Cardura XL 8 mg Prolonged-release tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Doxazosin
Available from:
Pfizer Healthcare Ireland
ATC code:
C02CA; C02CA04
INN (International Name):
Doxazosin
Dosage:
8 milligram(s)
Pharmaceutical form:
Prolonged-release tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Alpha-adrenoreceptor antagonists; doxazosin
Authorization status:
Marketed
Authorization number:
PA0822/004/002
Authorization date:
1999-10-29

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Package leaflet: Information for the patient

CARDURA® XL 4mg

CARDURA® XL 8mg

Prolonged–release Tablets

Doxazosin (as mesilate)

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

You should take Cardura XL regularly to get the maximum benefit, even if you are feeling well.

Most people do not have serious problems when taking Cardura XL but side effects can occur. If you

experience swelling of the face, tongue or windpipe, see your doctor immediately. If you get any side

effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in

this leaflet. See section 4.

Taking other medicines may sometimes cause problems. Check with your doctor or pharmacist before

taking this or any other medicines.

If you are, or are trying to become, pregnant, do not take Cardura XL and tell your doctor or

pharmacist.

What is in this leaflet

What Cardura XL is and what it is used for

What you need to know before you take Cardura XL

How to take Cardura XL

Possible side effects

How to store Cardura XL

Contents of the pack and other information

1.

What Cardura XL is and what it is used for

Cardura XL is one of a group of medicines called alpha-blockers. It is used to treat high blood pressure.

Cardura XL can be used to treat high blood pressure (hypertension), by relaxing blood vessels so that

blood passes through them more easily. This helps to lower blood pressure.

In patients with an enlarged prostate gland, CARDURA XL is taken to treat poor and/or frequent passing

of urine. This is common in patients with an enlarged prostate gland. CARDURA XL works by relaxing

muscle around the bladder exit and prostate gland so urine is passed more easily.

2.

What you need to know before you take Cardura XL

Do not take Cardura XL:

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If you are allergic to doxazosin, other types of quinazolines (such as prazosin or terazosin), or

any of the other ingredients of this medicine (listed in section 6). This may have been itching,

reddening of the skin or difficulty in breathing.

If you have any form of obstruction of the digestive tract

If you are under 18 years of age

If you have a history of a condition known as ‘orthostatic hypotension’ which is a form of low

blood pressure that causes you to feel dizzy or light-headed when you stand up from sitting or

lying down

If you have an enlarged prostate gland with one of the following: any kind of congestion or

blockage in your urinary tract, a longstanding infection of the urinary tract or you have bladder

stones.

If you have an enlarged prostate gland and have overflow incontinence (you do not feel the urge

to urinate), or anuria (your body is not producing any urine) with or without kidney problems.

Warnings and precautions

Talk to your doctor or pharmacist before taking Cardura XL as it may not be suitable for you:

If you are pregnant or trying to become pregnant

If you have liver, kidney or heart disease

If you are also taking other medicines

If you have problems with your heart

If you are undergoing eye surgery because of cataract (cloudiness of the lens) please inform your eye

specialist before the operation that you are using or have previously used Cardura XL. This is because

this medicine may cause complications during the surgery which can be managed if your specialist is

prepared in advance.

Persistent painful erections may occur very rarely. If this happens you should contact a doctor

immediately.

When you start to take Cardura XL you may experience faintness or dizziness caused by low blood

pressure, when getting up from sitting or lying down. If you feel faint or dizzy, you should sit or lie down

until you feel better and avoid situations where you might fall or hurt yourself.

Before starting treatment with CARDURA XL your doctor may perform tests to rule out other conditions

such as prostate cancer that may cause the same symptoms as benign prostatic hyperplasia.

Other medicines and Cardura XL

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines,

including medicines obtained without a prescription.

