Active ingredients: Nadolol
NADOLOLO SANOFI 80 mg tablets - 30 tablets
Why is Nadolol used? What is it for?
Pharmacotherapeutic group
Non-selective, non-associated beta-blockers.
Therapeutic indications
Hypertension: alone or in combination with other antihypertensive drugs, in the long-term treatment of essential hypertension. Nadolol is less effective in the treatment of acute hypertension crises.
Angina pectoris: Long-term treatment of patients with angina pectoris who have not responded adequately to a conventional approach (e.g., weight control, rest, smoking cessation, use of sublingual nitroglycerin and removal of triggers).
Arrhythmias: paroxysmal atrial tachycardia, paroxysmal atrial fibrillation, ventricular and supraventricular extrasystoles, cardiovascular manifestations of hyperthyroid glands, functional signs of obstructive cardiomyopathy.
Contraindications When Nadolol should not be used
- hypersensitivity to the active substance or any of the excipients;
- bronchial asthma / bronchospasm;
- allergic rhinitis during the pollen season;
- sinus bradycardia and atrioventricular block greater than that of first degree;
- cardiogenic shock;
- right ventricular failure secondary to pulmonary hypertension;
- manifest heart failure (see Precautions for use);
- patients treated with catecholamine-enhancing psychotropic drugs (including MAOIs) and during the two weeks following discontinuation of this type of drug (see Interactions).
Precautions for use What you need to know before taking Nadolol
Exacerbation of coronary ischemic disease following abrupt withdrawal: Progressive dose reduction is not strictly necessary in hypertensive patients without manifestations of coronary insufficiency. However, it may be prudent not to abruptly discontinue nadolol treatment, even in patients being treated for hypertension alone, as coronary artery disease is common and often silent.
On the other hand, in the case of patients suffering from angina pectoris or other manifestations of coronary arterial insufficiency, the abrupt interruption of therapy with beta-blocking drugs can lead to worsening of angina and facilitate the onset of a myocardial infarction. In such patients, discontinuation of long-term nadolol treatment is envisaged, the dosage should be reduced gradually over a period of at least two weeks and the patient carefully monitored. nadolol administration should be resumed immediately, at least temporarily, and appropriate therapy for unstable angina should be instituted. In addition, the anginal patient should be informed of the risks involved in the event of abrupt interruption or suspension of nadolol therapy without having previously consulted your doctor. If you miss a dose, it is important to:
- do not double the next dose;
- do not take the one not taken if the next is expected within the next 8 hours.
Heart failure: Cases of heart failure have rarely been reported with nadolol. It should also be taken into consideration that sympathetic stimulation is a vital component in supporting circulatory function in congestive heart failure and that the inhibition of this stimulation by beta-block involves the risk of precipitating the insufficiency. Therefore, at the first sign or symptom of impending heart failure, the patient must be adequately scanned and the response to the drug carefully monitored.
The use of nadolol in patients with heart failure is recommended only in case of good clinical compensation, already on therapy with diuretics or digitalis. The patient should consult the doctor at the first symptoms or signs of heart failure.
Nadolol does not inhibit the inotropic action of digitalis on the heart muscle.
Major surgery: Beta-blocking drugs can alter the cardiac reflex response to stimuli and can increase the risks associated with general anesthesia and surgical procedures by generating prolonged hypotension or low cardiac output. Nadolol therapy should be discussed with the anesthetist prior to general anesthesia. If inhibition of sympathetic tone is deemed undesirable, nadolol may be discontinued (see warnings above for patients with coronary artery disease). In an emergency, the anesthetist should be advised that the patient is being treated with beta blockers.
Where beta-blockade is considered desirable or drug withdrawal is impractical, the chosen anesthetic should be as least as possible with negative inotropic activity and the patient completely atropinized.
Chronic obstructive pulmonary disease (e.g. chronic bronchitis, emphysema): nadolol should be administered with caution since it can inhibit bronchodilation caused by stimulation on beta2 receptors by endogenous and exogenous catecholamines.
