Summary for UKPID
Alfuzosin
Helen Seymour, BPharm (Hons)
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
SUMMARY
Type of product
Selective alpha-blocker used to relax smooth muscle in benign
prostatic hyperplasia
Ingredients
Tablets 2.5mg, 5mg SR
Presentation/packaging
60 or 90 tablets
Toxicokinetics
Peak plasma levels reached in 0.5 to 3 hours in therapeutic doses
Plasma half life range 3-5 hours
Volume of distribution 2.5L/kg
Extensively liver metabolised, metabolites pharmacologically
inactive
Features of toxicity
Flushing postural hypotension and tachycardia are common.
Tachycardia may be associated with signs and symptoms of angina
and myocardial infarction. Effects more pronounced in patients
with preexisting hypovolemia.
Dizziness CNS stimulation and seizures may occur
Vomiting abdominal pain and diarrhoea may occur following large
oral doses
Management
Administer activated charcoal if presentation within 2 hours
Hypotension will usually be corrected by lifting the feet 15 cm
above the trunk or by administering intravenous fluids.
Control convulsions with IV diazepam, 10mg.
Routine chemistry and pH monitoring are not required unless
otherwise indicated.
ECG
SUBSTANCE
Alfuzosin hydrochloride
NAME
Brand name Xatral
Generic name alfuzosin
CHEMICAL GROUP/FAMILY
selective alpha-blocker
BNF 7.4.1
a quinazoline derivative with structural similarities to prazosin
REFERENCE NUMBER
CAS
81403-80-7 (alfuzosin)
81403-68-1 (alfuzosin HCl)
PRODUCT LICENCE NUMBER
Xatral 2.5mg 4969/0010
Xatral SR 5mg 4969/0018
MANUFACTURER/SUPPLIER
Lorex
Lorex Synthelabo Ltd
Lunar House
Globe Park
Marlow
Bucks
SL7 1LW
Tel: 01628 488011
Fax 01628 471435
PRESENTATION
Form
tablets alfuzosin 2.5mg, SR 5mg
Pack size
60, 90
PHYSICO-CHEMICAL PROPERTIES (Martindale)
Chemical structure
N-19H27N5O4
Physical structure at room temperature
Solid
Colour
NIF
Odour
NIF
Viscosity
NA
pH
NA
Solubility
NA
USES
Indication
Relaxation of smooth muscle in benign prostatic hyperplasia
producing an increase in urinary flow-rate and an improvement in
obstructive symptoms.
Therapeutic Dosage (BNF)
Adults 2.5mg three times daily, max 10mg daily, elderly 2.5mg
twice daily initially.
First dose may cause collapse due to hypotensive effect
(therefore should be taken on retiring to bed). Patients should
be warned to lie down if symptoms such as dizziness, fatigue or
sweating develop, and to remain lying down until they abate
completely.
Contraindications (Data sheet)
Hypersensitivity to alfuzosin
History of orthostatic hypotension
Hepatic insufficiency
Concurrent use with other alpha-blockers
Abuses
NIF
HAZARD/RISK CLASSIFICATION
NIF
PHARMACOKINETICS
Absorption (Data sheet)
Oral - 64%
Distribution
(Micromedex - Drug evaluation monograph):
Volume of distribution (healthy subjects)2.5L/kg
Metabolism
Extensively liver metabolised
Metabolites pharmacologically inactive
Elimination
11% excreted unchanged in urine
Up to 30% of a dose is excreted renally as metabolites
Most of a dose of alfuzosin is excreted via the faeces
Half-life (Data Sheet)
Plasma half life range 3 - 5 hr
Special Populations (Micromedex - Drug evaluation
monographs)
Elderly - More rapid and complete oral absorption and higher
plasma levels of alfuzosin have been reported in elderly subjects
(>75 years) who may be more sensitive to alfuzosin-induced
vasodilation. Dose reduction may be necessary. For patients over
65 with benign prostatic hyperplasia, initial doses of 2.5mg
twice daily are recommended, increasing to 10mg daily, based on
clinical response.
Renal failure - dosage adjustments are not necessary
Hepatic disease- reduced doses are recommended in hepatic
disease, although specific guidelines are unavailable
BREAST MILK
NIF
TOXICOKINETICS
NIF
EPIDEMIOLOGY OF POISONING
NIF
ADVERSE EFFECTS
Most frequently observed: vertigo, dizziness, malaise, headache,
minor gastro-intestinal disorders (nausea, gastralgia, diarrhoea
or vomiting).
