Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Accord-UK Ltd (Trading style: Accord), Whiddon Valley, Barnstaple, Devon, EX32 8NS
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
Propranolol must not be used if there is a history of bronchial asthma, bronchospasm chronic obstructive airways disease. The product label states the following warning: “Do not take Propranolol if you have a history of asthma or wheezing”. A similar warning appears in the patient information leaflet.
Bronchospasm can usually be reversed by beta2 agonist bronchodilators such as salbutamol. Large doses of the beta2 agonist bronchodilator may be required to overcome the beta blockade produced by propranolol and the dose should be titrated according to the clinical response; both intravenous and inhalational administration should be considered. The use of intravenous aminophylline and/or the use of ipratropium (given by nebuliser) may also be considered. Glucagon (1 to 2 mg given intravenously) has also been reported to produce a bronchodilator effect in asthmatic patients. Oxygen or artificial ventilation may be required in severe cases.
Propranolol l as with other beta-blockers must not be used in patients with any of the following conditions: known hypersensitivity to the substance; bradycardia; cardiogenic shock; hypotension; metabolic acidosis; after prolonged fasting; severe peripheral arterial circulatory disturbances; second or third degree heart block; sick sinus syndrome; untreated phaeochromocytoma; uncontrolled heart failure or Prinzmetal’s angina.
Propranolol must not be used in patients prone to hypoglycaemia, i.e. patients after prolonged fasting or patients with restricted counter-regulatory reserves. Patients with restricted counter regulatory reserves may have reduced autonomic and hormonal responses to hypoglycaemia which includes glycogenolysis, gluconeogenesis and/or impaired modulation of insulin secretion. Patients at risk for an inadequate response to hypoglycaemia includes individuals with malnutrition, prolonged fasting, starvation, chronic liver disease, diabetes and concomitant use of drugs which block the full response to catecholamines.
Special care should be taken with patients whose cardiac reserve is poor. Beta-adrenoceptor blocking drugs should be avoided in overt heart failure; however, they may be used in patients whose signs of failure have been controlled.
Propranolol should not be used in combination with calcium channel blockers with negative inotropic effects (e.g. verapamil, diltiazem), as it can lead to an exaggeration of these effects particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.
Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.
Concomitant therapy with dihydropyridine calcium channel blockers, e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.
Although contraindicated in severe peripheral circulatory disturbances, beta adrenoreceptor blocking drugs may also aggravate less severe forms. Therefore, propranolol should be used with great caution in conditions such as Raynaud’s disease/syndrome or intermittent claudication.
Caution must be exercised if propranolol is given to patients with first degree heart block.
Propranolol may block/modify the signs and symptoms of the hypoglycaemia (especially tachycardia). Propranolol 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 propranolol has rarely presented with seizures and/or coma in isolated patients. Caution must be exercised in the concurrent use of propranolol and hypoglycaemic therapy in diabetic patients. Propranolol may prolong the hypoglycaemic response to insulin (see section 4.3).
Heart failure due to thyrotoxicosis often responds to propranolol alone, but if other adverse factors co-exist myocardial contractility must be maintained and signs of failure controlled with digitalis and diuretics. Propranolol may mask the important signs of thyrotoxicosis and hyperthyroidism.
Beta adrenoreceptor blocking drugs should not be used in untreated phaeochromocytoma (See section 4.3), however, in patients with phaeochromocytoma an alpha-blocker may be given concomitantly.
One of the pharmacological actions of propranolol is to reduce the heart rate; in the instance when symptoms may be attributable to slow heart rate, the dose may be reduced.
Beta adrenoceptor blocking drugs may cause a more severe reaction to a variety of allergens, when given to patients with a history of anaphylactic reaction to such allergens. Such patients may be unresponsive to the usual doses of adrenaline used to treat the allergic reactions. Particular caution is necessary, when beta adrenoceptor blocking drugs are used in patients with a history of anaphylaxis.
As with other beta-adrenoceptor blocking agents, in patients with ischaemic heart disease, treatment should not be discontinued abruptly. Either the equivalent dosage of another beta-adrenoceptor blocker may be substituted or the withdrawal of propranolol should be gradual.
Isolated reports of myasthenia gravis like syndrome or exacerbation of myasthenia gravis have been reported in patients administered propranolol.
Psoriasis may be aggravated by the use of beta adrenoreceptor blocking drugs.
Abrupt withdrawal of beta-blockers is to be avoided. The dosage should be withdrawn gradually over a period of 7 to 14 days. Patients should be followed during withdrawal especially those with ischaemic heart disease.
Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. In the rare event of intolerance, manifested as bradycardia and hypotension, the drug should be withdrawn and, if necessary, treatment for overdosage instituted. The sudden withdrawal of beta-receptor antagonists may result in severe exacerbation of angina pectoris, acute myocardial infarction, sudden death, malignant tachycardia, sweating, palpitation and tremor. Withdrawal should be accomplished over 10 to 14 days however caution must be exercised as this does not always prevent rebound effects.
When withdrawing a beta-blocker in preparation for surgery, therapy should be discontinued for at least 24 hours. Continuation of beta-blockade reduces the risk of arrhythmias during induction and intubation, although there may be an increased risk of hypertension. If treatment is continued, caution should be observed with the use of certain anaesthetic drugs and the chosen anaesthetic should have as little negative inotropic activity as possible. The anaesthetist should always be informed about the use of a beta-blocking drug. The patient may be protected against vagal reactions by the intravenous administration of atropine.
Since the half-life may be increased in patients with significant hepatic or renal impairment, care should be taken when starting treatment and selecting the initial dose.
Propranolol should be used with caution in patients with decompensated cirrhosis.
Liver function will deteriorate in patients with portal hypertension and hepatic encephalopathy may develop. There have been some reports suggesting that treatment with propranolol may increase the risk of developing hepatic encephalopathy.
Interference with laboratory tests: Propranolol has been reported to interfere with the estimation of serum bilirubin by the diazo method and with the determination of catecholamines by methods using fluorescence.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine as it contains lactose.
Propranolol 10mg tablets contain carmoisine (E122) which may cause allergic reactions.
Care should be taken in the parenteral administration of preparations containing adrenaline (epinephrine) to patients taking beta-adrenoceptor blocking drugs as, in rare cases, vasoconstriction, hypertension and bradycardia may result.
Care should be taken when using anaesthetic agents with propranolol. The anaesthetist should be informed and the choice of anaesthetic should be the agent with as little negative inotropic activity as possible.
Use of betablockers with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.
Caution must be exercised in co-prescribing beta-adrenoceptor blockers with Class I anti-arrhythmic agents such as disopyramide, quinidine, flecainide and amiodarone may have potentiating effects on arterial conduction time and induce negative inotropic effect. Administration of propranolol during infusion of lidocaine may increase the plasma concentration of lidocaine by approximately 30%. Patients already receiving propranolol tend to have higher lidocaine levels than controls. The combination should be avoided.
Combined use of beta-adrenoceptor blocking drugs and calcium channel blockers with negative inotropic effects eg verapamil, diltiazem can lead to prolongation of SA and AV conduction particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-adrenoceptor blocking drug nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other. Digitalis glycosides used in association with beta-adrenoceptor blockers may increase AV conduction time.
Propranolol may cause a reduction in clearance and an increase in plasma concentrations of warfarin.
Propranolol modifies the tachycardia of hypoglycaemia; caution should therefore be exercised in the concomitant use of propranolol and hypoglycaemic therapy in diabetic patients. Propranolol may prolong the hypoglycaemic response to insulin.
Beta-adrenoceptor blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the drugs are co-administered, the beta-adrenoceptor blocking drug should be withdrawn several days before discontinuing clonidine. If replacing clonidine with beta-adrenoceptor therapy the introduction of the beta-adrenoceptor blocking drug should be delayed for several days after clonidine administration has stopped. Concomitant use of moxonidine and beta blockers may result in an enhanced hypotensive effect. The steps for moxonidine withdrawal/introduction should be the same as for clonidine. Hypotensive effect may be enhanced when propranolol is taken with diuretics, methyldopa or levodopa.
Prazosin or other alpha-adrenoreceptor blockers may potentiate postural hypotension, tachycardia and palpitations.
Caution is necessary if ergotamine, dihydroergotamine or related compounds are given in combination with propranolol since vasospastic reactions have been reported in a few patients. Simultaneous administration of rizatriptan and propranolol can cause an increased rizatriptan AUC and Cmax by approximately 70-80%. The increased rizatriptan exposure is presumed to be caused by inhibition of first-passage metabolism of rizatriptan through inhibition of monoamine oxidase-A. A dose reduction to 5mg is recommended. Administration should be separated by 2 hours.
The metabolism of propranolol may be increased by potent liver enzyme inducer barbiturates.
Concomitant administration of propranolol and chlorpromazine may result in an increase in plasma levels of both drugs. This may lead to an enhanced antipsychotic effect for chlorpromazine and an increased antihypertensive effect for propranolol.