Diabetes and Hypoglycemia: Beta-receptor blockade can prevent the onset of the warning signs and symptoms (alteration of heart rate and blood pressure) that accompany acute hypoglycemia. This is particularly important in unstable forms of diabetes. The diabetic patient must. therefore be advised of this and that nadolol can alter blood glucose levels Beta-blockade also reduces insulin release in response to hyperglycaemia, therefore dosage adjustment of antidiabetic drugs may be necessary.
Thyrotoxicosis: Beta-blockers may mask some clinical symptoms of hyperthyroidism (e.g. tachycardia). In such patients, abrupt discontinuation of treatment may result in a thyroid storm.
Treatment of anaphylactic reactions: in the course of treatment with beta-blockers, the patient with a clinical history of severe anaphylactic reactions may have a more severe allergic reaction in the case of a new contact with allergenic substances. Therefore, patients with allergies to food, medication or insect bites should consult a physician upon the onset of severe allergies. In addition, such patients may be less sensitive to the usual doses of epinephrine used to treat anaphylactic reactions.
Stress Testing: Beta blockers, including nadolol, can significantly affect the accuracy of all types of exercise testing.
Pediatric Use: The efficacy of nadolol and its safety in use have not been adequately evaluated in pediatric subjects.
Concomitant use of antiadrenergic drugs: patients treated with catecholamine-depleting drugs, such as eg. reserpine, must be scrupulously monitored if undergoing therapy with nadolol. The additional beta-blocking activity of nadolol may in fact cause an "excessive reduction" of the autonomic nervous system activity at rest.
Occasionally, beta-blockade with drugs such as nadolol can cause hypotension and / or marked bradycardia resulting in dizziness, syncopal attacks, or orthostatic hypotension.
In these cases, as well as in the event that granulocytopenia, thrombocytopenic purpura, rash appear, it is necessary to interrupt the therapy and immediately contact the doctor who will be able to establish a suitable treatment.
Interactions Which drugs or foods can modify the effect of Nadolol
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The following drugs can interact with beta blockers when given concurrently:
Anesthetics: Beta-blockers may increase hypotension induced by general anesthetics, therefore nadolol therapy should be reported prior to general anesthesia (see Precautions for use).
Antidiabetic drugs (oral hypoglycemic agents and insulin): beta-blockers can alter the response of antidiabetic drugs by inducing both hyperglycemia and hypoglycemia. Dosage adjustment is required (see Precautions for use).
Antimuscarinic agents: can counteract the bradycardia induced by beta-blockers.
Calcium antagonists: generally potentiate the antihypertensive action of beta-blockers. In the case of combining the two treatments, the patient will be carefully monitored for the potential onset of undesirable cardiovascular events.
Antiadrenergic drugs (eg reserpine): can have additive effects with beta-blockers. Patients treated with both drugs may show signs and symptoms of hypotension and / or bradycardia (eg, dizziness, syncope, postural hypotension) (see Precautions for use).
Other antiarrhythmic drugs: Both additive and antagonistic effects are possible.
Fingolimod: Concomitant use of fingolimod with beta-blockers may potentiate its bradycardic effects and is not recommended. If such co-administration is deemed necessary, appropriate monitoring is recommended at the start of treatment, and at least until the next morning.
Other antihypertensive drugs / diuretics: pay attention to potential additive effects.
Lidocaine i.v .: In the case of concomitant administration of beta-blockers, a reduction in the clearance of lidocaine may occur.
MAO inhibitors: sporadic cases of bradycardia have been observed during concomitant administration of beta-blockers and MAOIs (see Contraindications).
NSAIDs: the antihypertensive effect of beta-blockers can be reduced by NSAIDs and by the administration of indomethacin.
Phenothiazines and other antipsychotics: Additive effects on the antihypertensive activity of beta-blockers have been observed when administered concomitantly with phenothiazines or haloperidol.
Vasoconstrictors: sometimes it is possible to find an additive effect, eg. in association with ergot alkaloids.
Warnings It is important to know that:
The drug should be administered with particular caution to patients with impaired hepatic or renal function (see also Dose, method and time of administration), avoiding its use in severe forms.
As with any drug administered over long periods of time, it is necessary to check the progress of laboratory parameters (blood count, liver, kidney, respiratory function) at regular intervals.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
No adequate and well-controlled clinical studies have been conducted to indicate beta-blocker treatment in pregnancy. Therefore nadolol should be used during pregnancy only if the expected benefits outweigh the potential risks to the fetus and under the direct supervision of the physician.
