Otrivin^® Complex (Spray) Instructions for Use

Marketing Authorization Holder

Cheleon Rus, JSC (Russia)

Manufactured By

Haleon CH, SARL (Switzerland)

Contact Information

CHELEON RUS JSC (Russia)

ATC Code

R01AB06 (Xylometazoline in combination with other drugs)

Active Substances

Xylometazoline (Rec.INN registered by WHO)

Ipratropium bromide (Rec.INN registered by WHO)

Dosage Form

Otrivin® Complex

Metered-dose nasal spray 84 mcg+70 mcg/1 dose: 10 ml bottle with dosing device, tip and protective cap

Dosage Form, Packaging, and Composition

Metered-dose nasal spray as a clear, colorless or slightly colored solution.

Excipients: glycerol (85%), disodium edetate dihydrate, hydrochloric acid*, sodium hydroxide**, purified water.

* During production, if pH adjustment is necessary, a 0.1M hydrochloric acid solution is used.
** During production, if pH adjustment is necessary, a 30% sodium hydroxide solution is used.

10 ml (60 doses) – HDPE bottles (1) with a vertical pump dosing device with a tip and a protective cap – cardboard packs.
10 ml (60 doses) – HDPE bottles (1) with a pump dosing device with a side activation button with a tip and a protective cap – cardboard packs.

The secondary packaging may have a first-opening control.

Clinical-Pharmacological Group

Vasoconstrictor drug for topical use in ENT practice

Pharmacotherapeutic Group

Drugs for the treatment of nasal diseases; decongestants and other drugs for topical use; sympathomimetics, combinations without corticosteroids

Pharmacological Action

Xylometazoline belongs to the group of topical vasoconstrictors (decongestants) with alpha-adrenomimetic action, it causes constriction of the blood vessels of the nasal mucosa, eliminating swelling and hyperemia of the nasopharyngeal mucosa. It relieves congestion, facilitating nasal breathing in rhinitis.

Ipratropium bromide has an anticholinergic effect. When used intranasally, it reduces nasal secretion, stopping a runny nose by competitively inhibiting cholinergic receptors located in the nasal cavity epithelium.

In therapeutic concentrations, it does not irritate the mucous membrane and does not cause its hyperemia.

The drug begins to act within 5-10 minutes and has a lasting effect for 6-8 hours.

Pharmacokinetics

When applied intranasally, ipratropium bromide and xylometazoline hydrochloride are poorly absorbed and are present in the blood plasma in insignificant amounts.

Indications

For adults:

• Acute respiratory diseases with symptoms of rhinitis (runny nose);
• Acute allergic rhinitis;
• Hay fever;
• Sinusitis;
• Eustachitis;
• Otitis media (as part of combination therapy to reduce swelling of the nasopharyngeal mucosa);
• Preparation of the patient for diagnostic manipulations in the nasal passages.

ICD codes

Dosage Regimen

Adults

1 spray into each nostril 3 times/day.

The interval between repeated applications should be at least 6 hours.

The drug should not be used more than 3 times/day in each nostril.

It is not recommended to use the drug for more than 7 days without consulting a doctor.

Do not exceed the indicated dose.

Experience with the drug in elderly patients over 70 years of age is limited.

Method of administration

Intranasally.

Bottle with vertical pump dosing device

The bottle with a vertical pump dosing device ensures precise distribution of the drug over the surface of the nasal mucosa.

Before first use, spray the spray into the air with several presses until the drug is distributed evenly. If the spray has not been used for several days or there is no uniform distribution, the procedure should be repeated. If the spray dose was not administered completely, do not repeat the administration.

Do not cut the tip of the dosing device.

Avoid contact with eyes.

1. Thoroughly clean your nose.
2. Hold the bottle vertically, supporting the bottom with your thumb, the nozzle is between your middle and index fingers.
3. Point the nozzle into the nostril, slightly tilting the bottle forward.
4. Press the spray device, spraying the drug, and simultaneously inhale through your nose.
5. After use, the nozzle should be cleaned and dried before closing it with the protective cap.

To avoid possible spread of infection, the drug should be used by only one person.