There are some medicines that may interact with Cardura XL. Ask your doctor or pharmacist before use

if you are taking any of these medicines as they may change the effect of Cardura XL:

Some patients who take alpha-blocker therapy for the treatment of high blood pressure or

prostate enlargement may experience dizziness or light-headedness, which may be caused by low

blood pressure upon sitting or standing up quickly. Certain patients have experienced these

symptoms when taking medicines called PDE-5 inhibitors for the treatment of erectile

dysfunction (impotence) with alpha-blockers e.g. sildenafil, tadalafil or vardenafil (please see

Section “Warnings and precautions”. In order to reduce the likelihood that these symptoms

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occur, you should be on a regular daily dose of your alpha blocker before you start drugs for

erectile dysfunction.

Cardura XL may also increase the effects of drugs used to treat high blood pressure

(hypertension).

Medicines to treat bacterial or fungal infections, e.g. clarithromycin, itraconazole, ketoconazole,

telithromycin, voriconazole.

Medicines used in the treatment of HIV e.g. indinavir, nelfinavir, ritonavir, saquinavir.

Nefazodone, a medicine used to treat depression.

Cardura XL with food and drink

See section 3 How to take Cardura XL.

Pregnancy and breast-feeding

The safety of using Cardura XL during pregnancy has not been established. If you are pregnant or trying

to become pregnant speak to your doctor, who will decide if this medicine is suitable for you. Do not take

Cardura XL if you are breast-feeding.

Driving and using machines

Take care if you drive or operate machinery. Your tablets may affect your ability to drive or operate

machinery safely, particularly when you first start to take them. They may cause drowsiness and could

also make you feel weak or dizzy. If you are affected, do not drive or operate machinery and contact your

doctor immediately.

Cardura XL contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially

‘sodium-free’.

3.

How to take Cardura XL

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Cardura XL is a prolonged-release tablet. The medicine is contained within a non-absorbable

shell that has been specially designed to slowly release the medicine. Once swallowed, the

medicine (doxazosin) is slowly released into the body from the tablet, until the tablet is empty.

Since the empty tablet is eliminated from the body in bowel movements, you may occasionally

observe in the stools, something that looks like a tablet. This is to be expected and you should

not be concerned.

How to take your medicine

- The usual dose of Cardura XL is one 4mg prolonged-release tablet taken once a day. Your

doctor may wish to increase your dose to 8mg. This is the maximum dose of this medicine.

- Cardura XL can be taken with or without food.

- Swallow your medicine whole with water. Do not chew, divide or crush the tablets.

- Take your tablets as your doctor told you.

- It is important to keep taking your tablets. They help to control your blood pressure.

- Don't change the dose or stop taking the tablets without first checking with your doctor.

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- Don't wait until your tablets are finished before seeing your doctor.

- If you are still not sure how to take your tablets, ask your doctor or pharmacist.

If you take more Cardura XL than you should

Taking too many tablets at once may make you unwell. If several tablets are taken it may be dangerous.

Tell your doctor immediately or go to your nearest hospital casualty department immediately.

If you forget to take Cardura XL

Do not worry. If you forget to take a tablet, leave that dose out completely. Then go on as before. Do not

take a double dose to make up for a forgotten tablet.

4.

Possible side effects

Like all medicines, this medicine can cause side effects although not everybody gets them.

STOP taking Cardura XL and call an ambulance immediately if you experience any of the

following:

Heart attack

Increased, decreased or irregular heartbeat

Weakness of arms, legs or problems speaking which may be symptoms of a stroke

Allergic reactions (hypersensitivity). Symptoms include sudden wheeziness, tightness in

chest, difficulty in breathing, swelling of the face, tongue or throat, rash or itching

(especially affecting the whole body)

Tell your doctor immediately if you experience any of the following symptoms after taking Cardura XL:

Chest pain (angina), wheezing, shortness of breath, difficulty breathing

Feeling your heartbeat (palpitations)

Fainting

Yellowing of the skin or the eyes (jaundice)

