Cetirizine/ pseudoephedrine is indicated for symptomatic treatment of acute rhinitis with nasal congestion and hypersecretion, nose and/ or eye itching and watery eyes.

It should be administered when both the anti-allergenic properties of cetirizine dihydrochloride and the nasal decongestant activity of pseudoephedrine hydrochloride are desired.

The tablet should be swallowed whole with some liquid, and must not be broken, chewed or crushed. It may be taken with or without food.

After consultation with the doctor, duration of treatment should not exceed the period of acute symptoms and should not exceed 2 - 3 weeks. After improvement of nasal symptoms, treatment should be continued only with cetirizine, where appropriate.

Route of Administration 

For oral use.

Adults and Children aged 12 years and older 

One tablet twice daily (morning and evening).

Children under 12 years of age

Cetirizine/ pseudoephedrine is contraindicated in children under 12 years of age (see Sections: Contraindications; Special warnings and precautions for use).

Elderly

No data.

Renal impairment 

The dose should be reduced to one tablet daily in patients with moderate renal insufficiency. Cetirizine/ pseudoephedrine is contraindicated in severe renal insufficiency (see Section Contraindications).

Hepatic impairment 

The dose should be reduced to one tablet daily in patients with moderate hepatic insufficiency.

Cetirizine/ pseudoephedrine is contraindicated in: • known hypersensitivity to the active substances or excipients, to ephedrine or any other piperazine, • severe hypertension or severe ischaemic heart disease, • severe renal insufficiency, • uncontrolled hyperthyroidism, • severe arrhythmias, • phaeochromocytoma, • elevated intraocular pressure, • urinary retention, • glaucoma, • history of stroke • high risk of haemorrhagic stroke (see Section Special warnings and precautions for use), • concomitant administration of dihydroergotamine (see Section Interactions), • concomitant treatment with MAOI and within 2 weeks after their discontinuation (see Section Interactions), • children under 12 years of age (see Section Special warnings and precautions for use).

General precautions

Due to the presence of pseudoephedrine, cetirizine/pseudoephedrine should be used with caution in patients with diabetes mellitus, hyperthyroidism, arterial hypertension, tachycardia, cardiac arrhythmia, ischaemic heart disease, moderate hepatic or renal insufficiency, and also in the elderly.

Caution is also required in patients taking:

·       sympathomimetics including decongestants (e.g. phenylpropanolamine, phenylephrine, ephedrine), anorexigenic substances or psychostimulants such as amphetamines (combined effects on the cardiovascular system),

·       tricyclic antidepressants,

·       antihypertensives drugs (reduction of antihypertensive effects) (see Section Interactions),

·       alcohol and other central nervous system (CNS) depressants (increased depressing action on the CNS and reduced performance),

·       cardiac glycosides such as digoxin or digitoxin (risk of cardiac arrhythmia) (see Section Interactions),

·       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.

 

Posterior reversible encephalopathy (PRES)/reversible cerebral vasoconstriction syndrome (RCVS)

There have been rare cases of posterior reversible encephalopathy (PRES)/reversible cerebral vasoconstriction syndrome (RCVS) reported with sympathomimetic drugs, including pseudoephedrine. Symptoms reported included sudden onset of severe headache, nausea, vomiting, and visual disturbances. Most cases improved or resolved within a few days following appropriate treatment. Pseudoephedrine should be discontinued immediately and medical advice sought if signs/symptoms of PRES/RCVS develop.

Vasoconstrictor effect

Caution should also be taken in patients with factors which could increase the risk of haemorrhagic stroke (including concomitant use of vasoconstrictors such as bromocriptine, pergolide, lisuride, cabergoline, ergotamine), or any other decongestant drug used as nasal decongestant, either by oral route or by nasal route (for example phenylpropanolamine, phenylephrine, ephedrine), due to the risk of vasoconstriction and increased blood pressure.

Due to vasoconstrictor effect of pseudoephedrine, caution is recommended in patients who are at risk for hypercoagulability, as in inflammatory bowel disease.

Use with NSAIDs in hypertensive patients

Caution is required in hypertensive patients who are treated concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs), because both pseudoephedrine and NSAIDs can increase blood pressure.

Cases of abuse

As with centrally acting stimulants, cases of abuse have been observed with pseudoephedrine.

