SUMMARY OF PRODUCT CHARACTERISTICS
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1. NAME OF THE MEDICINAL PRODUCT
Cirrus 5 mg/120 mg Prolonged Release Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet provides 5 mg cetirizine dihydrochloride for immediate release, and 120 mg pseudoephedrine hydrochloride for prolonged release.
Excipients with known effect: one tablet contains 43.23 mg lactose monohydrate
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Prolonged release tablet. White to off-white, round, biconvex circle-embossed, film-coated tablet, having a circular logo on one side.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Cetirizine-pseudoephedrine is indicated for the treatment of symptoms such as nasal congestion, sneezing, rhinorrhoea, and nasal and ocular pruritus associated with seasonal or perennial allergic rhinitis. Cetirizine-pseudoephedrine should be administered when the anti- allergic properties of cetirizine dihydrochloride and the nasal decongestant activity of pseudoephedrine hydrochloride are desired.
4.2 Posology and method of administration
Posology Adults One tablet two times a day (morning and evening), corresponding to the maximum recommended dose of 10 mg of cetirizine dihydrochloride and 240 mg of pseudoephedrine hydrochloride daily.
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Special populations
Paediatric population Adolescents from 12 years of age and above: 1 tablet two times a day (morning and evening), with or without food.
Children under 12 years of age: the use of the product is contraindicated (see sections 4.3 and 4.4).
Renal impairment The dose should be reduced to 1 tablet daily in patients with moderate renal insufficiency.
Hepatic impairment The dose should be reduced to 1 tablet daily in patients with moderate hepatic insufficiency.
Duration of treatment The duration of treatment should not exceed the period of symptoms and should not exceed 2 to 3 weeks at the recommended dose (1 tablet, twice daily). After disappearance of nasal symptoms, treatment should be continued with an antihistamine alone.
Method of administration Tablets should be swallowed whole with some liquid, and must not be broken, chewed or crushed. They may be taken with or without food.
4.3 Contraindications
Cetirizine-pseudoephedrine is contra-indicated in patients with: • known hypersensitivity to the active substances or to any of the excipients listed in section 6.1, to ephedrine or piperazine • hypertension or ischaemic heart disease • severe renal insufficiency • uncontrolled hyperthyroidism • severe arrhythmias • pheochromocytoma • elevated intraocular pressure • urinary retention • during administration of antihypertensives such as ß-blockers, sympathomimetics, dihydroergotamine or amphetamines • during treatment with monoamine oxidase inhibitors (MAOI), up to 2 weeks after their discontinuation
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• a history of stroke or increased risk of haemorrhagic stroke. This includes concomitant treatment with vasoconstrictors (e.g. bromocriptine, pergolide, lisuride, cabergoline, ergotamine, dihydroergotamine) or any other decongestant drug (e.g. phenylpropanolamine, phenylephrine, ephedrine) used either by oral route or by nasal route, as vasoconstriction and elevated blood pressure increase the risk of haemorrhagic stroke.
Cetirizine-pseudoephedrine is contraindicated in children under 12 years of age (see section 4.2 and 4.4).
4.4 Special warnings and precautions for use
The physician or pharmacist should reassure himself that sympathomimetic containing preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations).
Cetirizine-pseudoephedrine should be used with caution in patients over 50 years of age, patients with diabetes mellitus, hyperthyroidism, tachycardia, cardiac arrhythmia, angina, moderate hepatic or renal insufficiency, and in cases of ingestion of alcohol or other central nervous system (CNS) depressants and also in the elderly.
Caution should be taken in patients with medical conditions where anticholinergic activity is undesirable and specifically in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia, prostatic hypertrophy, or bladder outflow obstruction) as cetirizine/pseudoephedrine may increase the risk of urinary retention.
Cetirizine-pseudoephedrine is contraindicated in children under 12 years of age (see section 4.2 and 4.3) because the combination has not been studied in this age group and due to the presence of pseudoephedrine.
Caution should also be exercised in patients with a history of stroke or at high risk of such.
Due to the vasoconstrictor effect of pseudoephedrine, caution is recommended in patients who are at risk for hypercoagulability, as in inflammatory bowel disease.
Some cases of ischaemic colitis have been reported with pseudoephedrine. The product should be discontinued, and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.
