Non-cardioselective b-blockers (beta-blockers).

Generic

Oxprenolol hydrochloride EP 160mg.

Tablets.

Hypertension: As monotherapy or for use in combination with other antihypertensives, e.g. with a diuretic, peripheral vasodilator, calcium channel blocker or ACE inhibitor.

Angina Pectoris: For long-term prophylactic use (if necessary nitrates should be employed for alleviating acute attacks)

The dosage should be individualised. Before raising the dosage, the heart rate at rest should always be checked. If it is 50-55 beats/min, the dosage should not be increased, see contraindications. The tablets should be swallowed with liquid.

If the maximum recommended dose is insufficient to produce the desired response appropriate combined therapy should be considered.

When discontinuing prolonged treatment with a beta-blocker, the medication should not be interrupted abruptly, but withdrawn gradually.

The sustained-release formulation provides a longer pharmacological action from a given dose, thus allowing once daily administration. When the dose is raised to more than one TRASICOR sustained-release tablet, it is usual for this to continue to be given once daily.

The sustained-release tablets should be swallowed whole with liquid. Oxprenolol is only gradually released from the sustained-release tablet, extending the duration of effect. The occurrence of high peak concentrations in the plasma is thus avoided.

 Adults

Hypertension: 160mg once daily. If necessary, the dosage can be raised to 320mg.

Angina pectoris: 160mg once daily. If necessary, the dosage can be raised to 320mg.

No adequate experience has been acquired on the use of SLOW TRASICOR in children.

No special dosage regime is necessary but concurrent hepatic insufficiency should be taken into account.

SLOW TRASICOR is contraindicated in patients with

• Hypersensitivity to oxprenolol and related derivatives, cross-sensitivity to other beta-blockers or to any of the excipients.

• Cardiogenic shock.

• Second or third degree atrioventricular block.

• Uncontrolled heart failure.

• Sick-sinus syndrome.

• Bradycardia ( < 45–50bpm).

• Hypotension.

• Untreated phaeochromocytoma.

• Severe peripheral arterial circulatory disturbances.

• History of bronchospasm and bronchial asthma. (A warning stating “Do not take this medicine if you have a history of wheezing or asthma” will appear on the label)

• Prinzmetal's angina (variant angina pectoris).

• Use of anaesthetics which are known to have a negative inotropic effect.

• Metabolic acidosis.

Owing to the risk of bronchoconstriction, non-selective beta-blockers such as SLOW TRASICOR should be used with particular caution in patients with chronic obstructive lung disease.

As beta-blockers increase the AV conduction time, beta-blockers should only be given with caution to patients with first degree AV block.

Beta-blockers should not be used in patients with untreated congestive heart failure. This condition should first be stabilised.

If the patient develops increasing bradycardia less than 50-55 beats per minute at rest and the patient experiences symptoms related to bradycardia, the dosage should be reduced or gradually withdrawn (see “Contra-indications”).

Beta-blockers are liable to affect carbohydrate metabolism. Diabetic patients, especially those dependent on insulin, should be warned that beta-blockers can mask symptoms of hypoglycaemia (e.g. tachycardia) (see “Interactions with other medicaments and other forms of interaction”). Hypoglycaemia, producing loss of consciousness in some cases, may occur in non-diabetic individuals who are taking beta-blockers, particularly those who undergo prolonged fasting or severe exercise. The concurrent use of beta-blockers and anti-diabetic medication should always be monitored to confirm that diabetic control is well maintained.

Beta-blockers may mask certain clinical signs (e.g. tachycardia) of hyperthyroidism and the patient should be carefully monitored.

Beta-blockers may reduce liver function and thus affect the metabolism of other drugs. Like many beta-blockers oxprenolol undergoes substantial first-pass hepatic metabolism. In the presence of liver cirrhosis the bioavailability of oxprenolol may be increased leading to higher plasma concentrations. Patients with severe renal failure might be more susceptible to the effects of antihypertensive drugs due to haemodynamic effects. Careful monitoring is advisable (see “Pharmacokinetic properties”).

In patients with peripheral circulatory disorders (e.g. Raynaud's disease or syndrome, intermittent claudication), beta-blockers should be used with great caution as aggravation of these disorders may occur.

In patients with phaeochromocytoma a beta-blocker should only be given together with an alpha-blocker.

Owing to the danger of cardiac arrest, a calcium antagonist of the verapamil type must not be administered intravenously to the patient already receiving treatment with a beta-blocker. Furthermore, since beta-blockers may potentiate the negative-inotropic and dromotropic effects of calcium antagonists, like verapamil or diltiazem, any oral co-medication (e.g. in angina pectoris) requires close clinical control.

Anaphylactic reactions precipitated by other agents may be particularly severe in patients taking beta-blockers, especially non-selective drugs, and may require higher than normal doses of adrenaline for treatment. Whenever possible, beta-blockers should be discontinued in patients who are at increased risk for anaphylaxis.

