Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Neon Healthcare Ltd., 8 The Chase, John Tate Road, Hertford, SG13 7NN, United Kingdom
As with other beta-adrenoceptor antagonists, celiprolol should not be used in cases of:
Celectol film-coated 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: Do not take this medicine if you have wheezing or asthma.
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 15-40 ml 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 15 ml 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-blockers 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 section 4.5). 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) excluding patients in the late stage (see section 4.3), 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 blockers such as celiprolol may be considered in these patients, but the utmost care should be exercised.
Celiprolol should be used with caution in patients with treated phaeochromocytoma and must not be administered 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.
Patients with psoriasis or a history of psoriasis should only be given beta-blockers after careful consideration, as psoriasis may be aggravated.
Although celiprolol does not interfere with the metabolism of carbohydrates, latent diabetes mellitus may become manifest or already existing diabetes mellitus may worsen (see sections 4.5 and 4.8). In addition, celiprolol as other beta-blockers may mask the symptoms of hypoglycaemia (in particular tachycardia) (see section 4.5).
In patients with hyperthyroidism, the clinical signs of thyrotoxicosis (tachycardia and tremor) may be masked.
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.
This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.
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 both clinical signs and ECG monitored carefully. Patients with pre-existing conduction abnormalities should not be given the two drugs together.
In case of shock or hypotension due to floctafenine, beta-blockers may reduce the effectiveness of drugs used to compensate these symptoms.
Association with beta-blockers may increase A-V conduction time.
Concomitant use of fingolimod with beta-blockers may potentiate bradycardic effects and is not recommended. Where such co-administration is considered necessary, appropriate monitoring at treatment initiation, i.e. at least overnight monitoring, is recommended.
Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-blockers should be withdrawn several days before discontinuing clonidine.
There is a theoretical risk that concurrent administration of monoamine oxidase inhibitors and high doses of beta-blockers, even if they are cardio-selective, can produce hypotension. Co-administration of beta-blockers with MAOIs is not recommended.
Celiprolol is a substrate of the intestinal uptake transporters OATPs, specifically OATP1A2 and OATP2B1. OATP inhibitors may result in a decrease in celiprolol absorption. Citrus juices have been shown to decrease the absorption of celiprolol from the gastrointestinal tract through inhibition of OATP2B1 uptake transporter activity, resulting in approximately 90% decrease in AUC and Cmax. Patients should be advised to avoid such beverages.
Care should be taken in prescribing beta-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. Clinical and ECG monitoring must be performed.
An increased risk of depression has been reported when beta-blockers are co- administered with diltiazem (see section 4.8).
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-blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia (in particular, tachycardia).
Therapy with beta-blockers must be reported to the anaesthetist prior to general anaesthesia as they may attenuate the reflex tachycardia and increase the risk of hypotension (see section 4.4).
Celiprolol is a substrate for the P-glycoprotein (P-gp) efflux transporter. Concomitant uses with drugs that inhibit P-gp (e.g. verapamil, erythromycin, clarithromycin, ciclosporin, quinidine, ketoconazole and itraconazole) are likely to result in increased plasma concentrations of celiprolol. A dose reduction of celiprolol could be considered when concomitantly used with drugs that inhibit P-gp.
Concomitant use with drugs that induce P-gp (e.g. rifampicin and St. John’s Wort) could result in decreased plasma concentrations of celiprolol. A dosage adjustment of celiprolol might be necessary when treatment with a P-gp inducing drug is initiated or discontinued.
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 or uncontrolled cardiac insufficiency. Blood pressure should be closely monitored in case of co-administration of celiprolol and dihydropyridine derivatives especially when therapy is initiated.
Drugs inhibiting prostaglandin synthetase, such as ibuprofen or indomethacin, may decrease the hypotensive effects of beta-blockers.
Sympathomimetic agents, such as adrenaline, may counteract the effects of beta- blockers.
Concomitant administration may potentiate the anti-hypertensive effect of beta- blockers and the risk of orthostatic hypotension.
Concomitant therapy with mefloquine may cause bradycardia.
The safety of this medicinal product for use in human pregnancy has not been established. An evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to reproduction, development of the embryo or fetus, the course of gestation and peri- and post-natal development.
However, beta-blockers in general have been associated with reduced placental perfusion, which may result in intrauterine fetal death, immature and premature deliveries. Celiprolol should therefore not be used during pregnancy unless there is no safer alternative.
In the newborn of treated mothers, beta-blocking activity persists for several days after birth and this may result in an increased risk of cardiac and pulmonary complications in the neonate in the post-natal period. In addition, adverse effects (especially hypoglycaemia, bradycardia and respiratory distress) may occur in fetus and neonate. Therefore close monitoring of the neonate is recommended for the first 3-5 days of life.
Most beta-blockers will pass into breast milk, although to variable extents. The use of Celectol is therefore not recommended in breast-feeding mothers.
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.
Adverse drug reactions are listed below by system organ class and frequency. Frequencies are defined as: 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).
Beta-blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia (in particular, tachycardia).
The following undesirable effects, listed by body system, are generally attributable to the pharmacological activity of beta-blockers:
Not known: hypoglycaemia, hyperglycemia (see sections 4.4 and 4.5)
Common: depression
Uncommon: insomnia
Not known: libido decrease, hallucination, nightmare Confusion and psychoses have also been reported.
Common: tremor, paraesthesia, headache, asthenia, somnolence, dizziness
Not known: xerophthalamias, impaired vision
Uncommon: palpitations
Not known: bradycardia, syncope, cardiac failure and arrhythmias (including slowed A-V conduction and in susceptible patients there may be precipitation of existing A-V block).
Common: hot flush, aggravation of peripheral vascular disorders such as intermittent claudication, or Raynaud’s phenomenon (see sections 4.3 and 4.4)
Uncommon: hypotension, peripheral coldness
Uncommon: dyspnoea
Not known: bronchospasm (in patients with bronchial asthma or with a history of bronchial complaints) and interstitial pneumonitis
Common: vomiting, nausea, abdominal pain, dry mouth
Not known: diarrhoea
Common: hyperhidrosis, erythema, rash, pruritus
Not known: dermatitis psoriasiform, aggravation of psoriasis
Uncommon: muscle spasms
Not known: systemic lupus erythematosus, arthralgia
Common: erectile dysfunction
Common: increase in antinuclear antibodies (ANAs)
Not known: hepatic transaminases increased
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None stated.
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