Caution is also essential in patients taking sympathomimetics (decongestants, anorexigenic substances or psychostimulants such as amphetamines), tricyclic antidepressants, linezolid, guanethidine, reserpine, phenothiazines, antihypertensives (see section 4.5), cardiac glycosides such as digoxin or digitoxin (risk of cardiac arrhythmia).
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Caution is required in hypertensive patients who are treated concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs), because both pseudoephedrine and NSAIDs can increase blood pressure.
This product may act as a cerebral stimulant giving rise to insomnia, nervousness, hyperpyrexia, tremor and epileptiform convulsions.
As with centrally acting stimulants, cases of abuse have been observed with pseudoephedrine.
At therapeutic doses, no clinically significant interactions of cetirizine have been demonstrated with alcohol (for a blood alcohol level of 0.5 g/L). Nevertheless, precaution is recommended if alcohol or other substances with CNS depressant activity is taken concomitantly with cetirizine-pseudoephedrine
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free.
Ischaemic optic neuropathy Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with the combination medicinal product cetirizine-pseudoephedrine.
No clinically significant interaction has been described with cetirizine, but caution is recommended on concomitant use of sedatives.
In a multiple dose study of theophylline (400 mg once a day) and cetirizine, there was a small (16%) decrease in clearance of cetirizine, while exposure to theophylline was not altered by concomitant cetirizine administration.
In a multiple dose study of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), the extent of exposure to cetirizine was increased by about 40% while the exposure to ritonavir was slightly altered (-11%) further to concomitant cetirizine administration.
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Concomitant use of cetirizine-pseudoephedrine and MAOI or ß-blockers can cause blood pressure to increase. Given the long duration of action of MAOI, this interaction is still possible 2 weeks after discontinuation of such treatment.
An increase in blood pressure can also occur on concomitant administration of dihydroergotamine or linezolid.
The following combinations are not recommended as there is a risk of vasoconstriction and increased blood pressure: bromocriptine, cabergoline, lisuride, pergolide, as well as dihydroergotamine, ergotamine, methylergometrine, and other vasoconstrictors used as oral or nasal decongestants (phenylpropanolamine, phenylephrine, ephedrine, …).
Sympathomimetic amines can reduce the antihypertensive effect of drugs which interfere with sympathetic activity including methyldopa, α- and β-adrenergic blocking agents.
Tricyclic antidepressants can potentiate the hypertensive effect of pseudoephedrine.
The ectopic activity of a pacemaker can be increased when pseudoephedrine is used with cardiac glycosides, such as digoxin or digitoxin; use of cetirizine-pseudoephedrine is therefore not advised in patients treated with cardiac glycosides.
Antacids and proton pump inhibitors increase the absorption of pseudoephedrine, kaolin reduces absorption.
Concurrent use with halogenated anaesthetic agents such as chloroform, enflurane, isoflurane, cyclopropane, halothane may provoke or worsen ventricular arrhythmia.
The concurrent use of alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance, although cetirizine does not potentiate the effect of alcohol (0.5 g/L blood levels). No negative effects of pseudoephedrine have been reported nor are they expected.
Antihistamines can interfere with cutaneous tests for allergies and an appropriate wash-out period of 3 days is required before conducting such tests.
4.6 Fertility, pregnancy and lactation
Pregnancy There are no or limited amount of data on the use of cetirizine-pseudoephedrine in pregnant women. Cetirizine-pseudoephedrine is not recommended during pregnancy. The use of pseudoephedrine during the first trimester of pregnancy has been associated with an increased frequency of gastroschisis (a developmental defect in the abdominal wall with intestinal herniation) and of small intestinal atresia (congenital obstruction of small intestine).
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Due to the vasoconstrictive properties of pseudoephedrine, cetirizine-pseudoephedrine should not be used during the third trimester as it can induce a reduction in uteroplacental circulation. Data on a limited number of exposed pregnancies indicate no adverse effects of cetirizine on pregnancy or on the health of the fetus/ newborn child. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).
Breast-feeding Cetirizine and pseudoephedrine are excreted into human milk. Therefore, cetirizine- pseudoephedrine is not recommended during breast-feeding.
