Atenolol + Nifedipine

Oral
Angina pectoris

Oral
Hypertension

Oral:
Hypertension: Dose reduction may be required. Max dose: 1 capsule once daily.

CrCl (mL/min)	Dosage
<15	Contraindicated.

Angina pectoris: Dose reduction may be required. Max dose: 1 capsule daily.

CrCl (mL/min)	Dosage
<15	Contraindicated.

Oral:
Hypertension: Dose reduction may be required. Max dose: 1 capsule once daily.
Angina pectoris: Dose reduction may be required. Max dose: 1 capsule daily.

History of wheezing, asthma, obstructive respiratory disease, pronounced bradycardia (resting heart rate <50 beats/min prior to treatment), 2nd or 3rd degree heart block, sick sinus syndrome, SA block, systolic pressure <90 mmHg, overt or decompensated cardiac failure (NYHA grades III & IV), aortic stenosis, unstable angina, acute attacks of angina, acute MI or within 1 mth of MI, or for secondary prevention of MI, cardiogenic shock, severe peripheral arterial circulatory disorders, acidosis, severe renal impairment, untreated phaeochromocytoma, malignant hypertension. Lactation, pregnancy, women of child-bearing age.

Conduction defects, poor cardiac reserve, controlled CHF, peripheral circulatory disorders, 1st degree heart block, mild heart failure (NYHA grade II), Prinzmetal's angina, renal or hepatic impairment. Discontinue use if heart rate is reduced at a dose of 1 capsule daily or if there is ischaemic pain within 1-4 hr of initiation of therapy. Withdraw gradually in patients with ischaemic heart disease. Adjustment in diabetic control may be required; may mask signs of thyrotoxicosis and modifies tachycardia of hypoglycaemia. Family history of psoriasis.

Headache, flushing, purpura, impotence, dizziness, GI upsets, oedema, fatigue.

Symptoms: Bradycardia, hypoglycaemia, bronchospasm, hypotension and acute cardiac failure. Treatment: Unabsorbed drug may be removed by gastric lavage, activated charcoal and a laxative. Symptomatic treatment may be required.

If used with clonidine, atenolol can worsen rebound hypertension following clonidine withdrawal. Reduced hypotensive effect of atenolol with ibuprofen and indometacin. May increase digoxin level and AV conduction time. Theophylline levels may be increased. Reduced efficacy of nifedipine with phenytoin, carbamazepine or phenobarbital. Increased plasma levels of nifedipine with cisapride, quinupristin/dalfopristin, nefazodone, valproic acid and other CYP3A4 enzyme inhibitors (e.g. erythromycin, ketoconazole, itraconazole, fluconazole, fluoxetine, protease inhibitors). May potentiate the action of non-depolarising muscle relaxants. Vagal dominance may occur with anaesthetic agents with cardiac depressant effects. Increased antihypertensive effect with cimetidine, TCAs, narcotics, barbiturates, nitrates or phenothiazines. Additive myocardial depression with lidocaine, chloroform, procainamide, β-adrenoceptor stimulants (e.g. isoprenaline) and α-adrenoceptor stimulants (e.g. noradrenaline). Nifedipine may reduce quinidine levels and increase tacrolimus levels. Marked heart rate reduction with reserpine, methyldopa, clonidine, guanethidine. Increased hypoglycaemia with insulin and oral antidiabetics. Potentiation of atrial conduction time and -ve inotropic effect with class I anti-arrhythmics (e.g. disopyramide and amiodarone).
Potentially Fatal: Exaggeration of bradycardia, hypotension and conduction disturbances with Ca-channel blockers with -ve inotropic effects (e.g. diltiazem and verapamil). Reduced efficacy of nifedipine with rifampicin. Excessive increase in BP with MAOIs, adrenaline and noradrenaline.

Do not take with grapefruit juice as the bioavailability of nifedipine will be increased.

Spectrophotometric values of urinary vanillylmandelic acid may be falsely increased by nifedipine.

Description:
Mechanism of Action: Atenolol is a β₁-selective adrenergic receptor blocker. It has marked -ve inotropic and chronotropic effects which result in reduction of BP (particularly during exercise), myocardial oxygen demand and cardiac output. Nifedipine is a dihydropyridine calcium-channel blocker. It is a coronary and peripheral vasodilator, which reduces BP and peripheral resistance, and increases myocardial oxygen demand.
Pharmacokinetics:
Absorption: Atenolol: Consistent but incomplete; about 40-50% of a dose is absorbed from the GI tract. Nifedipine: Almost completely absorbed from the GI tract.
Distribution: Atenolol: 6-16% bound to plasma proteins. Enters breast milk & crosses placenta. Nifedipine: 92-98% bound to plasma proteins. Enters breast milk.
Metabolism: Atenolol: Little or no hepatic metabolism. Nifedipine: Extensive hepatic first-pass metabolism via CYP3A4 isoenzyme.
Excretion: Atenolol: Mainly via renal route; plasma half-life: About 6-7 hr. Nifedipine: 80-95% of dose excreted mainly in the urine, remainder is via the faeces as inactive metabolites; plasma half-life: 6-11 hr (sustained release).

Store below 30°C. Protect from light and moisture.

Beta-Blockers / Calcium Antagonists