Cardoxan Tablets 2mg
Hypertension: CARDOXAN is indicated for the treatment of hypertension and can be used as the initial agent to control blood pressure in the majority of patients. In patients not adequately controlled on a single antihypertensive agent, CARDOXAN may be used in combination with another agent such as a thiazide diuretic, a beta-blocker, a calcium antagonist or an angiotensin-converting enzyme inhibitor.
Benign Prostatic Hyperplasia: CARDOXAN is also indicated for the treatment of the urinary outflow obstruction and symptoms associated with benign prostatic hyperplasia (BPH). CARDOXAN may be used in BPH patients who are either hypertensive or normotensive. While the blood pressure changes in normotensive patients with BPH are clinically insignificant, patients with hypertension and BPH have had both conditions effectively treated with CARDOXAN monotherapy.
CARDOXAN
Doxazosin mesylate 2mg and 4mg tablets
Presentation
CARDOXAN is available as white capsule shaped tablets with a break score and embossed with CN 2 on one face, the other face blank containing doxazosin mesylate equivalent to 2mg doxazosin; and white flat rhombus shaped tablets embossed with CN 4 on one face, the other face blank, containing doxazosin mesylate equivalent to 4mg doxazosin.
The dimensions of the tablets are:
2mg: 9mm (long) x 4.5mm (wide) x 2.8mm (deep)
4mg: 12mm (long) x 9mm (wide) x 4.2mm (deep)
Uses
Actions
Doxazosin exerts its vasodilator effect via selective and competitive blockade of post-junctional alpha-1 adrenoceptors.
Administration of CARDOXAN 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-adrenoceptors 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. A gradual reduction in blood pressure occurs with maximum reductions usually occurring 2 to 6 hours after dosing. In patients with hypertension, blood pressures during CARDOXAN treatment were similar in both the supine and standing positions. Unlike non-selective alpha adrenoceptor blocking agents, tolerance has not been observed in long term CARDOXAN therapy. Elevations of plasma renin activity and tachycardia were seen infrequently in sustained therapy.
CARDOXAN produces favourable effects on blood lipids, with a significant increase in the HDL/total cholesterol ratio and tends 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 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.
Treatment with CARDOXAN has been shown to result in regression of left ventricular hypertrophy, inhibition of platelet aggregation and enhanced tissue plasminogen activator capacity.
Additionally, CARDOXAN improves insulin sensitivity in patients who have impairment.
In a controlled clinical trial in hypertensive patients, treatment with doxazocin was associated with improvement of erectile dysfunction. In addition, the patients who received doxazosin reported fewer new cases of erectile dysfunction than those who received other antihypertensive agents.
Administration of CARDOXAN to patients with symptomatic Benign Prostatic Hyperplasia (BPH) results in a significant improvement in urodynamics and symptoms. The effect in BPH is thought to result from selective blockade of the alpha-adrenoceptors located in the prostatic muscular stroma, capsule and bladder neck.
Doxazosin has been shown to be an effective blocker of the 1A subtype of the alpha-1-adrenoceptor which accounts for over 70% of the subtypes in the prostate. This accounts for the action in BPH patients.
Doxazosin has demonstrated sustained efficacy and safety in the long term treatment of BPH (ie, up to 48 months).
An in vitro study has demonstrated the antioxidant properties of the 6' - and 7' - hydroxy metabolites of doxazosin at concentrations of 5 micromolar.
Pharmacokinetics
CARDOXAN is well absorbed with peak blood levels occurring at about 2 hours after oral administration of therapeutic doses. Plasma elimination is biphasic with a terminal elimination half-life of 22 hours; this provides the basis for once daily dosing.
Following both oral and intravenous administration of CARDOXAN, the major route of elimination of parent compound and metabolites is via the faeces (approximately 65%). CARDOXAN is extensively metabolised, with <5% excreted unchanged, the remainder undergoing demethylation or hydroxylation. Studies on circulating parent compound and metabolites indicate that the antihypertensive effect of CARDOXAN is due almost exclusively to the parent compound.
Pharmacokinetic studies in the elderly and patients with renal insufficiency have shown no significant alterations compared to younger 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 (eg cimetidine). As with any drug wholly metabolized by the liver, use of doxazosin in patients with altered liver function should be undertaken with caution ( see Warnings & Precautions ).
Indications
Hypertension: CARDOXAN is indicated for the treatment of hypertension and can be used as the initial agent to control blood pressure in the majority of patients. In patients not adequately controlled on a single antihypertensive agent, CARDOXAN may be used in combination with another agent such as a thiazide diuretic, a beta-blocker, a calcium antagonist or an angiotensin-converting enzyme inhibitor.
Benign Prostatic Hyperplasia: CARDOXAN is also indicated for the treatment of the urinary outflow obstruction and symptoms associated with benign prostatic hyperplasia (BPH). CARDOXAN may be used in BPH patients who are either hypertensive or normotensive. While the blood pressure changes in normotensive patients with BPH are clinically insignificant, patients with hypertension and BPH have had both conditions effectively treated with CARDOXAN monotherapy.