Fertility A study in rats did not reveal any impact on fertility at an oral dose of 160 mg/kg (containing 6.4 mg/kg cetirizine and 153.6 mg/kg pseudoephedrine), producing systemic exposure to cetirizine 2 fold higher than the therapeutic exposure in humans (section 5.3). There are no available data on fertility in humans.
Pseudoephedrine affected spermatogenesis in the rat following i.p. administration but the relevance to humans following oral administation is unknown (see section 5.3).
4.7 Effects on ability to drive and use machines
Patients intending to drive vehicles, to perform potentially hazardous activities or operating machinery should not exceed the recommended dose and take into account the individual’s response to the medicinal product. Patients who experience somnolence should refrain from driving, engaging in potentially hazardous activities or operating machinery.
In patients administered with cetirizine at the approved dose of 10 mg/day, objective measurements of driving ability, sleep latency and assembly line performance, have not demonstrated any clinically relevant effects. Nonetheless, concurrent use of cetirizine with alcohol or other substances with CNS depressant activity may cause additional reductions in alertness and impairment of performance.
No negative effects of pseudoephedrine on the ability to drive and use machines have been reported nor are they expected.
It should nevertheless be noted that variations in these effects exist with different drugs in different individuals: in clinical trials, subjective feelings of somnolence have been reported. At doses higher than normally recommended, central nervous system effects may occur.
4.8 Undesirable effects
Post-marketing experience
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The following table lists the undesirable effects by body system and by frequency. The frequencies are defined as follows: very common (1/10); common (1/100, <1/10); uncommon (1/1000, <1/100); rare (1/10000, <1/1000); very rare (<1/10000), not known (cannot be estimated from the available data).
Immune system disorders: Rare: hypersensitivity reactions (including anaphylactic shock)
Psychiatric disorders: Common: nervousness, insomnia Uncommon: agitation, anxiety Rare: hallucinations Very rare, including isolated cases: psychotic disorder
Nervous system disorders: Common: vertigo, dizziness, headache, drowsiness Rare: convulsions, tremor Very rare: dysgeusia, cerebrovascular accident (stroke)
Eye disorders: Not known: accommodation disorder, blurred vision, mydriasis, eye pain, visual impairment, photophobia, ischaemic optic neuropathy
Cardiac disorders: Common: tachycardia Rare: arrhythmia Not Known: palpitations
Vascular disorders: Rare: pallor, arterial hypertension Very rare: circulatory collapse
Respiratory, thoracic and mediastinal disorders: Not known: dyspnoea
Gastrointestinal disorders: Common: dry mouth, nausea Rare: vomiting Not known: ischaemic colitis
Hepatobiliary disorders:
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Rare: abnormal hepatic function (elevation in transaminases, alkaline phosphatases, gamma-GT and bilirubin)
Skin and subcutaneous tissue disorders: Rare: dry skin, rash, sweating increased, urticaria Very rare: angioneurotic oedema, fixed drug eruption Not known: acute generalized exanthematous pustulosis
Renal and urinary disorders: Rare: dysuria Not known: urinary retention
Reproductive system and breast disorders Not known: erectile dysfunction
General disorders and administration site conditions: Common: asthenia
Isolated cases of hepatitis have been reported when cetirizine alone is administered
Reporting of suspected adverse reactions 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 national reporting system listed in Appendix V.
4.9 Overdose
1. Pseudoephedrine
Symptoms: A severe overdose of pseudoephedrine can cause vomiting, mydriasis, tachycardia, arrhythmia, hypertension, signs of CNS depression (sedation, apnoea, loss of consciousness, cyanosis and cardiovascular collapse) or CNS stimulation (insomnia, hallucinations, tremors, convulsions) that can be fatal.
Treatment: Treatment for overdose, preferably given in hospital, should be symptomatic and supportive. Consideration should be given to the possible concomitant ingestion of other drugs. If spontaneous vomiting does not occur, it should be induced; gastric lavage is recommended. After vomiting, the drug remaining in the stomach can be absorbed by administration of an aqueous suspension of charcoal. The usual supportive measures should be undertaken, including frequent monitoring of vital signs.
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No antidote is known. Sympathomimetic amines should not be used. Hypertension should be controlled with an alpha-adrenergic blocking agent and tachycardia by a beta-adrenergic blocker. Epileptic seizures can be treated with 10 mg of diazepam intravenously (or by 0.5 mg/kg by the rectal route in children). Cetirizine and pseudoephedrine are poorly eliminated by haemodialysis.
