Otrivin extra

I N S T R U C T I O N for medical use of the medicinal product OTRIVIN EXTRA (OTRIVIN® EXTRA)

Composition:

Active substances: xylometazoline hydrochloride, ipratropium bromide;

1 ml of the preparation contains xylometazoline hydrochloride 0.5 mg, ipratropium bromide 0.6 mg;

Excipients: disodium edetate dihydrate; glycerol (85%); hydrochloric acid concentrated (for pH adjustment); sodium hydroxide (for pH adjustment); purified water.

Pharmaceutical form. Nasal spray, metered.

Main physicochemical characteristics: clear solution. Colorless or slightly colored solution.

Pharmacotherapeutic group. Agents used in diseases of the nasal cavity. Decongestants and other agents for local use in nasal diseases. Sympathomimetics in combination with other agents (excluding corticosteroids). Xylometazoline. ATC code R01A B06.

Pharmacological Properties.

Pharmacodynamics.

Xylometazoline hydrochloride is a sympathomimetic agent acting on α-adrenergic receptors of the nasal mucosa. It causes vasoconstriction of the nasal mucosal blood vessels, thereby reducing edema and hyperemia of the nasal and nasopharyngeal mucosa. It facilitates nasal breathing in rhinitis. It also reduces associated symptoms of mucus hypersecretion and improves drainage of secretions. This alleviates nasal congestion and enables patients suffering from nasal obstruction to breathe more easily through the nose.

Ipratropium bromide is a quaternary ammonium compound with anticholinergic effects. When administered intranasally, it reduces nasal secretion by competitively inhibiting cholinergic receptors located in the nasal epithelium.

The effect of xylometazoline begins within 5–10 minutes and lasts for 6–8 hours.

The effect of ipratropium usually begins within 15 minutes and lasts on average for 6 hours. At therapeutic concentrations, it does not irritate the mucosa or cause hyperemia. When applied locally, the drug is poorly absorbed, and the active components are present in plasma in negligible amounts. A slight reduction in ipratropium effect may be observed, while maximum concentrations of xylometazoline may be slightly increased.

Pharmacokinetics.

Based on available pharmacokinetic data, accumulation of both xylometazoline and ipratropium bromide is possible. However, this is not expected to have clinically significant consequences when used according to instructions at a dosage of up to 3 times daily.

Clinical characteristics.

Indications.

Symptomatic treatment of acute respiratory diseases associated with rhinitis (nasal congestion) and rhinorrhea.

Contraindications.

• Hypersensitivity to the active ingredients or excipients of the drug;
• Increased sensitivity to atropine or similar agents, such as hyoscine, scopolamine;
• Period following surgical interventions on the dura mater, for example after transsphenoidal hypophysectomy or other transnasal surgeries;
• Acute coronary conditions, coronary asthma;
• Hyperthyroidism;
• Closed-angle glaucoma;
• Dry or atrophic rhinitis.

Interaction with other medicinal products and other forms of interaction.

Monoamine oxidase inhibitors (MAO inhibitors). Otivin Extra should not be used concomitantly with MAO inhibitors or within 2 weeks after discontinuation of their use. Sympathomimetic agents cause the release of catecholamines, leading to intense norepinephrine release, which in turn produces a vasoconstrictive effect, resulting in increased blood pressure.

In case of critical elevation of blood pressure, treatment with Otivin Extra should be discontinued and symptomatic therapy initiated.

Tricyclic and tetracyclic antidepressants. Concomitant use with sympathomimetic agents may enhance the sympathomimetic effect of xylometazoline; therefore, this combination is not recommended.

Concomitant use of other anticholinergic agents may lead to an increased anticholinergic effect.

The above interactions have been studied separately for each active component of the drug, not in combination.

Beta 2-agonists. Concurrent use with ipratropium bromide may increase the risk of acute glaucoma in patients with a history of closed-angle glaucoma.

Special precautions for use

The drug Otriven Extra should be used with caution in patients predisposed to developing angle-closure glaucoma, in patients with prostate hypertrophy, and in those with bladder neck obstruction.

