Doxadura 2 mg Tablets

Doxazosin 2 mg Tablets

Doxazosin 2 mg contains 2.43 mg of doxazosin mesilate to the equivalent of 2 mg of the active constituent doxazosin.

For excipients, see section 6.1.

Tablets.

Pink biconvex uncoated tablets, scored with a division mark on both sides and embossed with "DZS 2" on one side.

Treatment of hypertension.

Doxazosin can be used as a mono-agent in the treatment of hypertension or in patients inadequately controlled on single antihypertensive therapy. Doxazosin tablets may be used in combination with thiazide diuretics, beta-adrenoceptor blocking agents, calcium antagonists or angiotensinconverting enzyme inhibitors.

Doxazosin is used in a once daily regimen. The dose of Doxazosin should be adjusted according to the patient's response. The initial dose of Doxazosin should be 1 mg per day. Dosage may then be increased in intervals of 1 or 2 weeks 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 level is achieved, or until undesirable effects occur.

Children up to 16 years of age:

There is insufficient experience to recommend the use of Doxazosin tablets in children.

Elderly:

Normal adult dosage is recommended.

Renal insufficiency:

There is no change in pharmacokinetics of Doxazosin in patients with impaired renal function. Normal adult dosage is recommended. Doxazosin is not dialysable.

Hepatic insufficiency:

Up to now no studies have been performed with Doxazosin in patients with liver impairment. Since Doxazosin is extensively metabolised in the liver, it should be used with care in such patients.

Doxazosin is contraindicated in:

Doxazosin is contraindicated as monotherapy in patients with either overflow bladder or anuria with or without progressive renal insufficiency.

Initiation of Therapy: in relation to the alpha-blocking properties of doxazosin, patients may experience postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness (syncope), particularly with the commencement of therapy. Therefore, it is prudent medical practice to monitor blood pressure on initiation of therapy to minimise the potential for postural effects. The patient should be cautioned to avoid situations where injury could result should dizziness or weakness occur during the initiation of doxazosin therapy.

Use in patients with Acute Cardiac Conditions: as with any other vasodilatory anti-hypertensive agent it is prudent medical practice to advise caution when administering doxazosin to patients with the following acute cardiac conditions:

Use in Hepatically Impaired Patients: as with any drug wholly metabolised by the liver, doxazosin should be administered with particular caution to patients with evidence of impaired hepatic function. Since there is no clinical experiences in patients with severe hepatic impairment, use in these patients is not recommended.

Use with PDE-5 inhibitors: concomitant administration of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil and vardenafil) and doxazosin may lead to symptomatic hypotension in some patients. In order to minimise the risk for developing postural hypotension the patient should be stable on the alpha-blocker therapy before initiating use of phosphodiesterase-5-inhibitors.

Furthermore, it is recommended to initiate phosphodiesterase-5-inhibitor treatment with the lowest possible dose and to respect a 6-hour time interval from intake of doxazosin. No studies have been conducted with doxazosin prolonged release formulations.

Use in patients undergoing 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.

Excipients: Doxadura tablets contain lactose. Therefore, they should not be administered to persons with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The excipient E110 is known to cause allergic reactions, including asthma. Allergy is more common in persons who are allergic to aspirin. This excipient is only used in the 2mg and 4mg tablets.

Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil and vardenafil) and doxazosin may lead to symptomatic hypotension in some patients (see section 4.4).

Most (98%) of plasma doxazosin is protein bound. In vitro data in human plasma indicate that doxazosin has no effect on protein binding of digoxin, warfarin, phenytoin or indometacin. Conventional doxazosin has been administered without any adverse drug interaction in clinical experience with thiazide diuretics, furosemide, beta-blockers, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycaemic drugs, uricosuric agents and anticoagulants. However data from formal drug/drug interactions studies are not present.

Doxazosin potentiates the blood pressure lowering activity of other alpha-blockers and other antihypertensives.