Cases of fetal growth retardation have been reported. Infants of mothers taking beta-blockers have sometimes experienced bradycardia, hypoglycemia, respiratory failure and associated symptoms at delivery.
Feeding time
Nadolol is excreted in breast milk and has the potential to induce adverse events in the newborn. Therefore the decision to treat the mother, which implies the suspension of breastfeeding, must be carefully evaluated in the light of the importance of nadolol for the mother herself.
For those who play sports:
The use of the drug without therapeutic necessity constitutes doping, it can in any case determine positive anti-doping tests and can harm health.
Effects on ability to drive and use machines
For possible side effects such as dizziness, the medicine may affect the ability to drive and use machines.
Dosage and method of use How to use Nadolol: Dosage
Dosage must be established individually.
The administration of nadolol is independent of food intake.
Hypertension: The starting dose is usually 40 mg once daily, either as monotherapy or in combination with diuretic therapy. The dosage can be gradually increased in 40-80 mg increments until optimal blood pressure is achieved. In some cases, doses of up to 240-320 mg in a single daily dose may be needed.
Angina pectoris: The starting dose is usually 40 mg once a day. Dosage may be gradually increased in 40-80 mg increments at intervals of 3-7 days until an optimal clinical response is achieved or marked bradycardia develops. In some cases, doses of up to 160-240 mg in a single daily dose may be needed.
The therapeutic utility and tolerability of doses above 240 mg / day in the treatment of angina pectoris have not been established. If treatment is to be discontinued, the dosage should be reduced gradually over at least two weeks (see Precautions for use).
Arrhythmias: starting with 40 mg administered as a once daily dose, the dosage may be increased, if necessary, up to 160 mg. If bradycardia occurs, the dosage should be reduced to 40 mg in a single daily administration.
Patients with impaired renal function: Since nadolol is mainly excreted via the kidney, an adjustment of the dosage and the interval between doses is necessary in case of renal insufficiency. The following intervals are recommended:
Elderly patients
Dosage adjustment may be necessary in elderly subjects with decreased renal function.
Overdose What to do if you have taken an overdose of Nadolol
In the event of overdose or exaggerated responses, the assessment of the duration of corrective therapy must take into account the long duration of the effect of nadolol. In addition to gastric lavage, the following measures should be taken.
Bradycardia: In case of excessive bradycardia resulting from therapy with beta-blocking drugs, atropine (0.25-1 mg) is administered. If no response to vagal blockage is observed, administer isoproterenol with caution.
Heart failure: administer digitalis and diuretics. It has also been reported that glucagon may be useful in these cases.
Hypotension: If fluid administration is ineffective, administer vasopressors such as dopamine, dobutamine, isoproterenol or norepinephrine or epinephrine. (There is reason to believe that the drug of choice is norepinephrine).
Bronchospasm: administer a beta2 agonist and / or derivatives of theophylline. Nadolol can be eliminated from the general circulation by means of hemodialysis. With this procedure, the clearance of nadolol ranges from 40 to 100 mL per minute. In case of accidental ingestion / intake of an excessive dose of Nadolol Sanofi, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Nadolol sanofi, ask your doctor or pharmacist.
Side Effects What are the side effects of Nadolol
Like all medicines, Nadolol sanofi can cause side effects, although not everybody gets them.
Below are the side effects of nadolol. Estimated frequencies of events are based on the following convention: common (≥ 1/100,
The data below are derived from clinical studies involving 1440 patients receiving nadolol.
