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    Summary for UKPID




    TERAZOSIN HYDROCHLORIDE




    Anne Prince, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP
    UK


    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information
    Service.


    Summary

    Brand name

         Hytrin, Hytrin BPH

    Generic

         Terazosin hydrochloride

    Chemical group/family

         Alpha-adrenoceptor blocker
         (BNF category 2.5.4 and 7.4.1)

    Reference Number

         CAS 63590-64-7 (terazosin)
         CAS 63074-08-8 (terazosin hydrochloride)
         CAS 70024-40-7 (terazosin hydrochloride dihydrate)

    Product licence numbers

                        Hytrin         Hytrin BPH
         1mg tablet     0037/0159      0037/0234
         2mg tablet     0037/0160      0037/0235
         5mg tablet     0037/0161      0037/0236
         10mg tablet    0037/0162      0037/0237

    Manufacturer/supplier

         Abbot Laboratories Limited,
         Abbott House,
         Norden Road,
         Maidenhead,
         Berks,
         SL6 4XE.

         Tel (01628) 773355

    Presentation

         Tablets 1mg,2mg, 5mg,10mg.
         Starter packs -7 x 1mg, 7 x 2mg, 21x2mg
         Original packs of 28 tablets for 2mg, 5mg,10mg

    Physio-chemical properties1

    Chemical structure
         (RS)-1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-((tetrahydro-2-
         furanyl)carbonyl)piperazine monohydochloride dihydrate.
         C19H25N5O4.HCL.2H2O.

    Molecular weight                   459.9
    (anhydrous free base)              (387.4)

    pKa                                7.1
    Solubility
         in alcohol                    1 in 244
         in water                      1 in 40

    Uses

    Indications:2

    Terazosin is indicated for the treatment of mild to moderate
    hypertension in combination with other drugs or as sole therapy. It is
    also indicated for the symptomatic treatment of urinary     
    obstruction caused by benign prostatic hyperplasia (BPH).

    Therapeutic Dose2

    Hypertension/BPH

    Initial dose of 1mg at bedtime. The dose may be doubled at weekly
    intervals. The usual maintenance dose is 2-10mg for hypertension and
    5-10mg for BPH.

    Renal Impairment

    No dosage alterations necessary.

    Elderly

    No dosage alterations necessary.

    Precautions2

    Caution in patients with a history syncope. Dizziness,
    light-headedness or drowsiness may occur with the initial dose, or in
    association with missed doses and subsequent reinitiation of therapy.
    Patients must be advised to avoid driving or alcohol for approximately
    12 hours after the first dose or when the dose is increased. Dizziness,
    light-headedness or fainting may occur when standing up quickly from
    a lying or sitting position and patients should be advised to lie down
    if these symptoms appear, and then to sit for a few minutes to prevent
    their recurrence.

    Contraindications

    Known hypersensitivity to terazosin.

    Pregnancy

    No teratogenic effects seen in animals. The safety of terazosin has
    not been established during pregnancy and therefore it should not be
    used unless the potential benefit outweighs the risk.

    Breast Feeding

    It has not been determined whether terazosin is excreted into breast
    milk, but it seems unlikely, on theoretical grounds that significant
    amounts will pass into the baby through the breast milk.

    Pharmacokinetics1

    oral absorption
         >95%

    presystemic metabolism
         <10%

    plasma half life
      range                            8-14 hours
      mean                             12 hours

    Volume of distribution
         28 L

    Plasma protein binding
         90-94%

    Total body clearance
         80ml.min-1

    Renal clearance
         10ml.min-1

    Metabolism (liver)
         60%

    Toxicokinetics
         No data

    Epidemiology of poisoning
         No data

    Adverse effects4

    Dizziness, lack of energy, peripheral oedema, somnolence, blurred
    vision, nausea, headache, nasal congestion, postural hypotension.

    Interactions

    Orthostatic or first dose hypotension may be promoted by concomitant
    beta-blockade, calcium channel blockade, sodium depletion secondary to
    diuretic administration or other drugs which lower the blood pressure.

    Mechanism of action/toxicity

    Terazosin is a selective long acting alpha-adrenergic antagonist. The
    exact mechanism of therapeutic effect is not known. Relaxation of
    peripheral blood vessels appears to be produced mainly by competitive
    antagonism of post synaptic alpha-1-adrenoceptors. Toxic effects are
    mainly extensions of its known pharmacological activity.

    Features of poisoning3

    Summary

    Severe hypotension and severe tachycardia are the most common effects
    following overdose with these agents.

    Cardiovascular

    Hypotension, tachycardia, palpitations and cardiac arrhythmias may be
    noted. Severe hypotension may result in myocardial and cerebral
    ischemia. Syncope may occur following 1st dose.

    Neurologic

    Headache, dizziness and sweating may be noted.

    Gastrointestinal

    Nausea and vomiting are common.

    Management3

    Treatment is primarily symptomatic and supportive.

    Decontamination

    One dose of activated charcoal can be administered to prevent further
    absorption if presentation is within 2 hours.

    Hypotension

    Restoration of blood pressure and normalisation of heart rate may be
    accomplished by keeping the patient in a supine position. Administer
    I.V. fluids and place in Trendelburg position. If unresponsive to
    these measures, administer dopamine or noradrenaline and titrate as
    needed to desired response.

    Monitor

    Check heart rate, blood pressure and obtain an ECG.
    Check renal function and maintain urine output.

    Elimination Techniques

    Dialysis is unlikely to be of benefit because terazosin is highly
    protein bound.

    Case Data

    No case reports of terazosin overdose reported in the literature.

    Author

    Anne Prince, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP
    UK

    This monograph was produced by the staff of the Newcastle Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Peer review was undertaken by the Directors of the UK National Poisons
    Information Service.

    Last updated February 1997

    References

    1.   Dollery C. Therapeutic Drugs (Suppl 2), Churchill Livingstone
         1994

    2.   ABPI. Compendium of Data Sheets and Summaries of Product
         Characteristics Datapharm Publications Ltd 1996-1997

    3.   Micromedex, Inc. Poisindex, Volume 91 Expiry Date:31/3/97

    4.   S.G.Carruthers. Adverse Effects of Alpha-1-Adrenergic Blocking
         Drugs

    5.   Drug Safety 11 (1):12-20 1994
    


    See Also:
       Toxicological Abbreviations