Ischaemic colitis

Some cases of ischemic colitis with pseudoephedrine-containing medicines have been reported. The use of the medicine should be discontinued and it is advisable to consult a doctor if abdominal pain, rectal bleeding or other symptoms of ischemic colitis occur suddenly.

Ischaemic optic neuropathy

Cases of ischaemic optic neuropathy have been reported with pseudoephedrine.

The use of the medicine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.

Children under 12 years of age

Cetirizine/pseudoephedrine is contraindicated in children under 12 years of age due to the presence of pseudoephedrine and because this combination has not been studied in this age group (see Section Contraindications).

Lactose

Cetirizine dihydrochloride/pseudoephedrine hydrochloride, 5mg/120 mg, prolonged-release tablet

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

No interaction studies have been performed with the combination cetirizine-pseudoephedrine.

Lack of interactions

Pharmacokinetic interaction studies were conducted with cetirizine and cimetidine, ketoconazole, erythromycin, azithromycin, antipyrine (phenazone) and pseudoephedrine; no pharmacokinetic interactions were observed.

Studies with cetirizine and cimetidine, glipizide, diazepam, and pseudoephedrine have

revealed no evidence of adverse pharmacodynamic interactions.

Studies with cetirizine and azithromycin, erythromycin, ketoconazole, theophylline, antipyrine (phenazone) and pseudoephedrine have revealed no evidence of adverse clinical interactions. In particular, concomitant administration of cetirizine with macrolides or ketoconazole has never resulted in clinically relevant ECG changes.

Theophylline

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 the elimination of theophylline was not altered by concomitant cetirizine administration.

Ritonavir

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 steady-state AUC (area under curve) value for ritonavir was slightly altered (-11%) by concomitant cetirizine administration.

MAO inhibitors

Concomitant use of sympathomimetic amines with monoamine oxidase (MAO) inhibitors can result in hypertensive crisis. Due to the long duration of action of MAO inhibitors, this interaction is still possible 15 days after discontinuation of their administration (see Section Contraindications).

Linezolid

Concomitant administration of linezolid and pseudoephedrine can increase arterial pressure in normotensive patients.

Reduction of the antihypertensive effects of drugs

Sympathomimetic amines may reduce the antihypertensive effects of beta-adrenergic blockers and of drugs that interfere with sympathetic nervous system activity such as methyldopa, guanethidine and reserpine (see Section Special warnings and precautions for use).

Cardiac glycosides

The ectopic pacemaker activity can be increased when pseudoephedrine is used with cardiac glycosides, such as digoxin or digitoxin; the use of cetirizine/pseudoephedrine, therefore should be avoided in patients treated with cardiac glycosides (see Section Special warnings and precautions for use).

Drugs increasing or decreasing cetirizine/pseudoephedrine absorption

Antacids and proton pump inhibitors increase the absorption of pseudoephedrine, kaolin reduces absorption.

Halogenated anaesthetic agents

Concurrent use with halogenated anaesthetic agents may provoke or worsen ventricular arrhythmia.

Allergy tests

Antihistamines can interfere with allergy tests and an appropriate wash-out period is required before conducting such tests.

Fat meal

A high fat meal was not found to modify the bioavailability of both active ingredients, but it resulted however in a reduced and delayed peak plasma concentration of cetirizine.

Fertility 

Studies conducted in rats showed no significant effect on fertility. There are no available data on fertility in humans.

Pregnancy 

Cetirizine/pseudoephedrine should not be used during pregnancy.

There are no adequate data on the use of cetirizine/pseudoephedrine in pregnant women. 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 bowel atresia (congenital obstruction of small bowel).

Due to the vasoconstrictive properties of pseudoephedrine, this product 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 foetus/ newborn child. There is insufficient animal data with respect to pregnancy, embryonal/foetal development, parturition or post natal development.

Lactation 

Cetirizine/pseudoephedrine should not be used during breast-feeding.

Cetirizine and pseudoephedrine are excreted into human milk.

Patients intending to drive, engaging in potentially hazardous activities or operating machines should not exceed the recommended dose and should take their individual response to the medicinal product into account. However, it should be noted that the effects of these drugs may vary depending on the individual response: clinical studies have shown cases of drowsiness. Effects on the central nervous system may occur with doses higher than those usually recommended.

