Consumer medicine information

Minipress Tablets

Prazosin

BRAND INFORMATION

Brand name

Minipress

Active ingredient

Prazosin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Minipress Tablets.

What is in this leaflet

This leaflet answers some common questions about Minipress. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Minipress against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What Minipress is used for

Minipress is used to treat:

  • high blood pressure, also called hypertension
  • benign prostatic hyperplasia or BPH ('prostate trouble') in men waiting for prostate surgery
  • Raynaud's disease, where the fingers become white and painful when cold
  • certain types of heart failure.

When used to treat high blood pressure or heart failure, Minipress is often used in combination with other medicines.

Minipress contains the active ingredient prazosin and belongs to a family of medicines called alpha blockers.

These medicines work by relaxing muscles in the walls of blood vessels and reducing the resistance to blood flow. They also relieve prostate problems by relaxing muscles in the prostate gland and increasing the flow of urine.

Your doctor may have prescribed Minipress for another reason.

Ask your doctor if you have any questions about why Minipress has been prescribed for you.

This medicine is only available with a doctor's prescription.

Before you take Minipress

When you must not take it

Do not take Minipress if you have an allergy to:

  • any medicine containing prazosin
  • any of the ingredients listed at the end of this leaflet
  • any other alpha blocker medicine (e.g. Hytrin).

Ask your pharmacist if you are not sure if you are taking one of these medicines.

Symptoms of an allergic reaction to these medicines may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take Minipress if:

  • the packaging is torn or shows signs of tampering
  • the expiry date (EXP) printed on the pack has passed.

If you are not sure whether you should be taking Minipress, contact your doctor.

Use in children

Minipress is not recommended for use in children under 12 years of age. Safety in children younger than 12 years has not been established.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • heart problems such as heart failure or angina
  • kidney or liver problems.

Tell your doctor if you are pregnant or breastfeeding or plan to become pregnant or breastfeed. Your doctor will discuss the risks and benefits of taking it during pregnancy or while breastfeeding.

If you have not told your doctor about any of the above, tell them before you start Minipress.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop. Some medicines and Minipress may interfere with each other.

Your doctor or pharmacist has a complete list of medicines to be careful with or avoid while taking Minipress.

If you have not told your doctor or pharmacist about these things, tell them before you start taking Minipress.

In particular, tell your doctor if you are taking:

  • medicines used to lower blood pressure
  • fluid tablets (diuretics)
  • medicines to treat impotence (erectile dysfunction).

Other medicines that lower high blood pressure may have an additive effect with Minipress and make your blood pressure too low. As a result, their dose may need to be changed when Minipress is started.

How to take Minipress

Take Minipress exactly as your doctor has prescribed.

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

Minipress is usually started at a low dose of 0.5 mg (half a 1 mg tablet) taken twice a day.

Starting with a low dose reduces the risk of too great a drop in your blood pressure which can make you dizzy, lightheaded or faint.

Your doctor may gradually increase this dose as required. This may depend on your age, your condition and whether or not you are taking any other medicines.

Hypertension (high blood pressure)
The usual starting dose is 0.5 mg (half a 1 mg tablet) taken twice a day increasing to 1 mg taken two or three times a day. Your doctor may increase this up to 20 mg a day, taken in divided doses.

Heart failure
The usual starting dose is 0.5 mg (half a 1 mg tablet) increasing to 4 mg a day, divided into three or four doses. This may be increased by your doctor up to 20 mg a day, taken in divided doses.

Raynaud's disease
The usual starting dose is 0.5 mg (half a 1 mg tablet) taken twice a day. Your doctor may increase this up to 1 mg or 2 mg taken twice a day.

Benign prostatic hyperplasia (BPH)
The usual starting dose is 0.5 mg (half a tablet) taken twice a day. Your doctor may increase this to 2 mg taken twice a day.

When to take it

Take your Minipress tablets at the same time each day. Taking your tablets at about the same time each day will have the best effect. This will also help you remember when to take them.

When you first start taking Minipress or if your doctor increases your dose, take the first dose last thing at night, just before going to bed.

Be especially careful if you need to get up during the night, because you may feel dizzy and could fall.

