PRETENOL-C 100 TABLET : A white, 9mm round tablet scored on one
side and with marking 'd' on another side.
PRETENOL-C 50 TABLET : A white,
'D'-shaped tablet with marking 'duo862'.
PRETENOL-C 100 TABLET : Each tablet contains Atenolol 100 mg,
Chlorthalidone 25 mg
PRETENOL-C 50 TABLET : Each tablet contains Atenolol 50 mg, Chlorthalidone
Atenolol and Chlorthalidone have been used singly and
concomitantly for the treatment of hypertension. The antihypertensive
effects of these agents are additive and studies have shown that there is no
significant interference with bioavailability when these agents are given
together in the single combination tablet In patients with more severe
hypertension Pretenol-C may be administered with other antihypertensive such
Atenolol: A beta-adrenoceptor blocking drug which acts
preferentially on beta-receptors in the heat Selectivity decreases with
increasing dose. I has little intrinsic sympathomimetic activity and no
membrane stabilising activity, Atenolol is a racemic mixture and its
activity resides in the S(-) enantiomer. It reduces raised blood pressure by
an unknown mechanism and also inhibits exercise induced tachycardia and
decreases plasma renin concentration. It causes sight airways obstruction
but less than that seen with non-selective beta-blockers. The inhibition of
exercise induced tachycardia is correlated with blood levels, but there is
no correlation between plasma concentrations and antihypertensive effect
Atenolol is effective and well-tolerated in most ethnic populations although
the response may be less Afro-Caribbean black patents.
The possible mechanism of the anti-anginal activity of Atenolol appears to be
due to a reduction in left ventricular work and oxygen utilisation resulting
(mainly) from the decrease in heart rate and contractility. The
anti-arrhythmic effect of Atenolol is apparently due to its anti-sympathetic
effect There is no evidence that membrane stabilising activity or intrinsic
sympathomimetic activity are necessary for anti-arrhythmic efficacy. By its
anti-sympathetic effect, Atenolol depresses sinus node function,
atrioventricular node function and prolongs atrial refractory periods. It
has no direct effect on electrophysiological properties of the HIS-Purkinje
Because of their negative inotropic effects, beta-adrenoreceptor blocking
agents should be avoided in uncontrolled heart failure.
Chlorthalidone: A monosulfanomyl diuretic which differs chemically from
thiazide diuretics in that a double ring system is incorporated in its
structure. It is an oral diuretic with prolonged action and low toxicity.
The diuretic effect of the drug occurs within 2 hours of an oral dose and
continues for up to 72 hours. it produces copius diuresis with greatly
increased excretion of sodium and chloride. At maximal therapeutic dosage
chlorthalidone is approximately equal in its diuretic effect to comparable
maximal therapeutic doses of benzothiazine diuretics. The site of action
appears to be the cortical diluting segment of the ascending limb of Henle's
Atenolol: Although absorption of Atenolol is variable and incomplete
(40-60%) the virtual lack of liver metabolism results in a relatively
systemic bioavailability compared to other beta-blockers. Blood levels in
man peak two to four hours after a single 100 mg oral dose and are of the
order of 0.4 to 0.9 microgram I ml. Blood levels are consistent and the
levels after chronic oral administration are in good agreement with those
predicted from single dose results The drug is distributed throughout the
body tissues and about 10% of the drug is metabolised. The minor urinary
metabolite identified is a hydroxylated derivative. It is reported to be one
tenth as active atenolol. The main route of elimination is renal excretion.
The plasma half-life, measured by blood level decay or urinary build-up is
approximately 7 to 9 hours. In patients with impaired renal function, there
is a progressive prolongation of the half life, in patients with normal
renal function the therapeutic effect that is, control of raised blood
pressure, lasts for at least 24 hours following a 50 mg oral dose.
Chlorthalidone: Absorption and plasma concentration: The bioavailability of
an oral dose of 50mg Hygroton is approximately 64%, peak blood
concentrations being attained after 8 to 12 hours. For doses of 25 and 50
mg, Cmax values average 1.5 mcg/mL(4.4 micromol/L) and 3.2 mcg/mL (9.4
micromol/L) respectively. For doses up to 100 mg there is a proportional
increase in AUC. On repeated daily doses of 50mg, steady-state blood
concentrations, measured at the end of the 24-hour-dosage interval,
averaging 7.2 mcg/mL (21.2 micromol/L) are reached after 1 to 2 weeks.
