COMPOSITION: Each 1 mg, 2 mg and 4 mg ADCO-DOXAZOSIN tablet contains doxazosin mesylate equivalent to 1 mg, 2 mg and 4 mg free base respectively.
PHARMACOLOGICAL CLASSIFICATION: A 7.1 Vasodilators, hypotensive medicines.
PHARMACOLOGICAL ACTION: Doxazosin mesylate is a quinazoline derivative, with the chemical name:
1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-[(2,3-dihydro-1,4-benzodioxan-2-yl) carbonyl]piperazine monomethanesulphonate.
ADCO-DOXAZOSIN is a selective postsynaptic alpha1-adrenoceptor antagonist. Blockade of this receptor causes vasodilatation, decrease in peripheral resistance and decrease in blood pressure. Doxazosin therapy is accompanied by little or no reflex tachycardia.
ADCO-DOXAZOSIN is well absorbed after oral administration, and peak plasma concentration levels of Doxazosin occur after approximately 2 hours.
The plasma elimination half-life is biphasic with a mean terminal half-life of approximately 19 to 22 hours, hence providing the basis for once-daily dosing. ADCO-DOXAZOSIN is extensively metabolised in the liver with less than 5% of the unchanged medicine excreted in the faeces. The metabolites are mainly excreted via the faeces.
Following an oral dose, maximum reduction in blood pressure is reported to occur after approximately 2 - 6 hours.
Doxazosin is highly bound to plasma proteins (98%). In vitro data in human plasma indicates that ADCO-DOXAZOSIN has no effect on protein binding of the medicines tested (digoxin, phenytoin, warfarin or indomethacin).
INDICATIONS: ADCO-DOXAZOSIN is indicated for the treatment of mild to moderate hypertension. ADCO-DOXAZOSIN is also indicated for the treatment of benign prostatic hyperplasia (BPH) to relieve urinary obstruction. ADCO-DOXAZOSIN may be used in BPH patients who are either hypertensive or normotensive.
CONTRA-INDICATIONS: ADCO-DOXAZOSIN is contra-indicated in patients with a known hypersensitivity to quinazolines. ADCO-DOXAZOSIN should not be used in patients with impaired hepatic or renal function.
Use During Pregnancy and Lactation: Use during pregnancy or lactation has not yet been established.
Use for Children: There is insufficient experience to recommend the use of ADCO-DOXAZOSIN Tablets in children.
WARNINGS: Concurrent use of diuretics, other antihypertensives and alcohol may increase the hypotensive effect of doxazosin especially the first dose effect. In fact diuretics and ß adrenergic antagonists may enhance the effect of doxazosin, however, dosage adjustments should be made if using concomitantly.
Patients using beta blockers and calcium-channel blockers may increase the risk of hypotensive effect if initiating doxazosin therapy as well. Sympathomimetics reduce the antihypertensive effect of doxazosin when used together.
DOSAGE AND DIRECTIONS FOR USE:
Hypertension ADCO-DOXAZOSIN is used in a once-daily regimen. The dose of doxazosin should be adjusted according to the patients response. The initial dose of Doxazosin should be 1 mg per day at bedtime. Dosage may then be increased in intervals of 1 or 2 weeks of therapy to 2 mg and thereafter to 4 mg.
If necessary, dosage can be further increased to 8 mg or the maximum recommended dose of 16 mg.