If patients experience drowsiness or vertigo, they should not drive.

Objective measurements of driving ability, sleep latency and assembly line performance,

following the administration of cetirizine, have not demonstrated any clinically relevant effects at the recommended dose of 10 mg/day. No negative effects associated with the use of pseudoephedrine have been reported and are expected to occur.

Concurrent use of cetirizine with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.

Clinical Trial Data 

In controlled clinical trials, adverse reactions reported in more than 1 % of the patients receiving the combination cetirizine/pseudoephedrine, were not different from those reported for cetirizine or pseudoephedrine alone.

Post Marketing Data 

Undesirable effects encountered with cetirizine are mainly related to CNS depressant or

paradoxical CNS stimulation effects, to anticholinergic-like activity or hypersensitivity reactions (including anaphylactic shock), while the undesirable effects of pseudoephedrine are more likely related to CNS stimulation, and cardiovascular disorders. Cases of abnormal hepatic function with increased hepatic enzymes levels, accompanied by elevated bilirubin, where reported; the majority of the cases were resolved after interrupting the treatment with cetirizine dihydrochloride. Isolated cases of stroke and ischemic colitis associated with pseudoephedrine use have been identified in literature.

Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and by frequency.

Frequencies are defined as:

Very common ≥1/10

Common ≥1/100 to <1/10

Uncommon ≥1/1000 to <1/100

Rare ≥1/10000 to <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: anxiety, agitation

Rare: hallucination

Very rare: psychotic disorder

Nervous system disorders

Common: vertigo, dizziness, headache, somnolence

Rare: convulsions, tremor

Very rare: dysgeusia, cerebrovascular accident (stroke)

Eye disorders

Not known: accommodation disorder, vision blurred, mydriasis, eye pain, visual impairment, photophobia, ischaemic optic neuropathy

Cardiac disorders

Common: tachycardia

Rare: arrhythmia

Not known: palpitations

Vascular disorders:

Rare: pallor, hypertension

Very rare: circulatory collapse

Respiratory, thoracic and mediastinal disorders

Not known: dyspnoea

Gastrointestinal disorders

Common: dry mouth, nausea

Rare: vomiting

Very rare: colitis ischaemic

Hepatobiliary disorders

Rare: hepatic function disorders (increase in transaminases, alkaline phosphatase, gamma-GT, bilirubin)

Skin and subcutaneous tissue disorders

Rare: dry skin, rash, hyperhidrosis, urticaria

Very rare: fixed drug eruption, angioneurotic oedema

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

For any information about this medicinal product, please contact:

GlaxoSmithKline - Head Office, Jeddah

·       Tel:  +966-12-6536666

·       Mobile: +966-56-904-9882

·       Email: gcc.medinfo@gsk.com

·       Website: https://gskpro.com/en-sa/

·       P.O. Box 55850, Jeddah 21544, Saudi Arabia

To report any side effect(s): 

Kingdom of Saudi Arabia

-National Pharmacovigilance centre (NPC)

• SFDA Call Centre: 19999
• E-mail: npc.drug@sfda.gov.sa
• Website: https://ade.sfda.gov.sa

-GlaxoSmithKline - Head Office, Jeddah

• Tel:  +966-12-6536666
• Mobile: +966-56-904-9882
• Email: saudi.safety@gsk.com 
• Website: https://gskpro.com/en-sa/
• P.O. Box 55850, Jeddah 21544, Saudi Arabia 

Symptoms and signs 

Cetirizine

Symptoms observed after an overdose of cetirizine are mainly associated with CNS effects or with effects that could suggest an anticholinergic effect.

Pseudoephedrine

In large doses, sympathomimetics may induce a toxic psychosis with delusions and hallucinations. Some patients may develop cardiac arrhythmias, circulatory collapse, convulsions, coma, and respiratory failure, which can be fatal.

Cetirizine/ pseudoephedrine

Acute overdosage with cetirizine/ pseudoephedrine may cause diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, urinary retention, tachycardia, cardiac arrhythmia, arterial hypertension, signs of CNS depression (sedation, apnoea, unconsciousness, cyanosis and cardiovascular collapse) or CNS stimulation (insomnia, hallucinations, tremor, seizures) which could be fatal.