Bottle with pump dosing device with side activation button

The bottle with a vertical pump dosing device ensures precise distribution of the spray over the surface of the nasal mucosa, creating a cloud of fine spray.

Before first use of the spray, press the pump dosing device 5 times. During further use, no additional activation of the dosing device is required. If uneven dosing of the spray is observed or the break in using the drug was more than 7 days, it is necessary to activate the dosing device by pressing it 2 times.

Avoid contact with eyes.

1. Thoroughly clean your nose.
2. Hold the bottle vertically, placing your thumb on the activation button.
3. To avoid droplet formation, stand up straight and insert the nozzle into the nostril.
4. Press the button with one finger, spraying the drug, and simultaneously inhale gently through your nose.
5. Repeat the procedure (steps 1 through 4) for the other nostril.
6. After use, the nozzle should be cleaned and dried before closing it with the protective cap until an audible click is heard.

To avoid possible spread of infection, the drug should be used by only one person.

Adverse Reactions

The frequency of adverse reactions was determined in accordance with the WHO classification: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare ( ≥ 1/10000, <1/1000); very rare (<1/10000); frequency not known (cannot be estimated from the available data).

Immune system disorders frequency not known – hypersensitivity reactions (anaphylactic reaction, angioedema, rash, itching, laryngospasm).

Nervous system disorders common – taste disturbance, headache; uncommon – smell disturbance, dizziness, tremor; very rare – insomnia, convulsions, hallucinations.

Eye disorders uncommon – eye irritation, dry eye; frequency not known – increased intraocular pressure, mydriasis, eye pain, photopsia, worsening of closed-angle glaucoma, impaired visual acuity, pupil dilation, halo effect (presence of rainbow circles around a light source in the field of vision).

Cardiac disorders uncommon – palpitations, supraventricular tachycardia, arterial hypertension; very rare – arrhythmic pulse; frequency not known – atrial fibrillation.

Respiratory, thoracic and mediastinal disorders very common – epistaxis, irritation and/or dryness of the nasopharyngeal mucosa; common – burning sensation, tingling, nasal hypersecretion, sneezing, nasal congestion (with frequent and/or prolonged use of the drug), dry throat, throat irritation, rhinalgia, rhinorrhea; uncommon – nasal ulcer, pharyngeal pain, cough, dysphonia; frequency not known – discomfort in the paranasal sinus area, laryngeal spasm, pharyngeal edema.

Gastrointestinal disorders common – dry mouth; uncommon – dyspepsia, nausea; frequency not known – difficulty swallowing.

Skin and subcutaneous tissue disorders frequency not known – itching, skin rash, urticaria.

Renal and urinary disorders frequency not known – difficulty urinating.

General disorders and administration site conditions uncommon – discomfort, fatigue; frequency not known – chest discomfort, thirst.

If any of the above side effects worsen, or the patient notices any other side effects, they should inform their doctor.

Contraindications

• Hypersensitivity to xylometazoline or ipratropium bromide or any of the excipients of the drug;
• Arterial hypertension;
• Tachycardia;
• Severe atherosclerosis;
• Hypersensitivity to atropine or atropine-like compounds (such as hyoscyamine, scopolamine);
• Glaucoma;
• Hyperthyroidism;
• Atrophic rhinitis;
• Inflammatory diseases of the skin or mucous membrane of the nasal vestibule;

• Surgical interventions on the meninges (in history);
• Condition after transsphenoidal hypophysectomy;

• Pregnancy;
• Breastfeeding period;
• Use of MAO inhibitors (including 14 days after their discontinuation), tricyclic or tetracyclic antidepressants;
• Age under 18 years.

With caution

Diabetes mellitus;

Severe cardiovascular diseases (including coronary artery disease, angina pectoris);

Bladder neck obstruction;

Stenosis of the interureteric fold;

Prostatic hyperplasia;

Pheochromocytoma;

Porphyria;

Hypersensitivity to adrenergic drugs, accompanied by insomnia, dizziness, tremor, increased blood pressure;

Patients with long QT syndrome;

Patients predisposed to paralytic ileus;

Patients with cystic fibrosis; patients with a predisposition to nosebleeds;

Patients with a history of immediate-type hypersensitivity reactions, including urticaria, angioedema, rash, bronchospasm, laryngeal edema and anaphylactic reactions.