Dosage and Administration
Hypertension: The full dosage range of CARDOXAN is 1 to 16mg daily. It is recommended that therapy be initiated at 1mg (half a 2mg tablet) given once daily for one or two weeks. The dosage may then be increased to 2mg once daily for an additional one or two weeks. If necessary, the daily dosage should then be increased gradually at similar intervals to 4mg, 8mg, and 16mg as determined by patient response to achieve the desired reduction in blood pressure. The usual dose is 2-4mg once daily.
Benign Prostatic Hyperplasia: The initial dosage of CARDOXAN is 1mg given once daily. Depending on the individual patient's urodynamics and BPH symptomatology, dosage may then be increased to 2mg and thereafter, to 4mg and up to the maximum recommended dose of 8mg. The recommended titration interval is 1-2 weeks. The usual recommended dose is 2-4mg once daily.
Usage in renally impaired: Since the phamacokinetics of CARDOXAN are unchanged in patients with renal insufficiency, and there is no evidence that CARDOXAN aggravates existing renal dysfunction, the usual dosages may be used in these patients.
Contraindications
CARDOXAN is contraindicated in patients with a known hypersensitivity to quinazolines.
Warnings and Precautions
CARDOXAN has been shown to be free of adverse metabolic effects and is suitable for use in patients with asthma, diabetes, gout, and in elderly patients and in those patients with left ventricular dysfunction.
As with any drug wholly metabolised by the liver, doxazosin should be administered with caution to patients with evidence of impaired hepatic function.
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.
Use During Pregnancy and Lactation: Although no teratogenic effects were seen in animal testing, reduced foetal survival was observed in animals at extremely high doses. As there are no adequate and well controlled studies in pregnant and nursing women, the safety of CARDOXAN's use during pregnancy or lactation has not yet been established. Accordingly, during pregnancy or lactation, CARDOXAN should be used only when in the opinion of the physician, potential benefit outweighs potential risk.
Use in Children: No experience is available on the use of CARDOXAN in children.
Adverse Effects
Hypertension: In controlled hypertension clinical trials, the most common reactions associated with CARDOXAN therapy were of the postural type (rarely associated with syncope) or non-specific and included dizziness, headache, fatigue, malaise, postural dizziness, vertigo, oedema, asthenia, somnolence, nausea and rhinitis. Extremely rare cases of urinary incontinence were reported; this effect may be related to CARDOXAN's pharmacologic action.
Cases of skin rash, pruritus, thrombocytopenia, purpura, epistaxis, leukopenia, hematuria, cholestasis, hepatitis, jaundice, abnormal liver function tests and blurred vision have also been reported.
Isolated cases of priapism have been reported to be associated with alpha-1-agonists, including doxazosin.
The following additional adverse events have been reported in marketing experience among patients treated for hypertension but these, in general, are not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin: tachycardia, palpitation, chest pain, angina pectoris, myocardial infarction, cerebrovascular accidents and cardiac arrhythmias.
Benign Prostatic Hyperplasia: Experience in controlled clinical trials in BPH indicates a similar adverse event profile to that seen in hypertension.
Interactions
Most (98%) of plasma CARDOXAN is protein bound. In vitro data in human plasma indicate that CARDOXAN has no effect on protein binding of digoxin, warfarin, phenytoin or indomethacin. CARDOXAN has been administered without any adverse interaction in clinical experience to date with thiazide diuretics, frusemide, beta-blocking agents, non-steroidal anti-inflammatory agents, antibiotics, oral hypoglycaemic agents, uricosuric agents, or anticoagulants.
Overdosage
Should overdosage lead to hypotension, the patient should be immediately placed in a supine, head down position. Other supportive measures should be performed if thought appropriate in individual cases. Since doxazosin is highly protein bound, dialysis is not indicated.
Pharmaceutical Precautions
Store below 30°C
Medicine Classification
Prescription Medicine
Package Quantities
2mg x 28 tablets in calendar blister packs.
4mg x 28 tablets in calendar blister packs.
Further Information
Doxazosin mesylate is a quinazoline derivative, having the following chemical name: 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-yl-carbonyl) piperazine methanesulphonate.
Doxazosin mesylate is soluble in dimethylsulphoxide and dimethylformamide; slightly soluble in methanol and sparingly soluble in water (<0.1% at 25°C), ethanol, acetone and chloroform. It has a molecular weight of 547.6 (free base 451.5).
Other ingredients of the tablets are: Microcrystalline cellulose, Lactose, Sodium starch glycollate, Sodium lauryl sulfate and Magnesium stearate.
Name and Address of Company
Lincoln Pharmaceuticals,
A Division of Douglas Pharmaceuticals Ltd,
Central Park Drive,
Lincoln,
PO Box 45027,
AUCKLAND 8,
NEW ZEALAND
