In the event of overdosage, nadolol may cause excessive bradycardia, cardiac failure, hypotension, or bronchospasm.
Transitory increase in BUN has been reported, and serum electrolyte changes may occur, especially in patients with impaired renal function.
Treatment
Nadolol can be removed from the general circulation by haemodialysis. In determining the duration of corrective therapy, note must be taken of the long duration of the effect of nadolol.
In addition to gastric lavage, the following measures should be employed, as appropriate:
Excessive Bradycardia - Administer atropine (0.25 to 1.0 mg). If there is no response to vagal blockade, administer isoprenaline cautiously.
Cardiac Failure - Administer a digitalis glycoside and diuretic. It has been reported that glucagon may also be useful in this situation.
Hypotension - If fluid administration is ineffective, administer vasopressors such as dopamine, dobutamine or adrenaline.
Bronchospasm - Administer a beta-2-agonist agent and/or a theophylline derivative.
Stupor or coma - Supportive therapy as warranted.
Gastrointestinal Effects - Symptomatic treatment as needed.
BUN and/or Serum Electrolyte Abnormalities - Institute supportive measures as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function.
-
- Bronchial asthma or a history of asthma
- Sinus bradycardia
- Greater than first degree atrioventricular conduction block
- Cardiogenic shock
- Right ventricular failure secondary to pulmonary hypertension
- - Special warnings and precautions for use)
- Previously demonstrated hypersensitivity to nadolol
Not applicable.
The following CIOMS frequency rating is used, when applicable:
Very common > 10 %; Common > 1 % and < 10 %;
Uncommon > 0.1 % and < 1 %; Rare > 0.01 % and < 0.1 %;
Very rare < 0.01%; Unknown (cannot be estimated from available data);
Most adverse effects have been mild and transient and have rarely required withdrawal of therapy. The percentages given below were based on a population of 1440 patients taking nadolol in clinical trials.
| System organ class | Very common (> 10 %) | Common (> 1 % and < 10 %) | Uncommon (> 0.1 % and < 1 %) | Rare (> 0.01 % and < 0.1 %) | Very rare (< 0.01%) | Frequency not known (cannot be estimated from available data)* |
| Cardiac disorders | Bradycardia (heart rate <60 BPM) Heart rate <40 BPM and or symptomatic bradycardia (approx. 2%) Cardiac failure Rhythm/conduction disturbances (about 1%) | First degree and third degree heart block Intensification of AV block is a known effect of beta-blockers (see also section 4.3 Contra-indications, and section 4.4 Special warnings and precautions for use) | ||||
| Vascular disorders | Symptoms of peripheral vascular insufficiency usually of the Raynaud type (approx. 2%) Hypotension (about 1%) | |||||
| Nervous System Disorders | Dizziness (approx. 2%) | Paraesthesias and sedation (approx. 0.6%) Headache and slurred speech (0.1 to 0.5%) | Light-headedness | |||
| General disorders and administration site conditions | Fatigue (approx. 2%) | Cold extremities | ||||
| Psychiatric disorders | Change in behaviour (approx. 2%) | Insomnia | ||||
| Gastrointestinal disorders | Nausea, diarrhoea, abdominal discomfort, constipation, vomiting, indigestion, bloating and flatulence (0.1-0.5%) Dry mouth (0.1 - 0.5%) | |||||
| Metabolism and nutrition disorders | Anorexia (0.1% to 0.5%) | Hypoglycemia in neonates, infants, children, elderly patients, patients on haemodialysis, patients on concomitant anti-diabetic therapy, patients with prolonged fasting and patients with chronic liver disease has been reported | ||||
| Respiratory, thoracic and mediastinal disorders | Cough and nasal stiffness (0.1% to 0.5%). Bronchospasm (approx. 0.1%) (see section 4.3 ). | |||||
| Skin and subcutaneous tissue disorders | Rash, pruritus; dry skin; facial swelling and sweating 0.1% to 0.5%) | Reversible alopaecia (has been reported infrequently) | ||||
| Investigations | Weight gain (0.1% to 0.5% of patients | |||||
| Reproductive system and breast disorders | Impotence or decreased libido (0.1% to 0.5%) | |||||
| Eye disorder | Dry eyes and blurred vision (0.1% to 0.5%) | |||||
| Ear and labyrinth disorders | Tinnitus (0.1% to 0.5%) |
The events listed below have also occurred with nadolol and/or other beta-adrenergic blocking agents; however, no causal relationship to nadolol was established:
Psychiatric disorders - Reversible depression progressing to catatonia; hallucinations; an acute reversible syndrome characterised by disorientation for time and place, emotional lability, and decreased performance on neuropsychologic tests.
