Chemical formula: C₁₆H₂₁NO₂ Molecular mass: 259.343 g/mol PubChem compound: 4946
Propranolol interacts in the following cases:
Concomitant use of MAO inhibitors (except MAO-B inhibitors) with antihypertensive agents may diminish the antihypertensive effect and lead to hypertensive reactions.
Concomittant use of propranolol with alpha blockers increases the risk of hypotension, especially orthostatic hypotension, tachycardia and palpitations.
The plasma levels and the effects of beta-blockers are reduced by the barbiturates. Barbiturates are potent liver enzyme inducers which may increase the metabolism of propranolol.
Concomitant use of alcohol may increase the plasma levels of propranolol.
Concomitant use of propranolol with insulin and oral antidiabetic drugs may mask certain symptoms of hypoglycaemia (palpitations, tachycardia). Propranolol may prolong the hypoglycaemic response to insulin.
Digitalis glycosides, in association with beta-blockers, may increase atrio-ventricular conduction time.
Class I antiarrhythmic drugs and beta-blockers have additive negative inotropic effects which may result in hypotension and severe hemodynamic side effects in patients with impaired left ventricular function.
Concomitant use of propranolol with dihydropyridine calcium channel blockers may increase the risk of hypotension, and cardiac failure may occur with latent cardiac insufficiency.
Concomitant use of beta-adrenergic antagonists and anaesthetics may attenuate reflex tachycardia and increase the risk of hypotension. As a general rule, avoid sudden withdrawal of beta-blocker treatment. The anaesthesiologist should be informed when the patient is receiving beta-adrenergic antagonists. Anaesthetic agents causing myocardial depression are best avoided.
Non-cardioselective beta-blockers oppose the bronchodilator effects of beta-agonist bronchodilators, propranolol is contraindicated in patients with asthma.
Although some reversible effects on male and female fertilities were reported in adult rats receiving high doses of propranolol in the literature, the study performed in juvenile animals did not show any effect on fertility.
A few case reports suggest that patients treated with amiodarone can have severe sinus bradycardia when treated concomitantly with propranolol. Amiodarone has an extremely long half-life (about 50 days), which means that interactions may occur long after discontinuation of therapy.
The concurrent use of chlorpromazine with propranolol can result in a marked rise in plasma levels of both drugs, and thereby enhance its effects on heart rate and blood pressure as well as an enhanced antipsychotic effect for chlorpramazine and an increased antihypertensive effect for propranolol.
Cimetidine increases levels of propranolol in plasma, probably by inhibiting its first pass metabolism. There may be a risk of eg bradycardia with oral dosing.
Concomitant use of centrally acting antihypertensive drugs may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of “rebound hypertension”.
If the two drugs are co administered, the beta-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by beta blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.
A number of reports are available for severe hypertension and bradycardia in patients treated with propranolol and epinephrine. These clinical observations have been confirmed by studies in healthy volunteers. It has also been suggested that the intravascular administration of epinephrine may trigger these reactions.
Ergotamine with propranolol has resulted in reports of vasospastic reactions in some patients.
Potentiation of bradycardia effects with possible fatal outcomes in coadministration of fingolimod with beta blockers. Treatment with fingolimod should not be initiated in patients receiving beta blockers. In case of combination, appropriate monitoring for treatment initiation, at least overnight monitoring is recommended.
Fluvoxamine inhibits oxidative metabolism and increases plasma concentrations of propranolol. This may result in severe bradycardia.
Anti-inflammatory drugs of NSAID-type counter the antihypertensive effect of beta-blockers. It has been studied mainly in indomethacin.
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.
Plasma propranolol levels can be raised up to 100% by propafenone. This probably was because propranolol is partially metabolized by the same enzyme like propafenone (CYP2D6). This combination is also not advisable because propafenone has negative inotropic effects.
The metabolism of propranolol may be increased by potent liver enzyme inducer rifampicin.
During concomitant treatment with propranolol it inhibited the first-pass metabolism of rizatriptan whose AUC increases by 70-80%. A dose of 5 mg of rizatriptan is recommended for combination therapy.
Propranolol reduces the metabolic clearance of theophylline by about 30% at a dosage of 120 mg/day and 50% at doses of 720 mg/day.
