Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction
In the absence of specific studies in children, the drug interactions with propranolol are those known in adults. Combinations should consider the 2 following situations (not mutually exclusive):
•    infants given any other medicinal products, notably those mentioned below.
•    infants breastfed by mothers taking any other medicinal products, notably those mentioned below. In this case, the need of stopping breast-feeding should be discussed.
A close clinical surveillance of any impaired tolerance of propranolol is requested.

Concommitant use not recommended

Bradycardia –inducing calcium-channel blockers (diltiazem, verapamil, bepridil) Co-administration with propranolol can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and atrio-ventricular conduction disorders, and increased risk of ventricular arrhythmias (torsades de pointes) along with heart failure.
This combination must only be administered under close clinical and ECG monitoring, particularly at the start of the treatment.

Interactions requiring precautions for use

Cardiovascular Medicinal Products
Antiarrhythmics
• Propafenone has negative inotropic and beta-blocking properties that can be additive to those of propranolol.
• The metabolism of propranolol is reduced by co-administration of quinidine, leading to a two-three-fold increased blood concentration and greater degrees of clinical beta-blockade.
• Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with β-blockers such as propranolol. Automatism and conduction disorders are expected because of the suppression of sympathetic compensative mechanisms.
• The metabolism of intravenous lidocaine is inhibited by co-administration of propranolol, resulting in a 25% increase in lidocaine concentrations. Lidocaine toxicity (neurological and cardiac adverse events) has been reported following co-administration with propranolol.

Digitalis glycosides
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. The advice of a cardiologist should be sought.

Dihydropyridines
Caution should be exercised when patients receiving a beta blocker are administered a dihydropyridine. Both agents may induce hypotension and/or heart failure in patients whose cardiac function is partially controlled because of additive inotropic effects. Concomitant use may reduce the reflex sympathetic response involved when excessive distal vasodilatation.

Antihypertensives (ACE Inhibitors, angiotensin II-receptors antagonists, diuretics, alpha- blockers whatever the indication, centrally-acting antihypertensives, reserpine, etc) When combined with beta-blockers, medicinal products that decrease arterial pressure can cause or increase hypotension, notably orthostatic. With regard to centrally-acting antihypertensives, beta-blockers may exacerbate the rebound hypertension after clonidine abrupt withdrawal, and propranolol should be stopped several days before discontinuing clonidine.

Non-Cardiovascular Medicinal Products

Corticosteroids
Patients with infantile haemangioma may be at increased risk if they have received or are concomitantly receiving treatment with corticosteroids because adrenal suppression may result in loss of the counterregulatory cortisol response and increase the risk of hypoglycaemia. This also applies when children are breastfed by mothers treated with corticosteroids in case of high dosage or prolonged treatment (see section 4.4 concerning hypoglycaemia).


Medicinal products inducing orthostatic hypotension
Medicinal products that induce postural hypotension (nitrates derivatives, type 5- phosphodiesterase inhibitors, tricyclic antidepressants, antipsychotics, dopaminergic agonists, levodopa, amifostine, baclofen…) may add their effects to that of beta-blockers. The advice of a cardiologist should be sought.

Enzyme inducers
Blood levels of propranolol may be decreased by co-administration of enzyme inducers like rifampicin or phenobarbital.

Hypoglycaemic agents
All beta-blocking agents can mask certain symptoms of hypoglycaemia: palpitations and tachycardia.
Use of propranolol alongside hypoglycaemic therapy in diabetic patients should be with caution since it may prolong the hypoglycaemic response to insulin. In this case, inform the caregiver, and increase monitoring of blood glucose levels, particularly at the start of treatment.

Lipid lowering medicinal products
Co-administration of cholestyramine or colestipol with propranolol resulted in up to 50% decrease in propranolol concentrations.

Halogenated Anesthetic Agents
They may depress myocardial contractility and vascular compensating response when administered with propranolol. Beta stimulating agents may be used to counteract the beta- blockade.