Tenormin

Approximately 40 to 50% of an oral dose of atenolol is absorbed from the gastrointestinal tract, the remainder being excreted unchanged in the feces. Peak plasma concentrations occur 2 to 4 hours after dosing and are subject to a 4-fold variability. The plasma levels are proportional to dose over the range 50 to 400 mg and 6 to 16% of atenolol is bound to plasma proteins. The mean peak plasma concentrations of atenolol were approximately 300 and 700 ng/mL following 50 and 100 mg, respectively. The plasma half-life is approximately 6 to 7 hours. Atenolol is extensively distributed to extravascular tissues, but only a small amount is found in the CNS.

There is no significant hepatic metabolism of atenolol in man and more than 90% of the absorbed dose reaches the systemic circulation unaltered. Small quantities of a hydroxy metabolite and a glucuronide are produced but neither has major pharmacological activity. As a consequence no accumulation occurs in patients with liver disease and no dosage adjustment is required. Approximately 47% and 53% of the oral dose is eliminated in the urine and feces, respectively. Recovery is complete after 72 hours.

Atenolol is primarily eliminated by the kidney, predominantly by glomerular filtration. The normal elimination half-life may increase in severe renal impairment but no significant accumulation occurs in patients who have creatinine clearance greater than 35 mL/min. The oral dose should be reduced in patients with a creatinine clearance less than 35 mL/min (see Dosage).

Following i.v. administration, peak plasma levels were reached within 5 minutes. Declines from peak plasma levels are rapid (5- to 10-fold) during the first 7 hours; thereafter, plasma levels decay with a half-life similar to that of orally administered drug. Over 85% of an i.v. dose is excreted in urine within 24 hours.

Atenolol is excreted in human breast milk and crosses the placental barrier—the maternal to cord blood ratio being about unity.

Clonidine: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Reserpine or Guanethidine: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored because the added β-adrenergic blocking action of atenolol may produce an excessive reduction of sympathetic activity. Atenolol should not be combined with other β-blockers.

Antiarrhythmic Agents: Class I antiarrhythmic drugs (e.g. disopyramide) and amiodarone may have potentiating effect on atrial-conduction time and induce negative inotropic effect.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function, conduction abnormalities, or diminished cardiac output. This may result in severe hypotension, bradycardia and cardiac failure. Concomitant therapy with dihydropyridines, e.g., nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.

Digitalis Glycosides: Digitalis glycosides may potentiate the bradycardia of β₁-blockade.

Nonsteroidal Anti-inflammatory Agents: The concomitant use of nonsteroidal anti-inflammatory agents may blunt the antihypertensive effects of β-blockers.

Anesthetic Agents: Anesthetics can produce a hypotensive state with associated reflex tachycardia. Since β-blockade will inhibit reflex tachycardia, the hypotensive potential of anesthetic agents is increased with concomitant use of atenolol. The anesthetist should be informed and the choice of anesthetic should be an agent with as little negative inotropic activity as possible (Contraindications and Precautions, Elective or Emergency Surgery).

Clinical studies of atenolol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic renal, or cardiac function, and concomitant diseases or other drug therapy.

Activities Requiring Mental Alertness: Use of atenolol is unlikely to result in any impairment of the ability of patients to drive or operate machinery. However, it should be taken into account that dizziness or fatigue may occur.

In humans, there is a significant accumulation of atenolol in the breast milk of lactating women. Neonates born to mothers who are breastfeeding may be at risk for hypoglycemia and bradycardia. If the use of atenolol is considered essential, then mothers should stop nursing.

There is no experience with atenolol in the treatment of pediatric age groups.

Each scored, white to off-white, biconvex, film-coated tablet, embossed with TENORMIN 50 on one face and scored on the reverse, contains: atenolol 50 mg. Nonmedicinal ingredients: gelatin, glycerol, heavy magnesium carbonate, hydroxypropyl methylcellulose, magnesium stearate, maize starch, sodium lauryl sulfate and titanium dioxide. Calendar packs of 30.

Each scored, white to off-white, biconvex, film-coated tablet, embossed with TENORMIN on one face and scored on the reverse, contains: atenolol 100 mg. Nonmedicinal ingredients: gelatin, glycerol, heavy magnesium carbonate, hydroxypropyl methylcellulose, magnesium stearate, maize starch, sodium lauryl sulfate and titanium dioxide. Calendar packs of 30.

Store between 15 and 25°C. Protect from light and moisture.

Atenolol can cause fetal harm when administered to a pregnant woman. Atenolol crosses the placental barrier and appears in the cord blood.