In an open-label, randomised, placebo-controlled trial in 22 healthy male volunteers, the administration of a single 1mg dose of doxazosin on day 1 of a four-day regiment of oral cimetidine (400mg 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 of doxazosin with placebo.

As there are no adequate and well controlled studies in pregnant women, the safety of doxazosin during pregnancy has not been established. Accordingly, during pregnancy, doxazosin should be used only if the potential benefit outweighs the risk. Although no teratogenic effects were seen in animal testing, reduced foetal survival was observed in animals at high doses (see section 5.3 Preclinical Safety Data).

Doxazosin is contraindicated during lactation as the drug accumulates in milk of lactating rats and there is no information about the excretion of the drug into the milk of lactating women. Alternatively, mothers should stop breast-feeding when treatment with doxazosin is necessary (see section 5.3 Preclinical Safety Data).

The ability to engage in activities such as operating machinery or operating a motor vehicle may be impaired, especially when initiating therapy.

Frequencies used are as follows: very common 1/10, common 1/100 and < 1/10, uncommon 1/1,000 and < 1/100, rare 1/10,000 and <1/1,000, very rare <1/10,000.

Should overdose 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.

If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressor should then be used. Renal function should be monitored and supported as needed.

The ATCcode of Doxazosin is C02CA04. The ATCclassification is: Cardiovascular system; antihypertensives; antiadrenergic agents, peripherally acting; alphaadrenergic blocking agents.

Doxazosin is a selective postsynaptic α₁adrenoceptor antagonist. Blockade of this receptor causes vasodilation, decrease in peripheral resistance and decrease in blood pressure. Doxazosin therapy is accompanied by little or no reflex tachycardia.

Maximal hypotensive effects occur after approximately 2 to 6 hours. With once daily dosing, clinically significant reductions in blood pressure are maintained throughout the day and at 24 hours postdose.

After initiation of therapy increase in heart rate can occur, as well as changes in vasoactive hormones. After longterm treatment these effects are abolished.

Doxazosin has a favourable effect on blood lipids: it decreases the LDL cholesterol, the total cholesterol and triglyceride levels. It increases the HDL/total cholesterol ratio.

Doxazosin has been shown to be free of adverse metabolic effects and is suitable for use in patients with obstructive airway disease, noninsulin dependent diabetes mellitus and left ventricular hypertrophy.

Following oral administration of therapeutic doses of Doxazosin, peak plasma levels are reached after 2 to 4 hours. The bioavailability is approximately 63%. Doxazosin is 98% bound to plasma protein. Plasma elimination halflife is approximately 22 hours, providing the basis for once daily dosing. Doxazosin is extensively metabolized in the liver with less than 5% of the unchanged drug excreted in the faeces. The metabolites are mainly excreted via the faeces.

There are no preclinical data of relevance to the prescriber other than those mentioned in previous sections.

The following inactive ingredients are used in the tablets: microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, magnesium stearate, sodium lauryl sulphate and colloidal silicon dioxide.

Sunset yellow FCF (E110) is an additional excipient present in the 2 and 4mg tablets.

Not applicable.

The shelf life of the product is 3 years for all tablet strengths. The expiry date is printed on the package and on the blister ("EXP"). The first two digit numbers represent the month and the last four digit numbers represent the year. Do not use after this expiry date.

Doxazosin tablets should be stored in the original package in a dry place. Do not store above 25ºC.

Keep all medicines out of the reach of children.

PVC/PVDCAl. blisters of 28 or 56 tablets in lithographed carton boxes together with a patient information leaflet.

Glass (type III) bottles or HDPE containers with child resistant closures (PP), with patient information leaflets attached.

Not applicable.

Genus Pharmaceuticals Limited

T/A Genus Pharmaceuticals

Park View House

65 London Road

Newbury

Berkshire

RG14 1JN

United Kingdom

PL 06831/0092

Date of first authorisation: 12 July 2002

Date of latest renewal: 25 March 2009

13 May 2010