Spraying the product into or around the eyes must be avoided.

If the product comes into contact with the eyes, the following reactions may occur: temporary blurred vision, irritation, pain, and redness of the eyes. An acute attack of angle-closure glaucoma may also develop. Patients should be advised to rinse the eyes immediately with cold water if contact occurs and to seek medical advice if eye pain or visual disturbances persist.

Otriven Extra should be used with caution in patients prone to nosebleeds (especially elderly patients), in patients with paralytic intestinal obstruction, and in patients with cystic fibrosis.

As with other sympathomimetic agents, Otriven Extra should be used cautiously in patients who are hypersensitive to adrenergic drugs, as this may lead to insomnia, dizziness, tremor, cardiac arrhythmia, or increased blood pressure. Otriven Extra should be used with caution in patients with diabetes mellitus, arterial hypertension, cardiovascular disorders, or phaeochromocytoma. Patients with long QT syndrome who are receiving xylometazoline may be at increased risk of serious ventricular arrhythmias.

Immediate hypersensitivity reactions may occur, including urticaria, angioedema, rash, bronchospasm, laryngeal edema, and anaphylactic reactions.

The duration of treatment should not exceed 7 days. Prolonged use of xylometazoline may lead to rebound nasal mucosal swelling and increased secretion due to increased cellular sensitivity—the so-called rebound effect (medication-induced rhinitis).

Rare cases of posterior reversible encephalopathy syndrome (PRES) / reversible cerebral vasoconstriction syndrome (RCVS) have been reported with the use of sympathomimetic agents. Reported symptoms include sudden severe headache, nausea, vomiting, and visual disturbances. In most cases, symptoms resolved or improved within a few days after appropriate treatment. Otriven Extra should be discontinued immediately and medical advice sought if signs or symptoms of PRES/RCVS occur.

Use during pregnancy or breastfeeding

There is insufficient data on the use of the drug during pregnancy. Available data suggest that xylometazoline has the potential to cause systemic vasoconstriction. Therefore, the use of xylometazoline during pregnancy is not recommended. The clinical safety of ipratropium bromide during pregnancy has not been established. The drug is not recommended during pregnancy.

There is insufficient data on whether ipratropium bromide and xylometazoline pass into breast milk. Systemic exposure to ipratropium bromide and xylometazoline hydrochloride is low. Otriven Extra should be used during breastfeeding only if clearly needed and after consultation with a physician. If treatment is necessary, the lowest effective dose should be used for the shortest possible duration. Exceeding the recommended dose must be avoided.

Fertility
There are no data available on the effect of the drug on fertility. Systemic exposure to the drug components is low. Therefore, an effect of the drug on fertility is unlikely.

Ability to affect reaction speed when driving or operating machinery

Visual disturbances (including blurred vision and mydriasis), dizziness, and fatigue may occur during treatment. Patients should be advised that if such reactions occur, they should avoid driving, operating machinery, or engaging in any activity that could pose a risk to their health or life.

Dosage and Administration.

Intranasal use. Do not cut off the spray pump nozzle. The nasal spray is a metered dose spray, ready for use.

The recommended dose for adults is 1 spray 3 times daily into each nostril. The interval between applications of Otriven Extra should be at least 6 hours. The medication should be used no more than 3 times daily in each nostril.

The duration of treatment should not exceed 7 days. Do not exceed the recommended dosage. The lowest effective dose for the shortest duration of treatment should be used. After symptoms have resolved, treatment with the medication should be discontinued to minimize the risk of adverse reactions.

The spray should be used as follows:

• thoroughly clear the nose before applying the medication;
• hold the bottle vertically, supporting the bottom with the thumb and positioning the nozzle between two fingers;
• slightly tilt the bottle and insert the nozzle into the nostril;
• administer a spray while simultaneously taking a gentle nasal inhalation;
• after use, before covering the nozzle with the cap, clean and dry the nozzle;

To prevent infection, each bottle of medication should be used by only one person.

