QUALITATIVE AND QUANTITATIVE COMPOSITION
Each prolonged release tablet contains 5 mg cetirizine dihydrochloride and
120 mg pseudoephedrine hydrochloride.
Prolonged release tablet
White to off-white, round biconvex tablet
The pharmacodynamic activity of ZYRTEC-D (ATC code R01B A52) is directly
related to an additive effect of the activity of each of its components. Cetirizine is a potent and selective H1-receptor antagonist with additional
anti-allergic properties: it inhibits the histamine-related early phase of
the allergic reaction and also reduces the migration of certain inflammatory
cells and the release of certain mediators associated with the late allergic
response; it inhibits the histamine or pollen-induced reactions in nasal
Pseudoephedrine is an orally active sympathomimetic amine
with alpha-mimetic activity predominating over beta-mimetic activity; due to
its vasoconstrictor action, it has a decongestant effect on the nasal
After oral administration, cetirizine is rapidly and almost completely
absorbed. Maximal plasma concentrations are generally obtained within 1 hour
under fasting conditions. Cetirizine does not undergo any appreciable first
pass metabolism. After repeated oral administration, the daily urinary
excretion of unchanged cetirizine is approximately 65% of the dose. The
absorption and the elimination of cetirizine are independent of the dose.
Inter- and intra-subjects variations are low. The plasma half-life of
cetirizine is approximately 9 hours. This value is increased in patients
with reduced renal function.
Cetirizine is highly bound to plasma proteins (93%). Its volume of
distribution is small: approximately 0.5 l/kg.
Pseudoephedrine given as the sustained-release formulation ZYRTEC-D provides
maximum plasma levels 2 to 6 hours after multiple dosing. 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.
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. There was no evidence for a relevant
pharmacokinetic interaction between cetirizine and pseudoephedrine.
should be reduced to half the usual recommended dose in patients with renal
ZYRTEC-D is indicated for the treatment of symptoms associated with seasonal
and perennial allergic rhinitis such as nasal congestion, sneezing,
rhinorrhea, nasal and ocular pruritus. It should be administered when both
the antiallergic properties of cetirizine dihydrochloride and the nasal
decongestant activity of pseudoephedrine hydrochloride are desired.
Posology and method of administration
Adults and children aged 12 years and older: one tablet twice daily (morning
and evening), with or without food. The tablets should be swallowed with
some liquid and should not be chewed or crushed.
The duration of treatment
should not exceed the period of symptoms, and should not exceed 2 to 3
weeks. When adequate relief from nasal symptoms is obtained, treatment with cetirizine should be continued, if appropriate.
In patients with moderate renal or hepatic insufficiency, dosage should be
reduced to one tablet per day.
ZYRTEC-D is contra-indicated:
• in cases of known hypersensitivity to one of its ingredients, to ephedrine
any other piperazine
• in cases of severe hypertension or severe coronary artery disease
• in patients receiving dihydroergotamine
• in cases of severe renal
insufficiency, uncontrolled hyperthyroidism, severe arrhythmias,
pheochromocytoma, elevated intraocular pressure or urinary retention
• during treatment with monoamine oxidase (MAO) inhibitor and also for 2
weeks after their discontinuation.
• in patients with a history of stroke
• or in patients at high risk of developing haemorrhagic stroke
ZYRTEC-D is not recommended in children under 12 years of age as it has not
been studied in this age group.
Special warnings and special precautions for use
Due to the presence of pseudoephedrine, ZYRTEC-D should be used with caution
in patients with diabetes mellitus, hyperthyroidism, arterial hypertension,
tachycardia, cardiac arrhythmia, ischemic heart disease, moderate renal or
hepatic insufficiency, and in the elderly.
Caution is also required in patients taking:
- sympathomimetic drugs such as decongestants, appetite suppressants,
psychostimulants such as amphetamines (combined effects on the
- tricyclic antidepressants
- antihypertensive drugs (reduction of antihypertensive effects)
- alcohol or other CNS depressants (enhanced CNS depression and impaired
- digitalis (risk of cardiac arrhythmia)
- as well as in conditions where anticholinergic activity is undesirable,
such as prostatic hypertrophy or bladder outflow obstruction.
Caution should also be exercised in patients with factors which could
increase the risk of haemorrhagic stroke, as 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 (phenylpropanolamine, phenylephrine,
ephedrine), due to the risk of vasoconstriction and increased blood
Due to vasoconstrictor effect of pseudoephedrine, caution is recommended in
patients who are at risk for hypercoagulabiliy, as in inflammatory bowel
Caution is required in
hypertensive patients who are treated concomitantly with NSAIDs, because
both pseudoephedrine and NSAIDs can increase blood pressure.
As for other centrally acting stimulants, abuse has been observed for
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this
Interaction with other medicinal products and other forms of interaction
Pharmacokinetic interaction studies were conducted with cetirizine and
cimetidine, ketoconazole, erythromycin, azithromycin and pseudoephedrine; no
pharmacokinetic interactions were observed.
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 disposition of theophylline
was not altered by concomitant cetirizine administration. 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, 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.
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 disposition of
ritonavir was not altered by concomitant cetirizine administration.
Concomitant use of symphatomimetic amines with monoamine oxidase (MAO)
inhibitors can result in hypertensive crisis. Because of the long duration
of action of MAO inhibitors, this interaction is still possible 15 days
after stopping such a treatment.
Sympathomimetic amines may reduce the antihypertensive effects of
betaadrenergic blockers and of drugs that interfere with sympathetic
activity such as methyldopa, guanethidine and reserpine; (see Special
Administration of linezolid with
pseudoephedrine may result in an increase in blood pressure in normotensive
Increased ectopic pacemaker
activity can occur when pseudoephedrine is used concomitantly with
digitalis; use of ZYRTEC-D is therefore to be avoided in digitalized
Antacids and proton pump inhibitors increase the rate of pseudoephedrine
absorption; kaolin decreases it.
Concurrent use with halogenated anaesthetic agents may provoke or worsen
Allergy skin tests are inhibited by antihistamines and an appropriate
wash-out period is required before performing them.
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.