Low numbers of white blood cells or blood platelets, which may result in bruising or easy

bleeding

The following events have been reported in patients being treated with Cardura XL. If any of these side

effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Common side effects: may affect up to 1 in 10 people

Dizziness, feeling of spinning or rotation of surroundings (vertigo), headache

Low blood pressure

Swelling of feet, ankles or fingers

Bronchitis, coughing, respiratory tract (nose, throat, lungs) infection

Nasal stuffiness, sneezing and/or runny nose caused by inflammation of the lining of the nose

(rhinitis)

Stomach/abdominal pains, feeling/being sick

Urinary tract infection, urinary incontinence (inability to control passing urine), inflammation of

the bladder (cystitis)

Sleepiness, general weakness

Indigestion, dry mouth

Itching

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Back pain, painful muscles

Flu-like symptoms

Uncommon side effects: may affect up to 1 in 100 people

Constipation, wind, inflammation of the stomach and intestines (gastroenteritis) which can cause

diarrhoea and vomiting

Pain or discomfort on passing urine, increased frequency in passing urine, blood in urine

Inflammation of the joints (gout), painful joints, general pain

Sleeplessness, anxiety, depression

Reduced or altered sense of touch or sensation of the hands and feet

Increased appetite or loss of appetite, weight gain

Nose bleeds

Skin rash

Ringing or noise in the ears, tremor

Failure/ inability to achieve penile erection

Liver enzyme increases which may have an effect on some medical tests

Stroke

Rare side effects: may affect up to 1 in 1,000 people

Blockage of the digestive tract

Very Rare side effects: may affect up to 1 in 10,000 people

Faintness or dizziness caused by low blood pressure when getting up from a sitting or lying

position

Agitation or nervousness

Hepatitis (liver inflammation) or bile disorder

Hives, hair loss, red or purple patches on the skin, bleeding under the skin

Tingling or numbness of the hands and feet

Tiredness, generally feeling unwell

Blurred vision

Hot flushes

Muscle cramps, muscle weakness

Disorder in passing urine, needing to pass urine at night, increased number of times of passing

urine, increased volume of urine passed

Discomfort or enlargement of the breasts in men

Persistent painful erection of the penis. Seek urgent medical advice

Not known: frequency cannot be estimated from the available data

Little or no semen ejaculated at sexual climax, cloudy urine following sexual climax

Eye problems may occur during eye surgery for cataract (cloudiness of the lens of the eye). See

section “Warnings and precautions”.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not

listed in this leaflet. You can also report side effects directly via HPRA Pharmacovigilance, Earlsfort

Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:

medsafety@hpra.ie. By reporting side effects you can help provide more information on the safety of this

medicine.

5.

How to store Cardura XL

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Keep this medicine out of the sight and reach of children.

Do not use Cardura XL after the expiry date which is stated on the carton and tablet blister after EXP.

The expiry date refers to the last day of that month.

Do not store above 30ºC. Keep your tablets in the original packaging in order to protect from to moisture.

The tablets should be whole to work effectively, if you notice any defects (such as broken tablets) consult

your pharmacist immediately.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Cardura XL contains

The active substance is doxazosin as doxazosin mesilate. Each tablet contains either 4.85mg doxazosin

mesilate equivalent to 4mg doxazosin or 9.70mg doxazosin mesilate equivalent to 8mg doxazosin within

a shell that has been specially designed to slowly release the drug.

The other ingredients are polyethylene oxide, sodium chloride, hypromellose, red ferric oxide (E172),

titanium dioxide (E171), magnesium stearate, cellulose acetate, Macrogol, pharmaceutical glaze, black

iron oxide (E172), ammonium hydroxide and propylene glycol

What Cardura XL looks like and contents of the pack

Cardura XL tablets are white film coated, round biconvex shaped with a hole in one side, marked CXL4

for the 4mg and CXL8 for the 8mg.

