Celectol 400 Tablets (Celiprolol Hydrochloride Tablets 400mg for “own label” distribution).

White film coated biconvex heart shaped tablets engraved with the Celectol logo on one face with 400 on the other

The management of mild to moderate hypertension

The initial dose is 200mg orally taken once daily with a glass of water. Celectol should be taken on rising, half an hour before food. If response is inadequate, the dose may be increased to 400 mg once daily.

Not recomended

Dosage as for adults

As with other beta-adrenoceptor antagonists, celiprolol should not be used in cases of cardiogenic shock, uncontrolled heart failure, sick-sinus syndrome, second or third degree heart block, severe bradycardia, severe renal impairment with creatinine clearance less than 15ml per minute, acute episodes of asthma, untreated phaeochromocytoma, metabolic acidosis, hypotension, hypersensitivity to the substance, or severe peripheral arterial circulatory disturbances.

Although cardio selective beta blockers may have less effect on lung function than non selective beta blockers, as with all beta blockers these should be avoided in patients with chronic obstructive airways disease, and in patients with a history of bronchospasm or bronchial asthma, unless there are compelling clinical reasons for their use. Where such reasons exist, celiprolol may be used but with the utmost caution The label will carry the following warning: If you have a history of asthma or wheezing, please ask your doctor before taking this medicine.

Celectol tablets should not be prescribed for patients being treated with theophylline.

The pharmacokinetics are not significantly different in the elderly, however these patients should be regularly monitored and due regard made for decreased renal and liver function in this age group.

Celectol may be used in patients with mild to moderate degrees of reduced renal function as celiprolol is cleared by both renal and non-renal excretory pathways. A reduction in dosage by half may be appropriate in patients with creatinine clearances in the range of 15 to 40ml per minute. However, careful surveillance of such patients is recommended until steady state blood levels are achieved which typically would be within one week. Celectol is not recommended for patients with creatinine clearance less than 15ml per minute. Patients with hepatic impairment should also be carefully monitored after commencing therapy and a reduced dosage should be considered.

Sudden withdrawal of beta-adrenoceptor blocking agents in patients with ischemic heart disease may result in the appearance of anginal attacks of increased frequency or severity or deterioration in cardiac state. Although no adverse effects due to abrupt cessation of Celectol have been seen in clinical trials, therapy should be gradually reduced over 1-2 weeks, at the same time, if necessary, initiating replacement therapy to prevent exacerbation of angina pectoris.

Celectol therapy must be reported to the anaesthetist prior to general anaesthesia. If it is decided to withdraw the drug before surgery, 48 hours should be allowed to elapse between the last dose and anaesthesia. Continuation of beta blockade reduces the risk of arrhythmias during induction and intubation, although reflex tachycardia may be attenuated and the risk of hypotension may be increased (see “Interactions”). In the event of continuation of Celectol treatment special care should be exercised when using anaesthetic agents such as ether, cyclopropane or trichloroethylene. The patient may be protected against vagal reactions by the intravenous administration of atropine.

Celectol should only be used with caution in patients with controlled congestive cardiac failure. Evidence of decompensation should be regarded as a signal to discontinue therapy.

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

Celiprolol may induce bradycardia. If the pulse rate decreases to less than 50-55 beats per minute at rest and the patient experiences symptoms related to the bradycardia, the dosage should be reduced.

Due to its negative effect on conduction time, celiprolol should only be given with caution to patients with first degree heart block.

Beta blockers may increase the number and the duration of anginal attacks in patients with Prinzmetal's angina, due to unopposed alpha-receptor mediated coronary artery vasoconstriction. The use of beta-i selective adrenoceptor blocking drugs such as celiprolol may be considered in these patients, but the utmost care should be exercised.

Beta blockers have been reported to exacerbate psoriasis, and patients with a history of psoriasis should take celiprolol only after careful consideration.

Celiprolol should be used with precaution in treated pheochromocytoma and blood pressure levels should be closely monitored.In patients with a history of anaphylactic reactions induced by other drugs, beta blockers may increase the sensitivity to allergens and the seriousness of the reactions.