2. Cetirizine
Symptoms: Sedation can be a symptom of overdose; it appears with a single dose of 50 mg upwards.
Treatment: At the present time there is no specific antidote. In the case of massive overdose, gastric lavage should be performed as soon as possible. The usual supportive measures should be undertaken, with frequent monitoring of vital signs.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Nasal decongestants for systemic use, ATC code: R01B A52
The pharmacodynamic activity of cetirizine-pseudoephedrine is directly related to the effects of its active constituents.
1. Cetirizine:
In animal studies, cetirizine acts as a H1-antagonist devoid of significant anticholinergic and antiserotoninergic effects. In pharmacologically active doses, it induces neither sedation nor behavioural changes, which may be due to the absence of passage through the blood-brain barrier.
In human pharmacological studies, cetirizine has been shown capable of inhibiting some of the effects of exogenous histamine. The onset of this action is rapid. Cetirizine also inhibits the effects of endogenous histamine liberated in vivo by a histamine-releasing agent such as compound 48/80 (synthetic polyamine, condensation product of N-methyl-p- methoxyphenylethylamine with formaldehyde). In addition, it inhibits the skin reaction induced by VIP (Vasoactive Intestinal Polypeptide) and substance P, both of which are neuropeptides considered to be involved in the allergic reaction. Cetirizine inhibits the histamine-mediated early phase of the allergic reaction. It also significantly inhibits the migration of inflammatory cells (including eosinophils) and the release of mediators associated with the late allergic response.
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Moreover, it reduces the allergic reaction caused by specific antigens. These effects are achieved without any objective effect on the central nervous system, either in psychometric tests or in the quantitative EEG.
2. Pseudoephedrine:
Pseudoephedrine, a stereoisomer of ephedrine, is an orally active sympathomimetic, whose alpha-mimetic effects are greater than its beta-mimetic activity; due to its vasoconstrictor action, it has a decongestant effect on the nasal mucosa. In recommended doses, it can induce other sympathomimetic effects such as a rise in blood pressure, tachycardia or symptoms of central excitation such as insomnia.
5.2 Pharmacokinetic properties
1. Cetirizine:
Cetirizine is rapidly and almost completely absorbed after oral administration. Under fasting conditions, peak plasma concentrations are generally obtained after 1 hour. The degree of absorption is not reduced by the presence of food, but the rate of absorption is slowed and peak concentrations do not appear until 3 hours after administration. Cetirizine is not subject to appreciable metabolism during the first hepatic passage. After repeated oral administration, the daily urinary excretion of unchanged cetirizine is approximately 65% of the administered dose. Absorption and elimination of cetirizine are independent of the dose. The degree of inter- and intra-individual variation is low. The plasma half-life of cetirizine is 9 hours and this value increases in patients with renal insufficiency. Cetirizine is highly bound to plasma proteins (93%).
2. Pseudoephedrine:
Pseudoephedrine is rapidly and completely absorbed after oral administration. Pseudoephedrine in a sustained release form allows maximum plasma concentrations to be reached after 8 hours.
Between a quarter and half of the administered dose of pseudoephedrine is transformed in the liver by N-demethylation into an active metabolite, nor-pseudoephedrine. This metabolite, together with the remaining non-metabolised pseudoephedrine, is excreted in the urine. The rate of urinary excretion is increased if the pH of the urine is decreased and decreased in the case of urinary alkalinisation. A meal rich in fat does not affect the absorption of pseudoephedrine.
On repeated oral administration (every 12 hours), the steady state is reached after 6 days of treatment and the half-life has been estimated as 15 hours.
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3. Combination:
There is no evidence of a significant pharmacokinetic interaction between cetirizine and pseudoephedrine.
5.3 Preclinical safety data
Animal studies have demonstrated no-toxic effect levels at 40 mg/kg/day in the Cynomolgus monkey (3.7- and 1.8-fold human exposure for pseudoephedrine and cetirizine respectively) and at 30 mg/kg/day in the rat (0.6-fold human exposure for pseudoephedrine; ratio for cetirizine unknown).