Eye Disorders - Visual disturbances
Nervous system disorders - An acute reversible syndrome characterised by short term memory loss and slightly clouded sensorium.
Gastrointestinal disorders - Ischaemic colitis
Vascular disorders - Mesenteric arterial thrombosis
Investigation - Elevated liver enzymes
Blood and lymphatic system disorders - Agranulocytosis and thrombocytopaenic purpura.
Skin and subcutaneous tissue disorders - Non-thrombocytopaenic purpura; pemphigoid rash
General disorders and administration site conditions - Fever combined with aching.
Immune System Disorders - Hypertensive reaction in patients with pheochromocytoma; sleep disturbances; Peyronie's disease.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
None stated.
Nadololo Sanofi-Aventis is indicated in the management of:
Angina Pectoris:
For the long-term management of patients with angina pectoris by continuous medication.
Hypertension:
For the long-term management of essential hypertension, either alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.
Arrhythmias:
For the treatment of cardiac tachyarrhythmias.
Migraine:
For the prophylactic management of migraine headache. The efficacy of Nadololo Sanofi-Aventis in the treatment of a migraine attack that has already started has not been established, and Nadololo Sanofi-Aventis is not indicated for such use.
Thyrotoxicosis:
For the relief of the symptoms of hyperthyroidism and the pre- operative preparation of patients for surgery. Nadolol may be used in conjunction with conventional antithyroid therapy.
Pharmacotherapeutic group: Beta blocking agents; Beta blocking agents, non-selective.
ATC code: C07AA12
Nadolol is a beta-adrenergic receptor blocking agent with a prolonged activity, permitting once-daily dosage in angina, hypertension, cardiac arrhythmias, the prophylaxis of migraine, and the relief of hyperthyroid symptoms.
Nadolol is not metabolised. It has no membrane stabilising or intrinsic sympathomimetic activity, and its only effect on the autonomic nervous system is one of beta-adrenergic blockade. Nadolol is nonselective.
Receptor blockade by nadolol results in protection from excessive inappropriate sympathetic activity. Nadolol reduces the number and severity of attacks of angina pectoris by blocking response to catecholamine stimulation and thus lowers the oxygen requirement of the heart at any given level of effort.
Nadolol reduces both supine and erect blood pressure. Like other beta-blockers nadolol exerts an antiarrhythmic action. Nadolol has been shown to reduce the rapid ventricular response which accompanies atrial fibrillation/flutter by slowing conduction through the A-V node. Beta-blockade is of particular value in arrhythmias caused by increased levels of, or sensitivity of the heart to, circulating catecholamines, e.g. arrhythmias associated with phaeochromocytoma, thyrotoxicosis, or exercise. Nadolol is effective in reducing ventricular premature beats in selected patients.
Nadolol exerts an effect in the prophylaxis of migraine by a mechanism which may involve prevention of vasoconstriction in the area served by the internal carotid artery and prevention of excessive adrenergic vasodilation in the external carotid artery.
Nadolol alleviates the symptoms of thyrotoxicosis and provides symptomatic control before and during thyroid surgery.
Beta-blocking agents have been shown in large scale studies to reduce mortality by preventing reinfarction and sudden death in patients surviving their first myocardial infarction.
Absorption: About 30 percent of an oral dose of Nadololo Sanofi-Aventis is absorbed. The presence of food in the gastrointestinal tract does not affect the rate or extent of Nadololo Sanofi-Aventis absorption.
Distribution: Peak serum concentrations usually occur in 3 to 4 hours after drug administration. Approximately 30 percent of the Nadololo Sanofi-Aventis present in serum is reversibly bound to plasma protein.
Biotransformation: Nadololo Sanofi-Aventis is not metabolised.
Elimination: Unlike most available beta-blocking agents, Nadololo Sanofi-Aventis is not metabolised, and is excreted unchanged principally by the kidneys. The serum half-life of therapeutic doses of Nadololo Sanofi-Aventis is relatively long, ranging from 20 to 24 hours (permitting once daily dosage).
Characteristics in specific groups of subjects or patients: A significant correlation between minimum steady-state serum concentrations of Nadololo Sanofi-Aventis and total oral daily dose has been demonstrated in hypertensive patients; however, the observed dose-response range is wide and proper dosage requires individual titration.
- Previously demonstrated hypersensitivity to nadolol
4.4 Special warnings and precautions for useWarnings
Exacerbation of Ischaemic Heart Disease Following Abrupt Withdrawal
Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina, hypertension, and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy.2 Posology and method of administration).
Nonallergic Bronchospasm (e.g. chronic bronchitis, emphysema) - Patients with bronchospastic diseases should not, in general, receive beta-blockers since they may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta receptors.