Cardura XL tablets are available in strengths of 4mg and 8mg in cartons containing blister strips of 28

tablets.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pfizer Healthcare Ireland

9 Riverwalk

National Digital Park

Citywest Business Campus

Dublin 24

Ireland

Manufacturer

R-Pharm Germany GmbH

Heinrich-Mack-Str. 35

89257 Illertissen

Germany

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Pfizer Manufacturing Deutschland GmbH, Betriebsstätte Freiburg, Mooswaldallee 1, 79090 Freiburg,

Germany

Company contact address:

For further information on your medicine contact Medical Information at the following address:

Pfizer Healthcare Ireland, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24,

Ireland

Telephone 1800 633 363

This leaflet was last revised in MM/YYYY.

Ref: CX 30_1

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Cardura XL 8 mg Prolonged-release tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Doxazosin mesilate: 9.70 mg equivalent to 8 mg doxazosin.

For the full list of excipients see section 6.1.

3 PHARMACEUTICAL FORM

Prolonged-release tablet.

White, film coated, round, biconvex shaped tablets with an orifice on one side, marked CXL8.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Hypertension:

Cardura XL is indicated for the treatment of hypertension and can be used as a sole agent to control blood pressure in

hypertensive patients.

In patients inadequately controlled on single antihypertensive therapy, Cardura XL may be used in combination with a thiazide

diuretic, beta-adrenoceptor blocking agent, calcium antagonist or an angiotensin-converting enzyme inhibitor.

Benign prostatic hyperplasia:

Cardura XL is indicated for the treatment of urinary outflow obstruction and symptoms associated with benign prostatic

hyperplasia (BPH).

Cardura XL may be used in BPH patients who are either hypertensive or normotensive. While the blood pressure changes in

normotensive patients with BPH are not usually clinically significant, patients with hypertension and BPH have had both

conditions effectively treated with doxazosin monotherapy.

4.2 Posology and method of administration

Posology

The initial dose of Cardura XL is 4mg once daily. A significant number of patients will be controlled on this dose. If necessary,

the dosage may be increased to 8mg once daily according to patient response.

The maximum recommended dose is 8mg once daily.

Elderly patients:

In common with other drugs of this class, the dosage should be kept as low as possible and increments made under close

supervision.

Patients with renal impairment:

Since the pharmacokinetics of doxazosin are unchanged in patients with renal insufficiency, and there is no evidence that

doxazosin aggravates existing renal dysfunction, the usual dosages may be used in these patients. Cardura XL is not dialysable.

Patients with hepatic impairment:

There are only limited data in patients with liver impairment and on the effects of drugs known to influence hepatic

metabolism (e.g. cimetidine). As with any drug metabolised wholly by the liver, Cardura XL should be used with care in patients

with significant existing hepatic dysfunction. (see section 4.4 and section 5.2).

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Paediatric population:

The safety and efficacy of Cardura XL in children and adolescents have not been established.

Method of administration

Cardura XL can be taken with or without food.

The tablets should be swallowed whole with a sufficient amount of liquid. They should not be cut, crushed or chewed (see

section 4.4).

4.3 Contraindications

Cardura XL is contraindicated in:

Patients who are hypersensitive to doxazosin, other types of quinazolines (e.g. prazosin, terazosin), or to any of the

excipients listed in section 6.1.

Patients with a history of orthostatic hypotension.

Patients with benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary

tract infection or bladder stones.

Patients with a history of gastro-intestinal obstruction, oesophageal obstruction, or any degree of decreased

lumen diameter of the gastro-intestinal tract (For patients taking the sustained release tablets only).

Patients with hypotension (For benign prostatic hyperplasia indication only)

Doxazosin is contraindicated as monotherapy in patients with either overflow bladder or anuria with or without progressive

renal insufficiency.

4.4 Special warnings and precautions for use

Information to be given to the patient:

Patients should be informed that Cardura XL tablets should be swallowed whole. Patients should not chew, divide or crush the

tablets (see section 4.2).