Concomitant use of cimetidine will increase, where as alcohol will decrease the plasma levels of propranolol.
Concomitant use of hydralazine will increase, where as alcohol will decrease the plasma levels of propranolol.
Propranolol may cause plasma concentrations of imipramine to increase.
The hypotensive effects of beta-blockers may be enhanced by MAOIs.
Concomitant use of prostaglandin synthetase inhibiting drugs eg, ibuprofen and indometacin, may decrease the hypotensive effects of propranolol.
This may be particularly significant in patients with poorly controlled hypertension.
The metabolism of propranolol may be increased by potent liver enzyme inducer rifampicin.
Fluvoxamine inhibits oxidative metabolism and increases plasma concentrations of propranolol. This may result in severe bradycardia.
Propranolol reduces the clearance and consequentially increases the plasma concentration of theophylline.
Pharmacokinetic studies have shown that the following agents may interact with propranolol due to effects on enzyme systems in the liver which metabolise propranolol and these agents: propafenone, thioridazine, dihydropyridine and calcium channel blockers such as nifedipine, nisoldipine, nicardipine, isradipine and lacidipine.
Smoking tobacco may oppose the effects of beta blockers in the treatment of angina or hypotension. Patients should be encouraged to stop smoking, apart from its other toxic effects, it aggravates ocardial ischaemia, increases heart rate and can impair blood pressure control. If patient continues to smoke, dosage of the beta blocker may need to be increased or a cardio-selective beta blocker may be more appropriate.
As with all other drugs, propranolol should not be given in pregnancy or lactation unless its use is essential. There is no evidence of teratogenicity with propranolol. However beta-adrenoceptor blocking drugs reduce placental perfusion, which may result in intra-uterine foetal death, immature and premature deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia in the neonate and bradycardia in the foetus) may occur. There is an increased risk of cardiac and pulmonary complications in the neonate in the post-natal period.
Most beta-adrenoceptor blocking drugs, particularly lipophilic compounds, will pass into breast milk although to a variable extent. Breast feeding is therefore not recommended following administration of these compounds.
The use of propranolol is unlikely to result in any significant impairment of the ability of patients to drive or operate machinery. However, patients should be warned that visual disturbances, hallucinations, mental confusion, dizziness, drowsiness or fatigue may occur and they should not drive or operate machinery if they feel affected.
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).
The following undesired events, listed by body system, have been reported:
Rare: thrombocytopenia
Frequency not known: agranulocytosis
Frequency not known: masking signs of thyrotoxicosis
Frequency not known: hypoglycaemia in neonates, infants, children, elderly patients, patients on haemodialysis, patients on concomitant antidiabetic therapy, patients with prolonged fasting and patients with chronic liver disease has been reported. Changes in lipid metabolism (changes in blood concentrations of triglycerides and cholesterol)
Common: sleep disturbances, nightmares
Frequency not known: depression, confusion
Rare: hallucinations, psychoses, mood changes, confusion, memory loss, dizziness, paraesthesia
Very rare: isolated reports of myasthenia gravis like syndrome or exacerbation of myasthenia gravis have been reported
Frequency not known: headache, seizure linked to hypoglycaemia
Rare: visual disturbances, dry eyes
Frequency not known: conjunctivitis
Common: bradycardia
Rare: Heart failure deterioration, precipitation of heart block, postural hypotension which may be associated with syncope
Frequency not known: worsening of attacks of angina pectoris
Common: cold extremities, Raynaud’s syndrome
Rare: exacerbation of Intermittent claudication
Rare: Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints, sometimes with fatal outcome.
Frequency not known: dyspnoea.
Uncommon: diarrhoea, nausea, vomiting
Frequency not known: constipation, dry mouth
Rare: alopecia, purpura, psoriasiform skin reactions, exacerbation of psoriasis, rash
Frequency not known: arthralgia
Frequency not known: reduced renal blood flow and GFR
Frequency not known: sexual dysfunction
Common: fatigue and/or lassitude (often transient)
Very rare: an increase in ANA (antinuclear antibodies) has been observed with many beta blockers, however the clinical relevance of this is not clear
Discontinuance of the drug should be considered if, according to clinical judgement, the well being of the patient is adversely affected by any of the above reactions. Cessation of therapy with a beta-blocker should be gradual (see section 4.4). In the rare event of intolerance manifested as bradycardia and hypotension, the drug should be withdrawn and, if necessary, treatment for overdosage instituted (see section 4.9).
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 the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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