Duaklir Genuair (Powder) Instructions for Use

Marketing Authorization Holder

AstraZeneca UK Limited (United Kingdom)

Manufactured By

Industrias Farmaceuticas Almirall, S.A. (Spain)

Contact Information

R-PHARM JSC (Russia)

ATC Code

R03AL05 (Formoterol and aclidinium bromide)

Active Substances

Formoterol (Rec.INN registered by WHO)

Aclidinium bromide (Rec.INN registered by WHO)

Dosage Form

Duaklir Genuair

Metered dose powder for inhalation 340 mcg+11.8 mcg/1 dose: inhaler 60 doses

Dosage Form, Packaging, and Composition

Metered dose powder for inhalation – cartridge contents: a white or almost white, fine, free-flowing powder, free of visible agglomerates or foreign particles.
The inhaler is white with an orange protective cap, an orange dose release button, and a fixed sliding cover with a cartridge containing the drug and a 60-dose counter.

* the delivered dose of aclidinium bromide is 396 mcg, which corresponds to an aclidinium content of 340 mcg.
** the delivered dose of formoterol fumarate dihydrate is 11.8 mcg.

Excipients : lactose monohydrate – 11.588 mg.

60 doses – dose counter inhalers (1) – laminated aluminum foil bags (1) with a desiccant sachet – cardboard packs with first-opening control.

Clinical-Pharmacological Group

Bronchodilator drug

Pharmacotherapeutic Group

Combined bronchodilator agent (selective β₂-adrenomimetic + m-cholinergic blocker)

Pharmacological Action

Mechanism of action

Duaklir Genuair contains 2 bronchodilators:

• Aclidinium – a long-acting muscarinic receptor antagonist (also called an anticholinergic);
• Formoterol – a long-acting β₂-adrenergic receptor agonist.

The combination of these substances with different mechanisms of action provides an additive effect compared to the use of individual components. Due to the different density of muscarinic and β₂-adrenoceptors in the central and peripheral airways, muscarinic receptor antagonists are more effective in relaxing the central airways, and β₂-adrenergic receptor agonists are more effective in relaxing the peripheral airways; thus, the use of combination therapy may enhance the beneficial effect on lung function.

Aclidinium is a competitive, selective muscarinic receptor antagonist with a longer binding time to M₃ receptors than to M₂ receptors. M₃ receptors mediate the contraction of airway smooth muscle. Inhaled aclidinium bromide acts locally in the lungs as an M₃ receptor antagonist on airway smooth muscle and causes bronchodilation. The use of aclidinium in patients with chronic obstructive pulmonary disease (COPD) also leads to a reduction in symptom severity, improvement in disease-related health status, reduction in the frequency of exacerbations, and improvement in exercise tolerance. Since aclidinium bromide is rapidly broken down in blood plasma, the number of systemic anticholinergic side effects is low.

Formoterol is a potent selective β₂-adrenoceptor agonist. Bronchodilation is achieved by relaxing the airway smooth muscle due to an increase in cAMP levels after adenylate cyclase activation. In addition to improving lung function, formoterol reduces symptom severity and improves quality of life in patients with COPD.

Pharmacodynamics

Clinical studies have shown that Duaklir Genuair provides a clinically significant improvement in lung function (assessed by FEV₁) for >12 hours after administration.

Duaklir Genuair has a rapid onset of action – within 5 minutes after the first inhalation compared to placebo. The onset of action of Duaklir Genuair was comparable to the effect of the fast-acting β₂-adrenoceptor agonist formoterol at a dose of 12 mcg. Maximum bronchodilation (maximum FEV₁) compared to baseline was achieved from the first day (304 ml) and maintained throughout the therapy period of >6 months (326 ml).

Cardiac electrophysiology

No clinically significant effect of Duaklir Genuair on ECG parameters, including the QT interval, was identified compared to aclidinium, formoterol, and placebo, nor on heart rate during 24-hour Holter monitoring.

Clinical efficacy

The Phase III clinical trial program involving approximately 4000 patients with a clinical diagnosis of moderate or severe COPD included two 6-month randomized studies with placebo and active control (ACLIFORM-COPD and AUGMENT), a 6-month extended phase of the AUGMENT study, and an additional 12-month randomized, controlled study.