Distribution: In blood, only a small fraction of chlorthalidone is tree, due
to extensive accumulation in erythrocytes and binding to plasma proteins.
Owing to the large degree of high-affinity binding to the carbonic anhydrase
of erythrocytes, only some 1.4% of the total amount of chlorthalidone in
whole blood was found in plasma at steady state during treatment with 50 mg
doses. In vitro, plasma protein binding of chlorthalidone is about 76%, and
the major binding protein is albumin. Chlorthalidone crosses the placental
barrier and passes into breast milk. In mothers treated with 50 mg
chlorthalidone daily before and after delivery chlorthalidone levels in
foetal whole blood are about 15% of those found in maternal blood.
Chlorthalidone concentrations in amniotic fluid and in the maternal milk are
approximately 4% of the corresponding maternal blood level. Metabolism and
elimination: Chlorthalidone is eliminated from whole blood and plasma with
an elimination half-life averaging 50 hours. The elimination hag-life is
unaltered after chronic administration. The major part of an absorbed dose
of chlorthalidone is excreted by the kidneys, with a mean renal plasma
clearance of 60 mL/min. Metabolism and hepatic excretion into bile
constitute a minor way of elimination. Within 120 hours, about 70% of the
dose is excreted in the urine and in the faeces mainly in unchanged form.
Special patient groups: Renal dysfunction does not seem to alter the
pharmacokinetics of chlorthalidone, the rate-limiting factor in the
elimination of the drug from blood or plasma being most probably the
affinity of the drug to the carbonic anhydrase of erythrocytes. In elderly
patents, the elimination of chlorthalidone is slower than in healthy young
adults, although absorption is the same. Therefore, close medical
observation is indicated when treating patents of advanced age with
Treatment of hypertension in patients for whom the effect of
treatment with either beta-blockers or diuretic alone is inadequate. The
patient should be stabilised on the two drugs individually before transfer
to the fixed combination if the dosage is appropriate.
Dosage of individual drugs to be titrated and patients
to be stabilized on the two drugs individually before transfer to the fixed
combination if dosage is appropriate. One (50mg) I hat (100 mg) tablet daily
of Pretenol C should prove effective in most cases. If the response is
considered inadequate then two (50 mg tablets / one (100 mg) tablet daily
should be tried. However, higher doses offer a significant risk of
hypokalaemia and periodic monitoring of potassium levels should always be
undertaken in these patients. Above this dose level there is unlikely to be
any further fall in blood pressure and another anti-hypertensive drug such
as a vasodilator should be added.
Children: There is no paediatric
experience with Pretenol-C therefore this preparation is not recommended for
A daily dosage of one (100 mg) / two (50 mg) Pretenol C tablets may be
inappropriate in the older patient. For these patents, one (50mg) / half
(100mg) tablet daily is recommended. The addition of a small dose of a third
agent, eg. a vasodilator, may be appropriate should hypertensive control not
be achieved on one (50 mg) / half (100mg) Pretenol C tablet daily alone. In
patents with severe renal impairment a reduction in daily dose or in
frequency of administration may be necessary.
1. Bronchospasm: Beta adrenergic blockade of the smooth muscle of bronchi and
bronchioles may result in an increased airways resistance. These drugs also
reduce the effectiveness of asthma treatment This may be dangerous in
susceptible patients. Therefore, beta blockers are contraindicated in any
patents with a history of airways obstruction or tendency to bronchospasm.
Use of cardioselective beta-blockers can also result in severe bronchospasm.
If such therapy must be used, great caution should be exercised. Alternative
therapy should be considered.
2. Congestive heart failure.
3. Allergic disorders (including allergic rhinitis) which may suggest a
predisposition to bronchospasm.
4. Right ventricular failure secondary to pulmonary hypertension.
5. Significant right ventricular hypertrophy.
6. Sick sinus syndromes.
7. Sinus bradycardia (less than 45-50 beats/minute)
8. Second and third degree AV block
9. Shock (including cardiogenic and hypovolaemic shock)
10. Anaesthesia with agents that produce myocardial depression leg. ether,
11. Hypersensitivity to the drug or other sulphonamide-derived drugs
13. Metabolic acidosis
14. Severe peripheral arterial circulatory disturbances
15. Untreated phaeochromocytoma
16. Pregnancy and lactation (see Warning: Use in pregnancy and lactation)
17. Hypertension during pregnancy
18. Creatinine clearance lower than 30mL/min
19. Conditions involving enhanced potassium loss, salt-losing nephropathies
and prerenal (cardiogenic) impairment of kidney function.