How to take it

Swallow the tablets with a glass of water or other liquid.

It does not matter if you take Minipress before or after food.

How long to take it

Keep taking Minipress every day until your doctor tells you to stop.

If you are taking Minipress for high blood pressure, heart failure or Raynaud's disease, you may need to take it for a long time.

Minipress will help control these conditions, but will not cure them. Therefore, it must be taken every day.

If you are taking Minipress for prostate problems, you will only have to take it until your operation.

If you forget to take it

If it is almost time for your next dose (e.g. within 3 hours), skip the dose you missed and take the next dose when you are meant to.

Otherwise, take it as soon as you remember, then go back to taking it as you would normally.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, check with your doctor or pharmacist.

If you miss two (2) doses or more, you will need to restart at a low dose and build up again gradually to your usual dose.

Ask your doctor how to do this.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency (Casualty) at your nearest hospital if you think that you, a child or anyone else may have taken too much Minipress. Do this even if there are no signs of discomfort or poisoning.

If you take too much Minipress, you may feel lightheaded, dizzy, have a fast or irregular heartbeat, or you may faint.

While you are taking it

Things you must do

Get up slowly after you have been sitting or lying down. Minipress can cause dizziness, lightheadedness and fainting, particularly if you get up too quickly. This is also more likely to occur if you have just started Minipress or the dose of Minipress has just been increased.

These symptoms can be dangerous, particularly if you are 65 years or older and have heart disease.

If you feel dizzy or lightheaded, lie down so that you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning.

If these symptoms continue, tell your doctor. A change in dose may be needed.

See your doctor as soon as possible if you experience painful erections or if your erection continues for longer than four hours. You may need urgent medical attention.

If you become pregnant while taking Minipress, tell your doctor immediately.

If you are about to start any new medicines, tell your doctor and pharmacist that you are taking Minipress.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Minipress.

Things you must not do

Do not give Minipress to anyone else, even if they have the same condition as you.

Do not use Minipress to treat any other complaints unless your doctor tells you to.

Do not stop taking Minipress, or lower the dosage, without checking with your doctor. Your doctor will reduce your dose of Minipress gradually if you are to stop taking this medicine.

Things to be careful of

Be careful driving or operating machinery until you know how Minipress affects you. Minipress may cause dizziness, lightheadedness or fainting in some people, especially after the first dose or after a dose increase. Blurred vision or drowsiness may also occur.

Make sure you know how you react to Minipress before you drive a car, operate machinery or do anything else that could be dangerous if you are dizzy, drowsy, or are not alert.

Be careful to limit the amount of alcohol you drink while taking Minipress. Also, take extra care during exercise or hot weather or if you have to stand for a long time. Dizziness, lightheadedness, or fainting is more likely to occur if you drink alcohol, stand for a long time, exercise or the weather is hot.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Minipress.

Minipress helps most people but it may have some unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

If you are 65 years or older, you should be especially careful while taking Minipress. Report any side effects promptly to your doctor.

Following is a list of possible side effects. Do not be alarmed by this list. You may not experience any of them.

Tell your doctor if you notice any of the following and they worry you:

  • feeling sick, vomiting or dry mouth
  • constipation, diarrhoea
  • weakness or lack of energy
  • headache or drowsiness
  • stuffy nose.

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • fast or pounding heartbeat, chest pain,
  • fainting, dizziness or lightheadedness when standing up
  • shortness of breath or difficulty breathing
  • blurred vision
  • rash, itching or other skin problems
  • sharp pain in the stomach or back
  • persistent painful erection of the penis which occurs without sexual arousal
  • tingling or numbness of the hands or feet
  • swelling of the hands, feet or ankles
  • feelings of nervousness or depression.

These may be serious side effects. You may need urgent medical attention.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

If you notice any other symptoms that worry you, check with your doctor.

Ask your doctor or pharmacist if you don't understand anything in this list.

After taking Minipress

Storage

Keep your tablets in their pack until it is time to take them. If you take them out of their packaging, they will not keep well.

Keep them in a cool, dry place where the temperature stays below 30°C. Do not store them, or any other medicine in the bathroom or near a sink.