In long-term safety studies, Duaklir Genuair showed sustained efficacy with a duration of use of more than 1 year, with no signs of tachyphylaxis.

Effect on lung function

Duaklir Genuair (340 mcg+11.8 mcg/dose twice daily) provided a clinically significant improvement in lung function (assessed by FEV₁, forced vital capacity, and inspiratory capacity) compared to placebo. A clinically significant bronchodilator effect was achieved within 5 minutes after taking the first dose of the drug and was maintained throughout the interdose interval.

In the ACLIFORM-COPD study, Duaklir Genuair provided an improvement in FEV₁ 1 hour after dose administration compared to placebo and aclidinium, by 299 ml and 125 ml, respectively (p< 0.0001 in both comparisons), and an improvement in trough FEV₁ compared to placebo and formoterol, by 143 ml and 85 ml, respectively (p< 0.0001 in both comparisons). In the AUGMENT study, the improvement in FEV₁ 1 hour after dose administration compared to placebo and aclidinium was 284 ml and 108 ml, respectively (p< 0.0001 in both comparisons), and the improvement in trough FEV₁ compared to placebo and formoterol was 130 ml (p< 0.0001) and 45 ml (p=0.01), respectively.

Symptom relief and improvement in disease-related health status

Dyspnea and other symptoms. Duaklir Genuair provided a clinically significant improvement in dyspnea (assessed using the Transition Dyspnea Index (TDI)), with an increase in the TDI score after 6 months of therapy compared to placebo by 1.29 units in the ACLIFORM-COPD study (p< 0.0001) and by 1.44 units in the AUGMENT study (p< 0.0001).

A pooled analysis of these two studies showed that the use of Duaklir Genuair was associated with a statistically significantly greater improvement in the TDI score compared to aclidinium (by 0.4 units; p=0.016) or formoterol (by 0.5 units; p=0.009).

Duaklir Genuair improved daytime COPD symptoms, particularly dyspnea, chest symptoms, cough, and sputum production (assessed using the E-RS total score), as well as the overall severity of nighttime symptoms, early morning symptoms, and symptoms limiting activity in the early morning hours, compared to placebo, aclidinium, and formoterol, although this improvement was not always statistically significant. The aclidinium/formoterol combination did not show a statistically significant reduction in the average number of nighttime awakenings due to COPD compared to placebo or formoterol.

Health-related quality of life. In the AUGMENT study, Duaklir Genuair provided a statistically significant improvement in disease-related health status (assessed using the St. George’s Respiratory Questionnaire (SGRQ)), with an improvement in the total SGRQ score of -4.35 units compared to placebo (p< 0.0001). In the ACLIFORM-COPD study, only a slight decrease in the total SGRQ score was observed compared to placebo due to an unexpectedly pronounced response to placebo therapy (p=0.598), and the percentage of patients who achieved a clinically significant improvement from baseline was 55.3% in the Duaklir Genuair group and 53.2% in the placebo group (p=0.669).

A pooled analysis of data from these two studies showed a greater improvement in the total SGRQ score with Duaklir Genuair compared to formoterol (-1.7 units; p=0.018) or aclidinium (-0.79 units; p=0.273).

Reduction in the frequency of COPD exacerbations

As part of a pooled efficacy analysis of two 6-month studies, a statistically significant 29% reduction in the frequency of moderate or severe exacerbations (requiring antibiotic or corticosteroid therapy, or leading to hospitalization) was demonstrated during therapy with Duaklir Genuair compared to placebo (rate per patient per year: 0.29 vs. 0.42, respectively; p=0.036), as well as an increase in the time to the first moderate or severe exacerbation compared to placebo (hazard ratio 0.70; p=0.027).

Use of rescue medication

Duaklir Genuair reduced the need for rescue medication over more than 6 months compared to placebo (by 0.9 inhalations/day (p< 0.0001)), aclidinium (by 0.4 inhalations/day (p< 0.001)) and formoterol (by 0.2 inhalations/day (p=0.062)).

Pharmacokinetics

The pharmacokinetic parameters of aclidinium and formoterol when administered by inhalation in combination did not differ significantly from those observed with the individual components.

