Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom
Hypersensitivity to prazosin, other quinazolines, or to any of the excipients listed in section 6.1.
Hypovase is not recommended for patients with a history of micturition syncope.
Hypovase 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. Close observation is especially recommended. For patients taking medications that are known to lower blood pressure, Hypovase may augment the efficacy of antihypertensive therapy, consequently, close observation is especially recommended for patients taking medications that are known to lower blood pressure. Hypovase should not normally be administered to patients already receiving another alpha-1-antagonist.
Hypovase is not recommended in the treatment of congestive cardiac failure due to mechanical obstruction such as aortic valve stenosis, mitral valve stenosis, pulmonary embolism and restrictive pericardial disease. Adequate data are not yet available to establish efficacy in patients with heart failure due to recent myocardial infarction.
When Hypovase 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 Hypovase followed by gradual dosage increase is particularly important.
The clinical efficacy of Hypovase 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 Hypovase will usually restore clinical efficacy.
A very small percentage of patients may respond in an abrupt and exaggerated manner to the initial dose of Hypovase. Postural hypotension evidenced by dizziness and weakness, or rarely loss of consciousness, has been reported, particularly with the commencement of therapy, but this effect is readily avoided by initiating treatment with a low dose of Hypovase 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.
Because Hypovase decreases peripheral vascular resistance, careful monitoring of blood pressure during initial administration and during subsequent dosage increments of Hypovase is suggested. Close observation is especially recommended for patients already taking medications that are known to lower blood pressure.
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 minimise the risk for developing postural hypotension the patient should be stable on the alpha-blocker therapy before initiating use of PDE-5 inhibitors.
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 seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
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.
Hypovase 1 mg tablets contain less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Hypovase 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: chlordiazapoxide, 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, indomethacin and phenylbutazone.
There is evidence that adding Hypovase to 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 Hypovase.
A decrease in fertility in male and female rats treated with prazosin hydrochloride was observed at high non-clinically relevant doses (225 times the usual maximum recommended human dose). However no adverse effects were observed at doses up to 75 times the usual maximum recommended human dose.
Prazosin hydrochloride was not teratogenic in rats and rabbits.
Although no teratogenic effects were seen in animal testing, the safety of Hypovase during pregnancy has not yet been established. The use of Hypovase and a beta-blocker for the control of severe hypertension in 44 pregnant women revealed no drug-related foetal abnormalities or adverse effects. Therapy with Hypovase was continued for as long as 14 weeks. No foetal or neonatal abnormalities have been reported with the use of prazosin hydrochloride.
Hypovase has also been used alone or in combination with other hypotensive agents in severe hypertension of pregnancy.
Hypovase should be used only when, in the opinion of the physician, potential benefit outweighs potential risk.
Hypovase has been shown to be excreted in small amounts in human milk. Caution should be exercised when Hypovase is administered to nursing mothers.
When instituting therapy with any effective antihypertensive agent, the patient should be advised on 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 Hypovase therapy (i.e. driving or operating machinery).
The following side-effects have been associated with Hypovase therapy:
Adverse reactions reported as more than an isolated case are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100, to 1/10), uncommon (≥1/1,000, to 1/100), rare (≥1/10,000 to 1/1,000), very rare (<1/10,000) and not known (frequency cannot be estimated from the available data).
Rare: Allergic reaction
Common: Depression, nervousness
Uncommon: Insomnia
Rare: Hallucinations
Common: Dizziness, drowsiness, headache, faintness, syncope
Uncommon: Paraesthesia
Rare: Worsening of pre-existing narcolepsy
Common: Blurred vision
Uncommon: Eye pain, reddened sclera
Common: Vertigo
Uncommon: Tinnitus
Common: Palpitations
Uncommon: Angina pectoris, tachycardia,
Rare: Bradycardia
Rare: Flushing, hypotension, orthostatic hypotension, vasculitis
Common: Dyspnoea, nasal congestion
Uncommon: Epistaxis
Common: Constipation, diarrhoea, dry mouth, nausea, vomiting
Uncommon: Abdominal discomfort and/or pain
Rare: Pancreatitis
Rare: Liver function abnormalities
Common: Rash
Uncommon: Diaphoresis, pruritis, urticaria
Rare: Alopecia, lichen planus
Uncommon: Arthralgia
Common: Urinary frequency
Rare: Incontinence
Uncommon: Impotence
Rare: Gynaecomastia, priapism
Common: Oedema, lack of energy, weakness
Rare: Fever, pain
Rare: Positive ANA titer
The frequency of side-effects observed in patients being managed for left ventricular failure with Hypovase when used in conjunction with cardiac glycosides and diuretics is shown below:
Common: Dizziness
Uncommon: Headache
Rare: Drowsiness
Common: Blurred vision
Rare: Palpitations
Common: Postural hypotension
Rare: Nasal congestion
Common: Dry mouth, nausea
Uncommon: Diarrhoea
Common: Impotence
Rare: Oedema
In most instances these occurrences have been mild to moderate in severity and have resolved with continued therapy or have been tolerated with no decrease in drug dosage.
Reporting suspected adverse reactions after authorisation 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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
By reporting side effects you can help provide more information on the safety of this medicine.
Not applicable.
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