Amlodipine with Atenolol
Indication
- Hypertension
- Chronic stable angina
Dosage and Administration
The recommended dosage is one tablet daily. If necessary, the dosage may be increased to two tablets daily. The
dosage however should be individualized.
Renal lmpairment
Dosage should be adjusted in cases of severe impairment of
renal function. Dosage of atenolol should not exceed 50 mg/day when creatinine
clearance is 15-35 ml/min/1.73 m2. While in patients with creatinine clearance<15 ml/min/1.73 m2, the maximum dosage of atenolol should be 25 mg/day.
Hepatic impairment
The recommended initial dose in patients with hepatic impairment is half tablet.
Elderly patients
Dose selection for an elderly patient should be cautious, usually starting at half
tablet.
Contraindications
Hypersensitivity to either component, sinus bradycardia, second and higher
degrees of heart block, cardiogenic shock, hypotension and overt cardiac failure.
Warnings and Precautions
Pregnancy
The combination should be used during pregnancy only if the expected benefit
outweighs the potential fetal risk.
Lactation
The combination should not be used by nursing mothers. If its use is considered
necessary, breast feeding should be stopped.
Pediatric use
Safety and effectiveness of this combination has not been evaluated in
pediatrics.
Geriatric Use
In general, dose selection should be done with caution in elderly patients, usually
starting at the low end of the dosing range, reflecting the greater frequency of
decreased hepatic, renal, or cardiac function, and of concomitant disease
other drug therapy.
Renal Impairment
Since atenolol is excreted via the kidneys, dosage of atenolol should be reduced
in patients with a creatinine clearance <35 ml/min/1.73 m2.
Hepatic Impairment
Caution may be necessary in the use of the combination in patients with severe
liver damage because of the prolongation of the elimination half-life of
amlodipine.
Hypotension
Excessive fall of blood pressure can occur in some patients especially the
elderly.
Aggravation of Angina
Rarely patients, particularly those with severe obstructive coronary artery
disease, have developed increased frequency, duration and/or severity of angina
or acute myocardial infarction on starting calcium channel blocker therapy or at
the time of dosage increase.
Congestive Heart Failure
In general, calcium channel blockers should be used with caution in patients with
heart failure. Placebo-controlled trials of amlodipine in patients with New York
Heart Association (NYHA) Class III or IV heart failure showed no overall adverse
effect on survival or cardiac morbidity. In NYHA class II/III heart failure patients,
there was no evidence of worsened heart failure based on measures of exercise
tolerance, NYHA classification, symptoms or left ventricular ejection fraction
(LVEF).
Sympathetic stimulation is necessary in supporting circulatory function in
congestive heart failure, and beta blockade carries the potential hazard of further
depressing myocardial contractility and precipitating more severe failure. In
patients who have congestive heart failure controlled by digitalis and/or diuretics,
atenolol should be administered cautiously. Both digitalis and atenolol slow AV
conduction.
In Patients without a History of Cardiac Failure
Continued depression of the myocardium with beta-blocking agents over a period
of time can, in some cases, lead to cardiac failure. At the first sign or symptom of
impending cardiac failure, patients should be treated appropriately according to
currently recommended guidelines, and the response observed closely. If cardiac
failure continues despite adequate treatment, AMLOPRES-AT should be
withdrawn.
Bronchospasm
The combination should be used with caution in patients with airway obstruction
who do not respond to, or cannot tolerate, other antihypertensive treatment.
Cessation of Therapy
Patients with coronary artery disease, who are being treated with amlodipine+atenolol,
should be advised against abrupt discontinuation of therapy. Severe
exacerbation of angina and the occurrence of myocardial infarction and
ventricular arrhythmias have been reported in angina patients following the
abrupt discontinuation of therapy with beta-blockers. The last two complications
may occur with or without preceding exacerbation of the angina pectoris. When
discontinuation of amlodipine+atenolol is planned, as done during every beta-blocker
withdrawal, the patients should be carefully observed and advised to limit
physical activity to a minimum. If the angina worsens or acute coronary
insufficiency develops, it is recommended that amlodipine+atenolol be promptly
reinstituted, at least temporarily. Because coronary artery disease is common
and may be unrecognized, it may be prudent not to discontinue amlodipine+atenolol
therapy abruptly even in patients treated only for hypertension.