Cardiovascular pathologies
Common:
- bradycardia below 60 bpm
- marked bradycardia (
- peripheral vascular insufficiency (often Raynaud type)
- Heart failure, hypotension and cardiac conduction disturbances
Rare:
- 1st and 3rd degree AV block (according to the slowing mechanism of atrioventricular conduction of beta-blockers - see Contraindications and Precautions for use)
Nervous system disorders
Common:
- asthenia
- dizziness
Uncommon:
- paraesthesia
- sedation and behavioral alterations
- headache
- confused speech
Ear and labyrinth disorders
Uncommon:
- tinnitus
Respiratory, thoracic and mediastinal disorders
Uncommon:
- bronchospasm
- cough
- nasal occlusion
Gastrointestinal disorders
Uncommon:
- nausea, diarrhea, vomiting
- abdominal pain
- constipation
- indigestion
- anorexia
- abdominal bloating
- flatulence
- dry mouth
Disorders of the immune system
Uncommon:
- skin rash, itching
Eye disorders
Uncommon:
- dry eyes
- blurred vision
Skin and subcutaneous tissue disorders
Uncommon:
- dry skin
- sweating
- facial swelling
Rare:
- reversible alopecia
Diseases of the reproductive system and breast
Uncommon:
- reduced libido
- impotence
Metabolism and nutrition disorders
Uncommon:
- weight gain
The undesirable effects listed below have been observed during treatment with nadolol or with other beta-blockers, without a causal relationship being established.
Nervous system disorders
- Reversible depression with evolution towards catatonia, visual disturbances, hallucinations, acute reversible syndrome characterized by spatio-temporal disorientation, short-term amnesia, emotional lability, mild sensory blunting, reduced performance on neuropsychological tests. Sleep disorders.
Gastrointestinal disorders
- Thrombosis of the mesenteric artery, ischemic colitis, increased liver enzymes.
Disorders of the blood and lymphatic system
- Agranulocytosis, thrombocytopenia, non-thrombocytopenic purpura.
Disorders of the immune system
- Pharyngodynia and fever, laryngospasm, respiratory disorders. Pemphigoid rash
Cardiovascular pathologies
- Hypertensive crisis in subjects with pheochromocytoma
Musculoskeletal and connective tissue disorders
- Peyronie's disease
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
The expiry date refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.
Other information
Composition
One tablet contains:
- Active ingredient: nadolol 80 mg
- Excipients: Magnesium stearate, microcrystalline cellulose
Pharmaceutical form and content
Tablets.
Carton containing 30 tablets of 80 mg.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
NADOLOLO SANOFI 80 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains:
Active principle: nadolol 80 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Hypertension: as monotherapy or in combination with other antihypertensive drugs, in the long-term treatment of essential hypertension. Nadolol is less effective in the treatment of acute hypertension crises.
Angina pectoris: Long-term treatment of patients with angina pectoris who have not responded adequately to a conventional approach (e.g., weight control, rest, smoking cessation, use of sublingual nitroglycerin and removal of triggers).
Arrhythmias: paroxysmal atrial tachycardia, paroxysmal atrial fibrillation, ventricular and supraventricular extrasystoles, cardiovascular manifestations of hyperthyroid glands, functional signs of obstructive cardiomyopathy.
04.2 Posology and method of administration
Dosage must be established individually
The administration of nadolol is independent of food intake.
Hypertension: The starting dose is usually 40 mg once a day, either as monotherapy or in combination with diuretic therapy. The dosage can be gradually increased in 40-80 mg increments until optimal blood pressure is achieved. In some cases, doses of up to 240-320 mg in a single daily dose may be needed.
Angina pectoris: The starting dose is usually 40 mg once a day. Dosage may be gradually increased in 40-80 mg increments at intervals of 3-7 days until an optimal clinical response is achieved or marked bradycardia develops. In some cases, doses up to 160-240 mg in a single daily dose may be needed. The therapeutic utility and tolerability of doses above 240 mg / day in the treatment of angina pectoris have not been determined. be discontinued, the dosage should be reduced gradually over at least two weeks (see section 4.4).
Arrhythmias: starting with 40 mg administered as a once daily dose, the dosage may be increased, if necessary, to 160 mg. If bradycardia occurs, the dosage should be reduced to 40 mg in a single daily administration.
Patients with impaired renal function: Since nadolol is mainly excreted via the kidney, an adjustment of the dosage and the interval between doses is necessary in case of renal insufficiency. The following intervals are recommended:
Elderly patients
dosage adjustment may be necessary in elderly subjects with decreased renal function.
04.3 Contraindications
- hypersensitivity to the active substance or to any of the excipients
- bronchial asthma / bronchospasm;
- allergic rhinitis during the pollen season;
- sinus bradycardia and atrioventricular block greater than that of the first degree;
- cardiogenic shock;
- right ventricular failure secondary to pulmonary hypertension;
- manifest heart failure (see section 4.4);
- patients treated with catecholamine-enhancing psychotropic drugs (including MAOIs) and during the two weeks following discontinuation of this type of drug (see section 4.5).