Dosage may be increased until the desired blood pressure is achieved, or undesirable effects occur. ADCO-DOXAZOSIN may be used in combination with a thiazide diuretic, or a beta-blocking agent in patients not adequately controlled on a single antihypertensive agent. Benign Prostatic Hyperplasia The initial dosage of ADCO-DOXAZOSIN is 1 mg given once daily at bedtime. The dosage may then be increased to 2 mg and thereafter to 4 mg and up to the maximum recommended dose of 8 mg, depending on the individual patients urodynamics and BPH symptomatology. The recommended titration interval is 1-2 weeks and the usual recommended dose is 2-4 mg once-daily. Blood pressure should be evaluated routinely in these patients. Dosing guidelines for Geriatrics and Paediatrics:
Geriatrics: The dosage is the same as for adults. However, the hypotensive effects may be more pronounced. Caution should be exercised in patients with hepatic or renal impairment. Paediatrics: The use of doxazosin has not been established.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS: The most common undesirable effects associated with ADCO-DOXAZOSIN therapy are postural hypotension, rarely associated with fainting, dizziness and vertigo. Other undesirable effects are: headache, fatigue, oedema, insomnia, nausea, nervousness, palpitation, rash, rhinitis, asthenia, abnormal vision, chest pain, depression, diarrhoea, dry mouth, dyspnoea, sexual dysfunction somnolence, tachycardia and malaise.
Urinary incontinence is a very rarely reported undesirable effect of ADCO-DOXAZOSIN and this effect may be related to ADCO-DOXAZOSINs pharmacological action.
In post-marketing experience, the following have been reported: angina pectoris, myocardial infarction, cerebrovascular accidents and cardiac arrhythmia, drowsiness, vomiting, paraesthesiae, hallucinations, epistaxis, tinnitus, abnormal liver enzymes, pancreatitis, pruritus, diaphoresis, priapism. Driving/Use of Machinery It is recommended that the initial dosage, or dosage increments, should be given at a time when the patient is not required to undertake any activity such as driving or operating machines. Interactions In clinical experience to date, no adverse drug interaction has been noted with thiazide diuretics, furosemide, beta-blocking agents, antibiotics, oral hypoglycaemic drugs, uricosuric agents, or anticoagulants.
Doxazosin has a favourable effect on blood lipids: it decreases the LDL-cholesterol, the total cholesterol and plasma concentrations of triglycerides and it increases the HDL-cholesterol. When a thiazide-type diuretic is given concurrently these potentially favourable effects on lipids persist. The long-term consequences of these medicine-induced changes in lipids are not known.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: Treatment is symptomatic and supportive. Patients who experience severe hypotension should be placed in a supine position, with their legs raised. Volume expanders and vasopressor infusion can be used but with caution.
Dialysis is not indicated, since ADCO-DOXAZOSIN is highly protein bound.
ADCO-DOXAZOSIN 1 mg Tablets: White to off-white, odourless biconvex uncoated tablets, scored with a division mark on both sides and embossed with DZS 1on one side. ADCO-DOXAZOSIN 2 mg Tablets: Light orange to pink, odourless biconvex uncoated tablets, scored with a division mark on both sides and embossed with DZS 2on one side. ADCO-DOXAZOSIN 4 mg Tablets: Light orange to pink, odourless biconvex uncoated tablets, scored with a division mark on both sides and embossed with DZS 4on one side.
PRESENTATION: ADCO-DOXAZOSIN 1 mg, 2 mg and 4 mg Tablets:
PVC/Aluminium blisters with 10, 14, 20, 28, 30, 50 or 100 tablets or HDPE containers, containing 100 or 500 tablets with child resistant closures or Amber Glass Jars with child resistant closures containing 50, 100 or 500 tablets.
STORAGE INSTRUCTIONS: Store in a dry place, below 25°C in a well-closed container protected from light. Do not remove the blister from the carton until required for use.
KEEP OUT OF REACH OF CHILDREN.
ADCO-DOXAZOSIN 1 mg Tablets:
ADCO-DOXAZOSIN 2 mg Tablets:
ADCO-DOXAZOSIN 4 mg Tablets:
NAME AND BUSINESS ADDRESS OF APPLICANT: Adcock Ingram Limited
Adcock Ingram Park
17 Harrison Avenue
Private Bag X69, Bryanston, 2021
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 05/09/2003
New addition to this site: April 2004
Source: Pharmaceutical Industry