Before first use, prime the spray pump by pressing it several times into the air until a uniform spray is achieved. After this, the spray pump will be ready for use throughout the entire treatment period. If the spray does not dispense when pressing the pump, or if the spray has not been used for several days, the spray pump should be re-primed by several sprays into the air. Do not repeat the dose if an incomplete dose has been administered.

One spray (approximately 140 µL) of Otriven Extra contains approximately 70 µg of xylometazoline and 84 µg of ipratropium bromide.

Experience with the use of the medication in elderly patients (over 70 years of age) is limited. Dose adjustment is not required.

Children.

There is insufficient data on the use of the medication in children (under 18 years of age); therefore, the medication is not recommended for this patient group.

Overdose.

With excessive use of xylometazoline, the following symptoms may occur: severe dizziness, sweating, sharp drop in body temperature, headache, bradycardia, arterial hypertension, respiratory depression, coma, and convulsions. Following arterial hypertension, arterial hypotension may develop. Children are more sensitive to toxic effects than adults.

With excessive use of ipratropium bromide, overdose is unlikely due to extremely low systemic absorption; however, symptoms such as dry mouth, accommodation disturbances, and tachycardia may occur.

Significant overdose may cause anticholinergic symptoms affecting the central nervous system, including hallucinations, which require administration of cholinesterase inhibitors. Treatment is symptomatic.

Appropriate supportive measures are necessary for all individuals suspected of overdose; urgent symptomatic therapy under medical supervision should be administered as needed. The patient should be observed for at least 6 hours. In cases of severe overdose with cardiac arrest, resuscitation measures should be continued for at least 1 hour.

Adverse Reactions

The most common adverse reactions are nasal bleeding (14.8%) and nasal dryness (11.3%).

Undesirable effects are classified by frequency of occurrence as follows: very common (≥ 1/10), common (≥ 1/100 – < 1/10), uncommon (≥ 1/1,000 – < 1/100), rare (≥ 1/10,000 – < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be determined from available data, includes isolated cases).

Immune system disorders: not known – hypersensitivity.

Psychiatric disorders: uncommon – insomnia.

Nervous system disorders: common – dysgeusia, headache; uncommon – parosmia, paraesthesia, dizziness, tremor.

Eye disorders: uncommon – visual disturbance, dry eyes, corneal swelling, conjunctival hyperemia; not known – accommodation disorders, acute angle-closure glaucoma, photopsia, eye irritation and pain, increased intraocular pressure, blurred vision, presence of halos, pupil dilation.

Cardiac disorders: uncommon – palpitations, tachycardia; not known – atrial fibrillation.

Respiratory, thoracic and mediastinal disorders: very common – nasal bleeding, nasal dryness; common – discomfort, dryness in the throat, burning sensation/pain in the nose or throat, hypersalivation, nasal congestion; uncommon – nasal mucosal irritation, nasal mucosal ulceration, nasopharyngitis, sneezing, cough, dysphonia; rare – rhinorrhea; not known – discomfort in the nasal sinuses, laryngospasm, laryngeal edema.

Gastrointestinal disorders: common – dry mouth, gastrointestinal motility disorders; uncommon – dyspepsia, nausea, vomiting, stomatitis, constipation; not known – dysphagia.

Skin and subcutaneous tissue disorders: not known – pruritus, rash, urticaria.

Renal and urinary disorders: not known – urinary retention.

General disorders and administration site conditions: uncommon – feeling of discomfort, increased fatigue; not known – chest discomfort, thirst, allergic reactions including angioedema of the tongue, lips, face, anaphylactic reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product.

Shelf life.

3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in a place inaccessible to children. Do not freeze.

Packaging.

10 ml in a bottle with a dosing device. 1 bottle in a cardboard box.

Availability category.

Over-the-counter.

Manufacturer.

Haleon CH S.a.r.l. / Haleon CH S.a.r.l.

Manufacturer's address and location of business activity.

Route de l’Etraz 2, Nyon, 1260, Switzerland / Route de l’Etraz 2, Nyon, 1260, Switzerland.