A no-effect level of 40 mg/kg/day was established in reproduction toxicity studies in the rat. Due to the low level of systemic exposure obtained in this species, these results cannot be considered as demonstrating the safety of use in pregnant and breast-feeding women.
Fertility in male and female rats was unimpaired at oral doses up to 160 mg/kg/day (1:24) in reproduction toxicology studies, which represents a systemic exposure 2- fold the therapeutic exposure in humans to cetirizine. Overall, the cetirizine/pseudoephedrine combination did not produce any adverse effects on embryo-foetal viability and development of the offspring, at clinically relevant doses. At doses of 160 mg/kg/day in pregnant rats (~7.5- x therapeutic exposure in humans for pseudoephedrine, and around therapeutic exposure for cetirizine) observations included decreased pup survival, a small increase in bone deformations, and delay of some development parameters.
Pseudoephedrine affected spermatogenesis in the rat after i.p. administration at doses 5-fold the maximum human recommended dose based on allometric scaling. Based on oral bioavailability, higher safety margins can be expected following p.o. administration. The relevance of this non-clinical observation with a different route of administration to humans is unknown.
There has been no carcinogenicity studies conducted with pseudoephedrine in combination with cetirizine.
The combination cetirizine/pseudoephedrine is neither mutagenic nor clastogenic and therefore unlikely to present a carcinogenic risk for humans. Cetirizine did not have any carcinogenic potential in rats and mice when dosed up to maximum tolerated dose (23 and 2.3 times the highest recommended daily dose in man, based on body surface area). No carcinogenicity study was performed with pseudoephedrine. However conventional carcinogenicity studies in mice and rats with the diastereomer ephedrine were concluded negative. Although there is a lack of carcinogenicity studies performed with combination
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6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core: • Hypromellose • Microcrystalline cellulose • Colloidal silica anhydrous • Magnesium stearate • Lactose monohydrate • Croscarmellose sodium
Coating material: Opadry Y-1-7000 which consists of: • Hypromellose (E464) • Titanium dioxide (E171) • Macrogol 400
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
The tablets are packed in thermoformed blisters (polyvinylchloride - aluminium) 6 or 14 tablets per blister; 1 blister per box.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
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Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORIZATION HOLDER
[To be completed nationally]
8. MARKETING AUTHORIZATION NUMBER
[To be completed nationally]
9. DATE OF FIRST AUTHORIZATION/RENEWAL OF AUTHORIZATION
Date of first authorisation: 4th September 1995 Date of latest renewal: 20th June 2011
10. DATE OF REVISION OF THE TEXT
{MM/YYYY}
LABELLING
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PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON BOX
1. NAME OF THE MEDICINAL PRODUCT
Cirrus 5 mg/120 mg prolonged-release tablets
Cetirizine dihydrochloride/Pseudoephedrine hydrochloride
2. STATEMENT OF ACTIVE SUBSTANCE(S)
One tablet contains 5 mg cetirizine dihydrochloride and 120 mg pseudoephedrine hydrochloride
3. LIST OF EXCIPIENTS
Contains lactose. See leaflet for further information.
4. PHARMACEUTICAL FORM AND CONTENTS
6 prolonged release tablets 14 prolonged release tablets
5. METHOD AND ROUTE(S) OF ADMINISTRATION
Take the tablet whole. Do not break, chew or crunch. Read the package leaflet before use. Oral use.
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN
Keep out of the sight and reach of children.