Absorption

After a single inhalation of Duaklir Genuair, aclidinium and formoterol were rapidly absorbed into the blood plasma, reaching C_max within 5 minutes after inhalation in healthy volunteers and within 24 minutes after inhalation in patients with COPD. The maximum C_ss of aclidinium and formoterol in patients with COPD receiving Duaklir Genuair twice daily for 5 days were reached within 5 minutes after inhalation and were 128 pg/ml and 17 pg/ml, respectively.

Distribution

The total amount of aclidinium reaching the lungs via the Genuair inhaler was approximately 30% of the metered dose. The binding of aclidinium to plasma proteins in vitro most likely corresponds to the binding of metabolites to proteins, due to the rapid hydrolysis of aclidinium in blood plasma. Binding to plasma proteins was 87% for the carboxylic acid metabolite and 15% for the alcohol metabolite. The main plasma protein that binds aclidinium is albumin.

The binding of formoterol to plasma proteins is 61%-64% (34% – mainly to albumin). No saturation of binding sites was noted in the concentration range achieved when using the drug in therapeutic doses.

Metabolism

Aclidinium is rapidly and extensively hydrolyzed to pharmacologically inactive alcohol derivative and carboxylic acid derivative. Chemical (non-enzymatic) and enzymatic hydrolysis by esterases occurs. The main esterase involved in hydrolysis in humans is butyrylcholinesterase. The plasma concentration of the acid metabolite after inhalation is approximately 100 times higher than the concentration of the alcohol metabolite and the unchanged active substance.

The low absolute bioavailability of aclidinium after inhalation (<5%) is due to its intensive systemic and presystemic hydrolysis both in the lungs and upon oral intake. Biotransformation involving cytochrome P450 (CYP450) isoenzymes plays a minor role in the overall metabolic clearance of aclidinium. In vitro studies have shown that aclidinium at a therapeutic dose or its metabolites do not inhibit or induce any CYP450 isoenzymes and do not inhibit esterases (carboxylesterase, acetylcholinesterase, and butyrylcholinesterase). It has also been established in vitro that aclidinium or its metabolites are not substrates or inhibitors of P-glycoprotein.

Formoterol is eliminated primarily through metabolism. The main pathway is direct glucuronidation with O-demethylation followed by conjugation with glucuronide. The O-demethylation of formoterol involves the CYP2D6, CYP2C19, CYP2C9, and CYP2A6 isoenzymes. At therapeutically significant concentrations, formoterol does not inhibit CYP450 isoenzymes.

Excretion

After inhalation of Duaklir Genuair 340 mcg+11.8 mcg/dose, the terminal T_1/2 of aclidinium and formoterol is approximately 5 h and 8 h, respectively. After intravenous administration of 400 mcg of radiolabeled aclidinium to healthy volunteers, about 1% of the administered dose was excreted unchanged in the urine. Up to 65% of the drug dose was excreted as metabolites in the urine and up to 33% as metabolites in the feces. After inhalation of 200 mcg and 400 mcg of aclidinium by healthy volunteers and patients with COPD, the excretion of unchanged aclidinium in the urine was very low (approximately 0.1% of the administered dose), indicating that renal clearance plays a minor role in the overall clearance of aclidinium from plasma.

The main part of the administered dose of formoterol was metabolized in the liver and subsequently excreted by the kidneys. After inhalation, 6%-9% of the delivered dose of formoterol is excreted in the urine unchanged or as formoterol conjugates.

Pharmacokinetics in special patient groups

Elderly patients. Pharmacokinetic studies of the aclidinium/formoterol combination have not been conducted in elderly patients. Since dose adjustment of aclidinium or formoterol is not required for elderly patients, dose adjustment is also not required when using the aclidinium/formoterol combination.

Patients with renal or hepatic impairment. There are no data on the use of the aclidinium/formoterol combination in patients with renal or hepatic impairment. Since dose adjustment of aclidinium or formoterol is not required for patients with renal or hepatic impairment, dose adjustment is also not required when using the aclidinium/formoterol combination.

Indications

• As maintenance bronchodilator therapy to relieve symptoms of chronic obstructive pulmonary disease in adults.

ICD codes

Dosage Regimen

For inhalation use. The recommended dose is 1 inhalation of Duaklir Genuair (340 mcg+11.8 mcg/dose) twice daily.

If a dose is missed, the missed dose should be taken as soon as possible, and the next dose should be taken at the usual time. A double dose should not be taken to compensate for a missed dose.