Do not leave them in the car or on window sills. Heat and dampness can destroy some medicines.

Keep your tablets where young children cannot reach them. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Minipress, or the tablets have passed their expiry date, ask your pharmacist what to do with any left over.

Product description

What it looks like

  • Minipress 1mg - orange, capsule-shaped tablets marked MNP 1 on one side and scored on the other.
  • Minipress 2mg - white, round tablets marked MNP 2 on the scored side and plain on the other.
  • Minipress 5mg - white, diamond shaped tablets scored on both sides, marked MNP 5 on one side.

Each box contains 100 tablets.

Ingredients

Minipress tablets contain either 1 mg, 2 mg or 5 mg of prazosin as the active ingredient.

The other ingredients are:

  • maize starch
  • microcrystalline cellulose
  • magnesium stearate
  • sodium lauryl sulfate
  • calcium hydrogen phosphate
  • sunset yellow FCF (1 mg tablet only).

Minipress does not contain lactose, or sucrose.

Manufacturer

Minipress is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian Registration Numbers:

Minipress 1mg - AUST R 10756

Minipress 2mg - AUST R 10757

Minipress 5mg - AUST R 10758

This leaflet was prepared in November 2019

® = Registration Trademark

© Pfizer Australia Pty Ltd

Published by MIMS February 2020

BRAND INFORMATION

Brand name

Minipress

Active ingredient

Prazosin

Schedule

S4

 

1 Name of Medicine

Prazosin hydrochloride.

2 Qualitative and Quantitative Composition

Prazosin hydrochloride equivalent to 1 mg, 2 mg and 5 mg prazosin base.

3 Pharmaceutical Form

Tablet.
Minipress 1 mg tablets: orange, capsule-shaped with MNP 1 on one side and scored on the other.
Minipress 2 mg tablets: white, round, scored, marked with MNP 2 on the scored side.
Minipress 5 mg tablets: white, diamond-shaped, scored on both sides, marked with MNP 5 on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

In patients with hypertension.

Minipress (prazosin hydrochloride) is indicated in the treatment of hypertension of varied aetiology and all grades of severity. It can be used as the initial and sole agent or it may be employed in a treatment programme in conjunction with other antihypertensive agents.
Renal blood flow and glomerular filtration rate are not impaired by long-term oral administration. Minipress can be used with safety in hypertensive patients with impaired renal function.

In patients with congestive heart failure.

Minipress is indicated in the treatment of severe refractory congestive heart failure. Minipress may be added to the therapeutic regime in those patients who have become refractory to conventional therapy with cardiac glycosides and diuretics.

In patients with Raynaud's phenomenon and Raynaud's disease.

Minipress is indicated in the treatment of Raynaud's phenomenon and Raynaud's disease.

Benign prostatic hyperplasia.

Minipress is indicated as an adjunct in the symptomatic treatment of urinary obstruction caused by benign prostatic hyperplasia in patients awaiting prostatic surgery.

4.2 Dose and Method of Administration

General comments.

There is evidence that patient toleration is best when therapy is initiated with a low starting dose. The dose is to be adjusted on the basis of the patient's individual blood pressure response.
Response is usually seen early (1 to 14 days) if it is to occur at a given dose. If a response is seen, therapy should be continued at the dose until the degree of response has reached the optimum possible before adding the next increment.

Specific recommendations.

Hypertension.

Suggested initial dose range.

0.5 mg twice daily increasing to 1.0 mg twice daily or three times daily.

Usual maintenance dose.

3.0 mg to 20 mg daily in divided doses.
The following are given as guides to administration.

Patients receiving no antihypertensive therapy.

It is recommended that therapy be initiated at 0.5 mg twice daily for 3 days. Unless the patient is unusually sensitive, this dose should be increased to 1.0 mg twice daily or three times daily for a further 3 days and then to 2.0 mg twice daily or three times daily. Thereafter, as determined by the patient's response to the blood pressure lowering effect, the daily dose should be increased gradually to 20 mg. The optimal response may take up to 6 weeks. After initial titration some patients can be maintained on a twice daily dosage regimen.
A diuretic may be added to enhance the efficacy. It is recommended that this addition be considered when the prazosin dose is at 2 mg twice daily or three times daily.

