Celiprol

Celectol 200 Tablets (Celiprolol Hydrochloride 200mg Tablets for "own label" distribution).

White film coated biconvex heart shaped tablets engraved with 200 and a breakline on one face and the Celectol logo on the other face.

The management of mild to moderate hypertension.

As with other beta-adrenoceptor antagonists, celiprolol should not be used in cases of cardiogenic shock, uncontrolled heart failure, sick-sinus syndrome, (including sino-atrial block), second or third degree heart block, severe bradycardia (<45-50 beats per minute), severe renal impairment with creatinine clearance less than 15ml per minute, acute episodes of asthma, untreated phaeochromocytoma, metabolic acidosis, hypotension, hypersensitivity to the active substance or any of the excipients, or severe peripheral arterial circulatory disturbances.

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

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 under specialist supervision. 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 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.

In patients with coronary insufficiency, treatment should not be discontinued abruptly.

Sudden withdrawal of beta-adrenoceptor blocking agents in patients with ischaemic 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 well-controlled congestive cardiac failure under strict medical surveillance. 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. Close monitoring is advisable.

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-1 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 caution in patients with treated phaeochromocytoma and must not be adminstered until after alpha-blockade has been established. Close monitoring is advisable.

In patients with a history of anaphylactic reactions, beta blockers may increase the sensitivity to allergens and the seriousness of the reactions.

aution should be observed in patients with Diabetes Mellitus as beta blockers may mask the symptoms of hypoglycaemia (in particular, tachycardia).

Beta blockers may mask the symptoms of thyrotoxicosis.

Celiprolol may give a positive reaction when drug-screening tests are conducted in competitive sport since beta-blockers may be restricted in certain sports. Competitors should check with the appropriate sports authorities.

It has been shown that driving ability is unlikely to be impaired in patients taking Celectol. However, it should be taken into account that occasional dizziness or fatigue may occur as well as the potential for tremor, headaches or impaired vision. If affected, patients should be advised not to drive or operate machines.

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, hot flushes, asthenia, dizziness, fatigue, 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. Dyspnoea and interstitial pneumonitis have also been rarely reported.

Gastro-intestinal: vomiting, diarrhoea, nausea and gastralgia.

Integumentary: skin disorders (cutaneous effects including psoriasiform rash), dry eyes.

Reproductive system: Libido decrease, male impotency.

Eye: Visual disturbances have been reported including xerophthalamias.

Hepatobiliary: Increase in transaminases.

Metabolism and Nutritional: Hypoglycaemia, hyperglycemia.

Collagen disorders: Antinuclear antibodies have been observed, exceptional and reversible lupus syndrome.

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

No data are available regarding celiprolol overdose in humans.

The most common symptoms to be expected following overdosage with a beta-adrenoceptor blocking drug are bradycardia, hypotension, bronchospasm and acute cardiac insufficiency.

General treatment should be symptomatic and supportive and be conducted under close supervision, with the use of gastric lavage, activated charcoal and a laxative to prevent absorption of any drug still present in the gastro-intestinal tract. Haemodialysis or haemoperfusion may be considered.

Bradycardia or extensive vagal reactions should be treated with intravenous atropine, 1-2mg. Cardiac pacing should be considered in refractory bradycardia and heart block. Hypotension should be treated with plasma or plasma substitutes and, if necessary, intravenous catecholamines including dopamine and dobutamine.

Glucagon is the treatment of choice for severe hypotension, heart failure or cardiogenic shock. A bolus of 2-10mg IV in adults (50-150 micrograms/kg in a child) should be followed by an infusion of 1-5mg/hour (50 micrograms/kg/hour), titrated to clinical response. Note vials normally contain 1mg = 1 unit and other treatments may be more convenient to use. Some patients do not respond to glucagon and if vomiting occurs without any improvement in blood pressure, further glucagon is unlikely to be of benefit. Adverse effects of glucagon administration include vomiting, hyperglycaemia, hypokalaemia and hypocalcaemia.

If glucagon is not available or if there is severe bradycardia and hypotension, which is not improved by glucagon, use isoprenaline starting at an infusion rate of 5-10 micrograms/minute (0.02 micrograms/kg/min in children increasing to a maximum of 0.5 micrograms/kg/min) and increased as necessary depending on clinical response. Large doses (up to 800 micrograms/min) have been reported to be necessary on some occassions. Isoprenaline may be ineffective at improving blood pressure despite increasing heart rate.

In severe hypotension additional inotropic support may be necessary with a beta agonist such as dobutamine 2.5-40 micrograms/kg/min (adults and children). Other inotropes such as dopamine, adrenaline (epinephrine) or noradrenaline (norepinephrine) may occassionally be of benefit or consider the use of an intra-aortic balloon pump to sustain an adequate cardiac output. Management of cases of severe hypotension and cardiogenic shock should be discussed with your local poisons service in the UK NPIS 0844 892 0111.

Celiprolol is a vasoactive beta-l selective adrenoceptor antagonist with partial beta-2 agonist activity indicated in mild to moderate hypertension. The beta-2 agonist activity is thought to account for its mild vasodilating properties. It lowers blood pressure in hypertensive patients at rest and on exercise. The effects on heart rate and cardiac output are dependant on the pre-existing background level of sympathetic tone.

Under conditions of stress such as exercise celiprolol attenuates chronotropic and inotropic responses to sympathetic stimulation. However, at rest minimal impairment of cardiac function is seen.

Celectol therapy has not been shown to adversely effect plasma lipid profiles.

Celiprolol is a hydrophilic compound that is incompletely absorbed from the gastrointestinal tract. Plasma half-life is approximately 5-6 hours and pharmacodynamic effects are present for at least 24 hours. After once daily administration celiprolol is only slightly metabolised before excretion in the bile and urine in almost equal quantities.

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

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Mannitol BP

Microcrystalline Cellulose BP

Croscarmellose Sodium NF

Magnesium Stearate BP

Film coating:

Opadry YS-l-7006 (clear) contains E464 and polyethylene glycol.

Opadry Y-1-7000 (white) contains E171, E464 and polyethylene glycol.

None stated.

36 months.

Store below 25°C.

No special instructions.

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS, UK

Trading as: Winthrop Pharmaceuticals, PO Box 611, Guildford, Surrey, GU1 4YS, UK

or

Trading as: Zentiva, One Onslow Street, Guildford, Surrey, GU1 4YS, UK

PL 17780/0429

28/01/2009

14/08/2014