Less frequently reported: hypotension (postural), syncope,
tachycardia, palpitations, chest pain, fatigue, drowsiness, rash,
pruritis, flushes and oedema
INTERACTIONS - alpha blockers (BNF)
ACE Inhibitors:enhanced hypotensive effect
Aldesleukin:enhanced hypotensive effect
Anaesthetics:enhanced hypotensive effect
Analgesics:NSAIDs antagonise hypotensive effect
Antidepressants:enhanced hypotensive effect; manufacturer of
indoramin advises avoid MAOIs
Other antihypertensives: additive hypotensive effect
Antipsychotics:enhanced hypotensive effect
Anxiolytics and Hypnotics:enhanced hypotensive and sedative
effect
Beta-blockers:enhanced hypotensive effect; increased risk of
first-dose hypotensive effect of post-synaptic alpha-blockers
such as prazosin
Calcium-channel blockers:enhanced hypotensive effect, increased
risk of first-dose hypotensive effect
Corticosteroids:antagonism of hypotensive effect
Diuretics:enhanced hypotensive effect; increased risk of first-
dose hypotensive effect
Dopaminergics:levodopa enhances hypotensive effect
Muscle relaxants:enhanced hypotensive effect
Oestrogens and Progestogens:antagonise hypotensive effect
Ulcer-healing drugs: carbenoxolone antagonises hypotensive effect
MECHANISM OF ACTION:
Alfuzosin is a selective alpha-1 adrenoceptor antagonist, with
structural similarities to prazosin. In vitro and in vivo studies
have demonstrated potent and selective alpha-1 adrenoceptor
antagonistic effects of alfuzosin on the genitourinary tract
(proximal urethral, bladder base, prostatic and prostatic capsule
smooth muscle. Studies suggest that alfuzosin is more selective
for alpha-1 receptors in the genitourinary tract compared to the
vasculature than prazosin or terazosin and may reduce urethral
resistance at doses not affecting blood pressure.
FEATURES OF POISONING
Acute - Ingestion
CARDIOVASCULAR
Postural hypotension and tachycardia are common. Tachycardia may
be associated with signs and symptoms of angina and cardiac
infarction. Effects are more pronounced in patients with
preexisting hypovolemia, or states associated with increased
catecholamine secretion.
NEUROLOGICAL
Dizziness, CNS stimulation, and seizures may occur.
GASTROINTESTINAL
Vomiting, abdominal pain, and diarrhoea may occur following large
oral doses
DERMATOLOGICAL
Flushing is common
CHRONIC TOXICITY
NIF
MANAGEMENT (Micromedex - Poisindex - Alpha adrenergic
blockers)
6th March 1995
Decontamination
Administer activated charcoal if presentation within 2 hours
Supportive care
Seizures
Administer diazepam, 10mg by slow intravenous injection.
Hypotension
Administer IV fluids and place in Trendleburg position.
Alpha agonist agents may only be effective at very high dose.
Adrenaline stimulates both alpha and beta receptors. In the
presence of alpha blockade, the net effect is vasodilation and
worsening of hypotension.
Similarly dopamine is primarily a beta-adrenergic agent and has
produced fatal cardiac arrest secondary to hypotension when given
with tolazoline
Noradrenaline primarily stimulates alpha receptors and is
preferable (Prod info Dibenyline 1993)
Suggested initial dose of noradrenaline
Adults: 8 to 12 mcg/ minute
Adult and child: 0.1 to 0.2 mcg/kg/minute. Titrate to
maintain adequate blood pressure
Maintenance dose
2 to 4 mcg / minute
Monitoring (Micromedex -Poisindex)
Blood levels of alpha blockers are not clinically useful
following acute overdose. No specific laboratory measurements are
necessary unless otherwise indicated.
(From Micromedex - drug evaluation monographs)
Blood pressure and heart rate
ECG monitoring in patients with coronary artery disease
Antidotes
None
Elimination techniques
None
Investigations
Routine chemistry
ECG
Management controversies
None
CASE DATA
None
OTHER TOXICOLOGICAL DATA
None
ENVIRONMENTAL DATA
No info on LC50
Author
Helen Seymour, BPharm (Hons)
National Poisons Information Service (Newcastle Centre)
Regional Drug & Therapeutics Centre
Wolfson Building
Claremont Place
Newcastle upon Tyne
NE1 4LP
UK
This monograph was produced by the staff of the Newcastle Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
Last updated January 1997
REFERENCES
British National Formulary, Number 30 (September 1995) London. British
Medical Association and The Pharmaceutical Press 1995
Drug Evaluation Monographs(R) Micromedex Inc, Denver Colorado, Edition
expires 31/3/96
Martindale The Extra Pharmacopeia 13th Ed, London The Pharmaceutical
Press 1993
Poisindex System(R) Micromedex Inc, Denver Colorado, Edition expires
31/3/96