Dose adjustment is not required in elderly patients (see the "Pharmacokinetics" section).

Dose adjustment is not required in patients with renal impairment (see the "Pharmacokinetics" section).

Dose adjustment is not required in patients with hepatic impairment (see the "Pharmacokinetics" section).

The drug is not intended for use in children and adolescents under 18 years of age with COPD.

Instructions for the correct use of Duaklir Genuair

Patients should be instructed on the principles of correct drug use.

Before first use, the sealed bag should be opened along the arrow lines, the Genuair inhaler should be removed, and its components should be familiarized with. The bag and the desiccant sachet should be disposed of.

Before using the Genuair inhaler, the patient should carefully read the instructions.

How to use Duaklir Genuair

General information

To use the Genuair inhaler after removing the cap, the patient needs to take 2 steps

Step 1 Press and release the orange button and exhale fully, but not into the inhaler.

Step 2 Place lips tightly around the mouthpiece and take a strong and deep breath through the inhaler.

After inhalation, remember to put the protective cap back on.

Starting use

When taking a dose of the medication, remove the protective cap by lightly squeezing the arrows on each side and pulling the cap outward (Fig. 1).

Fig. 1

Make sure that nothing is blocking the mouthpiece.

Hold the Genuair inhaler horizontally, with the mouthpiece facing the patient. The orange button should be pointing straight up (Fig. 2).

Fig. 2

Step 1.Press the orange button all the way down and then release it (Fig. 3 and 4).

Do not hold the orange button pressed down.

Fig.3

Fig. 4

Stop and check that the dose is ready for inhalation – the control window has turned green (Fig. 5).

The green color of the control window confirms that the medication is ready for inhalation.

Fig. 5

If the control window remains red, press and release the orange button again (see step 1).

Before bringing the inhaler to the mouth, exhale fully. Do not exhale into the inhaler.

Step 2. Place lips tightly around the mouthpiece of the Genuair inhaler, take a strong and deep breath through the mouthpiece (Fig. 6).

Such a strong, deep breath delivers the medication through the inhaler into the lungs.

Fig. 6

During inhalation, the patient will hear a click, indicating the correct use of the Genuair inhaler.

To receive the full dose, continue to inhale even after hearing the inhaler’s click.

Remove the Genuair inhaler from the mouth and hold your breath for as long as is comfortable, then exhale slowly through the nose.

Note. Some patients, depending on individual characteristics, may perceive a slight sweet or bitter taste during inhalation of the medication. An additional dose should not be taken if the patient did not perceive any taste after inhalation.

Stop and check that the inhalation was performed correctly: ensure that the control window has turned red (Fig. 7). This confirms that the patient has correctly inhaled the full dose.

Fig. 7

If the color control window remains green, it is necessary to take another strong and deep breath through the mouthpiece (see step 2).

If the control window still does not change color to red, the patient may have forgotten to release the orange button before inhalation or may have inhaled incorrectly. If so, try again: ensure the orange button is released, take a strong deep breath through the mouthpiece.

Note. If after several attempts the patient still cannot perform the inhalation correctly, they should consult their doctor.

Once the control window turns red, place the protective cap onto the mouthpiece (Fig. 8).

Fig. 8

When the patient needs a new Genuair inhaler

The Genuair inhaler is equipped with a dose indicator showing approximately how many doses remain in the inhaler. The dose indicator slowly descends, reflecting intervals of 10 (60, 50, 40, 30, 20, 10, 0) (Fig. A). Each Genuair inhaler contains at least 60 doses of the medication.

When the strip with red stripes appears on the dose indicator (Fig. A), this means the medication is running out and a new Genuair inhaler needs to be purchased.

Fig. A

Note. If the Genuair inhaler becomes damaged or the cap is lost, the inhaler must be replaced. The Genuair inhaler does not need to be cleaned. However, if necessary, this should be done using a dry cloth or paper tissue on the outside of the mouthpiece.

Never use water to clean the Genuair inhaler, as this may damage the medication.

How to know that the Genuair inhaler is empty

When the number 0 (zero) appears in the middle of the dose indicator, it is necessary to continue using all remaining doses in the Genuair inhaler.