In Cardura XL, the active compound is surrounded by an inert, non-absorbable shell that has been specially designed to control

the release of the drug over a prolonged period. After transit through the gastrointestinal tract, the empty tablet shell is

excreted. Patients should be advised that they should not be concerned if they occasionally observe remains in their stools that

look like a tablet.

Abnormally short transit times through the gastrointestinal tract (e.g. following surgical resection) could result in incomplete

absorption. In view of the long half life of doxazosin the clinical significance of this is unclear.

Postural Hypotension / Syncope:

Initiation of therapy – In relation with the alpha-blocking properties of doxazosin, patients may experiencepostural hypotension

evidenced by dizziness and weakness, or rarely loss of consciousness (syncope), particularly with the commencement of

therapy. Therefore, it is prudent medical practice to monitor blood pressure on initiation of therapy to minimise the potential

for postural effects.

When instituting therapy with any effective alpha-blocker, the patient should be advised how to avoid symptoms resulting

from postural hypotension and what measures to take should they develop. The patient should be cautioned to avoid

situations where injury could result should dizziness or weakness occur during the initiation of Cardura XL therapy, such as

driving or operating machinery.

Use in Patients with Acute Cardiac Conditions:

As with any other vasodilatory anti-hypertensive agent it is prudent medical practice to advise caution when administering

doxazosin to patients with the following acute cardiac conditions:

- pulmonary oedema due to aortic or mitral stenosis

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- heart failure at high output

- right-sided heart failure due to pulmonary embolism or pericardial effusion

- left ventricular heart failure with low filling pressure.

Use in Hepatically Impaired Patients:

As with any drug wholly metabolised by the liver, Cardura XL should be administered with particular caution to patients with

evidence of impaired hepatic function (see sections 4.2 and 5.2). Since there is no clinical experience in patients with severe

hepatic impairment use in these patients is not recommended.

Use in Patients with Impaired Renal Function:

There is no evidence that Cardura XL aggravates renal dysfunction. However, Cardura XL dosage introduction and adjustments

should be carried out with great care.

Use with Phosphodiesterase Type-5Inhibitors:

Concomitant administration of doxazosin with phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, and vardenafil) should

be done with caution as both drugs have vasodilating effects and may lead to symptomatic hypotension in some patients. To

reduce the risk of orthostatic hypotension it is recommended to initiate the treatment with phosphodiesterase-5-inhibitors

only if the patient is hemodynamically stabilized on alpha-blocker therapy. Furthermore, it is recommended to initiate

phosphodiesterase-5-inhibitor treatment with the lowest possible dose and to respect a 6-hour time interval from intake of

doxazosin. No studies have been conducted with doxazosin prolonged release formulations.

Use in Patients Undergoing Cataract Surgery:

Intraoperative Floppy Iris Syndrome

The 'intraoperative floppy iris syndrome' (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in

some patients on or previously treated with tamsulosin. Isolated reports have also been received with other alpha-1 blockers

and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the

cataract operation current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of

surgery.

Screening for Prostate Cancer:

Carcinoma of the prostate causes many of the symptoms associated with BPH and the two disorders can co-exist. Carcinoma of

the prostate should therefore be ruled out prior to commencing therapy with doxazosin for treatment with BPH symptoms.

Priapism:

Prolonged erections and priapism have been reported with alpha-1 blockers including doxazosin in post marketing experience.

If priapism is not treated immediately, it could result in penile tissue damage and permanent loss of potency, therefore the

patient should seek immediate medical assistance.

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium free'.

4.5 Interaction with other medicinal products and other forms of interactions

Phosphodiesterase Type-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil)

Concomitant administration of an alpha blocker with a PDE-5 inhibitor may lead to symptomatic hypotension in some patients

(see section 4.4). No studies have been conducted with Cardura XL.