04.4 Special warnings and appropriate precautions for use
As with any drug administered over long periods of time, it is necessary to check the progress of laboratory parameters (blood count, liver, kidney, respiratory function) at regular intervals.
The drug should be administered with particular caution to patients with impaired hepatic or renal function (see also section 4.2), avoiding its use in severe forms.
Coronary ischemic disease exacerbation following abrupt withdrawal: Progressive dose reduction is not strictly necessary in hypertensive patients without manifestations of coronary insufficiency. However, it may be prudent not to abruptly discontinue nadolol treatment, even in patients being treated for hypertension alone, as coronary artery disease is common and often silent.
On the other hand, in the case of patients suffering from angina pectoris or other manifestations of coronary arterial insufficiency, the abrupt interruption of therapy with beta-blocking drugs can lead to worsening of angina and facilitate the onset of a myocardial infarction. . When discontinuation of long-term nadolol treatment is envisaged in such patients, the dosage should be gradually reduced over at least two weeks and the patient closely monitored. If angina worsens markedly or acute coronary insufficiency occurs. , nadolol administration should be resumed immediately, at least temporarily, and appropriate therapy for unstable angina instituted. In addition, the anginal patient should be informed of the risks involved in the event of abrupt interruption or discontinuation of nadolol therapy without have previously consulted the doctor If a dose is missed, the patient should be a warned of:
a) do not double the next dose;
b) do not take the one not taken if the next one is expected within the next 8 hours.
Heart failureCases of heart failure have been reported rarely with nadolol. It should also be taken into consideration that sympathetic stimulation is a vital component in supporting circulatory function in the course of congestive heart failure and that the inhibition of this stimulation by beta-block involves the risk of precipitating heart failure. . Therefore, at the first sign or symptom of impending heart failure, the patient must be properly scanned and the response to the drug carefully monitored. If the state of heart failure persists, nadolol therapy should be discontinued, taking into account the previous warning.
The use of nadolol in patients with heart failure is recommended only in case of good clinical compensation, already on therapy with diuretics or digitalis. The patient is invited to consult the doctor at the first symptoms or signs of heart failure.
Nadolol does not inhibit the inotropic action of digitalis on the heart muscle.
Major surgery: Beta-blocking drugs can alter the cardiac reflex response to stimuli and can increase the risks associated with general anesthesia and surgical procedures by generating prolonged hypotension or low cardiac output. Nadolol therapy should be discussed with the anesthetist prior to general anesthesia. If inhibition of sympathetic tone is deemed undesirable, nadolol may be discontinued (see warnings above for patients with coronary artery disease). In an emergency, the anesthetist should be advised that the patient is being treated with beta blockers. Where beta-blockade is considered desirable or drug withdrawal is impractical, the chosen anesthetic should be as least as possible with negative inotropic activity and the patient completely atropinized.
Chronic obstructive pulmonary disease (e.g. chronic bronchitis, emphysema): nadolol should be administered with caution since it can inhibit bronchodilation caused by stimulation on beta2 receptors by endogenous and exogenous catecholamines.
Diabetes and hypoglycemia: Blockade of beta-receptors can prevent the onset of the warning signs and symptoms (alteration of heart rate and blood pressure) that accompany acute hypoglycemia. This is particularly important in unstable forms of diabetes. The diabetic patient should therefore be warned of this and the fact that nadolol can alter blood glucose levels Beta-blockade also reduces insulin release in response to hyperglycaemia, so adjustments in the dosage of antidiabetic drugs may be necessary.
Thyrotoxicosis: Beta-blockers may mask some clinical symptoms of hyperthyroidism (e.g. tachycardia). In such patients, abrupt discontinuation of treatment may result in a thyroid storm.
Treatment of anaphylactic reactions: in the course of treatment with beta-blockers, the patient with a clinical history of severe anaphylactic reactions may have a more severe allergic reaction in the case of a new contact with allergenic substances. Therefore, patients with allergies to food, medication or insect bites should be advised to consult a physician upon the onset of severe allergies. In addition, such patients may be less sensitive to the usual doses of epinephrine used to treat anaphylactic reactions.