Combined use of beta-blockers and calcium channel blockers with negative inotropic effects (e.g. verapamil, diltiazem) can lead to an exaggeration of the negative AV conduction and sinus node function particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities. This may result in severe hypotension and bradycardia. The combination with proproanolol should be avoided, especially in patients with cardiac decompensation.
Propranolol may cause a reduction in clearance and an increase in plasma concentrations of warfarin.
Tobacco smoking can reduce the beneficial effects of the beta-blockers on heart rate and blood pressure.
Propranolol due to its negative effect on conduction time, caution must be exercised if it is given to patients with first degree heart block.
Propranolol may mask the signs of thyrotoxicosis.
Isolated reports of myasthenia gravis like syndrome or exacerbation of myasthenia gravis have been reported in patients administered propranolol.
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.
Although some reversible effects on male and female fertilities were reported in adult rats receiving high doses of propranolol in the literature, the study performed in juvenile animals did not show any effect on fertility.
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.
In clinical trials for proliferating infantile haemangioma, the most frequently reported adverse reactions in infant treated with propranolol were sleep disorders (16.7%), aggravated respiratory tract infections such as bronchitis and bronchiolitis associated with cough and fever, diarrhoea (16.5%), and vomiting (11.5%). Globally, the adverse reactions reported in the compassionate use program and in literature concerned hypoglycemia (and related event like hypoglycaemic seizure) and aggravated respiratory tract infections with respiratory distress.
The following list gives the adverse reactions, reported whatever dose and treatment duration, in three clinical studies, including 435 patients treated by propranolol at 1 mg/kg/day or 3 mg/kg/day for a maximum treatment duration of 6 months.
Their frequency is defined using the following conventions: 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); not known (cannot be estimated from the available data). Due to the clinical trial database size rare and very rare categories are not represented. Within each system organ class, adverse reactions are presented in order of decreasing seriousness.
Very common: Bronchitis
Common: Bronchiolitis
Common: Decreased appetite
Very common: Sleep disorder
Common: Agitation, Nightmares, Irritability
Common: Somnolence
Not known: Hypoglycemic seizure
Uncommon: AV block
Not known: Bradycardia
Common: Peripheral coldness
Not known: Hypotension, Vasoconstriction, Raynaud’s phenomenon
Common: Bronchospasm
Very common: Diarrhea, Vomiting
Common: Constipation, Abdominal pain
Common: Erythema, Dermatitis diaper
Uncommon: Urticaria, Alopecia
Not known: Dermatitis psoriasiform
Common: Decreased blood pressure
Uncommon: Decreased blood glucose, Decreased heart rate, Neutropenia
Not known: Agranulocytosis, Hyperkaliemia
Concerning the lower respiratory tract infections like bronchitis or bronchiolitis, an aggravation of symptoms (including bronchospasm) has been observed in patients treated with propranolol due to the bronchoconstrictive effect of propranolol. These effects rarely led to definitive treatment discontinuation.
Sleep disorders corresponded to insomnia, poor quality of sleep and hypersomnia. Other Central Nervous System disorders were principally observed during the early periods of treatment.
Diarrhea was frequently reported and was not always associated with an infectious gastrointestinal disease. The occurrence of diarrhea seems to be dose-dependent between 1 and 3 mg/kg/day. None of cases was of severe intensity and led to treatment discontinuation.
Cardiovascular events reported during clinical studies were asymptomatic. In the context of the 4 hours cardiovascular monitoring during the titration days, it was observed a decrease of heart rate (about 7 bpm) and of systolic blood pressure (less than 3 mmHg) following drug administration. One case of second degree atrioventricular heart block in a patient with underlying conduction disorder led to definitive treatment discontinuation. Isolated cases of symptomatic bradycardia and hypotension have been reported in literature.
Blood sugar decreases observed during clinical studies were asymptomatic. However, several reports of hypoglycaemia with related hypoglycaemic seizure were reported during the compassionate use program and in literature, especially in case of fasting period during intercurrent illness.
Concomitant treatment with systemic corticosteroids may increase the risk of hypoglycemia.
Hyperkalaemia has been reported in the literature in few patients with large ulcerated haemangioma.
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