Doxazosin is highly bound to plasma proteins (98%). In vitro data in human plasma indicates that doxazosin has no effect on

protein binding of the drugs tested (digoxin, phenytoin, warfarin or indometacin). However, the theoretical potential for

interaction with other protein bound drugs should be borne in mind.

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In vitro studies suggest that doxazosin is a substrate of cytochrome P450 3A4 (CYP 3A4). Caution should be exercised when

concomitantly administering doxazosin with a strong CYP 3A4 inhibitor, such as clarithromycin, indinavir, itraconazole,

ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole (see section 5.2).

Conventional doxazosin has been administered without anyadverse druginteractions in clinical experience with thiazide

diuretics, furosemide, beta-blocking agents, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycaemic drugs,

uricosuric agents, or anticoagulants. However, data from formal drug/drug interaction studies are not present.

Doxazosin potentiates the blood pressure lowering activity of other alpha-blockers and other antihypertensives.

In an open-label, randomized, placebo-controlled trial in 22 healthy male volunteers, the administration of a single 1 mg dose

of doxazosin on day 1 of a four-day regimen of oral cimetidine (400 mg twice daily) resulted in a 10% increase in mean AUC of

doxazosin, and no statistically significant changes in mean Cmax and mean half-life of doxazosin. The 10% increase in the

mean AUC for doxazosin with cimetidine is within intersubject variation (27%) of the mean AUC for doxazosin with placebo.

4.6 Fertility, pregnancy and lactation

For the hypertension indication:

Use during pregnancy:

As there are no adequate and well-controlled studies in pregnant women, the safety of Cardura XL during pregnancy has not

yet been established. Accordingly, during pregnancy, Cardura XL should be used only when, in the opinion of the physician, the

potential benefit outweighs the potential risk. Doxazosin crosses the placenta. Although no teratogenic effects were seen in

animal testing, reduced foetal survival was observed in animals at extremely high doses (see section 5.3). These doses were

approximately 300 times the maximum recommended human dose.

Use during lactation:

The excretion of doxazosin in breast milk was demonstrated to be very low (with the relative infant dose less than 1%) however

human data is very limited. A risk to the newborn or infant cannot be excluded and therefore doxazosin should be used only

when in the opinion of the physician, the potential benefit outweighs the potential risk.

4.7 Effects on ability to drive and use machines

The ability to engage in activities such as operating machinery or operating a motor vehicle may be impaired, especially when

initiating therapy. The drug may also induce drowsiness. Patients should not drive or operate machinery unless it has been

shown not to affect their alertness or dexterity.

4.8 Undesirable effects

In clinical trials, the most common reactions associated with Cardura XL were of a postural type (rarely associated with fainting)

or non-specific.

The undesirable effects for Cardura XL are similar to those with immediate release Cardura tablets.

The following undesirable effects have been observed and reported during treatment with Cardura XL with the following

frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to

<1/1,000); very rare (<1/10,000).

System Organ

Class

Very Common

(≥1/10)

Common

(≥1/100 to

<1/10)

Uncommon

(≥1/1,000 to

<1/100)

Rare

(≥1/10,000 to

<1/1,000)

Very Rare

(<1/10,000)

Unknown

Infections and

infestations

Respiratory

tract

infection,

urinary tract

infection

Blood and the

lymphatic

system disorders

Leukopenia,

thrombocytopenia

Immune system

Allergic drug

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disorders

reaction

Metabolism and

nutrition

disorders

Anorexia, gout,

increased

appetite

Psychiatric

disorders

Anxiety,

depression,

insomnia

Agitation,

nervousness

Nervous system

disorders

Dizziness,

headache,

somnolence

Cerebrovascular

accident,

hypoesthesia,

syncope, tremor

Dizziness postural,

paresthesia

Eye disorders

Blurred vision

Intraoperative

floppy iris

syndrome (see

section 4.4)