Especially in patients with ischaemic heart disease, treatment should not be discontinued suddenly. The dosage should gradually be reduced, i.e. over 1-3 weeks, if necessary, at the same time initiating alternative therapy, to prevent exacerbation of angina pectoris.

If a patient receiving oxprenolol requires anaesthesia, the anaesthetist should be informed of the use of the medication prior to the use of general anaesthetic to permit him to take the necessary precautions. The anaesthetic selected should be one exhibiting as little inotropic activity as possible, e.g. halothane/nitrous oxide. If on the other hand, inhibition of sympathetic tone during the operation is regarded as undesirable, the beta-blocker should be withdrawn gradually at least 48 hours prior to surgery.

The full development of the “oculomucocutaneous syndrome”, as previously described with practolol has not been reported with oxprenolol. However some features of this syndrome have been noted such as dry eyes alone or occasionally associated with skin rash. In most cases the symptoms cleared after withdrawal of the treatment. Discontinuation of oxprenolol should be considered, and a switch to another antihypertensive drug might be advisable, see advice on discontinuation above.

Calcium channel blockers: e.g. verapamil, diltiazem: Potentiation of bradycardia, myocardial depression and hypotension; particularly after intravenous administration of verapamil in patients taking oral beta-blockers, the possibility of hypotension and cardiac arrhythmias cannot be excluded.

Class I anti-arrhythmic drugs and amiodarone: Drugs like disopyramide, quinidine and amiodarone may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Sympathomimetic drugs: Non-cardioselective beta-blockers such as oxprenolol enhance the pressor response to sympathomimetic drugs such as adrenaline, noradrenaline, isoprenaline, ephedrine and phenylephrine (e.g. local anaesthetics in dentistry, nasal and ocular drops), resulting in hypertension and bradycardia.

Clonidine: When clonidine is used in conjunction with non-selective beta-blockers, such as oxprenolol, treatment with clonidine should be continued for some time after beta-blocker has been discontinued to reduce the danger of rebound hypertension.

Catecholamine-depleting drugs: e.g. guanethidine, reserpine, may have an additive effect when administered concomitantly with beta-blockers. Patients should be closely observed for hypotension.

Beta-blockers may modify blood glucose concentrations in patients being treated with insulin and oral antidiabetic drugs and may alter the response to hypoglycaemia by prolonging the recovery (blood glucose rise) from hypoglycaemia, causing hypotension and blocking tachycardia. In diabetic patients receiving beta-blockers hypoglycaemic episodes may not result in the expected tachycardia but hypoglycaemia-induced sweating will occur and may even be intensified and prolonged. 

Non-steroidal anti-inflammatory drugs (NSAIDs): Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of beta-blockade.

Cimetidine: Hepatic metabolism of beta-blockers may be reduced resulting in increased plasma levels of beta-blocker and prolonged serum half-life. Marked bradycardia may occur.

Ergot alkaloids: Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids.

Anaesthetic drugs: Beta-blockers and certain anaesthetics (e.g. halothane) are additive in their cardiodepressant effect. However, continuation of beta-blockers reduces the risk of arrhythmia during anaesthesia.

Digitalis glycosides: Beta-blockers and digitalis glycosides may be additive in their depressant effect on myocardial conduction, particularly through the atrioventricular node, resulting in bradycardia or heart block.

Lidocaine: Concomitant administration with beta-blockers may increase lidocaine blood concentrations and potential toxicity; patients should be closely monitored for increased lidocaine effects.

Alcohol and beta-blocker effects on the central nervous system have been observed to be additive and it is possible that symptoms such as dizziness may be exaggerated if alcohol and SLOW TRASICOR are taken together.

Side-Effects: Frequency estimate: very common> 10%, common> 1% - < 10%, uncommon> 0.1% - < 1%, rare> 0.01% - < 0.1%, very rare < 0.01%.

Central nervous system:

Common: Fatigue, dizziness, headache, mental depression.

Uncommon: Sleep disturbances, nightmares.

Rare: Hallucinations, exertional tiredness.

Cardiovascular system:

Common: Hypotension, heart failure, peripheral vascular disorders (e.g. cold extremities, paraesthesia).

Uncommon: Bradycardia, disturbance of cardiac conduction.

Rare: Raynaud-like symptoms.

Gastro-intestinal tract:

Very common: Dry mouth, constipation.

Common: Nausea.

Uncommon: Diarrhoea, vomiting, flatulence.

Skin and appendages:

Uncommon: Allergic skin rash (e.g. urticarial, psoriasiform, eczematous, lichenoid).

Rare: Worsening of psoriasis.

Respiratory system:

Common: Dyspnoea, bronchoconstriction.

Sense organs:

Uncommon: Visual disturbances (“blurred vision”, “vision abnormal”).

Rare: Dry eyes, keratoconjuctivitis.

Others:

Common: Disturbances of libido and potency.

Very rare: Thrombocytopenia.

Amdipharm

POM

24 June 2009