Selective a1 -blockers (alpha- blockers / alpha-adrenoceptor blocking drugs).

Doxazosin - BPH

Doxazosin mesilate: 1.213mg equivalent to 1mg doxazosin 2.43mg equivalent to 2mg doxazosin

Tablets for oral administration. 1mg round tablets marked CN1 on one side and 'PFIZER' on the other. 2mg oblong tablets marked CN2 on one side and 'PFIZER' on the other.

Hypertension: Cardura is indicated for the treatment of hypertension and can be used as the sole agent to control blood pressure in the majority of patients. In patients inadequately controlled on single antihypertensive therapy, Cardura 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 is indicated for the treatment of urinary outflow obstruction and symptoms associated with benign prostatic hyperplasia (BPH). Cardura may be used in BPH patients who are either hypertensive or normotensive.

Cardura may be administered in the morning or the evening.

Hypertension: Cardura is used in a once daily regimen: the initial dose is 1mg, to minimise the potential for postural hypotension and/or syncope. Dosage may then be increased to 2mg after an additional one or two weeks of therapy and thereafter, if necessary to 4mg. The majority of patients who respond to Cardura will do so at a dose of 4mg or less. Dosage can be further increased if necessary to 8mg or the maximum recommended dose of 16mg.

Benign prostatic hyperplasia: The recommended initial dosage of Cardura is 1mg given once daily to minimise the potential for postural hypotension and/or syncope. 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 daily.

Children: The safety and efficacy of Cardura in children have not been established.

Elderly: Normal adult dosage.

Patients with renal impairment: Since there is no change in pharmacokinetics in patients with impaired renal function, the usual adult dose of Cardura is recommended.

Cardura is not dialysable.

Patients with hepatic impairment: There are only limited data in patients with liver impairment and on the effect of drugs known to influence hepatic metabolism (e.g. cimetidine). As with any drug wholly metabolised by the liver, Cardura should be administered with caution to patients with evidence of impaired liver function.

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

Normal adult dosage.

Cardura is contraindicated in patients with a known hypersensitivity to quinazolines, (e.g. doxazosin), or any of the inert ingredients.

Use during lactation: Animal studies have shown that doxazosin accumulates in breast milk. The clinical safety of Cardura during lactation has not been established, consequently Cardura is contra-indicated in nursing mothers.

Postural Hypotension/Syncope: As with all alpha-blockers, a very small percentage of patients have experienced postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness (syncope), particularly with the commencement of therapy. 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 therapy.

Use with PDE-5 Inhibitors: Concomitant administration of an alpha blocker with a PDE-5 inhibitor should be used with caution as it may lead to symptomatic hypotension in some patients.

Impaired liver function: As with any drug wholly metabolised by the liver, Cardura should be administered with caution to patients with evidence of impaired hepatic function.

Cataract surgery: 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.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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 indomethacin). No adverse drug interactions have been observed with thiazide diuretics, frusemide, beta-blocking agents, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycaemic drugs, uricosuric agents, or anticoagulants.

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

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.

Hypertension: In clinical trials involving patients with hypertension, the most common reactions associated with Cardura therapy were of a postural type (rarely associated with fainting) or non-specific and included:

Ear and Labyrinth Disorders: vertigo

Gastrointestinal Disorders: nausea

General Disorders and Administration Site Conditions: asthenia, oedema, fatigue, malaise

Nervous System Disorders: dizziness, headache, postural dizziness, somnolence, syncope

Respiratory, Thoracic and Mediastinal Disorders: rhinitis

Benign prostatic hyperplasia: Experience in controlled clinical trials in BPH indicates a similar adverse event profile to that seen in hypertension.

In post marketing experience, the following additional adverse events have been reported:

Blood and Lymphatic Disorders: leucopenia, thrombocytopenia

Ear and Labyrinth Disorders: tinnitus

Eye Disorders: blurred vision

Gastrointestinal Disorders: abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, dry mouth, vomiting

General Disorders and Administration Site Conditions: pain

Hepatobiliary Disorders: cholestasis, hepatitis, jaundice

Immune System Disorders: allergic reaction

Investigations: abnormal liver function tests, weight increase

Metabolism and Nutrition: anorexia

Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain, muscle cramps, muscle weakness, myalgia

Nervous System Disorders: hypoaesthesia, paraesthesia, tremor

Psychiatric Disorders: agitation, anxiety, depression, insomnia, nervousness

Renal and Urinary System Disorders: dysuria, haematuria,, micturition disorder, micturition frequency, nocturia, polyuria, urinary incontinence

Reproductive System and Breast Disorders: gynaecomastia, impotence, priapism, retrograde ejaculation

Respiratory, Thoracic and Mediastinal Disorders: aggravated bronchospasm, coughing, dyspnoea, epistaxis

Skin and Subcutaneous Tissue Disorders: alopecia, pruritus, purpura, skin rash, urticaria

Vascular Disorders: hot flushes, hypotension, postural hypotension

The following additional adverse events have been reported in marketing experience among patients treated for hypertension. In general, these are not distinguishable from symptoms that might have occurred in the absence of exposure to Cardura: bradycardia, tachycardia, palpitations, chest pain, angina pectoris, myocardial infarction, cerebrovascular accidents and cardiac arrhythmias.

Pfizer

(POM)

31 August 2010