Stress test: beta blockers, including nadolol, can significantly affect the accuracy of all types of exercise testing.
Use in pediatrics: The efficacy of nadolol and its safety in use have not been adequately evaluated in pediatric subjects.
Concomitant use of antiadrenergic drugs: patients treated with catecholamine-depleting drugs, such as eg. reserpine, must be scrupulously monitored if undergoing therapy with nadolol. The additional beta-blocker activity of nadolol may in fact cause an "excessive reduction" of the autonomic nervous system activity at rest. , syncopal attacks or orthostatic hypotension. In this case, as well as in the event that granulocytopenia, thrombocytopenic purpura, rash appear, it is necessary to interrupt the therapy and institute a suitable treatment.
04.5 Interactions with other medicinal products and other forms of interaction
The following drugs can interact with beta blockers when given concurrently:
Anesthetics: Beta-blockers may increase hypotension induced by general anesthetics, therefore therapy with nadolol should be reported before general anesthesia (see section 4.4).
Antidiabetic drugs (oral hypoglycemic agents and insulin): Beta-blockers can alter the response of antidiabetic drugs inducing both hyperglycemia and hypoglycemia. Dosage adjustment is required (see section 4.4).
Antimuscarinic agents: they can counteract the bradycardia induced by beta-blockers.
Calcium channel blockers: generally potentiate the antihypertensive action of beta-blockers. In the case of combining the two treatments, the patient will be carefully monitored for the potential onset of undesirable cardiovascular events.
Antiadrenergic drugs (e.g. reserpine): may have additive effects with beta-blockers. Patients treated with both drugs may show signs and symptoms of hypotension and / or bradycardia (e.g. dizziness, syncope, postural hypotension) (see section 4.4).
Other antiarrhythmic drugs: both additive and antagonistic effects are possible.
Other antihypertensive / diuretic drugs: Pay attention to potential additive effects.
Lidocaine i.v.: In the case of concomitant administration of beta-blockers, a reduction in the clearance of lidocaine may occur.
MAO inhibitors: sporadic cases of bradycardia have been observed during concomitant administration of beta-blockers and MAOIs (see section 4.3).
NSAIDs: the antihypertensive effect of beta-blockers can be reduced by NSAIDs and by the administration of indomethacin.
Phenothiazines and other antipsychotics: Additive effects on the antihypertensive activity of beta-blockers have been observed when administered concomitantly with phenothiazines or haloperidol.
Vasoconstrictors: sometimes it is possible to find an additive effect, eg. in association with ergot alkaloids.
04.6 Pregnancy and breastfeeding
Pregnancy
No adequate and well-controlled clinical studies have been conducted to indicate beta-blocker treatment in pregnancy. Therefore nadolol should be used during pregnancy only if the expected benefits outweigh the potential risks to the fetus and under the direct supervision of the physician. Cases of fetal growth retardation have been reported. Infants of mothers taking beta-blockers have sometimes experienced bradycardia, hypoglycemia, respiratory failure and associated symptoms at delivery.
Feeding time
Nadolol is excreted in breast milk and has the potential to induce adverse events in the newborn. Therefore the decision to treat the mother, which implies the suspension of breastfeeding, must be carefully evaluated in the light of the importance of nadolol for the mother herself.
04.7 Effects on ability to drive and use machines
For possible side effects such as dizziness, the medicine may affect the ability to drive and use machines.
04.8 Undesirable effects
The following are the undesirable effects of nadolol organized according to the MedDRA system organ class.
Estimated frequencies of events are based on the following convention: common (≥ 1/100,
The data below are derived from clinical studies involving 1440 patients receiving nadolol.