No studies have been performed on the use of atenolol in the first trimester and the possibility of fetal injury cannot be excluded. Administration of atenolol, starting in the second trimester of pregnancy, has been associated with the birth of infants that are small for gestational age.

Studies in humans have shown that transplacental passage of atenolol does occur in pregnant women, with fetal drug serum levels equal to those of the mother. In a limited number of patients who were given the drug during the last trimester of pregnancy, low birth weight, neonatal hypoglycemia, bradycardia in the fetus/newborn, and placental insufficiency were observed.

Neonates born to mothers who are receiving atenolol at parturition or breast-feeding may be at risk for hypoglycemia and bradycardia. Caution should be exercised when atenolol is administered during pregnancy or to a woman who is breast-feeding (see Precautions, Lactation).

Atenolol has been shown to produce a dose-related increase in embryo/fetal resorptions in rats at doses equal to or greater than 50 mg/kg/day or 25 or more times the maximum recommended human dose.

mesenteric arterial thrombosis and ischemic colitis.

laryngospasm, status asthmaticus and fever combined with aching and sore throat.

aggressiveness, anxiety, short-term memory loss, and emotional lability with slightly clouded sensorium.

skin rash, itchy and/or dry eyes, psoriasiform skin reactions, exacerbation of psoriasis, decreased exercise tolerance, alopecia, epistaxis, flushes, impotence, decreased libido, sweating, general body aches, thrombocytopenia and purpura.

dyspnea, wheeziness, cough, bronchospasm.

blurred vision, burning, and grittiness.

agranulocytosis.

exfoliative dermatitis.

pulmonary edema, cardiac enlargement, hot flushes and sinus arrest.

During the postmarketing experience with Tenormin, cold extremities, gastrointestinal disturbances and fatigue were commonly reported. The following have been reported in temporal relationship to the use of the drug: elevated liver enzymes and/or bilirubin, headache, confusion, nightmares, impotence, Peyronie's disease, psoriasiform rash or exacerbation of psoriasis, purpura, reversible alopecia and thrombocytopenia. Rare cases of hepatic toxicity including intrahepatic cholestasis have been reported. Tenormin, like other β-blockers, has been associated with the development of antinuclear antibodies (ANA) and lupus syndrome.

In a long-term, well-controlled trial of 1627 elderly patients with systolic hypertension, the incidence of dry mouth was significantly higher in patients taking atenolol (12.2%).

Potential Adverse Reactions: The following adverse reactions have occurred with other β-blockers but have not been reported with atenolol:

Limited information is available with regard to overdosage with atenolol in humans. Overdosage with atenolol has been reported with patients surviving acute doses as high as 5 g. One death was reported in a man who may have taken as much as 10 g acutely.

The predominant symptoms reported following atenolol overdosage are lethargy, disorder of respiratory drive, wheezing, sinus pause and bradycardia. Additionally, common effects associated with overdosage of any β-adrenergic blocking agent are congestive heart failure, hypotension, bronchospasm and/or hypoglycemia.

Treatment should be symptomatic and supportive and directed to the removal of any unabsorbed drug by induced emesis, or administration of activated charcoal. Atenolol can be removed from the general circulation by hemodialysis. Further consideration should be given to dehydration, electrolyte imbalance and hypotension by established procedures.

Other treatment modalities should be employed at the physician's discretion and may include:

Bradycardia: Atropine 1-2 mg intravenously. If there is no response to vagal blockade, give isoproterenol cautiously. In refractory cases, a transvenous cardiac pacemaker may be indicated. Glucagon in a 10 mg intravenous bolus has been reported to be useful. If required, this may be repeated or followed by an intravenous infusion of glucagon 1-10 mg/h depending on response. If no response to glucagon occurs or if glucagon is unavailable, a beta-adrenoceptor stimulant such as dobutamine 2.5 to 10 µg/kg/minute by intravenous infusion or isoproterenol 10 to 25 µg given as an infusion at a rate not exceeding 5 µg/minute may be given, although larger doses may be required.

Heart Block (second or third degree): Isoproterenol, or transvenous pacemaker.

Congestive Heart Failure: Digitalize the patient and administer a diuretic. Glucagon has been reported to be useful.

Hypotension: Vasopressors such as dopamine or norepinephrine. Monitor blood pressure continuously.

Bronchospasm: A β₂-stimulant such as isoproterenol or terbutaline and/or intravenous aminophylline.

Hypoglycemia: Intravenous glucose.

Based on the severity of symptoms, management may require intensive support care and facilities for applying cardiac and respiratory support.