Patients receiving diuretic therapy with inadequate control of blood pressure.

The diuretic should be reduced to a maintenance dose level for the particular agent, and prazosin initiated at 0.5 mg twice daily or three times daily. After the initial period of observation, the dose of prazosin should be gradually increased as determined by the patient's response.

Patients receiving other antihypertensive agents but with inadequate control.

Because some additive effect is anticipated, the dosage level of other agents (e.g. beta-adrenergic blocking agent, alpha-methyldopa, reserpine, clonidine*, etc.) should be reduced and prazosin initiated at 0.5 mg twice daily. Subsequent dosage increase should be made depending upon the patient's response.
Though experience is limited, there is evidence that adding prazosin to beta-adrenergic blocking agents, calcium channel blockers or angiotensin converting enzyme (ACE) inhibitors may bring about a substantial reduction in blood pressure. Thus, the low initial dose regimen is strongly recommended.
* Termination of oral therapy should be gradual (e.g. over more than 7 days). Sudden cessation of antihypertensive therapy is known to be associated with rebound hypertension which in some cases may be severe. This may occur with clonidine particularly in patients receiving more than 900 microgram/day.
Congestive heart failure.

Suggested initial daily dose range.

0.5 mg increasing to 4.0 mg in divided doses.

Usual daily maintenance dose.

4.0 mg to 20 mg in divided doses.
In recumbent patients the recommended starting dose is 0.5 mg three or four times daily. Dosage should be titrated according to the patient's clinical response, based on careful monitoring of cardiopulmonary signs and symptoms or haemodynamic studies when indicated. Dosage titration steps may be performed as often as every 2 to 3 days in patients under close medical supervision. In severely ill, decompensated patients, rapid dose titration over 1 or 2 days may be indicated, and is best done when haemodynamic monitoring is available. In clinical studies to date the mean optimal daily dose during the initial treatment period was 11.5 mg, with therapeutic dosages ranging from 4 mg to 20 mg daily in divided doses. Retitration may be required in some patients to maintain optimal clinical improvement.
Raynaud's phenomenon and Raynaud's disease.

Suggested starting dosage.

0.5 mg twice daily.

Usual daily maintenance dosage.

1 mg or 2 mg twice daily. The recommended starting dosage is 0.5 mg twice daily given for a period of 3 to 7 days. Dosage should be adjusted according to the patient's clinical response.
Benign prostatic hyperplasia. The recommended starting dose is 0.5 mg twice daily, given for a period of 3 to 7 days and then adjusted according to clinical response. The maintenance dosage is 2 mg twice daily. The use of doses over 4 mg daily has not been studied, and cannot be recommended at present. Doses up to 4 mg daily have produced amelioration of symptoms for periods of up to 4 weeks but currently longer term data are not available. Postural hypotension may occur (see Section 4.4 Special Warnings and Precautions for Use, General (all patients)).

Dosage adjustment in renal impairment.

For patients with moderate to severe grades of renal impairment, evidence to date shows that prazosin does not further compromise renal function when used in patients with renal impairment. Because some patients in this category have responded to small doses of prazosin, it is recommended that therapy be initiated at 0.5 mg daily and that dose increases be instituted with caution.

4.3 Contraindications

Minipress is contraindicated in patients with a known sensitivity to quinazolines, prazosin or any other component of the tablets.

4.4 Special Warnings and Precautions for Use

General (all patients).

Syncope.

