosin is necessary and advice from LactMed, via TOXNET states that an alternative drug may be preferred especially whilst nursing a newborn or preterm infant. Information on LactMed also states that the pharmacological similar drug prazosin does not affect serum prolactin concentration in patients with hypertension. The prolactin level in a mother with established lactation may not affect her ability to breastfeed. Schaefer (2007) comments that doxazosin should not be taken during breastfeeding. If treatment has begun weaning is not necessary, however therapy should be changed to an antihypertensive of choice, including an acceptable calcium antagonist or, if really indicated, an ACE inhibitor with a low transfer dosage via breast milk. Hale recommends doxazosin is used with extreme caution and no paediatrics concerns have been reported via the milk.

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

Counselling

Advise patient that doxazosin therapy may impair ability to drive or operate machinery, especially when initiating treatment.

Advise patients on the measures they should take to avoid postural hypotension which may occur particularly when initiating treatment. The hypotensive effects may be exaggerated by alcohol ingestion.

Advise patient to swallow the tablet whole - the tablets should not be chewed, divided or crushed.

Advise patients that empty tablet may occasionally be observed in stools.

Advise patients not to purchase NSAIDs unless on medical advice if being treated for hypertension.

Advise patients the initial dose may be taken at bedtime to minimise first dose postural hypotension.

Side Effects

Abdominal pain
Abnormal ejaculation
Abnormal liver function tests
Agitation
Allergic reaction
Alopecia
Angina pectoris
Anorexia
Anxiety
Arrhythmias
Arthralgia
Asthenia
Back pain
Blurred vision
Bradycardia
Bronchitis
Bronchospasm
Cerebrovascular disorders
Chest pain
Cholestasis
Constipation
Cough
Cystitis
Depression
Diarrhoea
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Dysuria
Epistaxis
Fatigue
Flatulence
Flushing
Gastro-enteritis
Gastrointestinal obstruction
Gout
Gynaecomastia
Haematuria
Headache
Hepatitis
Hypoaesthesia
Hypotension
Impotence
Increased appetite
Influenza-like symptoms
Intraoperative floppy iris syndrome
Jaundice
Leucopenia
Malaise
Micturition disorders
Muscle cramps
Muscle weakness
Myalgia
Myocardial infarction
Nausea
Nervousness
Nocturia
Oedema
Pain
Palpitations
Paraesthesia
Peripheral oedema
Polyuria
Postural hypotension
Priapism
Pruritus
Purpura
Rash
Respiratory tract infection
Rhinitis
Sleep disturbances
Somnolence
Syncope
Tachycardia
Taste disturbances
Thrombocytopenia
Tinnitus
Tremor
Urinary incontinence
Urinary tract infections
Urticaria
Vertigo
Vomiting
Weight changes

Effects on Laboratory Tests

Doxazosin may influence plasma renin activity and the urinary excretion of vanillylmandelic acid.

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: June 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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.

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.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

Summary of Product Characteristics: Cardozin XL 4mg prolonged release tablets (doxazosin)(Arrow). Actavis UK Ltd. March 2012.

Summary of Product Characteristics: Cardura XL 4mg tablets. Pfizer Ltd. Revised November 2016.

Summary of Product Characteristics: Cardura XL 8mg tablets. Pfizer Ltd. Revised November 2016.

Summary of Product Characteristics: Colixil XL 4mg prolonged release tablets. Sandoz Ltd. Revised October 2012.

Summary of Product Characteristics: Doxadura XL 4mg prolonged release XL tablets. Discovery Pharmaceuticals Ltd. Revised April 2010.

Summary of Product Characteristics: Doxzogen XL 4mg prolonged release tablets. Generics UK Ltd. Revised November 2009.

Summary of Product Characteristics: Larbex XL 4mg prolonged release tablets. Teva UK Ltd. Revised November 2009.

Summary of Product Characteristics: Raporsin XL 4mg prolonged release tablets. Actavis. Revised September 2012.

Summary of Product Characteristics: Slocinx XL 4mg prolonged release tablets. Zentiva. Revised July 2012.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 28 June 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Doxazosin. Last revised: September 29, 2009
Last accessed: June 26, 2013