Zirtek Plus Decongestant 5mg/120mg Prolonged Release Tablets

PRAC recommendation under Art 31 referral on PRES and RCVS 

PRAC recommendation under Art 31 referral on PRES and RCVS 

Type II CCDS v.4.0 multiple updates (sections 4.2, 4.3, 4.4, 4.8 and 5.2)

Type II CCDS v.4.0 multiple updates (sections 4.2, 4.3, 4.4, 4.8 and 5.2) -Editorial correction 

Type II - CCDS v.4.0 multiple updates (sections 4.2, 4.3, 4.4, 4.8 and 5.2)

Addition of warning for urinary retention and EU excipients update

Addition of warning for urinary retention and EU excipients update

Section 4.4 - Special warnings and precautions for use

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.

Section 4.8 - Undesirable effects

Eye disorders:

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

Section 2 - Warnings and precautions

Reduction of blood flow to your optic nerve may occur with Zirtek Plus Decongestant. If you develop sudden loss of vision, stop taking Zirtek Plus Decongestant and contact your doctor or seek medical attention immediately. See section 4.

Section 4 - Possible side effects

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, Severe skin reactions characterised 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).

​​​​​​​4.4 Special warnings and precautions for use

[...]

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.

​​​​​​4.8 Undesirable effects

Gastrointestinal disorders:

Common: dry mouth, nausea

Rare: vomiting

Very rareNot known: ischaemic colitis ischaemic

2.       What you need to know before you take Zirtek Plus Decongestant

[...]

Warnings and precautions

Sudden abdominal pain or rectal bleeding may occur with Zirtek Plus Decongestant, due to inflammation of the colon (ischaemic colitis). If you develop these gastro-intestinal symptoms, stop taking Zirtek Plus Decongestant and contact your doctor or seek medical attention immediately. (see section 4)

4.       Possible side effects

[...]

Very rare side effects (may affect up to 1 in 10000 patients): circulatory collapse (circulatory disorder), inflammation of the colon due to insufficient blood supply (ischaemic colitis), altered taste (dysgeusia), cerebrovascular event (stroke), psychosis (in isolated cases), angioedema (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, accommodation disorder 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), difficulty in breathing (dyspnoea), erectile dysfunction, Severe skin reactions characterised by fever and numerous small, superficial pustules, arising within large areas of redness and, unpleasant sensation of faster and/or stronger/irregular beating of the heart and inflammation of the colon due to insufficient blood supply (ischaemic colitis).

4.4 Special warnings and precautions for use (text removed- updated)
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine
4.6 Fertility, pregnancy and lactation
Fertility (text removed- updated)
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  to 3 fold higher than the therapeutic exposure in humans (section 5.3).  There are no available data on fertility in humans.
4.8 Undesirable effects (text added-updated)
Cardiac disorders:
Common: tachycardia
Rare: arrhythmia
Not Known: palpitations
5.3 Preclinical safety data (text removed- updated)
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 between 2- 3  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. 
10. Date of Revision of the text (updated)
{11/2017}05/2018

Update section 4.8 of the SmPC as follows:

·         To update hypersensitivity to “hypersensitivity reactions (including anaphylactic shock)”

·         To add “acute generalized exanthematous pustulosis”

Update section 10 of the SmPC to amend the date of revision to November 2017.

2.           QUALITATIVE AND QUANTITATIVE COMPOSITION

·       Editorial changes to text.

4.2.        Posology and Method of Administration

·       Some text added and deleted.

4.3         Contraindications

·       Some text added and deleted.

4.4         Special warnings and precautions for use

• Text updated.

4.5         Interaction with other medicinal products and other forms of interaction

·       Some text added and deleted.

4.6         Fertility, pregnancy and lactation

·       Some text added and deleted.

4.7         Effects on ability to drive and use machines

• Text updated.

4.9         Overdose

·       Some text added and deleted.

5.3         Preclinical safety data

• Text updated.

6.6         Special precautions for disposal and other handling

• Text updated.

10          DATE OF REVISION OF THE TEXT

·       Date of revision updated.

 
4.2 Posology and method of administration
Posology
1 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.
Paediatric population
Children over 12 years of age: 1 tablet two times a day (morning and evening).
The safety and efficacy of Zirtek Plus Decongestant in children less than 12 years of age have not yet been established. No data are available.
Special populations
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 in no way should it be longer than 2 to 3 weeks at the recommended dose (1 tablet twice daily).
After disappearance of nasal symptoms, treatment can be continued with an antihistamine alone.
Method of administration
Tablets should be swallowed whole with a little liquid, without crunching or chewing them. They may be taken with or without food.


4.3 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with the combination cetirizine-pseudoephedrine.
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 slightly altered (-11%) further to concomitant cetirizine administration.
Concomitant use of Zirtek Plus Decongestant 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.

4.6 Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of Zirtek Plus Decongestant in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Zirtek Plus Decongestant is not recommended during pregnancy.
Lactation
Cetirizine and pseudoephedrine are excreted into human milk. Therefore, Zirtek Plus Decongestant is not recommended during breast-feeding.
Fertility
A study in animals has demonstrated that the combination of cetirizine:pseudoephedrine (1:24) has no impact on fertility at a dose of up to 10 times the recommended dose.
There are no available data on fertility in humans.


4.8 Undesirable effects
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).

General disorders and administration site conditions:
Common: asthenia
Renal and urinary disorders:
Rare: dysuria
Skin and subcutaneous tissue disorders:
Rare: dry skin, rash, sweating increased, urticaria
Very rare: angioneurotic oedema, fixed drug eruption
Eye disorders:
Not known: accommodation disorder, blurred vision, mydriasis, eye pain, visual impairment, photophobia
Respiratory, thoracic and mediastinal disorders:
Not known: dyspnoea

5.3 Preclinical safety data
Fertility in male and female rats was unimpaired at doses up to 160 mg/kg/day (1:24) in reproduction toxicology studies, which represents an estimated systemic exposure to pseudoephedrine 12 times higher than the therapeutic exposure in humans.