Anaesthesia and Major Surgery
It is not advisable to withdraw amlodipine+atenolol prior to surgery in the majority of
patients. However, care should be taken when using anaesthetic agents such as
those, which may depress the myocardium. Atenolol is a competitive inhibitor of
beta-receptor agonists and its effects on the heart can be reversed by
administration of such agents: eg, dobutamine or isoproterenol with caution.
Diabetes and Hypoglycaemia
Amlodipine+atenolol should be used with caution in diabetic patients if a betablocking
agent is required. Beta-blockers may mask tachycardia occurring with
hypoglycaemia, but other manifestations such as dizziness and sweating may
not be significantly affected. At recommended doses atenolol does not potentiate
insulin-induced hypoglycaemia and, unlike nonselective beta-blockers, does not
delay recovery of blood glucose to normal levels.
Thyrotoxicosis
Beta-adrenergic blockade may mask certain clinical signs (eg, tachycardia) of
hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid
storm; therefore, patients suspected of developing thyrotoxicosis from whom
amlodipine+atenolol therapy is to be withdrawn should be monitored closely.
Untreated Phaeochromocytoma
Amlodipine+atenolol should not be given to patients with untreated
phaeochromocytoma.
Aortic Stenosis
Caution should be exercised when administering AMLOPRES-AT in patients
with severe aortic stenosis.
Drug Interactions
Catecholamine depleting drugs: Coadministration with catecholamine
depleting drugs (eg. reserpine) may have additive effect when given with betablocker,
and hence patients taking both the drugs concomitantly should be
observed for hypotension and/or marked bradycardia.
Clonidine: Beta-blockers may exacerbate the rebound hypertension, which can
follow the withdrawal of clonidine. If the two drugs are coadministered,
amlodipine+atenolol should be withdrawn several days before
the gradual withdrawal of clonidine. If replacing clonidine by amlodipine+atenolol, the introduction of amlodipine+atenolol
should be delayed for several days after clonidine administration has stopped.
Prostaglandin synthase inhibiting drugs: Concomitant use of prostaglandin
synthase inhibiting drugs, e.g., indomethacin, may decrease the hypotensive
effects of beta-blockers.
Side effects
The combination of amlodipine and atenolol is well tolerated. Side effects include
headache, palpitations, flushing, edema, depression, dizziness, dyspepsia,
dyspnoea, muscle cramps, fatigue, cold extremities and bradycardia.
Overdosage
Amlodipine
If massive overdose should occur, active cardiac and respiratory monitoring
should be instituted. Frequent blood pressure measurements are essential.
Should hypotension occur, cardiovascular support including elevation of the
extremities and the judicious administration of fluids should be initiated. If
hypotension remains unresponsive to these conservative measures,
administration of vasopressors (such as phenylephrine) should be considered
with attention to circulating volume and urine output. Intravenous calcium
gluconate may help to reverse the effects of calcium entry blockade. As
amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
Atenolol
The predominant symptoms reported following atenolol overdose are lethargy,
disorder of respiratory drive, wheezing, sinus pause and bradycardia.
Additionally, common effects associated with overdosage of any beta-adrenergic
blocking agent and which might also be expected in atenolol overdose are
congestive heart failure, hypotension, bronchospasm and/or hypoglycemia.
Treatment of overdose should be directed to the removal of any unabsorbed drug
by induced emesis, gastric lavage, or administration of activated charcoal.
Atenolol can be removed from the general circulation by hemodialysis. Other
treatment modalities should be employed at the physician' discretion and may
include:
Bradycardia: Atropine intravenously. If there is no response to vagal blockade,
give isoproterenol cautiously. In refractory cases, a transvenous cardiac
pacemaker may be indicated.
Heart block (second or third degree): Isoproterenol or transvenous cardiac
pacemaker.
Cardiac failure: Digitalize the patient and administer a diuretic. Glucagon has
been reported to be useful.
Hypotension: Vasopressors such as dopamine or norepinephrine (levarterenol).
Monitor blood pressure continuously.
Bronchospasm: A beta2 stimulant such as isoproterenol or terbutaline and/or
aminophylline.
Hypoglycemia: Intravenous glucose.
|