ATODEL Tablet Ref.[28170] Active ingredients: Prazosin

In patients with benign prostatic hyperplasia

Atodel is not recommended for patients with a history of micturition syncope.

Prazosin decreases peripheral vascular resistance and since many patients with this disorder are elderly, careful monitoring of blood pressure during initial administration and during adjustment of dosage is recommended. The possibility of postural hypotension, or rarely, loss of consciousness, as reported in other patient groups should be borne in mind. Prazosin may augment the efficacy of antihypertensive therapy, consequently, close observation is especially recommended for patients taking medications that are known to lower blood pressure. Atodel should not normally be administered to patients already receiving another alpha-1-antagonist.

In patients with congestive cardiac failure

Adequate data are not yet available to establish efficacy in patients with heart failure due to recent myocardial infarction.

When Atodel is initially administered to patients with congestive cardiac failure who have undergone vigorous diuretic or other vasodilator treatment, particularly in higher than the recommended starting dose, the resultant decrease in left ventricular filling pressure may be associated with a significant fall in cardiac output and systemic blood pressure. In such patients, observance of the recommended starting dose of Atodel followed by gradual dosage increase is particularly important.

The clinical efficacy of prazosin in congestive cardiac failure has been reported to diminish after several months of treatment, in a proportion of patients. In these patients there is usually evidence of weight gain or peripheral oedema indicating fluid retention. Since spontaneous deterioration may occur in such severely ill patients, a causal relationship to prazosin therapy has not been established. Thus, as with all patients with congestive cardiac failure, careful adjustment of diuretic dosage according to the patient’s clinical condition is required to prevent excessive fluid retention and consequent relief of symptoms.

In those patients without evidence of fluid retention, when clinical improvement has diminished, an increase in the dosage of Atodel will usually restore clinical efficacy.

In patients with hypertension

A very small percentage of patients may respond in an abrupt and exaggerated manner to the initial dose of Atodel. Postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness.

Atodel is not recommended for patients with a history of micturition syncope.

Prazosin decreases peripheral vascular resistance and since many patients with this disorder are elderly, careful monitoring of blood pressure during initial administration and during adjustment of dosage is recommended. The possibility of postural hypotension, or rarely, loss of consciousness, as reported in other patient groups should be borne in mind. Prazosin may augment the efficacy of antihypertensive therapy, consequently, close observation is especially recommended for patients taking medications that are known to lower blood pressure. Atodel should not normally be administered to patients already receiving another alpha-1-antagonist.

In patients with congestive cardiac failure

Adequate data are not yet available to establish efficacy in patients with heart failure due to recent myocardial infarction.

When Atodel is initially administered to patients with congestive cardiac failure who have undergone vigorous diuretic or other vasodilator treatment, particularly in higher than the recommended starting dose, the resultant decrease in left ventricular filling pressure may be associated with a significant fall in cardiac output and systemic blood pressure. In such patients, observance of the recommended starting dose of Atodel followed by gradual dosage increase is particularly important.

The clinical efficacy of prazosin in congestive cardiac failure has been reported to diminish after several months of treatment, in a proportion of patients. In these patients there is usually evidence of weight gain or peripheral oedema indicating fluid retention. Since spontaneous deterioration may occur in such severely ill patients, a causal relationship to prazosin therapy has not been established. Thus, as with all patients with congestive cardiac failure, careful adjustment of diuretic dosage according to the patient’s clinical condition is required to prevent excessive fluid retention and consequent relief of symptoms.

as been reported, particularly with the commencement of therapy, but this effect is readily avoided by initiating treatment with a low dose of Atodel and with small increases in dosage during the first one to two weeks of therapy. The effect when observed is not related to the severity of hypertension, is self-limiting and in most patients does not recur after the initial period of therapy or during subsequent titration steps.

When instituting therapy with any effective antihypertensive agent, the patient should be advised how to avoid symptoms resulting from postural hypotension and what measures to take should they develop.

