Otrivin Comp

Document: Otrivin Comp nasal spray, solution ENG SmPC change

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Otrivin Comp 0.5 mg/ml + 0.6 mg/ml nasal spray, solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml contains 0.5 mg xylometazoline hydrochlorideand 0.6 mgipratropium bromide.

1 puff approx. 140 microliterscontains 70 micrograms xylometazoline hydrochloride and 84 micrograms ipratropium bromide.

For thefull list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Nasal spray, solution.

Clear, colourless solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Symptomatic treatment of nasal congestion and rhinorrhea in connection with common colds.

4.2 Posology and method of administration

Posology

Adults:1 puff in each nostril up to 3 times daily. At least 6 hours should elapse between two doses.Do not exceed 3 applications daily into each nostril.

The treatment duration should not exceed 7 days(see section 4.4).

It is recommended to stop treatment, when the symptoms have diminished, even before the

maximum duration of treatment of 7 days, in order to minimize the risk of adverse reactions

(see section 4.8).

Paediatric population

Otrivin Comp is not recommended for use in children and adolescents below 18 years of age due to lack of sufficient documentation.

Geriatrics

There is only limited experience of use in patients above 70 years of age.

Method of administration

Before the first application, prime the pump by actuating 4 times. Once primed the pump will normally remain charged throughout regular daily treatment periods. Should the spray not be ejected during the full actuation stroke, or if the product has not been used for longer than 6 days, the pump will need to be reprimed with 4 actuations as initially performed.

4.3 Contraindications

Otrivin Comp should not be given to children under the age of 18 due to lack of sufficient documentation.

Hypersensitivity to the active substances or to any of the excipientslisted in section 6.1.

Known hypersensitivity to atropine or similar substances, e.g. hyoscyamine and scopolamine.

After surgical operations where dura mater may have been penetrated, e.g. transsphenoidal hypophysectomy or other transnasal operations.

In patients with glaucoma.

In patients with rhinitis sicca.

4.4 Special warnings and precautions for use

The medicinal product must be administered with caution to patients with:

- hypertension, cardiovascular diseases

- hyperthyroidism, diabetes mellitus

- hypertrophy of the prostate, stenosis of the bladder bar

- pheochromocytoma

Caution is recommended in patients predisposed to:

- angle closure glaucoma

-epistaxis (e.g. elderly)

-paralytic ileus

-cystic fibrosis

Immediate hypersensitivity including urticaria, angioedema, rash, bronchospasm, pharyngeal oedema and anaphylaxis may occur.

The medicinal product must be used with caution in patients who are sensitive to adrenergic substances, which may give symptoms such as sleeping disturbances, dizziness, tremor, cardiac arrythmias or elevated blood pressure.

The treatment duration should not exceed 7 days, as chronic treatment with xylometazoline hydrochloride may cause swelling of the nasal mucosa and hypersecretion because of increased sensibility in the cells, ”rebound effect” (rhinitis medicamentosa).

Patients should be instructed to avoid spraying Otrivin Comp in or around the eye. If Otrivin Comp gets in contact with the eyes, the following may occur: temporary blurred vision, irritation, pain, red eyes. Aggravation of angle closure glaucoma may also develop.The patient should be instructed to rinse their eyes with cold water if Otrivin Comp gets in direct contact with the eyes and to contact a doctor if they experience pain in the eyes or blurred vision.

4.5 Interaction with other medicinal products and other forms of interaction

Monoaminoxidase inhibitors(MAO inhibitors): Concomitant use or use within the last 2 weeks of sympathomimetic preparations may induce severely elevated blood pressure and is therefore not recommended. Sympathomimetic preparationsrelease catecholamine, which results in a major release of noradrenaline which in turn has a vasoconstrictive effect resulting in elevated blood pressure. In critical cases of elevated blood pressure, treatment with Otricombshould be discontinued and the elevated blood pressure treated.

Tri- and tetra-cyclic antidepressants: Concomitant use or use within the last 2 weeks of tri-cyclic antidepressants and sympathomimetic preparations may result in an increased sympathomimetic effect of xylometazoline and is therefore not recommended.

Concomitant administration of other anticholinergic drugs may enhance the anticholinergic effect.

The above interactions have been studied individually for both of the active substances of Otrivin Comp, not in combination.

No formal interaction studies with other substances have been performed.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data fromthe use of Otrivin Comp in pregnant women. Animal studies are insufficient with respect toeffects on pregnancy, embryonalfoetaldevelopment, parturition and postnatal development. The potential risk for humans is unknown.Otrivin Compshould not be used in pregnancy unless clearly necessary.

Breast-feeding

It is not known whether ipratropium bromide and xylometazoline hydrochloride are excreted in the mother’s milk. The systemic exposure to ipratropium bromide and xylometazoline hydrochloride is low. Effects on the breast-fed infant are therefore unlikely. The mother’s need for treatment with Otrivin Comp and the advantages of breast-feeding must be weighed against the potential risks to the infant.