(NOTE: Nadololo Sanofi-Aventis is contra-indicated in asthmatic patients.)
Diabetes and Hypoglycaemia - Beta-adrenergic blockade may prevent the appearance of warning signs and symptoms (e.g. tachycardia and blood pressure changes) of acute hypoglycaemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycaemia; therefore, it may be necessary to adjust the dose of anti-diabetic drugs.
Occasionally causes hypoglycaemia, even in non-diabetic patients, e.g., neonates, infants, children, elderly patients, patients on haemodialysis or patients suffering from chronic liver disease and patients suffering from overdose. Severe hypoglycaemia associated with nadolol has rarely presented with seizures and/or coma in isolated patients.
Skin Rashes - There have been reports of skin rashes (including a psoriasiform type) and/or ocular changes (conjunctivitis and `dry eye') associated with the use of beta-adrenergic blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when the treatment was withdrawn. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. Cessation of the therapy with a beta-adrenergic blocker should be gradual.
Treatment for Anaphylactic Reaction - While taking beta-blockers, patients with a history of severe anaphylactic reaction may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
(NOTE: Epinephrine combined with non cardio-selective beta blockers such as nadolol can cause a hypertensive episode followed by bradycardia.)
Thyrotoxicosis - Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism (e.g. tachycardia). Abrupt withdrawal of nadolol in thyroid patients can precipitate thyroid storm.
Precautions
Occasionally, beta-blockade with drugs such as nadolol may produce hypotension and/or marked bradycardia, resulting in vertigo, syncope or orthostatic hypotension.
Impaired Renal or Hepatic Function - ).
Carcinogenesis, Mutagenesis, Impairment of Fertility - In chronic oral toxicologic studies lasting one to two years, nadolol did not produce any significant toxic effects in mice, rats, or dogs. In two-year oral carcinogenic studies in rats and mice, nadolol did not produce any neoplastic, pre-neoplastic, or non-neoplastic pathologic lesions. In fertility and general reproductive performance studies in rats, nadolol caused no adverse effects.
Stress tests - Beta blockers including nadolol significantly affect the accuracy of all types of stress tests.
There are no studies on the effect of this medicine on the ability to drive. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur.
Adults:
Dosage should be titrated gradually with at least a week between increments to assess response; individuals show considerable variation in their response to beta-adrenergic blockade.
Nadololo Sanofi-Aventis may be given in a once daily dosage without regard to meals. The dosage interval should be increased when creatinine clearance is below 50ml/min/1.73m2.
If Nadololo Sanofi-Aventis is to be discontinued, reduce dosage over a period of at least two weeks (see warnings).
Angina pectoris: | Initially 40mg once daily. This may be increased at weekly intervals until an adequate response is obtained or excessive bradycardia occurs. Most patients respond to 160mg or less daily. The value and safety of daily doses exceeding 240mg have not been established. |
Hypertension: | Initially 80mg once daily. This may be increased by a weekly increment of 80mg or less until an optimum response is obtained. Many patients respond to 80mg daily, and most patients respond to 240mg or less, daily, but higher doses have been required for a few patients. In some patients it is necessary to administer a diuretic, peripheral vasolidator and/or other antihypertensive agents in conjunction with nadolol in order to achieve satisfactory response. Treatment of hypertension associated with phaeochromocytoma may require the addition of an alpha-blocking agent. |
| Cardiac tachyarrhythmias: | |
Initially 40mg once daily. This may be increased if necessary to 160mg once daily. If bradycardia occurs dosage should be reduced to 40mg once daily. | |
Migraine: | The initial dose of nadolol is 40mg once daily. Dosage may be gradually increased in 40mg increments until optimum migraine prophylaxis is achieved. The usual maintenance dose is 80 to 160mg administered once daily. After 4 to 6 weeks at the maximum dose if a satisfactory response is not obtained, therapy with nadolol should be withdrawn gradually. |
Thyrotoxicosis: | The dosage range is 80-160mg once daily. It has been found that most patients require a dose of 160mg once daily. Nadolol may be used together with conventional anti-thyroid treatment. For the preparation of patients for partial thyroidectomy, nadolol should be administered in conjunction with potassium iodide for a period of 10 days prior to operation. Nadolol should be administered on the morning of operation. Post-operatively, nadolol dosage should be slowly reduced and then withdrawn following clinical stability. |
Paediatric population:
The safety and efficacy of nadolol in children has not been established.
Elderly:
In elderly patients a low initial dose should be used so that sensitivity to side-effects may be assessed.
Renal or hepatic impairment
As with all drugs patients with impaired renal or hepatic function should be monitored.
No special requirements