When the last dose is prepared for inhalation, the orange button will not return fully to its upper position but will remain locked in the middle position (Fig. B).

Fig. B

Even when the orange button is locked, the patient will still be able to take the last dose. After this, the Genuair inhaler cannot be used again, and it will be necessary to start using a new Genuair inhaler.

Adverse Reactions

The safety information presented below is based on experience with the drug Duaklir Genuair (at the recommended therapeutic dose for up to 12 months) and its individual components.

Adverse reactions associated with the use of Duaklir Genuair are similar to those observed with its individual components. Since Duaklir Genuair contains aclidinium and formoterol, adverse reactions described for these components can be expected during its use.

The most frequently reported adverse reactions with Duaklir Genuair were nasopharyngitis (7.9%) and headache (6.8%).

The frequency of adverse reactions is based on an assessment of overall incidence rates observed with Duaklir Genuair 340 mcg+11.8 mcg/dose in a pooled analysis of randomized, placebo-controlled Phase III clinical trials of at least 6 months duration.

The frequency of adverse reactions is presented using the following conventions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and frequency not known (cannot be estimated from the available data).

¹Adverse reactions observed with Duaklir Genuair but not listed in the prescribing information for its individual components.

²Adverse reactions observed with the drug, listed in the prescribing information for at least one of its individual components.

³Adverse reactions listed in the prescribing information for at least one of the individual components, but observed with a lower or comparable frequency compared to placebo when using the combination drug Duaklir Genuair 340 mcg+11.8 mcg/dose.

⁴Adverse reactions listed in the prescribing information for at least one of the individual components, but not observed with the combination drug Duaklir Genuair 340 mcg+11.8 mcg/dose; the frequency category is provided in accordance with the “Adverse Reactions” section of the prescribing information for the individual components.

Contraindications

• Hypersensitivity to aclidinium bromide, formoterol, or lactose;
• Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption;
• Children under 18 years of age (efficacy and safety not established).

With caution myocardial infarction within the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, hospitalization within the previous 12 months for heart failure of NYHA functional class III and IV, or other severe cardiovascular diseases; QTc interval (Bazett’s method) >470 ms; concomitant therapy with drugs that prolong the QTc interval; convulsive disorders; thyrotoxicosis; pheochromocytoma; symptomatic prostatic hyperplasia; urinary retention; narrow-angle glaucoma; hypokalemia.

Use in Pregnancy and Lactation

Pregnancy

There are no data on the use of Duaklir Genuair in pregnant women.

In animal studies, fetotoxicity was noted only at doses significantly exceeding the maximum human dose of aclidinium, and adverse effects in reproductive toxicity studies were only observed at very high systemic exposure to formoterol.

During pregnancy, Duaklir Genuair should be used only if the expected benefit outweighs the potential risks.

Breastfeeding period

It is unknown whether aclidinium (and/or its metabolites) or formoterol is excreted in breast milk. Since preclinical studies have shown that small amounts of aclidinium (and/or its metabolites) and formoterol pass into milk, Duaklir Genuair should be used during breastfeeding only if the expected benefit to the woman outweighs the potential risk to the infant.

Fertility

Preclinical studies revealed a slight decrease in fertility only at doses significantly exceeding the maximum human doses of aclidinium and formoterol. It is considered unlikely that the use of Duaklir Genuair at the recommended dose will affect human fertility.

Use in Hepatic Impairment

No dose adjustment is required in patients with renal impairment

Use in Renal Impairment

No dose adjustment is required in patients with renal impairment

Pediatric Use

Contraindicated in children and adolescents under 18 years of age (efficacy and safety not established).

Geriatric Use

No dose adjustment is required in elderly patients.

Special Precautions

Bronchial asthma

Duaklir Genuair should not be used for bronchial asthma; clinical trials of Duaklir Genuair in bronchial asthma have not been conducted.

Paradoxical bronchospasm

Cases of paradoxical bronchospasm were not noted in clinical trials with Duaklir Genuair at the recommended dose. However, paradoxical bronchospasm has been observed with other inhaled therapies. In case of its occurrence, use of the medicinal product should be discontinued and alternative therapy considered.

The drug is not intended for relief of acute attacks

Duaklir Genuair is not indicated for the treatment of acute episodes of bronchospasm.