Use in Pregnancy and Lactation

Pregnancy

Otrivin^® Complex is contraindicated during pregnancy.

Breastfeeding period

Otrivin^® Complex is contraindicated during breastfeeding.

Pediatric Use

Contraindicated for use under 18 years of age.

Geriatric Use

Experience with the drug in patients over 70 years of age is limited.

Special Precautions

Should not be used for a long time, for example, in chronic rhinitis.

Long-term use of xylometazoline can cause swelling of the nasal mucosa and increased secretion, which is due to the development of increased sensitivity of cells to the active substances of the drug, the so-called “rebound” effect.

It is recommended to stop treatment immediately after symptoms are relieved in order to minimize the risk of adverse events.

Avoid getting the drug into the eyes or around the eyes. In case of contact, temporary blurred vision, irritation, pain, redness of the eyes may occur, and exacerbation of closed-angle glaucoma may develop. The eyes should be rinsed thoroughly with cold water if the drug gets into them and a doctor should be consulted if there is eye pain or blurred vision.

Patients with long QT syndrome using Xylometazoline may be at increased risk of developing serious ventricular arrhythmias.

Rare cases of posterior reversible encephalopathy syndrome (PRES) or reversible cerebral vasoconstriction syndrome (RCVS) have been described during therapy with sympathomimetic drugs. Symptoms included sudden onset of severe headache, nausea, vomiting and visual disturbances. In most cases, the condition improved or the phenomenon resolved within a few days after appropriate treatment. If symptoms of PRES or RCVS develop, Otrivin^® Complex should be discontinued immediately and medical attention should be sought.

Effect on ability to drive vehicles and operate machinery

Cases of visual impairment (including blurred vision and pupil dilation), dizziness and fatigue have been observed with the use of Otrivin^® Complex. Patients should be warned that if such symptoms occur, they should refrain from driving vehicles, operating machinery, and performing activities where such symptoms could pose a risk to themselves and others.

Overdose

With nasal use of Otrivin^® Complex, acute overdose is unlikely, since the absorption of the drug is extremely insignificant.

Symptoms of xylometazoline when taken orally or when applied topically can cause severe dizziness, nausea, increased sweating, sharp decrease in body temperature, headache, bradycardia, accommodation disturbance, arterial hypertension, respiratory depression, coma, convulsions. Arterial hypertension may be replaced by arterial hypotension.

With excessive use of ipratropium bromide, overdose is unlikely due to the extremely insignificant absorption of the substance into the blood, but dry mouth, difficulty in accommodation, and tachycardia may develop.

Significant overdose can cause symptoms associated with the drug’s anticholinergic effect on the central nervous system, including hallucinations, for the elimination of which cholinesterase inhibitors are prescribed.

Treatment appropriate supportive measures should be taken for any suspicion of overdose, if necessary, immediate symptomatic treatment under medical supervision is indicated. Symptomatic therapy should be carried out under medical supervision. These measures should include monitoring the patient for 6 hours. In case of severe poisoning with cardiac arrest, resuscitation measures should continue for at least 1 hour.

Drug Interactions

The drug is incompatible with simultaneous use of MAO inhibitors, tri- and tetracyclic antidepressants, as well as if these drugs have been taken within the previous 2 weeks.

Sympathomimetic drugs cause the release of catecholamines, including norepinephrine, which has a vasoconstrictive effect, as a result of which blood pressure increases. If blood pressure increases significantly, treatment with Otrivin^® Complex should be discontinued and symptomatic treatment should be carried out.

Use with tri- and tetracyclic antidepressants may enhance the sympathomimetic effect of xylometazoline.

With concomitant use of other drugs with anticholinergic activity, the anticholinergic effect of ipratropium bromide may be enhanced.

Concomitant use of beta-2-agonists with ipratropium may lead to an increased risk of acute glaucoma in patients with a history of closed-angle glaucoma.

The above interactions were studied individually for both active substances included in Otrivin^® Complex. The above interactions for both active substances in combination have not been studied.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date stated on the packaging.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.