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7. OTHER SPECIAL WARNING(S), IF NECESSARY
8. EXPIRY DATE
EXP: {MM-YYYY}
9. SPECIAL STORAGE CONDITIONS
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
[To be completed nationally]
12. MARKETING AUTHORISATION NUMBER(S)
[To be completed nationally]
13. BATCH NUMBER
Batch: {number}
14. GENERAL CLASSIFICATION FOR SUPPLY
15. INSTRUCTIONS ON USE
Green = OTC specific information Purple = POM specific information Cirrus reliefs symptoms such as blocked nose, sneezing, runny nose, itchy nose or itchy eyes associated with allergic rhinitis (hay fever, house-dust allergy) Dosage: Adults and children over 12 years of age: take 1 tablet twice daily (one in the morning and one in the evening). If you suffer from kidney or liver disease a dose adjustment may be needed. Do not exceed the stated dose. Cirrus does not normally cause drowsiness. However, in rare cases Cirrus may reduce alertness. Use caution when taking Cirrus with alcohol or other sedatives as they may cause additional reductions in alertness and impairment of performance. If you are affected by this reduction in alertness, or if you suffer from tiredness or somnolence (drowsiness), you must not drive or use machines. Not recommended during pregnancy or breast-feeding. Ask your doctor or pharmacist for advice. Consult your doctor if symptoms persist after 7 days.> 16. INFORMATION IN BRAILLE Cirrus 5 mg/120 mg 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included. 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA PC: SN: NN: Green = OTC specific information Purple = POM specific information MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTER 1. NAME OF THE MEDICINAL PRODUCT Cirrus 5 mg/120 mg prolonged-release tablets Cetirizine dihydrochloride/Pseudoephedrine hydrochloride 2. NAME OF THE MARKETING AUTHORISATION HOLDER [To be completed nationally] 3. EXPIRY DATE EXP: {MM-YYYY} 4. BATCH NUMBER Batch: {number} 5. OTHER PACKAGE LEAFLET Green = OTC specific information Purple = POM specific information Package leaflet: Information for the patients Cirrus 5 mg/120 mg prolonged-release tablets (5 mg cetirizine dihydrochloride - 120 mg pseudoephedrine hydrochloride) What is in this leaflet: 1. What Cirrus is and what it is used for 2. What you need to know before you take Cirrus 3. How to take Cirrus 4. Possible side effects 5. How to store Cirrus 6. Contents of the pack and other information 1. What Cirrus is and what it is used for Cirrus 5mg/120mg prolonged release tablets contains two active substances: cetirizine dihydrochloride which is an antihistamine and pseudoephedrine hydrochloride which is a decongestant. Green = OTC specific information Purple = POM specific information Cirrus is a medicine that is used to relieve allergic symptoms, especially when the anti- allergy properties of cetirizine are combined with the effects of pseudoephedrine in reducing swelling of the mucous membranes inside the nose. Cirrus is indicated for the treatment of symptoms such as blocked nose, sneezing, runny nose, itchy nose or itchy eyes, which occur in seasonal allergic rhinitis (hay fever) or perennial allergic rhinitis (house-dust allergy). Cirrus is indicated for adults and adolescents from 12 years of age and above. 2. What you need to know before you take Cirrus Do not take Cirrus - if you are allergic to cetirizine, ephedrine or any of the other ingredients of this medicine (listed in section 6) or to piperazine derivative (closely related active sustances of other medicines). - if you have high blood pressure or coronary heart disease. - if you suffer from impaired kidney function, impaired thyroid function or a tumour called a phaeochromocytoma, if you have serious disturbances of heart rhythm, increased intraocular pressure (inside the eye) or urination problems. - if you are taking medication for high blood pressure such as beta-blockers, sympathomimetics (medicines that reduce swelling), dihydroergotamine (for problems with the circulation) or amphetamines (stimulants). - if you are receiving treatment with monoamine oxide inhibitors (MAOI; antidepressants) or have taken these within the last two weeks. - if you have had a cerebrovascular event (stroke) or display risk factors that increase the risk of a cerebrovascular haemorrhage, due to the blood-vessel-narrowing action of Cirrus in combination with medicines such as bromocriptine, pergolide, lisuride, cabergoline, ergotamine, dihydroergotamine or any other medicines that reduce swelling (phenylpropanolamine, phenylephrine, ephedrine etc.), irrespective of the method of administration. - if you are under 12 years of age Warnings and precautions Talk to your doctor or pharmacist before taking Cirrus: - if you are over 50 years of age. - if you are a diabetic or suffer from hyperthyroidism (overactive thyroid) or heart problems (too fast or irregular rhythm, angina pectoris). - if you suffer from moderate liver or kidney impairment. - if your prostate is enlarged or you have problems urinating. - if you regularly consume alcohol or take medication that depresses the central nervous system. Green = OTC specific information Purple = POM specific information - if you are taking/using medicines that belong to the class of drugs called sympathomimetics (medicines that reduce swelling, appetite suppressants, stimulants such as amphetamines). - if you are at risk of excessive blood clotting e.g. from chronic inflammatory bowel disease. - if you are taking medications for depression (tricyclic antidepressants), medication for the heart (cardiac glycosides such as digoxin or digitoxin), linezolide (antibiotic), guanethidine, reserpine, phenothiazine or antihypertensives. - if you have a medical condition that could lead to inability to empty the bladder (urinary retention) [e.g. spinal cord damage (spinal cord lesion), enlarged prostate gland (prostatic hypertrophy , prostatic hyperplasia) or difficulty passing urine (bladder outflow obstruction)] as Cirrus may increase the risk of urinary retentionif you suffer from high blood pressure and are taking non-steroidal anti-inflammatory drugs, your blood pressure may increase. - if you are already taking other medicines, please read the section “Other medicines and Cirrus”. - if you have had a cerebrovascular event (stroke) or have risk factors for experiencing such an event. - this medicine may act as a cerebral stimulant and make insomnia, nervousness, fever, tremors and epileptic seizures worse. Sudden abdominal pain or rectal bleeding may occur with Cirrus, due to inflammation of the colon (ischaemic colitis). If you develop these gastro-intestinal symptoms, stop taking Cirrus and contact your doctor or seek medical attention immediately. (see section 4) Reduction of blood flow to your optic nerve may occur with Cirrus. If you develop sudden loss of vision, stop taking Cirrus and contact your doctor or seek medical attention immediately. See section 4. Children Do not give this medicine to children under 12 years of age. Other medicines and Cirrus Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. - Combination with the following medicines should be avoided: bromocriptine, cabergoline, lisuride, pergolide, dihydroergotamine, ergotamine, methylergometrine and other vasoconstricting substances for oral use or local use in the nose (phenyl- propanolamine, ephedrine, phenylephrine etc). - Caution is advised with simultaneous administration of sedatives (tranquillisers), theophylline (anti-asthma medication), ritonavir (HIV medication), certain antidepressants (MAO inhibitors, even if you have not been taking them in the last two Green = OTC specific information Purple = POM specific information weeks) and tricyclic antidepressants), antihypertensives (alpha-blockers and beta- blockers, methyldopa), medicines for the circulation (dihydroergotamine), antibiotics containing linezolide, medications for the heart (cardiac glycosides such as digoxin or digitoxin). - Some antacids may increase the effect of Cirrus, others may reduce it (kaolin). - If you are scheduled for allergy testing, ask your doctor if you should stop taking Cirrus for 3 days before testing. This medicine may affect your allergy test results. Cirrus with food and drink Cirrus may be taken with or without food. Pregnancy, breast-feeding, and fertility Cirrus is not recommended during pregnancy and breast-feeding. If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice. Driving and using machines Patients intending to drive vehicles, to perform potentially hazardous activities or operating machinery should not exceed the recommended dose and take into account the individual response to Cirrus. Use caution when taking Cirrus with alcohol or other sedatives as they may cause additional reductions in alertness and impairment of performance. If you experience somnolence (drowsiness), you should refrain from driving, engaging in potentially hazardous activities or operating machinery. Cirrus contains lactose If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. Cirrus contains sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free. 3. How to take Cirrus Green = OTC specific information Purple = POM specific information The recommended dose is: 1 tablet twice daily (one in the morning and one in the evening). Use in children and adolescents Adolescents from 12 years of age and above: 1 tablet twice daily (one in the morning and one in the evening). Cirrus is contraindicated for children younger than 12 years. If you suffer from kidney or liver disease, please inform your doctor or pharmacist, who may adjust your dose. Method of administration and duration of treatment: Oral use. The tablet must be swallowed whole with a some liquid with or without food and must not be broken, crunched or chewed. After the allergy-induced symptoms have been relieved, it is often recommended that treatment is continued in the pollen season with a medication that contains only an anti- allergy substance. If symptoms have not subsided after 7 days, ask your doctor for advice. If you take more Cirrus than you should If you have taken or used more Cirrus than you should, contact your doctor or pharmacist immediately. A significant overdose can cause the following symptoms: vomiting, dilated (abnormally large) pupils, disturbances of