Ear and

labyrinth

disorders

Vertigo

Tinnitus

Cardiac

disorders

Palpitation,

tachycardia

Angina pectoris,

myocardial

infarction

Bradycardia,

cardiac

arrhythmias

Vascular

disorders

Hypotension,

postural

hypotension

Hot flushes

Respiratory,

thoracic and

mediastinal

disorders

Bronchitis,

cough,

dyspnoea,

rhinitis

Epistaxis

Bronchospasm

Gastrointestinal

disorders

Abdominal

pain,

dyspepsia,

dry mouth,

nausea

Constipation,

diarrhoea,

flatulence,

vomiting,

gastroenteritis

Gastrointestinal

obstruction

Hepato-biliary

disorders

Abnormal liver

function tests

Cholestasis,

hepatitis, jaundice

Skin and

subcutaneous

tissue disorders

Pruritus

Skin rash

Alopecia, purpura,

urticaria

Musculoskeletal,

connective

tissue and bone

disorders

Back pain,

myalgia

Arthralgia

Muscle cramps,

muscle weakness

Renal and

urinary

disorders

Cystitis,

urinary

incontinence

Dysuria,

hematuria,

micturition

frequency

Micturition

disorder, nocturia,

polyuria,

increased diuresis

Reproductive

system and

breast disorders

Impotence

Gynecomastia,

priapism

Retrograde

ejaculation

General

disorders and

administration

site conditions

Asthenia,

chest pain,

influenza-like

symptoms,

peripheral

oedema

Pain, facial

oedema

Fatigue, malaise

Investigations

Weight increase

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Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.

Website: www.hpra.ie; e-mail: medsafety@hpra.ie.

4.9 Overdose

Should overdosage lead to hypotension, the patient should be immediately placed in a supine, head down position. Other

supportive measures may be appropriate in individual cases. Since doxazosin is highly protein bound, dialysis is not indicated.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Alpha-adrenoreceptor antagonists

ATC code: C02CA04 (Hypertension)

Mode of action

Doxazosin is a potent and selective post-junctional alpha 1-adrenoceptor antagonist.

Administration of Cardura XL to hypertensive patients causes a clinically significant reduction in blood pressure as a result of a

reduction in systemic vascular resistance. This effect is thought to result from selective blockade of the

alpha-1-adrenoreceptors located in the vasculature. With once daily dosing, clinically significant reductions in blood pressure

are present throughout the day and at 24 hours post dose. The majority of patients are controlled on the initial dose. In

patients with hypertension, blood pressure during treatment with Cardura XL was similar in both the supine and standing

position.

Responder data from the 2 primary hypertension efficacy studies (including a total of 630 doxazosin treated patients) indicate

that those patients controlled on 1 mg, 2 mg or 4 mg doxazosin immediate release tablets would be equally well controlled on

4 mg Cardura XL.

Administration of Cardura XL to patients with symptomatic BPH results in a significant improvement in urodynamics and

symptoms. The effect in BPH is thought to results from selective blockade of the alpha adrenoceptors located in the muscular

stroma and capsule of the prostate and in the bladder neck.

Pharmacodynamic effects

Doxazosinhas been shown to be free of adverse metabolic effects and is suitable for use in patients with coexistent diabetes

mellitus, gout and insulin resistance.

Doxazosin is suitable for use in patients with coexistent asthma, left ventricular hypertrophy and in elderly patients. Treatment

with doxazosin has been shown to result in regression of left ventricular hypertrophy, inhibition of platelet aggregation and

enhanced activity of tissue plasminogen activator. Additionally, doxazosin improves insulin sensitivity in patients with

impairment.

Doxazosin produces favourable effects on blood lipids, with a significant increase in the high-density lipoprotein HDL/total

cholesterol ratio and trends to a favourable reduction in total triglycerides. It therefore confers an advantage over diuretics and

beta-adrenoceptor blocking agents which adversely affect these parameters. Based on the established association of

hypertension and blood lipids with coronary heart disease, the favourable effects of doxazosin therapy on both blood pressure

and lipids indicate a reduction in risk of developing coronary heart disease.