Raynaud’s phenomenon and Raynaud’s disease

Because prazosin decreases peripheral vascular resistance, careful monitoring of blood pressure during initial administration and during subsequent dosage increments of Atodel is suggested. Close observation is especially recommended for patients already taking medications that are known to lower blood pressure.

Use with phosphodiesterase Type-5 inhibitors

Concomitant use of phosphodiesterase type-5 (PDE-5) inhibitors (e.g. sildenafil, tadalafil, vardenafil) and prazosin hydrochloride may lead to symptomatic hypotension in some patients. In order to minimize the risk for developing postural hypotension the patient should be stable on the alpha-blocker therapy before initiating use of PDE-5 inhibitors.

No studies have been conducted with prazosin hydrochloride.

Priapism

Prolonged erections and priapism have been reported with alpha-1 blockers including prazosin in post marketing experience. In the event of an erection that persists longer than 4 hours, the patient should be advised to seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.

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-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.

This product contains lactose.

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

Prazosin has been administered without any adverse drug interaction in clinical experience to date with the following:

Cardiac glycosides – digitalis and digoxin.

Hypoglycaemic agents – insulin, chlorpropamide, phenformin, tolazamide and tolbutamide.

Tranquillizers and sedatives – chlordiazepoxide, diazepam and phenobarbital.

Agents for treatment of gout – allopurinol, colchicine and probenecid.

Anti-arrhythmic agents – procainamide and quinidine.

Analgesic, antipyretic and anti-inflammatory agents – dextropropoxyphene, aspirin, indometacin and phenylbutazone.

There is evidence that adding prazosin to angiotensin converting enzyme inhibitor, beta-adrenergic antagonist or calcium antagonist therapy may produce a substantial reduction in blood pressure. Therefore, the low initial dosage regimen is recommended.

PDE-5 Inhibitors

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

Drug/Laboratory Test Interactions

False positive results may occur in screening tests for phaeochromocytoma urinary vanillylmandelic acid (VMA) and methoxyhydroxyphenyl glycol (MHPG) metabolites of norepinephrine (noradrenaline) in patients who are being treated with prazosin.

Fertility

Studies in rats have shown reproductive toxicity at a dose of 75 mg/kg/day (see Section 5.3).

Pregnancy

In animal studies, prazosin hydrochloride did not indicate any teratogenic effects (see Section 5.3).

No foetal or neonatal abnormalities have been reported with the use of prazosin hydrochloride.

Atodel has also been used alone or in combination with other hypotensive agents in severe hypertension of pregnancy.

Atodel should be used only when, in the opinion of the physician, potential benefit outweighs potential risk.

Breast-feeding

Prazosin has been shown to be excreted in small amounts in human milk. Caution should be exercised when prazosin is administered to nursing mothers.

The patient should be advised that the ability to drive or use machinery may be impaired should dizziness or weakness occur during the initiation of prazosin therapy.

The following adverse reactions have been reported in patients taking prazosin. The adverse reactions are classified according to frequencies determined from clinical trials data.

Very common ≥1/10 (≥10%), Common ≥1/100 and <1/10 (≥1% and <10%), Uncommon ≥1/1000 and <1/100 (≥0.1% and <1%), Rare ≥1/10,000 and <1/1000 (≥0.01% and 0.1%), Very rare <1/10,000 (<0.01%).

If a listed adverse reaction term was not reported in clinical trials it was assumed to be rare, based on reporting rates versus estimated product use worldwide.

In patients with Hypertension:

Some of these reactions have occurred rarely, and in many instances the exact causal relationships have not been established.

Literature reports exist associating prazosin therapy with a worsening of pre-existing narcolepsy. A causal relationship is uncertain in these cases.

In patients with Congestive Cardiac Failure:

The frequency of side-effects observed in patients being managed for left ventricular failure with prazosin when used in conjunction with cardiac glycosides and diuretics is shown below:

In patients with Raynaud’s Phenomenon and Raynaud’s Disease and Benign Prostatic Hyperplasia:

The most common, although infrequently reported side-effect, is mild dizziness.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Cyprus, Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Fax: +357 22608649, Website: www.moh.gov.cy/phs.

Not applicable.