heart rhythm, high blood pressure, depression of the central nervous system (sedation, breathing difficulties, loss of consciousness, cyanosis (bluish discolouration due to oxygen deficiency), cardiovascular collapse (circulatory failure)) or stimulation of the central nervous system (insomnia, hallucinations, tremor, seizures) which may prove fatal. There is no specific antidote. Treatment should take place in a hospital. If the person affected does not vomit spontaneously, an attempt can be made to induce vomiting. Read also the section for healthcare professionals. If you forget to take Cirrus If you forget to take a tablet, take it as soon as you remember. However, the subsequent tablets must be spaced 12 hours apart. Do not take more than two tablets in 24 hours. Green = OTC specific information Purple = POM specific information If you stop taking Cirrus Only take this medicine if you suffer from allergy symptoms. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. The following are known side effects: Common side effects (may affect up to 1 in 10 patients): rapid heart rate, dry mouth, nausea, weakness (asthenia), dizziness, somnolence, headache, vertigo, nervousness, insomnia Uncommon side effects (may affect up to 1 in 100 patients): agitation, anxiety Rare side effects (may affect up to 1 in 1000 patients): disturbances of heart rhythm, pallor, arterial hypertension, vomiting, abnormal liver function (increase in certain enzymes), hypersensitivity reactions (including anaphylactic shock), convulsions, tremor, hallucinations, urination difficulties, dry skin, eruption, sweating, urticaria Very rare side effects (may affect up to 1 in 10000 patients): circulatory collapse (circulatory disorder), altered taste (dysgeusia), cerebrovascular event (stroke), psychosis (in isolated cases), serious allergic reaction which causes swelling of the face or throat (angioedema), fixed drug eruption Not known frequency of side effects (frequency cannot be estimated from the available data): blurred vision, eye disorder - difficulty focusing (accommodation disorder), abnormal dilation of the pupil of the eye (mydriasis), eye pain, visual impairment, abnormal eye sensitivity or intolerance to visual perception of light (photophobia), reduced blood flow to the optic nerve (ischaemic optic neuropathy), difficulty in breathing (dyspnoea), erectile dysfunction, difficulty emptying the bladder (urinary retention), Severe skin reactions characterized by fever and numerous small, superficial pustules, arising within large areas of redness, unpleasant sensation of faster and/or stronger/irregular beating of the heart and inflammation of the colon due to insufficient blood supply (ischaemic colitis). Isolated cases of inflammation of the liver (hepatitis) have been reported when cetirizine alone is administered. Reporting of side effects Green = OTC specific information Purple = POM specific information If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine. 5. How to store Cirrus Keep this medicine out of the sight and reach of children. This medicinal product does not require any special storage conditions. Do not use this medicine after the expiry date which is stated on the carton and blister pack after EXP. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. 6. Contents of the pack and other information What Cirrus contains - The active substances are cetirizine dihydrochloride and pseudoephedrine hydrochloride. Each prolonged release tablet contains 5 mg cetirizine dihydrochloride and 120 mg pseudoephedrine hydrochloride. - The other ingredients are: tablet: hypromellose, microcrystalline cellulose, colloidal anhydrous silica, magnesium stearate, lactose monohydrate, croscarmellose-sodium; coating: Opadry Y-1-7000 (= hypromellose (E464), titanium dioxide (E171), Macrogol 400). See section 2 “Cirrus contains lactose”. What Cirrus looks like and contents of the pack Cirrus is a prolonged-release film-coated tablet, i.e. the contents are released slowly in order to allow for an effective treatment over a period of approximately 12 hours. Each round, biconvex tablet has a round logo engraved on one side. Cirrus is available in boxes containing a blister with 6 or 14 tablets. Not all pack sizes may be marketed. Green = OTC specific information Purple = POM specific information Marketing Authorisation Holder and Manufacturer For more information about the medicine please contact your doctor or pharmacist. If you wish, you can also contact the local representative of the Marketing Authorisation Holder: [To be completed nationally] Manufacturer: This medicinal product is authorised in the Member States of the EEA under the following names: Belgium: Cirrus Cyprus: Zyrtec-D Ireland: Zirtek Plus Decongestant Malta: Cirrus This leaflet was last revised in {MM/YYYY} ------ The following information is intended for healthcare professionals only: Simultaneous administration of halogenated anaesthetics such as chloroform, enflurane, isoflurane, cyclopropane, halothane can trigger or exacerbate ventricular arrhythmia. In the event of an overdose cetirizine and pseudoephedrine are hardly eliminated at all by haemodialysis.