Treatment 

Treatment, preferably given in hospital, should be symptomatic and supportive. Consideration should be given to the possible concomitant ingestion of other drugs.

No antidote is known. Sympathomimetic amines should not be used. Hypertension and tachycardia can be controlled with use of alpha-blockers and/or beta-blockers. Epileptic seizures can be treated with diazepam intravenously (or by the rectal route in children).

Cetirizine and pseudoephedrine are poorly eliminated by haemodialysis.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

Pharmacotherapeutic group 

Nasal decongestants for systemic use.

ATC Code 

R01BA52

Mechanism of Action and Pharmacodynamic effects 

The pharmacodynamic activity of cetirizine – pseudoephedrine is directly related to the additive effect of the action of its constituents.

Cetirizine

Cetirizine is a potent and selective antagonist of the H1-receptor with anti-allergic proprieties; it inhibits the early phase of the histamine-related allergic reaction; in addition it reduces the migration of some type of inflammatory cells and the release of mediators associated with the late allergic response; it inhibits the reactions induced by histamine and pollens in nasal provocative tests.

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.

There was no evidence for a relevant pharmacokinetic interaction between cetirizine and pseudoephedrine.

Absorption and Distribution 

Cetirizine

After oral administration, cetirizine is rapidly and almost completely absorbed. Peak plasma concentrations are generally obtained within 1 hour under fasting conditions. The absorption is independent of the dose.

Inter- and intra-subjects variations are low.

Cetirizine is highly bound to plasma proteins (93 %).

Its volume of distribution is small: approximately 0.5 l/kg.

Pseudoephedrine

Pseudoephedrine given as the sustained-release formulation cetirizine/ pseudoephedrine provides maximum plasma levels 2 to 6 hours after multiple dosing.

Metabolism and Elimination 

Cetirizine

Cetirizine does not undergo any appreciable first pass metabolism. The plasma half-life of cetirizine is approximately 9 hours. This value is increased in patients with reduced renal function. After repeated oral administration, the daily urinary excretion of unchanged cetirizine is approximately 65 % of the dose. The elimination is independent of the dose.

Pseudoephedrine

It is excreted mainly unchanged in the urine. The rate of urinary excretion is increased when the pH of urine is reduced, and reduced in case of alkalinization of urine. After repeated oral administration (every 12 hours), at steady-state, the apparent elimination half-life is estimated to be approximately 9 hours.

Special patient populations 

Renal impairment 

The dose should be reduced to half the usual recommended dose.

Not relevant for this product.

Non-clinical information 

Animal studies have shown no toxic for doses equal or higher than 30 mg/kg/day in rats and 40 mg/kg/day in the Cynomolgus monkey (≥ 8 and 11 times the recommended dose in humans). The systemic exposure to these doses was higher in the monkey but lower in rats, compared to that obtained in humans. There are no carcinogenicity studies of pseudoephedrine in combination with cetirizine. The combination cetirizine/pseudoephedrine is neither mutagenic nor clastogenic.

Reproduction toxicology studies in male and female rats using oral doses up to 160 mg./kg./day (containing 6.4 mg/kg cetirizine and 153.6  mg/kg pseudoephedrine, 1:24), producing systemic exposure to cetirizine 2- to 3-fold higher than the therapeutic exposure in humans, have shown no effects at a dose of 40 mg/kg/day. Due to the low levels of systemic exposure in this species, these results cannot be considered significant to demonstrate a safe use in pregnant and lactating women.

At higher doses of 160  mg/kg/day, no teratogenic effects were observed, but effects on the mother and offspring were seen (total or partial loss of the litter, reduced growth of the offspring, delayed general development) (see section Fertility, Pregnancy and Lactation).

Cetirizine dihydrochloride/ pseudoephedrine hydrochloride, 5mg/120 mg, prolonged-release tablet

Hypromellose, Microcrystalline cellulose, Colloidal anhydrous silica, Magnesium stearate, Lactose monohydrate, Croscarmellose sodium, Titanium dioxide (E171), Macrogol 400.

There are no relevant data available.

The expiry date is indicated on the outer packaging.

Store below 30°C in dry place.

The tablets are packed in PVC-Aclar Rx 160/Aluminium foil blisters placed in a cardboard box containing 14 tablets.

Not all presentations are available in every country.

There are no special requirements for use or handling of this product.