Effect on the cardiovascular system

Duaklir Genuair should be used with caution in patients who have had a myocardial infarction within the previous 6 months, in patients with unstable angina, newly diagnosed arrhythmia within the previous 3 months, with a QTc interval (calculated by Bazett’s method) >470 ms, or who were hospitalized within the previous 12 months for heart failure of NYHA functional class III and IV, as these patients were not included in clinical trials.

In some patients, β₂-adrenergic receptor agonists can cause increased heart rate and blood pressure, ECG changes such as T-wave flattening, ST-segment depression, and prolongation of the QTc interval. If these effects develop, early discontinuation of therapy may be required. Long-acting β₂-adrenergic receptor agonists should be used with caution in patients with current or history of QTc interval prolongation, or those receiving drugs that affect the duration of the QTc interval (see section “Drug Interactions”).

Systemic effects

Duaklir Genuair should be used with caution in patients with severe cardiovascular disorders, convulsive disorders, thyrotoxicosis, and pheochromocytoma.

Use of high doses of β₂-adrenergic receptor agonists may lead to metabolic effects such as hyperglycemia and hypokalemia. In Phase III clinical trials, the frequency of significant increases in blood glucose with Duaklir Genuair was low (0.1%) and similar to the placebo group. Hypokalemia is usually transient and does not require additional therapy. In patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant therapy (see section “Drug Interactions”). Hypokalemia may increase the risk of arrhythmia.

Due to anticholinergic activity, Duaklir Genuair should be used with caution in symptomatic prostatic hyperplasia, urinary retention, or narrow-angle glaucoma (despite the fact that direct contact of the drug with the eyes is very unlikely). Dry mouth, noted during anticholinergic therapy, if persistent for a long time, may lead to dental caries.

Effect on ability to drive and use machines

Duaklir Genuair has no or negligible influence on the ability to drive and use machines. The development of blurred vision or dizziness may affect the ability to drive or operate machinery.

Overdose

Experience with overdose of Duaklir Genuair is limited.

Symptoms high doses of Duaklir Genuair may lead to an increase in the symptoms and manifestations of anticholinergic and/or β₂-adrenergic action; the most common of which are: blurred vision, dry mouth, nausea, muscle spasm, tremor, headache, palpitations, and hypertension.

Treatment in case of overdose, use of Duaklir Genuair should be discontinued. Supportive and symptomatic therapy is indicated.

Drug Interactions

Medicinal products for the treatment of COPD

Concomitant use of Duaklir Genuair with other anticholinergic agents and/or long-acting β₂-adrenergic receptor agonists has not been studied and is not recommended.

Although formal in vivo drug interaction studies with Duaklir Genuair have not been conducted, it has been used concurrently with other medicinal products for COPD therapy, including short-acting β₂-adrenergic receptor agonists, methylxanthines, as well as oral and inhaled corticosteroids, without clinical signs of drug interactions.

Metabolic interactions

In vitro studies have established that no interaction is expected between aclidinium at therapeutic dose or its metabolites with P-glycoprotein (Pgp) substrates and drugs metabolized by cytochrome P450 (CYP450) isoenzymes and esterases. At therapeutically significant concentrations, formoterol does not inhibit CYP450 isoenzymes (see section “Pharmacokinetics”).

Drugs causing hypokalemia

Concomitant use of methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalemic effect of β₂-adrenergic receptor agonists, therefore caution should be exercised when used concomitantly with these drugs (see section “Special Precautions”).

β₂-adrenergic receptor blockers

β₂-adrenergic receptor blockers may weaken or negate the effect of β₂-adrenergic receptor agonists. If the use of β-adrenergic receptor blockers (including in the form of eye drops) is necessary, cardioselective β-adrenergic receptor blockers are preferable, although they should also be used with caution.

Other pharmacodynamic interactions

Duaklir Genuair should be used with caution in patients receiving drugs that prolong the QTc interval, such as MAO inhibitors, tricyclic antidepressants, antihistamines, or macrolides, as they may potentiate the effect of formoterol on the cardiovascular system. Drugs that prolong the QTc interval increase the risk of ventricular arrhythmia.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 2 years. Do not use after the expiration date stated on the packaging.

Shelf life after first opening the pouch – 60 days.

Dispensing Status

The drug is dispensed by 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.