INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
CARDURA XL 4 mg Tablets
CARDURA XL 8 mg Tablets

Doxazosin mesylate
Cardura XL
Controlled-Release Tablets                S3
Prescription Required

SCHEDULING STATUS:
Schedule 3.

PROPRIETARY NAME
(and dosage form):

CARDURA XL 4 mg Tablets
CARDURA XL 8 mg Tablets

COMPOSITION
Doxazosin mesylate is a quinazoline derivative, having the chemical name:
1-(4-amino-6, 7-dimethoxy-2-quinazolinyl )-4-(1, 4-benzodioxan-2-yl-carbonyl)piperazine methanesulphonate. It is a white powder, slightly soluble in methanol and sparingly soluble in water, ethanol, acetone and chloroform, and has a molecular weight of 547,6 (free base 451,5).
Each 4 mg Cardura XL tablet contains 5,093 mg doxazosin mesylate equivalent to 4 mg doxazosin.
Each 8 mg Cardura XL tablet contains 10,185 mg doxazosin mesylate equivalent to 8 mg doxazosin.
Cardura XL tablets contain the following inert ingredients: Polyethylene oxide, Sodium chloride, Hydroxypropyl methylcellulose, Red ferric oxide, Titanium dioxide, Magnesium stearate, Cellulose acetate, Polyethylene glycol and Black Ink.

PHARMACOLOGICAL CLASSIFICATION
A.7.1 Vasodilators, hypotensive medicines.

PHARMACOLOGICAL ACTION
Doxazosin exerts a vasodilator effect via selective and competitive blockade of post-junctional alpha 1-adrenoceptors.
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 conventional Cardura tablets. Trough levels at 24 hours are, however, similar.
Doxazosin is extensively metabolised with less than 5% excreted as the unchanged drug
Peak/trough ratio of Cardura XL is less than half that of conventional Cardura tablets.
The plasma elimination of Cardura XL is biphasic with the terminal elimination half life being 22 hours, hence providing the basis for once daily dosing.
Most (98%) of plasma doxazosin is protein bound. In vitro data in human plasma indicates that doxazosin has no effect on protein binding of the agents tested (digoxin, phenytoin, warfarin or indomethacin).

INDICATIONS
Cardura XL is indicated for the treatment of mild to moderate hypertension.
Cardura XL is also indicated for the treatment of the 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.

CONTRA-INDICATIONS
Cardura XL is contra-indicated in:-

-	Patients with a known hypersensitivity to quinazolines.
-	Patients with a history of gastro-intestinal obstruction, oesophageal obstruction, or any degree of decreased lumen diameter of the gastro-intestinal tract.

Use During Pregnancy and Lactation
Use during pregnancy or lactation has not yet been established.
Use for Children
No experience is available on usage of doxazosin in children.

DOSAGE AND DIRECTIONS FOR USE
Patients established on conventional Cardura tablets 1 mg to 4 mg daily may be controlled on Cardura XL 4 mg daily.
Those patients established on conventional Cardura 8 mg daily may be controlled on Cardura XL 8 mg daily.
Hypertension
The majority of patients will be controlled on 4 mg daily. If necessary, the dosage may be increased to 8 mg once daily according to patient response.
In patients not adequately controlled on a single antihypertensive agent, doxazosin may be used in combination with a thiazide diuretic or a beta-blocking agent.
Benign Prostatic Hyperplasia
The recommended dosage of Cardura XL is 4 mg once daily. Depending on the individual patient's urodynamics and BPH symptomatology,dosage may then beincreased to 8 mg daily.
The recommended titration interval is 1-2 weeks. Blood pressure should be evaluated routinely in these patients.
Cardura XL can be taken with or without food. The tablets should be swallowed whole with a sufficient amount of liquid.

INFORMATION FOR THE PATIENT:
Patients should be informed that CARDURA XL tablets should be swallowed whole. Patients should not chew, divide or crush the tablets.
In Cardura XL the medication is contained within a non-absorbable shell that has been specially designed to slowly release the medicine. When this process is completed the empty tablet is eliminated from the body. Patients should be advised that they should not be concerned if they occasionally observe the empty tablet in the stools.

USE IN ELDERLY
Normal adult dosage is recommended. Pharmacokinetic studies with Cardura XL in the elderly have shown no significant alterations compared to younger patients.

USE IN HEPATICALLY IMPAIRED PATIENTS:
There are only limited data in patients with liver impairment and on the effects of medicines known to influence hepatic metabolism (eg. Cimetidine )
Doxazosin is wholly metabolised by the liver, and should be administered with caution to patients with evidence of impaired hepatic function.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
The most common reactions associated with doxazosin are dizziness, headache, fatigue, malaise, postural dizziness, vertigo, hypotension, oedema, asthenia, somnolence, nausea, rhinitis, depression, dry mouth, dyspnoea, insomnia, nervousness and sexual dysfunction.
The following additional adverse events have been reported: rare cases of non-specific gastric complaints such as abdominal pain, diarrhoea and vomiting, less frequent case of agitationand tremor.
Less frequent cases of urinary incontinence were reported; this effect may be related to doxazosin’s pharmacological action.
Less frequent cases of priapism and impotence have been reported to be associated with doxazosin. Less frequent cases of allergic medicine reactions (such as skin rash, pruritis, purpura, jaundice and elevated liver transaminases) and epistaxis have also been reported.
The following have also been reported: tachycardia, palpitation, chest pain, blurred vision, angina pectoris, myocardial infarction, cerebrovascular accidents and cardiac arrythmias.
Driving/Use of Machinery
The ability to engage in activities such as operating machinery or operating a motor vehicle may be impaired especially when initiating therapy.
Interactions
Administration of doxazosin may reduce plasma concentrations of triglycerides, total and LDL-cholestrol and increase HDL-cholestrol. These potentially favourable effects on lipids persist when a thiazide-type diuretic is given concurrently. The long-term consequences of these medicine-induced changes in lipids are not known.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Should overdosage lead to hypotension, the patient should be immediately placed in a supine, head down position.
Since doxazosin is highly protein bound, dialysis is not indicated.
Treatment is symptomatic and supportive.

IDENTIFICATION
Cardura XL 4 mg Tablet: A round, biconvex shaped white film coated tablet, approximately 9,0 mm in diameter with an orifice on one side.
Cardura XL 8 mg tablet: A round, biconvex shaped white film coated tablet, approximately 11,4 mm in diameter with an orifice on one side.

PRESENTATION
Cardura XL 4 mg and Cardura XL 8 mg Tablets:
White, opaque, high-density polyethylene bottles with Child resistant closures containing 30 or 100 Tablets.
or
Blister strips of either PVC/PVDC and aluminium foil or Aluminium foil / aluminium foil of 10, 30, 50, and 100 Tablets.

STORAGE INSTRUCTIONS
Store below 30°C. Protect from light.
Protect from moisture and humidity.
Keep out of reach of children.

REGISTRATION NUMBERS
Cardura XL 4 mg Tablets: 32/7.1/0556
Cardura XL 8 mg Tablets: 32/7.1/0557

NAME AND BUSINESS ADDRESS OF APPLICANT
Pfizer Laboratories (Pty) Limited
102 Rivonia Road
SANDTON
2196

DATE OF PUBLICATION OF THIS PACKAGE INSERT
28 JUNE 2000

ZIMBABWE DETAILS 12.3.1 –Vasodilators (Anti-hypertensive drugs) Cardura XL 4 mg: 2001/12.3.1/3952        PP Cardura XL 8 mg: 2001/12.3.1/3953        PP

Updated on this site: February 2005
Source: Pharmaceutical Industry
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