Cardiovascular pathologies
Common:
- bradycardia below 60 bpm
- marked bradycardia (
- peripheral vascular insufficiency (often Raynaud type)
- Heart failure, hypotension and cardiac conduction disturbances
Rare:
- Grade I and III AV block (in accordance with the slowing mechanism of atrioventricular conduction of beta-blockers - see sections 4.3 and 4.4)
Nervous system disorders
Common:
- asthenia
- dizziness
Uncommon:
- paraesthesia
- sedation and behavioral alterations
- headache
- confused speech
Ear and labyrinth disorders
Uncommon:
- tinnitus
Respiratory, thoracic and mediastinal disorders
Uncommon:
- bronchospasm
- cough
- nasal occlusion
Gastrointestinal disorders
Uncommon:
- nausea, diarrhea, vomiting
- abdominal pain
- constipation
- indigestion
- anorexia
- abdominal swelling
- flatulence
- dry mouth
Disorders of the immune system
Uncommon:
- Skin rash, itching
Eye disorders
Uncommon:
- dry eyes
- blurred vision
Skin and subcutaneous tissue disorders
Uncommon:
- dryness of the skin
- sweating
- facial swelling
Rare:
- reversible alopecia
Diseases of the reproductive system and breast
Uncommon:
- reduced libido
- impotence
Metabolism and nutrition disorders
Uncommon:
- weight gain
The undesirable effects listed below have been observed during treatment with nadolol or with other beta-blockers, without a causal relationship being established.
Nervous system disorders
Reversible depression with evolution towards catatonia, visual disturbances, hallucinations, acute reversible syndrome characterized by spatio-temporal disorientation, short-term amnesia, emotional lability, mild sensory blunting, reduced performance on neuropsychological tests. Sleep disorders
Gastrointestinal disorders
Thrombosis of the mesenteric artery, ischemic colitis, increased liver enzymes.
Disorders of the blood and lymphatic system
Agranulocytosis, thrombocytopenia, non-thrombocytopenic purpura.
Disorders of the immune system
Pharyngodynia and fever, laryngospasm, respiratory disorders. Pemphigoid rash
Cardiovascular pathologies
Hypertensive crisis in subjects with pheochromocytoma
Musculoskeletal and connective tissue disorders
Peyronie's disease
04.9 Overdose
In case of overdose or exaggerated responses, the evaluation of the duration of corrective therapy must take into account the long duration of the effect of nadolol. In addition to gastric lavage, the following measures should be taken:
BradycardiaIn case of excessive bradycardia resulting from therapy with beta-blocking drugs, atropine (0.25-1 mg) is administered. If no response to vagal blockage is observed, administer isoproterenol with caution.
Heart failure: administer digitalis and diuretics. It has also been reported that glucagon may be useful in these cases.
Hypotension: If fluid administration is ineffective, administer vasopressors such as dopamine, dobutamine, isoproterenol or norepinephrine or epinephrine. (There is reason to believe that the drug of choice is norepinephrine).
Bronchospasm: administer a beta2 agonist and / or derivatives of theophylline.
Nadolol can be eliminated from the general circulation by means of hemodialysis. With this procedure, the clearance of nadolol ranges from 40 to 100 mL per minute.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-selective, non-associated beta-blockers.
ATC code C07AA12.
Nadolol is a non-cardioselective beta-blocker. It competes specifically with beta-1 receptors located primarily in heart muscle and with beta-2 receptors located in bronchial and vascular smooth muscle. When access to the receptors is blocked by nadolol, the chronotropic, inotropic, and vasodilator responses following beta-blocker stimulation are proportionally reduced causing a slowing of sinus rhythm and atrioventricular conduction. Unlike most beta-blocking drugs, nadolol does not possess an anesthetizing activity that stabilizes the plasma membrane, so in tests conducted on experimental animals and on humans, nadolol has shown that it does not reduce myocardial contractility by itself.
By virtue of its pharmacological activity, this beta-blocker drug reduces blood pressure in the supine and standing position. Nadolol also decreases the increase in renin by blocking the beta-receptors responsible for releasing this substance from the kidneys, which may be one of its mechanisms of action in reducing blood pressure.
Blockade of beta receptors is useful in clinical conditions characterized by an excessive or inappropriate degree of sympathetic activity, due to organic or functional alterations. However, there are some situations in which sympathetic stimulation is of vital importance; for example, in patients with severe heart failure, ventricular function can be maintained at adequate levels by means of control exerted by the sympathetic system, which control must therefore be maintained. In the presence of atrioventricular block, inhibition of beta receptors may prevent the necessary cardiac conduction effect of the sympathetic system. With the use of beta-blockers, blockade of beta (beta2) receptors may result in passive constriction. bronchial as it interferes with the sympathetic bronchodilator action, which in subjects suffering from bronchospasm, must be maintained.