4.7 Effects on ability to drive and use machines

Visual disturbances (including blurred vision and mydriasis), dizziness and fatigue have been reported with Otrivin Comp. Patients should be advised that if affected they should not drive, operate machinery or take part in activities where these symptoms may put themselves or others at risk.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions are epistaxis occurring in 14.8 % and nasaldryness occurring in 11.3 % of patients.

Many of the adverse events reported are also symptoms of common cold.

Tabulated listof adverse reactions

The following adverse reactions were reported in two randomised clinical studies and onenon-interventional post-marketing study with the product as well as from post-marketing surveillance.

The adverse reactions are listed below by system organ class and frequency. Frequencies aredefined as:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1000 and <1/100)

Rare (≥1/10000 and <1/1000)

Very rare (< 1/10,000)

Not known (can not be estimated from the available data)

Frequency Organ class		Very Common	Common	Uncommon	Rare	Not known
Immune system disorders						Hypersensitivity
Psychiatric disorders				Insomnia
Nervous system disorders			Dysgeusia, headache	Parosmia, dizziness, tremor
Eye disorders				Eye irritation, dry eye		Accommodation disorder, aggravation of angle closure glaucoma, eye pain, photopsia, intraocular pressure increased, blurred vision, mydriasis, halo vision
Cardiac disorder				Palpitations, tachycardia		Atrial fibrillation
Respiratory, thoracic and mediastinal disorders	Epistaxis, nasal dryness		Nasal discomfort, nasal congestion, dry throat, throat irritation, rhinalgia	Nasal ulcer, sneezing, oropharyngeal pain, cough, dysphonia	Rhinorrhoea	Paranasal sinus discomfort, laryngospasm, pharyngeal oedema
Gastrointestinal disorders			Dry mouth	Dyspepsia, nausea		Dysphagia
Skin and subcutaneous disorders						Pruritus, rash, urticaria
Renal and urinary disorders						Urine retention
General disorders and administration site conditions				Discomfort, fatigue		Chest discomfort, thirst

Description of selected adverse reactions

Several of the adverse reactions listed under “Not known” have only been reported once for the product in clinical trials or are reported from postmarketing surveillance only, thus an estimate of the frequency based on the present number of patient treatedwith Otrivin Comp can not be given.

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

Overdose of oral or excessive administration of topical xylometazoline hydrochloride may cause severe dizziness, perspiration, severely lowered body temperature, headache, bradycardia, hypertension, respiratory depression, coma and convulsions. Hypertension may be followed by hypotension. Small children are more sensitive to toxicity than adults.

The absorption being very small after nasal or oral administration, an acute overdose after intranasal ipratropium bromide is unlikelybut if an overdose occurs the symptoms are dry mouth, accommodationdifficulties and tachycardia. The treatment is symptomatic.

A considerable overdose may cause anticholinergic CNS symptoms such as hallucinations, which must be treated with cholinesterase inhibitors.

Appropriate supportive measures should be initiated in all individuals suspected of an overdose, and urgent symptomatic treatment under medical supervision is indicated when warranted. This would include observation of the individual for at least 6 hours. In the event of a severe overdose with cardiac arrest, resuscitation should be continued for at least 1 hour.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Sympathomimetics, combinations excluding corticosteroids.

ATC code: R 01 AB 06

Xylometazoline hydrochloride is a sympathomimetic which acts on -adrenergic receptors. Xylometazoline has a vasoconstrictive effect. An effect is obtained after 5-10 minutes and lasts for 6-8 hours.

Ipratropium bromide is a quaternary ammonium combination with anticholinergic effect. Nasal administration reduces the nasal secretion through competitive inhibition of cholinergic receptors situated around the nasal epithelium. An effect is usually obtained within 15 minutes and lasts for 6 hours on an average.

5.2 Pharmacokinetic properties

After administration of one puff/nostril of 140 μg Xylometazoline and 84 μg Ipratropium bromide in 24 healthy subjects, mean maximum concentrations of 0.085 ng/ml and 0.13 ng/ml were reached 1 hour and 2 hours post administration for Ipratropium bromide and Xylometazoline, respectively. The blood levels are very low. However, based on data available, it is expected that Ipratropium bromide and especially Xylometazoline will accumulate at the proposed 3 times per day dosing.

5.3 Preclinical safety data

Both ipratropium bromide and xylometazoline were tested in preclinical studies, which revealed no relevant clinical safety problems with the actual doses of Otrivin Comp. Intranasal daily dose of Otrivin Comp in dogs for 28 days in doses up to four times the intended clinical dosing regimen has shown no local or systemic effects.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium edetate

Glycerol 85 per cent

Hydrochloric acid (for pH – adjustment)

Sodium hydroxide (for pH – adjustment)

Purified water

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

10 ml multidose approx. 70 puffsHDPE bottle mounted with metered-dose spray pump (materials in

contact with the solution: LDPE, HDPE, PE / butyl, stainless steel) and PP nozzle with protective cap.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

[To be completed nationally]

{Name and address}

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8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10. DATE OF REVISION OF THE TEXT

2014-11-28