Although celiprolol does not interfere with the metabolism of carbohydrates, Beta blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia (in particular, tachycardia).

Not recommended association

It has been shown that the bioavailability of celiprolol is impaired when it is given with food. Co-administration of chlorthalidone and hydrochlorothiazide also reduces the bioavailability of celiprolol.

Calcium channel antagonists such as verapamil (and to a lesser extent diltiazem) and beta blockers both slow A-V conduction and depress myocardial contractility through different mechanisms. When changing from verapamil to celiprolol and vice versa, a period between stopping one and starting the other is recommended. Concomitant administration of both drugs is not recommended and should only be initiated with ECG monitoring. Patients with pre existing conduction abnormalities should not be given the two drugs together.

Digitalis glycosides, in association with beta-adrenoceptor blocking drugs, may increase A-V conduction time.

Beta blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-adrenoceptor blocking drug should be withdrawn several days before discontinuing clonidine. There is a theoretical risk that concurrent administration of monoamine oxidase-A inhibitors and high doses of beta-adrenoceptor blockers, even if they are cardio selective, can produce hypertension.

Precautions for use

Care should be taken in prescribing beta-adrenoceptor blockers with Class I antiarrhythmic agents (e.g. disopyramide, quinidine) and amiodarone, since these agents may potentiate the negative effects on A-V conduction and myocardial contractility.

Beta blockers may intensify the blood sugar lowering effects of insulin and oral antidiabetic drugs, and the dosage of antidiabetics may therefore require adjustment. In addition, beta-adrenoceptor blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia (in particular, tachycardia).

Therapy with beta-adrenoceptor blockers must be reported to the anaesthetist prior to general anaesthesia (see “Special warnings and special precautions for use”). Continuation of beta blockade reduces the risk of arrhythmias during induction and intubation, but reflex tachycardia may be attenuated and the risk of hypotension may be increased. Anaesthetic agents causing myocardial depression (e.g. ether, cyclopropane, trichloroethylene) are best avoided.

Take into account

Concomitant therapy with dihydropyridine calcium channel antagonists, such as nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.

Drugs inhibiting prostaglandin synthetase, such as ibuprofen or indomethacin, may decrease the hypotensive effects of beta-adrenoceptor blocking drugs.

Sympathomimetic agents, such as adrenaline, may counteract the effects of beta blockers.

Concomitant use of other antihypertensive agents, or of tricyclic antidepressants, barbiturates or phenothiazines, may potentiate the hypotensive effects of beta blockers.

Beta-adrenoceptor blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia (in particular, tachycardia).

Occasional side effects, which are usually mild and transient have occurred. These include headache, dizziness, fatigue, nausea, somnolence and insomnia (sleep disturbances). Additional side effects associated with beta-2 agonist activity, tremor and palpitations, have been reported. These effects usually do not require withdrawal of therapy. Depression and hypersensitivity pneumonitis have been reported rarely.

Bronchospasm, skin rashes and/or visual disturbances have been reported in association with the use of beta blockers. Celectol should be discontinued if these effects occur.

In addition, the following undesirable effects, listed by body system, are generally attributable to the pharmacological activity of beta-adrenergic blockers:

Cardiovascular: bradycardia, slowed A-V conduction, hypotension, heart failure, cold and cyanotic extremities. In susceptible patients: precipitation of existing A-V block, exacerbation of intermittent claudication, Raynaud's disease or syndrome.

CNS: confusion, hallucinations, psychoses, nightmares.

Neurological: paraesthesia.

Respiratory: bronchospasm may occur in patients with bronchial asthma or with a history of bronchial complaints.

Gastro-intestinal: vomiting, diarrhoea.

Integumentary: skin disorders (especially rash), dry eyes.

Others: disturbances of libido and potency. An increase in ANA (antinuclear antibodies) has been reported, although its clinical relevance is not clear.

Winthrop Pharmaceuticals UK Ltd