Minipress may cause syncope with - sudden loss of consciousness. In most cases this is believed to be due to an excessive postural hypotensive effect although occasionally the syncopal episode has been preceded by a bout of severe tachycardia with heart rates of 120-160 beats per minute. Syncopal episodes have usually occurred within 30 to 90 minutes of the initial dose of the drug: occasionally they have been reported in association with rapid dosage increases or the introduction of another antihypertensive drug into the regimen of a patient taking high doses of Minipress. The incidence of syncopal episodes is approximately 1% in patients given an initial dose of 2 mg or greater. Clinical trials conducted during the investigational phase of this drug suggest that syncopal episodes can be minimised by limiting the initial dose of the drug to 0.5 mg, by subsequently increasing the dosage slowly and by introducing any additional antihypertensive drugs into the patient's regimen with caution (see Section 4.2 Dose and Method of Administration). Hypotension may develop in patients given Minipress who are also receiving a beta-blocker or a diuretic.
Addition of a diuretic or other antihypertensive agent to Minipress therapy has been shown to cause an additive hypotensive effect. This effect can be minimised by reducing the dose of Minipress to 1 mg or 2 mg twice daily, by introducing additional antihypertensive drugs cautiously and then retitrating Minipress based on clinical response.
If syncope occurs, the patient should be placed in the recumbent position and treated supportively as necessary. This adverse effect is self limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration.
Patients should always be started at a dose of 0.5 mg of Minipress. The 2 mg and 5 mg tablets are not indicated for initial therapy. Both lying and standing blood pressure should be measured.
More common than loss of consciousness are the symptoms often associated with lowering of the blood pressure, namely, dizziness and lightheadedness. The patient should be cautioned about these possible adverse effects and advised what measures to take should they develop. The patient should also be cautioned to avoid situations where injury could result should syncope occur during the initiation of Minipress therapy.

Priapism.

Prolonged erections and priapism have been reported with alpha-1 blockers, including prazosin, in postmarketing 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.

Patients with Raynaud's phenomenon or Raynaud's disease.

Because prazosin decreases peripheral vascular resistance, careful monitoring of blood pressure during initial administration and titration of Minipress is suggested (see Section 4.4 Special Warnings and Precautions for Use, General (all patients)).

Patients with congestive heart failure.

In patients with acute or chronic left ventricular failure who have undergone vigorous diuretic and vasodilator treatment, the resultant decrease in left ventricular filling may be associated with a significant fall in cardiac output and systemic blood pressure when Minipress is administered. In such patients, a low initial dose of Minipress and gradual titration with close observation is recommended (see Section 4.2 Dose and Method of Administration).
The haemodynamic response to Minipress in patients with congestive heart failure should be carefully monitored to ensure sustained clinical improvement as rapid attenuation of improved cardiac performance might occur in some patients.
In occasional patients the clinical efficacy of Minipress has been reported to diminish due to complete or partial tolerance to haemodynamic effects of prazosin. Evidence of efficacy for periods exceeding 6 months is lacking. 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 Minipress 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 recurrence of symptoms. In those patients without evidence of fluid retention, when clinical improvement has diminished, an increase in the dosage of Minipress, temporary withdrawal of the drug and/or addition of an aldosterone antagonist (e.g. spironolactone) to the treatment regimen will usually restore clinical efficacy.

Use in patients with congestive heart failure.

Minipress is not recommended in the treatment of congestive heart 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 congestive cardiac failure due to a recent myocardial infarction.

Patients with benign prostatic hyperplasia.

Minipress decreases peripheral vascular resistance, and since many patients with this disorder are elderly, standing and lying blood pressure should be carefully monitored during initial administration and during adjustment of the dose of Minipress (see Section 4.4 Special Warnings and Precautions for Use, General (all patients)). Close observation is especially recommended for patients taking medications that are known to lower blood pressure.

Patients with angina.

Minipress should be used cautiously in patients with ischaemic heart disease as angina may be exacerbated.

Use in hepatic impairment.

There are no data available on the use of Minipress in liver disease. However, as the drug is primarily metabolised by the liver and excreted in the bile and faeces, patients with impaired hepatic function may require a lower dose.

Use in renal impairment.

See Section 4.2 Dose and Method of Administration, Dosage adjustment in renal impairment.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Patients with benign prostatic hyperplasia; Section 4.8 Adverse Effects (Undesirable Effects), Serious or life-threatening reactions.

Paediatric use.

Minipress is not recommended for the treatment of children under the age of 12 years, since safe conditions for its use have not been established.

Effects on laboratory tests.

False positive results may occur in screening tests for phaeochromocytoma (urinary vanillylmandelic acid [VMA] and methoxyhydroxyphenylglycol [MHPG], urinary metabolites of noradrenaline) in patients who are being treated with Minipress.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Patients taking phosphodiesterase type-5 inhibitors.