The purpose of beta-blocker therapy is to reduce sympathetic stimulation, but not to the point of impairing the indispensable adrenergic support for the maintenance of vital functions. By blocking the increase in heart rate, speed and degree of myocardial contraction. , and of blood pressure due to catecholamines, nadolol generally succeeds in reducing the oxygen demand of the heart, at any degree of exertion, which explains its usefulness in the long-term treatment of angina pectoris.
Nadolol exerts an anti-arrhythmic effect at doses capable of causing beta-blockade. Furthermore, nadolol has been shown to reduce the rapid ventricular response that accompanies supraventricular tachyarrhythmias. Beta-adrenergic blockade appears to be of particular importance in arrhythmias caused by an increase in the amount of circulating catecholamines or by increased sensitivity of the heart to them, such as arrhythmias associated with pheochromocytoma, thyrotoxicosis or physical exercise.
In patients with essential hypertension treated with nadolol, there is an increase in total renal flow, and an intrarenal distribution of flow to the cortical nephrons, tending to make the fundamental renal dysfunction present in essential hypertension reversible. Nadolol in contrast to other beta-blockers does not reduce renal function and increases the rate of cardiac output to the kidneys.
The increase in renal excretion of sodium and potassium and the increase in urinary flow, noted after administration of nadolol, cannot be attributed to the glomerular filtration rate which, however, remains unchanged; the decrease in reabsorption following changes in blood flow. renal hemodynamics is, most likely, the responsible factor.
05.2 Pharmacokinetic properties
After oral administration, the absorption of nadolol averages 30% and the maximum plasma concentration is reached after 3-4 hours. The presence of food in the gastrointestinal tract does not affect the amount and rate of absorption of nadolol. Approximately 30. % of the product present in serum is reversibly bound to plasma proteins.
Unlike most beta-blockers available, nadolol does not undergo hepatic biotransformation and is excreted unchanged primarily by the kidney.
This drug has a plasma half-life of around 20-24 hours, a characteristic that allows a single daily administration. However, in the presence of renal insufficiency the half-life is prolonged due to almost exclusively urinary elimination.
Steady state serum concentration is observed after 6-9 days of once-a-day treatment in patients with normal renal function. However, the optimal dose must be progressively established due to the variability of individual responses as well as to the variability of the rate of absorption.
Nadolol has low lipophilicity, as shown by the octanol / water partition coefficient. The amount of product that crosses the blood brain barrier is limited.
05.3 Preclinical safety data
Toxicology - Acute toxicity: LD50 in rats 5.3 g / kg (p.os.); in mice 300 mg / kg (i.p.); 60-70 mg / kg (i.v.) and 4-6 g / kg (p.os).
Subacute toxicity: No signs of toxicity were detected after 1 month of administration at the following doses: in rats 25 mg / kg / day (ip), in dogs up to 12.5 mg / kg / day (iv), and at 3 months in monkeys 250 mg / kg / day (p.os).
Chronic toxicity: in dogs treated orally with doses up to 150 mg / kg / day for one year, the only change observed was a slight decrease in glucose tolerability (dose dependent). Studies in mice and rats treated for two years with doses, respectively up to 500 mg / kg / day and 1250 mg / kg / day in the diet showed no signs of toxicity and carcinogenicity.
Reproduction Studies: 300 mg / kg / day administered to rats, hamsters and rabbits produced no signs of teratogenicity.
In rats there was no change in fertility and reproduction; in rabbits 50 mg / kg / day had no effect, but 100 and 300 mg / kg / day were found to be embryo-toxic and feto-toxic.
Perinatal and postnatal studies in rats showed no significant effect from doses up to 1800 mg / kg.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Magnesium stearate, microcrystalline cellulose
06.2 Incompatibility
Not known.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Carton containing 30 tablets of 80 mg of nadolol each, in transparent PVC / aluminum blister.
06.6 Instructions for use and handling
No special instructions for handling.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
Nadololo Sanofi 80 mg tablets - 30 tablets AIC n. 041029012
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 1 February 2013
10.0 DATE OF REVISION OF THE TEXT
January 2015