Benign prostatic hyperplasia:

Doxazosin has been shown to be an effective blocker of the 1A subtype of the alpha 1 adrenoceptor, which account for over

70% of the subtypes in the prostate. This accounts for the action in BPH patients.

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Cardura XL has demonstrated sustained efficacy and safety in the long-term treatment of BPH.

Cardura XL given in the recommended dosage regimen has little or no effect on blood pressure in normotensive patients.

In a controlled clinical BPH trial, treatment with doxazosin in patients with sexual dysfunction was associated with improvement

in sexual function.

5.2 Pharmacokinetic properties

Absorption:

After oral administration of therapeutic doses, Cardura XL is well absorbed with peak blood levels gradually reached at 8 to 9

hours after dosing. Peak plasma levels are approximately one third of those of the same dose of immediate release Cardura

tablets. Trough levels at 24 hours are, however, similar.

The pharmacokinetic characteristics of Cardura XL will lead to a smoother plasma profile.

Peak/trough ratio of Cardura XL is less than half that of immediate release Cardura tablets.

At steady-state, the relative bioavailability of doxazosin from Cardura XL compared to the immediate release form was 54% at

the 4mg dose and 59% at the 8mg dose.

Pharmacokinetic studies with Cardura XL in the elderly have shown no significant alterations compared to younger patients.

Biotransformation / Elimination:

The plasma elimination is biphasic with the terminal elimination half-life being 22 hours and hence this provides the basis for

once daily dosing. Doxazosin is extensively metabolised with <5% excreted as unchanged drug.

Pharmacokinetic studies with immediate release Cardura in patients with renal impairment also showed no significant

alterations compared to patients with normal renal function.

There are only limited data in patients with liver impairment and on the effects of drugs known to influence hepatic

metabolism (e.g. cimetidine). In a clinical study in 12 patients with moderate hepatic impairment, single dose administration of

doxazosin resulted in an increase in AUC of 43% and a decrease in apparent oral clearance of 30%. See section 4.4.

Approximately 98% of doxazosin is protein-bound in plasma.

Doxazosin is primarily metabolised by O-demethylation and hydroxylation.

Doxazosin is extensively metabolized in the liver. In vitro studies suggest that the primary pathway for elimination is via CYP

3A4; however, CYP 2D6 and CYP 2C9 metabolic pathways are also involved for elimination, but to a lesser extent.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional animal studies in safety pharmacology, repeated

dose toxicity, genotoxicity, carcinogenicity and gastrointestinal tolerance.

Although no teratogenic effects were seen in animal testing, reduced foetal survival was observed in animals at doses

approximately 300 times greater than the maximum human recommended dose.

Studies in lactating rats given a single oral dose of 1 mg/kg of [2-14C]-doxazosin indicate that doxazosin accumulates in rat

breast milk with a maximum of concentration about 20 times greater than the maternal plasma concentration.

For further information see section 4.6.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Polyethylene oxide

Sodium chloride

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Hypromellose

Red ferric oxide (E172)

Titanium dioxide (E171)

Magnesium stearate

Cellulose acetate

Macrogol

Pharmaceutical glaze

Propylene glycol

Black iron oxide (E172)

Ammonium hydroxide

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 30°C.

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Calendar packs of 28 tablets.

Aluminium foil/aluminium foil blister strips in a carton.

6.6 Special precautions for disposal and other handling

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Pfizer Healthcare Ireland

9 Riverwalk

National Digital Park

Citywest Business Campus

Dublin 24

Ireland

8 MARKETING AUTHORISATION NUMBER

PA0822/004/002

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 29 October 1999

Date of last renewal: 29 October 2009

10 DATE OF REVISION OF THE TEXT

February 2020

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