As with other alpha-1 blockers, concomitant administration of prazosin hydrochloride with a phosphodiesterase type-5 (PDE-5) inhibitor should be used with caution, as it may lead to symptomatic hypotension in a few susceptible individuals. No studies have been conducted with prazosin hydrochloride.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In long-term studies for 1 year or more, testicular changes, necrosis and atrophy, have occurred at 25 mg/kg/day in rats and dogs. This is 60 times the usual maximum recommended dose of 20 mg per day in humans. Testicular weight was marginally depressed but no morphological testicular changes were seen in dogs at a daily dose of 10 mg/kg which is 24 times the usual maximum recommended dose of 20 mg per day in humans.
In view of the testicular changes observed in animals, 105 patients on long-term therapy with Minipress were monitored for 17-ketosteroid excretion and no changes indicating a drug effect were observed. In addition no changes in sperm morphology suggestive of drug effect were seen in 27 males given Minipress alone for up to 51 months.
(Category B2)
When both male and female rats were treated with prazosin at a dose of 75 mg/kg/day and then mated, there was a significant impairment of fertility. There is no information available as to whether prazosin crosses the placenta. No teratogenic effects were seen in animal testing. However, the safety of Minipress used during pregnancy has not been established. Accordingly, it should be used only when, in the opinion of the physician, potential benefit to the pregnant patient outweighs potential risk.
 Prazosin has been shown to appear in breast milk. Minipress should be administered to a nursing mother only when, in the opinion of the physician, the expected benefit outweighs any potential risk. Consideration should be given to not breastfeeding the baby.

4.7 Effects on Ability to Drive and Use Machines

Patients should be cautioned that their ability to drive or operate machinery may be impaired, especially when initiating prazosin therapy.

4.8 Adverse Effects (Undesirable Effects)

More common reactions.

Cardiovascular.

Postural hypotension (14%), palpitations (5%), oedema (4%).

Gastrointestinal.

Nausea (5%), dry mouth (4%).

General.

Lack of energy (7%), weakness (asthenia) (7%).

Nervous system.

Headaches (8%), drowsiness (8%), dizziness (faintness).

Ocular.

Blurred vision (4%).

Respiratory.

Nasal congestion (4%).

Less common reactions.

Body as a whole.

Allergic reaction, malaise, pain.

Cardiovascular.

Tachycardia (1%), syncope (1%), bradycardia, hypotension, vasculitis, angina pectoris.

Endocrine.

Gynaecomastia.

Dermatological.

Rash and pruritus (1%), alopecia, lichen planus, urticaria.

Gastrointestinal.

Vomiting (3%), constipation (3%), diarrhoea (2%), liver function abnormalities, pancreatitis, abdominal discomfort and/or pain.

Genitourinary.

Urinary incontinence, priapism, impotence, urinary frequency.

Nervous system.

Nervousness (2%), depression (2%), paraesthesiae, hallucinations, reddened sclera, tinnitus, worsening of pre-existing narcolepsy, vertigo, insomnia.

Respiratory.

Dyspnoea (2%), epistaxis.

General.

Fever, diaphoresis, positive ANA titre, arthralgia, flushing, eye pain.

Serious or life-threatening reactions.

