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

Doxazosin

Doxazosin mesilate: 4.85mg equivalent to 4mg doxazosin. 9.70mg equivalent to 8mg doxazosin

Modified release tablet Cardura XL 4mg and 8mg tablets are white, round, biconvex shaped tablets with a hole in one side, marked CXL4 and CXL8.

Hypertension: Cardura XL 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 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.

Hypertension and benign prostatic hyperplasia: The initial dose of Cardura XL is 4mg once daily. Over 50% of patients with mild to moderate severity hypertension will be controlled on Cardura XL 4mg once daily. Optimal effect of Cardura XL may take up to 4 weeks. If necessary, the dosage may be increased following this period to 8mg once daily according to patient response.

The maximum recommended dose of Cardura XL is 8mg once daily.

Cardura XL can be taken with or without food.

The tablets should be swallowed whole with a sufficient amount of liquid.

Patients with renal impairment: Since there is no change in pharmacokinetics in patients with impaired renal function the usual adult dose of Cardura XL is recommended. Doxazosin is not dialysable.

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

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

Normal adult dosage.

Cardura XL is contraindicated in:

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

Patients with a known hypersensitivity to quinazolines, (e.g. doxazosin, prazosin, terazosin), or any of the inert ingredients of Cardura XL.

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

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 drug. 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 in the stools something that looks like a tablet.

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 XL therapy.

Use with PDE-5 Inhibitors: Concomitant administration of doxazosin with a PDE-5 inhibitor should be used with caution as it may lead to symptomatic hypotension in some patients. No studies have been conducted with doxazosin GITS.

Impaired liver function: As with any drug wholly metabolised by the liver, Cardura XL 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.

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 doxazosin with a PDE-5 inhibitor may lead to symptomatic hypotension in some patients. No studies have been conducted with doxazosin GITS.

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

Cardiac Disorders: palpitation, tachycardia

Ear and Labyrinth Disorders: vertigo

Gastrointestinal Disorders: abdominal pain, dry mouth, nausea

General Disorders and Administration Site Conditions: asthenia, chest pain, peripheral oedema

Musculoskeletal and Connective Tissue Disorders: back pain, myalgia

Nervous System Disorders: dizziness, headache

Respiratory, Thoracic and Mediastinal Disorders: coughing, bronchitis

Skin and Subcutaneous Tissue Disorders: pruritis

Renal and Urinary Disorders: urinary incontinence, cystitis

Vascular Disorders: postural hypotension

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

Ear and Labyrinth Disorders: vertigo

Gastrointestinal Disorders: abdominal pain, nausea, dyspepsia

General Disorders and Administration Site Conditions: asthenia, peripheral oedema

Infection and Infestations: respiratory tract infection, influenza-like symptoms, urinary tract infections

Musculoskeletal and Connective Tissue Disorders: back pain, myalgia

Nervous System Disorders: dizziness, headache, somnolence

Respiratory, Thoracic and Mediastinal Disorders: dyspnoea, rhinitis, bronchitis

Vascular Disorders: hypotension, postural hypotension

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: constipation, diarrhoea, dyspepsia, flatulence, vomiting, dry mouth

General Disorders and Administration Site Conditions: fatigue, malaise, 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, muscle cramps, muscle weakness

Nervous System Disorders: postural dizziness, hypoaesthesia, paraesthesia, syncope, tremor

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

Renal and Urinary 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, epistaxis, coughing, dyspnoea

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

Vascular Disorders: hot flushes, hypotension

The following additional adverse events have been reported in marketing experience with immediate release doxazosin tabletsamong patients treated for hypertension. In general, these are not distinguishable from symptoms of the underlying disease 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.

The adverse events for Cardura XL are similar to those with immediate release doxazosin tablets

Pfizer

(POM)

31 August 2010