Postural hypotension, especially in elderly patients with cerebrovascular disease, may be dangerous. Exacerbation of pre-existing angina, new onset angina and myocardial infarction have been associated with prazosin, although a causal relationship has not been established.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Accidental ingestion of at least 50 mg of prazosin in a 2 year old child resulted in profound drowsiness and depressed reflexes. No decrease in blood pressure was noted. Recovery was uneventful.
Should overdosage lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalisation of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used. Renal function should be monitored and supported as needed. Laboratory data indicate prazosin is not dialysable because it is protein bound.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Prazosin causes a decrease in total peripheral resistance. Animal studies suggest that the vasodilator effect of prazosin is related to blockade of postsynaptic alpha-adrenoceptors. The results of dog forelimb experiments demonstrate that the peripheral vasodilator effect is confined mainly to the level of the resistance vessels (arterioles). Unlike conventional alpha-blockers, the antihypertensive action of prazosin is usually not accompanied by reflex tachycardia.
Haemodynamic studies have been carried out in hypertensive patients following acute single dose administration and during the course of long-term maintenance therapy. The results confirm that the usual therapeutic effect is a fall in blood pressure, unaccompanied by a clinically significant change in cardiac output, heart rate, renal blood flow, and glomerular filtration rate. There is no measurable negative chronotropic effect.
Prazosin may increase plasma renin activity in patients with congestive heart failure.
Clinically, the antihypertensive effect is believed to be a direct result of peripheral vasodilation. In humans, blood pressure is lowered in both the supine and standing positions. This effect is more pronounced on the diastolic blood pressure. Tolerance does not appear to develop in long-term clinical use in the treatment of hypertension.
Rebound elevation of blood pressure does not occur following abrupt cessation of Minipress therapy.
A variety of epidemiologic, biochemical and experimental studies have suggested that an elevated level of low density lipoprotein (LDL) cholesterol may be associated with an increased risk of coronary heart disease. There is also evidence that reduced levels of high density lipoprotein (HDL) cholesterol may be associated with an increased risk of coronary heart disease. Clinical studies have shown that Minipress therapy is not associated with adverse changes in the serum lipid profile.
Haemodynamic studies carried out in patients with congestive heart failure following acute oral dosing and during the course of longer-term maintenance therapy, both at rest and on exercise, indicate that the therapeutic effect in these patients is due to a reduction in left ventricular filling pressure, reduction in cardiac impedance, and an augmentation of cardiac output. These effects, as indicated in forearm plethysmographic studies in humans, are associated with a balanced vasodilator effect on both resistance vessels (arterioles) and capacitance vessels (veins). The use of Minipress in the treatment of congestive heart failure does not provoke a reflex tachycardia.
Enucleated hyperplastic glandular tissue and hypertrophied muscular tissue removed from the enlarged prostate gland is rich in alpha-adrenoceptor content. Variations in the tone of smooth muscle in the prostate will produce variations in the closure pressure exerted on the prostatic urethra. This finding has provided the basis of pharmacological treatment of benign prostatic hyperplasia (BPH) involving alpha-adrenoceptor antagonism.
There is evidence of statistically significant improvement in urinary flow following Minipress therapy in patients with BPH. There is also evidence for a reduction in the volume of residual bladder urine and improvement in symptoms of BPH such as frequency of micturition.
Raynaud's phenomenon and Raynaud's disease have been successfully treated with Minipress. The vasodilator action of the drug may increase blood flow to affected parts to reduce the severity of the signs and symptoms and the frequency and duration of the attacks.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration to normal volunteers and hypertensive patients, plasma concentrations reach a peak in 1 to 2 hours, with a plasma half-life of 2 to 3 hours. Pharmacokinetic data in a limited number of patients with congestive heart failure, most of whom showed evidence of hepatic congestion, indicate that peak plasma concentrations are reached in 2.5 hours and plasma half-life is approximately 7 hours. The bioavailability of oral prazosin was also increased 2-3 times in patients with congestive heart failure but the time to reach the peak was not affected in patients compared to normal volunteers. The mechanism of increase in plasma half-life and bioavailability of prazosin in congestive heart failure has not been satisfactorily explained.

Metabolism.

The drug is highly bound to plasma protein. Animal studies indicate that prazosin is extensively metabolised primarily by demethylation and conjugation. Less extensive human studies suggest similar metabolism in man.

Excretion.

Prazosin is excreted mainly via the bile and faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Calcium hydrogen phosphate, maize starch, microcrystalline cellulose, magnesium stearate, sodium lauryl sulfate. The 1 mg tablet also contains sunset yellow FCF.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

PVC/Al blister packs of 100 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Prazosin hydrochloride is a white or almost white powder, very slightly soluble in water, slightly soluble in alcohol and in methanol, practically insoluble in acetone.
Minipress (prazosin hydrochloride), a quinazoline derivative, was the first antihypertensive of its chemical class. It is the hydrochloride salt of 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(-2-furoyl) piperazine. Molecular weight is 419.87.

Chemical structure.

Its structural formula is:

CAS number.

19237-84-4.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes