Fluticasone Furoate & Oxymetazoline Hydrochloride Nasal Spray

Each spray delivers :

Fluticasone Furoate 27.5 mcg

Oxymetazoline Hydrochloride IP 50 mcg

Composition :

Fluticasone Furoate 0.028% w/w

Oxymetazoline Hydrochloride IP 0.050% w/w

Benzalkonium Chloride Solution IP 0.030% w/w

Nasal Spray, Fluticasone Furoate 27.5 mcg & Oxymetazoline Hydrochloride 50 mcg

4.1 Therapeutic indication

For the treatment of symptoms of allergic rhinitis with nasal congestion.

4.2 Posology and method of administration

The recommended dose is two spray actuations (27.5 micrograms of. Fluticasone Furoate and 50 mcg of Oxymetazoline Hydrochloride per spray actuation) in each nostril once daily (total daily dose, 110 micrograms of Fluticasone Furoate and 200 mcg of Oxymetazoline Hydrochloride). Once adequate control of symptoms is achieved, dose reduction to one spray actuation in each nostril (total daily dose 55 micrograms of Fluticasone Furoate and 100 mcg of Oxymetazoline Hydrochloride) may be effective for maintenance.

Fluticasone Furoate and Oxymetazoline Hydrochloride Nasal Spray is for administration by the intranasal route only.

The intranasal device should be shaken before use. The device is primed by pressing the mist release button for at least six spray actuations (until a fine mist is seen), whilst holding the device upright. Re-priming (approximately 6 sprays until a fine mist is seen) is only necessary if the cap is left off for 5 days or the intranasal device has not been used for 30 days or more.

Children < 12 years of age

Fluticasone Furoate and Oxymetazoline Hydrochloride Nasal Spray should not be used in children less than 12 years of age.

Elderly (≥ 65 years old)

No dose adjustment is required in this population.

Renal impairment

No dose adjustment is required in this population.

Hepatic impairment

No dose adjustment is required in this population.

4.3 Contraindications 

• Hypersensitivity to Fluticasone Furoate, Oxymetazoline or any other ingredients of this medicine.
• Age less than 12 years.
• In patients who have undergone recent trans-nasal surgery.
• In patients with chronic nasal inammation with very dry nasal passages (rhinitis sicca or atrophic rhinitis).
• In patients with cardiovascular disease, hyperthyroidism, angle closure glaucoma or prostatic enlargement.

4.4 Special warnings and precautions for use

Keep the spray away from the eyes.

Systemic corticosteroid effects

Systemic effects of nasal corticosteroid may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely tooccur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. Fluticasone furoate 110 micrograms once daily has not been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression in adult or adolescent subjects. However, the dose of intranasal fluticasone furoate should be reduced to the lowest dose at which effective control of the symptoms of rhinitis is maintained. As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed concurrently. If there is any reason to believe that adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to fluticasone furoate.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient present with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Growth retardation

Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses. A reduction in growth velocity has been observed in children treated with fluticasone furoate 110 micrograms daily for one year. Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control. It is recommended that the growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid if possible, to the lowest dose at which effective control of symptoms is maintained.

Patients on ritonavir

Concomitant administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone Furoate.

4.5 Drug interactions

Interaction with CYP3A inhibitors

Fluticasone furoate is rapidly cleared by extensive first-pass metabolism mediated by the cytochrome P450 3A4.

Based on data with another glucocorticoid (fluticasone propionate), that is metabolised by CYP3A4, coadministration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate. Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors including cobicistat containing products as an increase in the risk of systemic side effects is expected. Co-administration should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects, in which case patients should be monitored for systemic corticosteroid side effects. In a drug interaction study of intranasal fluticasone furoate with the potent CYP3A4 inhibitor ketoconazole there were more subjects with measurable fluticasone furoate concentrations in the ketoconazole group (6 of the 20 subjects) compared to placebo (1 out of 20 subjects). This small increase in exposure did not result in a statistically significant difference in 24-hour serum cortisol levels between the two groups.

The enzyme induction and inhibition data suggest that there is no theoretical basis for anticipating metabolic interactions between fluticasone furoate and the cytochrome P450 mediated metabolism of other compounds at clinically relevant intranasal doses. Therefore, no clinical studies have been conducted to investigate interactions of fluticasone furoate on other drugs Monoamine oxidase inhibitors (MAOIs), nonselective beta adrenergic antagonists, or tricyclic antidepressants.

Use of Oxymetazoline containing nasal spray in combination with monoamine oxidase inhibitors (MAOIs), nonselective beta adrenergic antagonists, or tricyclic antidepressants may cause hypertension and is not recommended.

4.6 Use in special populations

Pregnancy

There are no adequate data from the use of fluticasone furoate and Oxymetazoline containing nasal sprays in pregnant women. In animal studies glucocorticoids have been shown to induce malformations including cleft palate and intra-uterine growth retardation. This is not likely to be relevant for humans given recommended nasal doses which results in minimal systemic exposure.

Breast-feeding

It is unknown whether nasal administered fluticasone furoate or Oxymetazoline is excreted in human breast milk. Administration of Fluticasone Furoate and Oxymetazoline Hydrochloride Nasal Spray to women who are breast-feeding should only be considered if the expected benet to the mother is greater than any possible risk to the child.

Fertility

There are no fertility data in humans.

4.7 Effects on ability to drive and use machines

Fluticasone Furoate and Oxymetazoline Hydrochloride Nasal Spray has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

The most common AEs reported with the use of Fluticasone Furoate and Oxymetazoline containing Nasal Spray are epistaxis, nasal ulceration, nasal dryness & discomfort, sneezing and headache. The other AEs include : rhinalgia, transient ocular changes, vision blurred, nasal septum perforation, dry mouth, stomatitis, dry throat, local irritation, insomnia, sedation, anxiety, irritability, nausea, hypertension, irregular heart rate, increased heart rate, restlessness, somnolence, fatigue, hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria. Prolonged use may cause rebound congestion and rhinitis medicamentosa.

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 email to : medico@zuventus.com Website : https://www.zuventus.co.in/drug-safety-reporting By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Overdosage may give rise to local irritation and rebound congestion. Treatment need only be symptomatic

5.1 Pharmacodynamic properties

Fluticasone furoate is a synthetic tri-fluorinated corticosteroid that possesses a very high affinity for the glucocorticoid receptor and has a potent anti-inflammatory action.

Oxymetazoline is a direct-acting sympathomimetic amine. It acts on alpha-adrenergic receptors in the vessels of the nasal mucosa producing vasoconstriction and decongestion.

5.2 Pharmacokinetic properties

Fluticasone Furoate

Absorption: Fluticasone furoate undergoes incomplete absorption and extensive first-pass metabolism in the liver and gut resulting in negligible systemic exposure. The intranasal dosing of 110 micrograms once daily does not typically result in measurable plasma concentrations (<10 pgl ml). The absolute bioavailability for intranasal uticasone furoate is 0.50 %, such that less than 1 microgram of fluticasone furoate would be systemically available after administration of 110 micrograms

Distribution: The plasma protein binding of fluticasone furoate is greater than 99%. Fluticasone furoate is widely distributed with volume of distribution at steady-state of, on average, 608 L.

Biotransformation: Fluticasone furoate is rapidly cleared (total plasma clearance of 58.7 I/h) from systemic circulation principally by hepatic metabolism to an inactive 17p-carboxylic metabolite (GW694301X), by the cytOchrome P450 enzyme CYP3A4. The principal route of metabolism was hydrolysis of the S-fluoromethyl carbothioate function to form the 1713- carboxylic acid metabolite. In vivo studies have revealed no evidence of cleavage of the furoate moiety to form fluticasone.

Elimination: Elimination is primarily via the faecal route following oral and intravenous administration indicative of excretion of fluticasone furoate and its metabolites via the bile. Following intravenous administration, the elimination phase half-life averaged 15.1 hours. Urinary excretion accounted for approximately 1 % and 2 % of the orally and intravenously administered dose, respectively.

Oxymetazoline Hydrochloride

Oxymetazoline enters tissues rapidly and local vasoconstriction is normally achieved within 5-10 minutes of intranasal administration. The full effect lasts for 5-6 hours and then gradually subsides over the next 6 hours. Plasma half-life is 5-8 days with 30% of any absorbed drug being excreted in the urine unchanged and 10% being excreted in the faeces

6.1 Animal Toxicology or pharmacology

Fluticasone Furoate

Findings in general toxicology studies were similar to those observed with other glucocorticoids and are associated with exaggerated pharmacological activity. These findings are not likely to be relevant for humans given recommended nasal doses which results in minimal systemic exposure. No genotoxic effects of fluticasone furoate have been observed in conventional genotoxicity tests. Further, there were no treatment-related increases in the incidence of tumours in two-year inhalation studies in rats and mice.

Oxymetazoline Hydrochloride

There are no preclinical data of relevance

Fluticasone Furoate and Oxymetazoline Hydrochloride Nasal Spray is white to off white suspension in a pre-filled intranasal sprayer. The pH of suspension is 5.0 ± 1.0 The product contains two active ingredients : Fluticasone Furoate and Oxymetazoline Hydrochloride.

The chemical name of fluticasone Furoate is (6a,1113,16a,17a)-6,9- diuoro-17-{[(uoro-methypthioicarbony1}-11-hydroxy-16-methyl-3- oxoandrosta-1,4-dien-17-y1 2-furancarboxylate. The molecular weight is 538.6.

The chemical formula of Oxymetazoline Hydrochloride is 3-[(4,5- dihydro1H-imidazol-2-yOmethyl]-6-(1,1 ,-dimethylethyl)-2,4- dimethylphenol mono-hydrochloride. Its molecular weight is 296.8 for the hydrochloride salt and 260.4 for the free base.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

FLORESP-OX sales pack contains 7 gm (70 metered doses).

8.4 Storage and handling instructions

Store in a dry & dark place at a temperature not exceeding 25°C.

Keep out of reach of children.

• Keep the spray away from the eyes.
• Prolonged use of spray may lead to systemic corticosteroid effects. Consult your physician for duration of use of the product.
• Do not use the product in children less than 12 years of age
• Do not use the product if you have cardiovascular disease, hyperthyroidism, angle closure glaucoma or prostatic enlargement Do not use the product if you have undergone recent trans-nasal surgery, or in case of chronic nasal inflammation with very dry nasal passages (rhinitis sicca or atrophic rhinitis).

30 September 2024

Saline Nasal Solution IP

Sodium Chloride IP…………………………. 0.9 % w/v

in Purified Water IP q.s.

Nasal Spray

Sodium Chloride (0.9%w/v)

4.1 Therapeutic Indication 

• Gently cleans the nasal cavities when nose is blocked during colds or in allergic conditions.
• Moisturises the nasal mucosa when dry or irritated.
• Thins and loosens nasal secretions and helps their removal.

4.2 Posology and method of administration

Method of administration: Nasal use

Infants and toddlers up to 2 years: 1 spray/ nostril or 1-2 drops/nostril.

Adults and children > 2 years: 1-2 spray/ nostril or 2-3 drops/ nostril as needed. The usual frequency of use is 2 to 4 times a day per nostril. I Rinse is suitable for infants, children and adults. Seek medical advice before using I Rinse in an infant less than 2 weeks old. For children below 11 years, I Rinse should be used under adult supervision. For hygienic reasons and to avoid contamination, the nasal spray should be used by one person.

Method of Administration

I-Rinse can be used in any position. Remove the protective cap. Delicately insert the nozzle into the nostril. Press the nozzle, spray as long as necessary and allow the excess solution to trickle down. Clear your nose after 30 secs to 1 min. Repeat the procedure if required. Wash the nozzle with soapy water, wipe dry and replace protective cap. For infants & children administer under supervision.

4.3 Contraindications

Hypersensitivity to the active substance.

4.4 Special warnings and precautions for use 

• Consult a doctor before use if you are using the product after nasal surgery or injury.
• Due to its cleansing properties, it should be used first when using another local nasal product (e.g. for cold or allergic rhinitis).
• Keep out of reach and sight of Children.
• Do not use a broken, expired or damaged product.

4.5 Drugs interactions

No known drug-drug interaction.

4.6 Use in special populations

I Rinse nasal spray may be used during pregnancy and breast-feeding.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Stinging, sneezing increased nasal discharge or salty taste may occur. If any of these effects persists or worsen, notify your doctor. Tell your doctor immediately if frequent nosebleeds occur. If you notice any other effects not listed above, contact your doctor. 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 email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Treatment should be supportive and systematic.

5.1 Mechanism of Action/Pharmacodynamic properties

The exact mechanism of action of saline nasal irrigation is unknown. One possibility is that the breakdown of the protective function of the nasal mucosa plays a role in upper respiratory conditions. Saline nasal irrigation may improve nasal mucosa function through several physiologic effects, including direct cleansing, removal of inflammatory mediators and improved mucociliary function, as suggested by increasing ciliary beat frequency.

5.2 Pharmacokinetic properties

Absorption

Sodium chloride distributes primarily to extracellular compartments, including plasma and interstitial fluid; sodium is maintained outside the cell via the Na+/K+-ATPase pump, which exchanges intracellular sodium for extracellular potassium. Penetration across the blood-brain barrier is low. Sodium chloride is excreted primarily in the urine, but it is also excreted in sweat and stool. In healthy patients at steady state with minimal sweat losses, sodium excreted in urine is roughly the same as dietary intake. Sweat sodium concentration is increased in children with cystic fibrosis, aldosterone deficiency, or pseudohypoaldosteronism.

6.1 Animal Toxicology or Pharmacology

Not available.

Sodium chloride, also known as salt, common salt, table salt or halite, is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. Molecular Weight : 58.44 g/mol.

8.1 Incompatibilities

None known.

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

8.4 Storage and handing instructions

• Pressurised container. Keep away from heat and sunlight.
• Do not puncture, break or burn even when apparently empty.
• For external use only.
• Shake well before each use.
• Keep away from eyes.

• Shake the bottle before using the medicine.
• Clean your nose thoroughly before using the medicine.
• Insert the bottle tip into one nostril and close the other nostril.
• Direct the spray towards the sides of your nostril, away from the cartilage dividing the two sides of your nose.
• Breathe out gently through your mouth and repeat the same process for the other nostril.
• Avoid deep breathing as it will cause medication to go back to the throat and make it less effective.
• Avoid deep breathing as it will cause the medication to go back to the throat and make it less effective.
• Do not share the bottle with anyone else so that you do not spread germs.

06.01.2025

Levocetirizine HCl 5 mg & Pseudoephedrine HCl 120 mg SR Tablets

Each uncoated tablet contains

Levocetirizine HCl IP……………………………. 5 mg

Pseudoephedrine HCl IP……………………… 120 mg (as sustained release)

Excipients q.s.

Tablet Levocetrizine & Pseudoephedrine (5 mg + 120 mg)

4.1Therapeutic indications

For the treatment of seasonal allergic rhinitis.

4.2 Posology and method of administration

One tablet once daily.

4.3 Contraindications

• Hypersensitivity to the active substance, to cetirizine, to hydroxyzine, to pseudoephedrine or to any other piperazine derivatives.
• Patients with end stage renal disease with estimated Glomerular Filtration Rate (eGFR) below 15 ml/min (requiring dialysis treatment).
• Concomitant use of other sympathomimetic decongestants, beta-blockers or monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOI treatment. The concomitant use of MAOIs may cause a rise in blood pressure and/or hypertensive crisis.
• Cardiovascular disease including hypertension
• Diabetes mellitus
• Phaeochromocytoma
• Hyperthyroidism
• Closed angle glaucoma
• Severe acute or chronic kidney disease/renal failure

4.4 Special warnings and precautions for use

Precaution is recommended with concurrent intake of alcohol.

Caution should be taken in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as levocetirizine may increase the risk of urinary retention. Caution should be taken in patients with epilepsy and patients at risk of convulsion as levocetirizine may cause seizure aggravation.

Response to allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Pruritus may occur when levocetirizine is stopped even if those symptoms were not present before treatment initiation. The symptoms may resolve spontaneously. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.

Patients with difficulty in urination and/or enlargement of the prostate, or patients with thyroid disease who are receiving thyroid hormones should not take pseudoephedrine unless directed by a physician.

Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment and in occlusive vascular disease. If any of the following occur, this product should be stopped

• Hallucinations
• Restlessness
• Sleep disturbances

Severe Skin reactions

Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with pseudoephedrine-containing products. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, administration of this medicine should be discontinued, and appropriate measures taken if needed.

Ischaemic colitis

Some cases of ischaemic colitis have been reported with pseudoephedrine. Pseudoephedrine should be discontinued, and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.

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.

Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS)

Cases of PRES and RCVS have been reported with the use of pseudoephedrine-containing products. The risk is increased in patients with severe or uncontrolled hypertension, or with severe acute or chronic kidney disease/renal failure.

Pseudoephedrine should be discontinued and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with levocetirizine (including no studies with CYP3A4 inducers); studies with the racemate compound cetirizine demonstrated that there were no clinically relevant adverse interactions (with antipyrine, azithromycin, cimetidine, diazepam, erythromycin, glipizide, ketoconazole and pseudoephedrine). A small decrease in the clearance of cetirizine (16%) was observed in a multiple dose study with theophylline (400 mg once a day); while the disposition of theophylline was not altered by concomitant cetirizine administration.

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.

The extent of absorption of levocetirizine is not reduced with food, although the rate of absorption is decreased.

In sensitive patients the concurrent administration of cetirizine or levocetirizine and alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.

• MAOIs and/or RIMAs: Pseudoephedrine exerts its vasoconstricting properties by stimulating α -adrenergic receptors and displacing noradrenaline from neuronal storage sites. Since monoamine oxidase inhibitors (MAOIs) impede the metabolism of sympathomimetic amines and increase the store of releasable noradrenaline in adrenergic nerve endings, MAOIs may potentiate the pressor effect of pseudoephedrine. This product should not be used in patients taking monoamine inhibitors or within 14 days of stopping treatment as there is an increased risk of hypertensive crisis.
• Moclobemide: Risk of hypertensive crisis.
• Antihypertensives: Because of its pseudoephedrine content, this product may partially reverse the hypotensive action of antihypertensive drugs which interfere with sympathetic activity including bretylium, betanidine, guanethedine, debrisoquine, methyldopa, adrenergic neurone blockers and beta-blockers.
• Cardiac glycosides: Increased risk of dysrhythmias.
• Ergot alkaloids (ergotamine & methysergide): Increased risk of ergotism.
• Appetite suppressants and amphetamine-like psychostimulants: Risk of hypertension.
• Oxytocin: Risk of hypertension.
• Anticholinergic drugs: Enhances effects of anticholinergic drugs (such as Tricyclic antidepressants).
• Anaesthetic agents: Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.

4.6 Use in special populations

Pregnancy

The use of Elriz D tablet may be considered during pregnancy, if necessary.

Lactation

Elriz D tablet has been shown to be excreted in human milk. Adverse reactions associated with the drug may be observed in breastfed infants. Therefore, caution should be exercised when prescribing it to lactating women.

4.7 Effects on ability to drive and use machines

Elriz D Tablet may decrease alertness, affect your vision or make you feel sleepy and dizzy. Do not drive if these symptoms occur.

4.8 Undesirable effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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 email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

There is no known specific antidote. Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage may be considered shortly after ingestion of the drug.

5.1 Mechanism of action/ Pharmacodynamic properties

Levocetrizine

Levocetirizine, the (R) enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors.

Binding studies revealed that levocetirizine has high affinity for human H1-receptors (Ki = 3.2 nmol/l). Levocetirizine has an affinity 2-fold higher than that of cetirizine (Ki = 6.3 nmol/l). Levocetirizine dissociates from H1-receptors with a half-life of 115 ± 38 min. After single administration, levocetirizine shows a receptor occupancy of 90% at 4 hours and 57% at 24 hours.

Pharmacodynamic studies in healthy volunteers demonstrate that, at half the dose, levocetirizine has comparable activity to cetirizine, both in the skin and in the nose.

Pseudoephedrine

Pseudoephedrine has direct and indirect sympathomimetic activity and is an orally effective upper respiratory tract decongestant.

Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation in systolic blood pressure and considerably less potent in causing stimulation of the central nervous system.

5.2 Pharmacokinetic Properties

Levocetrizine

Absorption

Levocetirizine is rapidly and extensively absorbed following oral administration. In adults, peak plasma concentrations are achieved 0.9 h after dosing. Steady state is achieved after two days. Peak concentrations are typically 270 ng/ml and 308 ng/ml following a single and a repeated 5 mg o.d. dose, respectively. The extent of absorption is dose-independent and is not altered by food, but the peak concentration is reduced and delayed.

Distribution

No tissue distribution data are available in humans, neither concerning the passage of levocetirizine through the blood-brain-barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the CNS compartment. In humans, levocetirizine is 90% bound to plasma proteins. The distribution of levocetirizine is restrictive, as the volume of distribution is 0.4 l/kg.

Biotransformation

The extent of metabolism of levocetirizine in humans is less than 14% of the dose and therefore differences resulting from genetic polymorphism or concomitant intake of enzyme inhibitors are expected to be negligible. Metabolic pathways include aromatic oxidation, N- and O- dealkylation and taurine conjugation. Dealkylation pathways are primarily mediated by CYP 3A4 while aromatic oxidation involved multiple and/or unidentified CYP isoforms. Levocetirizine had no effect on the activities of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 at concentrations well above peak concentrations achieved following a 5 mg oral dose.

Due to its low metabolism and absence of metabolic inhibition potential, the interaction of levocetirizine with other substances, or vice-versa, is unlikely.

Elimination

The plasma half-life in adults is 7.9 ± 1.9 hours. The half-life is shorter in small children. The mean apparent total body clearance in adults is 0.63 ml/min/kg. The major route of excretion of levocetirizine and metabolites is via urine, accounting for a mean of 85.4% of the dose. Excretion via feces accounts for only 12.9% of the dose. Levocetirizine is excreted both by glomerular filtration and active tubular secretion.

Pseudoephedrine

Pseudoephedrine is rapidly and completely absorbed after oral administration. After an oral dose of 180 mg to man, peak plasma concentrations of 500-900 ng/ml were obtained about 2 hours post dose. The plasma half-life was about 5.5 hours and was increased in subjects with alkaline urine and decreased in subjects with acid urine. The only metabolism was N-demethylation which occurred to a small extent. Excretion was mainly via the urine.

6.1 Animal Toxicology or Pharmacology

Levocetrizine

No carcinogenicity studies have been performed with levocetirizine. However, evaluation of cetirizine carcinogenicity studies are relevant for determination of the carcinogenic potential of levocetirizine. In a 2-year carcinogenicity study, in rats, cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults, approximately 10 times the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 15 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). In a 2-year carcinogenicity study in mice, cetirizine caused an increased incidence of benign hepatic tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults, approximately 4 times the maximum recommended daily oral dose in children 6 to 11 years of age, and approximately 6 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). No increased incidence of benign tumors was observed at a dietary dose of 4 mg/kg (approximately 2 times the maximum recommended daily oral dose in adults, equivalent to the maximum recommended daily oral dose in children 6 to 11 years of age and approximately 2 times the maximum recommended daily oral dose in children 6 months to 5 years of age on a mg/m basis). The clinical significance of these findings during long-term use of levocetirizine dihydrochloride tablets is not known. Levocetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in mice. In a fertility and general reproductive performance study in mice, cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the recommended daily oral dose in adults on a mg/m basis).

Pseudoephedrine

Toxicology: Acute toxicity studies in animals have demonstrated that pseudoephedrine has a relatively high safety margin. However, at high doses, it can cause central nervous system stimulation, cardiovascular effects, and gastrointestinal disturbances.

Chronic Toxicity: Long-term studies in animals have indicated that chronic exposure to pseudoephedrine does not result in significant adverse effects at therapeutic doses. However, high doses can lead to hypertrophy of the heart and other organs.

Genotoxicity and Carcinogenicity: Pseudoephedrine has not shown any genotoxic or carcinogenic potential in standard assays.

Elriz D tablet consists of two medicines: Levocetirizine (antihistamine) and Pseudoephedrine (decongestant). Levocetirizine belongs to the class of antihistamines or anti-allergic that works by blocking the action of histamine, a substance responsible for causing allergic reactions.

8.1 Incompatibilities

Not applicable

8.2 Shelf Life

Refer on pack

8.3 Packaging Information

8.4 Storage and handing Instructions

• You have been prescribed Elriz D Tablet for the treatment of allergy symptoms such as sneezing, runny nose, watery eyes, etc.
• Stop taking Elriz D Tablet at least three days before taking an allergy test as it can affect the test results.
• Do not discontinue use without consulting your doctor, even if you feel better.
• If you drink alcohol while you are taking Elriz D Tablet, be aware of its effects on you and do not drink more than moderate amounts.
• Keep sipping water or try chewing sugar-free gum to get relief from dryness in the mouth.
• Inform your doctor if you are taking any other medications, e.g., anti-depressants.

17.12.2024

Tulobuterol transdermal patch 0.5 mg / 1 mg/ 2 mg.

Each 2.5 cm² patch contains 0.5 mg of tulobuterol

Transdermal patch

0.5 mg /1 mg /2 mg

4.1 Therapeutic indications

For treatment of patients with asthma and COPD without co-morbidity.

4.2 Posology and method of administration

Posology

Usually, 2 mg for adults, 0.5 mg for children aged between 0.5 and 3 years, 1 mg for children aged between 3 to 9 years or 2 mg aged over 9 years as tulobuterol is applied once daily on the chest, back or upper arm area.

Application site:

1)Before applying tulobuterol, clean and dry the application site.

2)Choose a new site each time to avoid cutaneous irritation.

3)Place tulobuterol on an area that is out of reach of children who may peel it off.

4)Tulobuterol should not be used within the wound as animal studies (rat) showed an increase in the blood level when tulobuterol was applied on the compromised skin.

4.3 Contraindications

Tulobuterol is contraindicated in the following patients: Patients with a history of drug hypersensitivity to any of the ingredients of tulobuterol

4.4 Special warnings and precautions for use

1.Careful Administration (Tulobuterol should be applied with care in the following patients.)

1.Patients with hyperthyroidism [Symptoms may be aggravated.]

2.Patients with hypertension [Blood pressure may be increased.]

3.Patients with heart disorder [Palpitation or arrhythmia may occur.]

4.Patients with diabetes mellitus [Glucose metabolism and blood glucose may increase.]

5.Patients with atopic dermatitis [Pruritus or redness may appear on application site.]

6.Elderly patients

2.Important Precautions

a. Anti-inflammatory drugs such as inhaled steroids are essential for principles of long-term management of the treatment of bronchial asthma. Only if no improvement of symptoms is noted or concomitant treatment with inhaled steroids, etc. are considered appropriate according to the severity of patient's condition, tulobuterol should be applied concomitantly with inhaled steroids. Since tulobuterol is not an alternative anti-inflammatory drug such as inhaled steroids, careful instruction should be given to the patients, the patient's guardian or other appropriate designated person that the patients should not to reduce or discontinue the inhaled steroids, etc. without a physician advice and to use tulobuterol alone even if the patients feel improvement of symptoms with the use of tulobuterol.

b. Careful instruction should be given to the patients, the patient's guardian or other appropriate designated person that the patients should use other appropriate drugs such as short-acting beta-stimulator for acute attack occurred during application of tulobuterol in the long-term management for the treatment of bronchial asthma. Further, if the doses of those drugs are increased or they become ineffective, careful instruction should be given to the patients, the patient's guardian or other appropriate designated person that the patients should visit medical institutions to receive treatment as soon as possible since asthma may not be adequately controlled. As this condition may be life-threatening, intensification of anti-inflammatory therapy should be pursued.

c. If tulobuterol is ineffective even when properly used according to dosage and administration (approx. One to two weeks as a guide), application should be discontinued as tulobuterol is considered inappropriate. In addition, proper instruction and adequate follow-up should be provided for pediatric use.

d. As continue use of tulobuterol beyond the dose range may cause arrhythmia or occasionally cardiac arrest, caution should be given not to use beyond the dose limit.

4.5 Interaction with other medicinal products and other forms of interaction

Precaution for coadminstration (Tulobuterol should be applied with care when coadministered with the following drugs.)

4.6 Use in special populations

Pregnancy & Lactation

• Tulobuterol may be applied to pregnant women or women who may be pregnant only when medical benefits outweigh the risk. [The safety of Tulobuterol in pregnancy has not been established.]
• If Tulobuterol is applied to nursing mothers, breast feeding should be avoided.

Pediatric Use

• The safety of Tulobuterol has not been established in infants less than 6 months of age.
• The safety of long term use of Tulobuterol has not been established in children.

Elderly population

Since physiological function is generally weakened in elderly people, Tulobuterol should be carefully applied, e.g., by starting with lower dose.

4.7 Effects on ability to drive and use machines

No known drug-drug interaction

4.8 Undesirable effect

No investigation of tulobuterol such as drug use surveillance to clarify the incidence of adverse reactions is performed.

1) Clinically significant adverse reactions (incidence unknown) (1) Anaphylactoid symptoms: Since anaphylactoid symptoms may occur, the patient should be closely observed. If any symptoms such as dyspnea, generalized flushing, angioedema and urticaria are noted, application should be discontinued and appropriate measures should be taken.

(2) Serious decreased serum potassium level: Serious decreased serum potassium has been reported with β2 stimulant. Since the serum potassium-lowering effect of β2 stimulant may increase with concomitant use of xanthine derivatives, steroids and diuretics, special caution should be given in patients with severe asthma. Furthermore, hypoxemia may enhance the effect of decreased serum potassium level on cardiac rhythm. In such case, serum potassium level should be monitored.

2) Other adverse reactions

If any symptoms are observed, application of tulobuterol should be discontinued.

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 email to:medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting&nbsp;

By reporting side effects, you can help provide more information on the safety of this medicine.

5.1 Mechanism of action/Pharmacodynamic properties

TULOBUTEROL has a selective β receptor stimulating activity. ATP is converted to cAMP and the contraction of bronchial smooth muscle is suppressed by activating adenylate cyclase after binding to β2 receptor.

5.2 Pharmacokinetic properties

Bioequivalence testing

The concentration of tulobuterol in plasma was measured (crossover method) after single transdermal application (chest, 24 hours) of tulobuterol patch 0.5 mg, 1 mg and 2 mg and standardized preparation corresponding to each standard to healthy adult males, and the statistical analysis of pharmacokinetic parameters (AUC, Cmax) confirmed bioequivalence for both drugs.

(The usual dose in adults is 2 mg per dose as tulobuterol.)

Pharmacokinetic parameters during application of tulobuterol patch

Serum concentration and parameters such as AUC and Cmax may differ from test conditions such as the selection of subjects, number of fluid collected and time.

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data

Tulobuterol is a β2-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. It is hydrochloride salt of 2-(tert-butylamino)-1-(2-chlorophenyl) ethan-1-ol. Its average molecular weight is 264.191 g/mol

• Tuloplast Transdermal Patch is prescribed for the treatment of asthma and COPD.
• Before using Tuloplast Transdermal Patch, clean and dry the application site.
• Apply Tuloplast Transdermal Patch once daily on chest, back, or upper arm as per the specified dosage regimen.
• Do not apply Tuloplast Transdermal Patch to damaged areas (irritated, injured, cut area of skin). Always use a new site for patch application to avoid skin irritation.
• Apply this medicine to a site where children cannot touch, since they might remove the tape.
• Inform your doctor if you are suffering from diabetes, high blood pressure, thyroid disorder, and heart disease. 
• Seek medical attention if you experience sudden difficulty in breathing, flushing, swelling of the lips and face, and skin rashes.
• Avoid smoking and minimise your exposure to pollution, dust, pollens and fumes. Along with that, a little exercise each day can help you stay strong.

14.10.2024

Tulobuterol transdermal patch 0.5 mg / 1 mg/ 2 mg.

Each 2.5 cm² patch contains 0.5 mg of tulobuterol

Transdermal patch

0.5 mg /1 mg /2 mg

4.1 Therapeutic indications

For treatment of patients with asthma and COPD without co-morbidity.

4.2 Posology and method of administration

Posology

Usually, 2 mg for adults, 0.5 mg for children aged between 0.5 and 3 years, 1 mg for children aged between 3 to 9 years or 2 mg aged over 9 years as tulobuterol is applied once daily on the chest, back or upper arm area.

Application site:

1)Before applying tulobuterol, clean and dry the application site.

2)Choose a new site each time to avoid cutaneous irritation.

3)Place tulobuterol on an area that is out of reach of children who may peel it off.

4)Tulobuterol should not be used within the wound as animal studies (rat) showed an increase in the blood level when tulobuterol was applied on the compromised skin.

4.3 Contraindications

Tulobuterol is contraindicated in the following patients: Patients with a history of drug hypersensitivity to any of the ingredients of tulobuterol

4.4 Special warnings and precautions for use

1.Careful Administration (Tulobuterol should be applied with care in the following patients.)

1.Patients with hyperthyroidism [Symptoms may be aggravated.]

2.Patients with hypertension [Blood pressure may be increased.]

3.Patients with heart disorder [Palpitation or arrhythmia may occur.]

4.Patients with diabetes mellitus [Glucose metabolism and blood glucose may increase.]

5.Patients with atopic dermatitis [Pruritus or redness may appear on application site.]

6.Elderly patients

2.Important Precautions

a. Anti-inflammatory drugs such as inhaled steroids are essential for principles of long-term management of the treatment of bronchial asthma. Only if no improvement of symptoms is noted or concomitant treatment with inhaled steroids, etc. are considered appropriate according to the severity of patient's condition, tulobuterol should be applied concomitantly with inhaled steroids. Since tulobuterol is not an alternative anti-inflammatory drug such as inhaled steroids, careful instruction should be given to the patients, the patient's guardian or other appropriate designated person that the patients should not to reduce or discontinue the inhaled steroids, etc. without a physician advice and to use tulobuterol alone even if the patients feel improvement of symptoms with the use of tulobuterol.

b. Careful instruction should be given to the patients, the patient's guardian or other appropriate designated person that the patients should use other appropriate drugs such as short-acting beta-stimulator for acute attack occurred during application of tulobuterol in the long-term management for the treatment of bronchial asthma. Further, if the doses of those drugs are increased or they become ineffective, careful instruction should be given to the patients, the patient's guardian or other appropriate designated person that the patients should visit medical institutions to receive treatment as soon as possible since asthma may not be adequately controlled. As this condition may be life-threatening, intensification of anti-inflammatory therapy should be pursued.

c. If tulobuterol is ineffective even when properly used according to dosage and administration (approx. One to two weeks as a guide), application should be discontinued as tulobuterol is considered inappropriate. In addition, proper instruction and adequate follow-up should be provided for pediatric use.

d. As continue use of tulobuterol beyond the dose range may cause arrhythmia or occasionally cardiac arrest, caution should be given not to use beyond the dose limit.

4.5 Interaction with other medicinal products and other forms of interaction

Precaution for coadminstration (Tulobuterol should be applied with care when coadministered with the following drugs.)

4.6 Use in special populations

Pregnancy & Lactation

• Tulobuterol may be applied to pregnant women or women who may be pregnant only when medical benefits outweigh the risk. [The safety of Tulobuterol in pregnancy has not been established.]
• If Tulobuterol is applied to nursing mothers, breast feeding should be avoided.

Pediatric Use

• The safety of Tulobuterol has not been established in infants less than 6 months of age.
• The safety of long term use of Tulobuterol has not been established in children.

Elderly population

Since physiological function is generally weakened in elderly people, Tulobuterol should be carefully applied, e.g., by starting with lower dose.

4.7 Effects on ability to drive and use machines

No known drug-drug interaction

4.8 Undesirable effect

No investigation of tulobuterol such as drug use surveillance to clarify the incidence of adverse reactions is performed.

1) Clinically significant adverse reactions (incidence unknown) (1) Anaphylactoid symptoms: Since anaphylactoid symptoms may occur, the patient should be closely observed. If any symptoms such as dyspnea, generalized flushing, angioedema and urticaria are noted, application should be discontinued and appropriate measures should be taken.

(2) Serious decreased serum potassium level: Serious decreased serum potassium has been reported with β2 stimulant. Since the serum potassium-lowering effect of β2 stimulant may increase with concomitant use of xanthine derivatives, steroids and diuretics, special caution should be given in patients with severe asthma. Furthermore, hypoxemia may enhance the effect of decreased serum potassium level on cardiac rhythm. In such case, serum potassium level should be monitored.

2) Other adverse reactions

If any symptoms are observed, application of tulobuterol should be discontinued.

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 email to:medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting&nbsp;

By reporting side effects, you can help provide more information on the safety of this medicine.

5.1 Mechanism of action/Pharmacodynamic properties

TULOBUTEROL has a selective β receptor stimulating activity. ATP is converted to cAMP and the contraction of bronchial smooth muscle is suppressed by activating adenylate cyclase after binding to β2 receptor.

5.2 Pharmacokinetic properties

Bioequivalence testing

The concentration of tulobuterol in plasma was measured (crossover method) after single transdermal application (chest, 24 hours) of tulobuterol patch 0.5 mg, 1 mg and 2 mg and standardized preparation corresponding to each standard to healthy adult males, and the statistical analysis of pharmacokinetic parameters (AUC, Cmax) confirmed bioequivalence for both drugs.

(The usual dose in adults is 2 mg per dose as tulobuterol.)

Pharmacokinetic parameters during application of tulobuterol patch

Serum concentration and parameters such as AUC and Cmax may differ from test conditions such as the selection of subjects, number of fluid collected and time.

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data

Tulobuterol is a β2-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. It is hydrochloride salt of 2-(tert-butylamino)-1-(2-chlorophenyl) ethan-1-ol. Its average molecular weight is 264.191 g/mol

• Tuloplast Transdermal Patch is prescribed for the treatment of asthma and COPD.
• Before using Tuloplast Transdermal Patch, clean and dry the application site.
• Apply Tuloplast Transdermal Patch once daily on chest, back, or upper arm as per the specified dosage regimen.
• Do not apply Tuloplast Transdermal Patch to damaged areas (irritated, injured, cut area of skin). Always use a new site for patch application to avoid skin irritation.
• Apply this medicine to a site where children cannot touch, since they might remove the tape.
• Inform your doctor if you are suffering from diabetes, high blood pressure, thyroid disorder, and heart disease. 
• Seek medical attention if you experience sudden difficulty in breathing, flushing, swelling of the lips and face, and skin rashes.
• Avoid smoking and minimise your exposure to pollution, dust, pollens and fumes. Along with that, a little exercise each day can help you stay strong.

14.10.2024

Levocloperastine Fendizoate Oral Suspension

Each 5 ml oral suspension contains:

Levocloperastine Fendizoate 35.4 mg (equivalent to 20 mg of Levocloperastine Hydrochloride)

Excipients q.s.

In a flavoured syrup base

Colour: Sunset Yellow FCF

Flavour: Mango

Oral suspension

20mg of Levocloperastine per 5ml

4.1 Therapeutic Indication

For the treatment of non-productive cough in adult patients

4.2 Posology and method of administration

Dose for Adults: 5 ml (20mg) three times daily.

4.3 Contraindications

• Known hypersensitivity to cloperastine or to any of the excipients.
• It should not be used in children under 2 years of age.
• Pregnant or breast-feeding women.
• Known hypersensitivity to antihistaminic agents.
• Patients receiving concomitant treatment with MAO inhibitors.
• Patients with hereditary fructose intolerance, glucose or galactose malabsorption, or sucrose isomaltase deficiency.
• Consumption of Alcohol is strictly contraindicated with Levocloperastine suspension.

4.4 Special warnings and precautions for use

Caution should be observed while prescribing Levocloperastine Fendizoate suspension to adults and children with hypertension, cardiovascular disease, uncontrolled diabetes mellitus, hyperthyroidism, seizures or in patients who are unusually hypersensitive to sympathomimetic amines.

Due to its mild anticholinergic activity, cloperastine should be administered with caution in patients with intraocular hypertension, narrow-angle glaucoma, prostatic hypertrophy, urine retention, hypertension, cardiac arrhythmia, myasthenia gravis, stenosing peptic ulcer or bowel obstruction affecting the oesophagus, intestine or bladder.

Persistent cough.

Caution is recommended in patients with chronic cough such as smoker's cough, pulmonary emphysema or asthma, as it inhibits the cough reflex and could therefore alter expectoration and increase airway resistance.

4.5 Drugs interactions

Levocloperastine Fendizoate suspension should not be concomitantly prescribed with sedatives or tranquilizers. Similarly, other antihistamine drugs should not be prescribed concomitantly.

As it has some antihistaminic activity, cloperastine can enhance the sedative effect of CNS

depressors such as anxiolytics, antipsychotic drugs, barbiturates, hypnotics, narcotics, sedatives, tranquilizers, some analgesics and alcohol.

Also due to this activity, cloperastine, antihistaminic agents and anticholinergic drugs (anti-parkinson's drugs, tricyclic antidepressants, MAO inhibitors, neuroleptic agents) can reciprocally increase their effects.

Expectorants and mucolytic drugs: Inhibition of the cough reflex could give rise to pulmonary obstruction in case of elevated volume or fluidity of bronchial secretions.

4.6 Use in special populations

Animal studies have not shown any evidence of damage to the foetus. In humans, its safety for use in pregnancy and lactation has not been established. Cloperastine should therefore not be used during pregnancy unless a doctor believes that the treatment's potential benefit for the mother exceeds all risks for the developing foetus or infant. As it is unknown whether the drug is excreted in human milk, its use during lactation is not recommended.

4.7 Effects on ability to drive and use machines

Levocloperastine can cause drowsiness, so caution is recommended when driving or using dangerous machinery. If drowsiness is noted at normal doses of cloperastine, do not drive or handle dangerous machinery.

4.8 Undesirable effects

Levocloperastine can produce minor and transient adverse reactions such as Dry mouth, GI effects, exhaustion, fainting, somnolence, sedation, clouding of consciousness, numbness, dizziness, headache, palpitations and allergic reaction.

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 email to:medico@zuventus.com

Website: https://www.zuventus.co.in/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

No cases of overdose have been reported.

Intoxication can occur after ingesting quantities that are much higher than the therapeutic doses.

Overdose could cause symptoms such as drowsiness, anticholinergic symptoms, hallucinations, excitation, ataxia, lack of motor coordination and convulsions. In case of overdose, symptomatic and maintenance treatment is recommended. Vomiting should be induced or stomach lavage should be performed with saline serum.

5.1 Mechanism of action

Levocloperastine is a cough suppressant. Levocloperastine is a novel antitussive agent having dual mechanism of action, it acts on both the central bulbar cough centre and on peripheral receptors in the tracheobronchial tree.

As demonstrated in a number of animal models, Levocloperastine acts at the CNS level by inhibiting the bulbar cough centre. In addition to this primary mechanism of action, peripheral effects related to its antihistamine, anti-serotonergic and smooth muscle-relaxant properties also contribute to the overall efficacy of Levocloperastine in the treatment of cough, bronchospasm and related symptoms.

5.2 Pharmacodynamic properties

The therapeutic efficacy of DL-cloperastine in reducing the intensity and frequency of cough is well established, with efficacy similar to that of codeine and superior to that of dextromethorphan.

In clinical trials, levocloperastine had a faster onset of action and produced greater reductions in the intensity and frequency of cough compared with DL-cloperastine, codeine and levodropropizine.

The antitussive effects (reduction in intensity and frequency of cough) of levocloperastine were observed after the first day of treatment in patients of all ages. In children, levocloperastine reduced night-time awakenings and irritability; in adults, it was also effective in treating ACE inhibitor cough.

Levocloperastine was generally well tolerated. There was no evidence of clinically significant central adverse events, whereas drowsiness, dry mouth and nausea were reported with comparator agents (levodropropizine, codeine, DL-cloperastine).

Levocloperastine represents an effective alternative to currently used antitussive agents with the added advantage of faster onset of action and improved tolerability in all patient groups.

5.3 Pharmacokinetic properties

The product is absorbed from the gastrointestinal tract and mostly excreted in urine.

After administration of 10ml of oral suspension containing levocloperastine fendizoate, peak plasma concentrations of 10 μg/L were reached 2 to 4 hours after administration, with a lag-time of approximately 45 minutes before detection of the drug in the bloodstream, suggesting a gradual and protracted absorption from the intestine.

Oral bioavailability was >40% based on the ratio of area under the plasma concentrationtime curve (AUC) of unmodified drug calculated after oral and intravenous administration, while substantially higher values were obtained in excretion studies conducted with radiolabelling techniques (14C).

The half-life of levocloperastine is 0.80 hours (distribution half-life), 1.68 hours (elimination half-life), and 6.58 hours (terminal elimination half-life). The volumes of distribution (Vd) were found to be 80 ml/kg (terminal) and 57 ml/kg (at steady state), and the protein-bound fraction was high. Total body clearance was 7.5 L/hour.

In preclinical studies, levocloperastine demonstrated antitussive effects similar to those observed with codeine. In acute and repeated-dose toxicity studies, levocloperastine was well tolerated in rodents and dogs, with no clinically significant cardiovascular or gastrointestinal adverse events. The pharmacokinetic behaviour of levocloperastine, best described by a two-compartmental model with absorption phase, is similar to that of the racemic compound DL-cloperastine.

Administration of levocloperastine 1 to 9 mg/kg to guinea pigs dose-dependently inhibited cough induced by citric acid or ammonia vapour, showing an antitussive effect similar to that of codeine. The 50% effective dose (ED50) values for levocloperastine vs codeine were, respectively, 2.6 vs 3.6 mg/kg in the citric acid test, and 2.9 vs 3.1 mg/kg in the ammonia test. Activities of levocloperastine, DL-cloperastine and dextrocloperastine were similar in the citric acid-induced cough model, suggesting that the antitussive efficacy of cloperastine compounds is independent of their enantiomeric structure.

Levocloperastine (as well as dextrocloperastine and DL-cloperastine) exhibited spasmolytic activity in guinea-pigs via its antihistamine properties in vitro (inhibition of histamine-induced contraction in isolated tracheal rings) and in vivo (dose-dependent inhibition of bronchospasm induced by histamine aerosol). Similarly, serotonin-antagonist activity was demonstrated in vitro.

Unlike opioid antitussives, such as codeine, the CNS activity of levocloperastine is highly selective for the cough centre, thus avoiding central adverse effects such as sedation. This attenuation of CNS adverse effects is a differential feature of levocloperastine and is related to its specific stereoisomeric properties, since dextrocloperastine and DL-cloperastine, administered orally or intraperitoneally, induced sedative and stimulant effects of much greater magnitude (by approximately 50%) in tests of CNS function in rodents.

Both acute and repeated-dose toxicity studies found levocloperastine to be well tolerated in rodents and dogs. The 50% lethal dose (LD50) value of levocloperastine could not be calculated because the oral/intraperitoneal doses tested (up to 2000 mg/kg) did not cause death in any of the experimental animals. By comparison, the enantiomer dextrocloperastine was more toxic, with LD50 values of 466 mg/kg in the mouse and 1226 mg/kg in the rat after oral administration, and 155 and 177 mg/kg, respectively, after intraperitoneal administration.

In chronic toxicity studies, levocloperastine at dosages up to 75 mg/kg/day (corresponding to 45 times the therapeutic daily dosage in humans) for 6 months was considered 'safe' in rats and dogs. Mild adverse events (including vomiting, anorexia and transient biochemical/ histological signs of liver and kidney dysfunction) were observed only with dosages of 250 mg/kg/day following 6 months' treatment. Levocloperastine did not show mutagenic or carcinogenic effects in specific in vitro and in vivo studies.

Levocloperastine, the levorotatory isomer of DLcloperastine, is a centrally active, non-opioid antitussive agent with a chemical structure and pharmacological profile distinct from that of the racemate. It is devoid of central antinociceptive activities, does not cause addiction or dependence phenomena, and does not interfere with cardiovascular or gastrointestinal functions.

Cloperastine fendizoate is a N-oxyethylpiperidine. It is functionally related to a benzoate.

Structure of Cloperastine fendizoate

Molecular Formula: C₄₀H₃₈ClNO₅

Molecular Weight: 648.2 g/mol

8.1 Incompatibilities

None known.

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

A bottle of 100 ml.

8.4 Storage and handing instructions

Store in a cool place. Protect from light. Keep out of reach of children. Shake well before each use.

• You have been prescribed Soventus-DC Oral Suspension for the symptomatic relief of dry cough.
• It is usually taken for a short time, until the symptoms clear up.
• Measure the syrup with a special dose-measuring spoon or cup, not a regular table spoon.
• Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication.
• It should not be administered to patients with chronic cough or where cough is accompanied by excessive secretions.
• Inform your doctor if your cough lasts more than 7 days, comes back, or occurs with fever, rash or headache. These could be signs of a serious condition.

19-09-2024

Saline Nasal Solution IP

Sodium Chloride IP 0.65% w/v

In an Aqueous Isotonic Solution

using Purified Water IP

Excipients q.s.

Benzalkonium Chloride IP 0.01% w/v

(As a preservative)

Nasal Spray

Sodium Chloride (0.65%w/v)

4.1 Therapeutic Indication

Naturally provides instant, soothing relief for dry, irritated nasal passages caused by colds, allergies, dry air, pollution, smoke, air travel, and the use of decongestants or steroidal sprays.

4.2 Posology and method of administration

Method of administration: Nasal use

• Clean nose by blowing.
• For children and adults: In erect posture, insert nozzle into nostril, squeeze bottle once & inhale spray.
• For infants/babies: tilt head far back while lying down or sitting. Turn bottle upside down. Allow 2-3 drops into nostril & spread.
• Repeat for other nostril

4.3 Contraindications

Maxtra-S Nasal Spray should not be used in the following conditions:

In case of hypersensitivity to the active substance or to any of the excipients listed in the formulation.

4.4 Special warnings and precautions for use

• The use of this Maxtra®-S Nasal Spray by more than one person may spread infection.
• Avoid if you are allergic to any of the ingredients in the formulation.
• Signs of an allergic reaction may include: rash, hives, itching, red-swollen-blistered or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, unusual hoarseness or swelling of the mouth, face, lips, tongue or throat. Very severe nasal irritation.
• The product contains benzalkonium chloride which may cause irritation or swelling inside the nose, especially if used for a long time. Long term use may cause oedema of the nasal mucosa.
• Ensure that the container is undamaged and the contents clear in appearance before use. After use, discard any remaining solution.

4.5 Drugs interactions

None.

4.6 Use in special populations

Safe to use during pregnancy and lactation.

4.7 Effects on ability to drive and use machines

None known.

4.8 Undesirable effects

Usually do not occur, however rarely occurring side effects may include:

-if the inside of the nose is very dry and irritated, stinging may occur.

-allergic reactions

-sneezing

-cough

-nose irritation

-abnormal taste

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 email to: medico@zuventus.com

Website: https://www.zuventus.co.in/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

None

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Decongestants and other nasal preparations, sodium chloride nasal spray

ATC code: R01AX10

The exact mechanism of action of saline nasal irrigation is unknown. One possibility is that the breakdown of the protective function of the nasal mucosa plays a role in upper respiratory conditions. Saline nasal irrigation may improve nasal mucosa function through several physiologic effects, including direct cleansing, removal of inflammatory mediators and improved mucociliary function, as suggested by increasing ciliary beat frequency.

5.2 Pharmacokinetic properties

Absorption

Sodium chloride distributes primarily to extracellular compartments, including plasma and interstitial fluid; sodium is maintained outside the cell via the Na+/K+-ATPase pump, which exchanges intracellular sodium for extracellular potassium. Penetration across the blood-brain barrier is low. Sodium chloride is excreted primarily in the urine, but it is also excreted in sweat and stool. In healthy patients at steady state with minimal sweat losses, sodium excreted in urine is roughly the same as dietary intake. Sweat sodium concentration is increased in children with cystic fibrosis, aldosterone deficiency, or pseudohypoaldosteronism.

No further information other than that which is included in the Summary of Product Characteristics.

6.1 Animal Toxicology or Pharmacology

No information provided.

Sodium chloride, also known as salt, common salt, table salt or halite, is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. It is listed on the World Health Organization Model List of Essential Medicine.

Molecular Weight : 58.44 g/mol.

8.1 Incompatibilities

None known.

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

A bottle of 20 ml.

8.4 Storage and handing instructions

Store at temperature not exceeding 30°C. Protect from light and moisture. Keep out of reach of children. Shake well before each use.

Do not accept the pack if cap seal is broken on the bottle.

Close the cap tightly after use.

Preserve in tight container.

Alcohol Free Safe for Children Safe for repeated daily use

18-09-2024

Ambroxol Hydrochloride, Terbutaline Sulphate, Guaifenesin & Menthol Syrup

Each 5 ml Contains:

Ambroxol Hydrochloride IP….20 mg

Terbutaline Sulphate IP……….1.25 mg

Guaifenesin IP……………….50 mg

Menthol IP…………………...0.5 mg

Excipients …... …………………. q. s.

Colour Tartrazine Supra

In a flavoured syrup base

Syrup

4.1 Therapeutic indication

For the symptomatic relief of bronchospasm in bronchial asthma & chronic bronchitis.

4.2 Posology and method of administration

Adults (12 years & above) 10 ml (2 teaspoonful) 3 times a day.

Children (6-12 years) 5 - 10 ml (1 - 2 teaspoonful) 3 times a day

Paediatric population

Not recommended for children below 6 years of age.

Hepatic & Renal Insufficiency

Caution should be exercised in patients with moderate to severe renal impairment and liver disease.

4.3 Contraindications

• hypersensitivity to any of the components of the formulation.
• patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.
• patients with gastric ulceration.

4.4 Special warnings and precautions for use

In cases of severe renal failure, an accumulation of metabolites formed in the liver must be considered, and a reduction in the maintenance dose of Ambroxol or an increase in the

dose interval must be performed. In patients with a tendency for peptic ulcers, the use of Ambroxol hydrochloride should be carefully considered.

For Terbutaline, caution should be observed in patients with thyrotoxicosis. Cardiovascular effects may be seen with sympathomimetic drugs, including terbutaline.

Guaifenesin should not be used for persistent or chronic cough, such as occurs with asthma, or where cough is accompanied by excessive secretions, unless directed by a physician. Caution should be exercised in the presence of severe renal or severe hepatic impairment. The concomitant use of cough suppressants is not recommended.

Menthol based cough syrups should not be used in consistent and chronic cough with excessive mucin secretions.

4.5 Drugs interactions

The concomitant use of antitussives along with ambroxol may impair the coughing up of the liquefied bronchial mucous and cause a secretory obstruction.

The administration of ambroxol with antibiotics (amoxicillin, cefuroxime, and erythromycin) increases the concentration of antibiotics in bronchopulmonary secretions and sputum.

Terbutaline and non-selective β-blockers should not be administered concurrently. Terbutaline should be used with caution in patients receiving other sympathomimetics. Terbutaline should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of these agents, since the action of terbutaline on the vascular system may be potentiated.

The concomitant use of menthol cough syrup with warfarin may reduce the therapeutic effects of war farin. Large doses of menthol may affect the felodipine metabolism by inhibiting CYP3A4.

4.6 Use in special populations (such as pregnant women, lactating women, paediatric patients, geriatric patients etc.)

Pregnancy

Since there are no adequate and well-controlled studies of this combination in pregnant women, this medicine should be administered with caution.

Lactation

Terbutaline is secreted into breast milk, but any effect on the infant is unlikely at therapeutic doses. Transient hypoglycaemia has been reported in newborn preterm infants after maternal β-2 agonist treatment. Since Guaifenesin is excreted in breast milk in small amounts, decision must be made to continue with the medicine if benefit of drug outweighs the risks of treatment. It is preferable to avoid use of menthol based cough syrups during pregnancy or lactation.

Geriatric Population

They are more sensitive to the effects of terbutaline; hence a lower dose may be required.

4.7 Effects on ability to drive and use machines

Patients should be cautioned against engaging in activities requiring complete mental alertness, and motor coordination such as operating machinery until their response to Soventus syrup is known.

4.8 Undesirable Effects

The most common adverse reactions with Ambroxol are nausea, oral and pharyngeal hypoesthesia, dyspepsia, dry mouth, abdominal pain and allergic reactions such as skin rash or urticaria can also occur.

Tremor and headache are the most common adverse events observed with Terbutaline administration. Tachycardia, palpitations, muscle spasms and hypokalaemia are few other common adverse reactions observed.

Guaifenesin has occasionally been reported to cause gastro-intestinal discomfort, nausea and vomiting, particularly in very high doses. Allergic reactions, angioedema, anaphylactic reactions, dyspnoea (reported in association with other symptoms of hypersensitivity), nausea, vomiting, abdominal discomfort, rash and urticaria may also occur.

Possible side effects from the use of high doses of Menthol are allergic reactions, facial swelling, throat disorder, nausea, vomiting, vertigo, ataxia, drowsiness, exhaustion and stomach pain.

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 email to:medico@zuventus.com

Website : http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Ambroxol: Symptoms largely correspond with the known adverse effects in case of unintentional overdosing and/or medication errors. Symptomatic treatment is recommended if manifestations of poisoning do occur.

Possible symptoms and signs of Terbutaline overdose is headache, anxiety, tremor, nausea, tonic cramp, palpitations, tachycardia, arrhythmia. A fall in blood pressure sometimes occurs. Hypokalaemia, hyperglycaemia and lactic acidosis may also occur in case of drug overdose. Dose can be reduced in mild and moderate cases whereas gastric lavage or administration of activated charcoal can be followed in severe cases.

The effects of acute toxicity from Guaifenesin may include gastrointestinal discomfort, nausea and drowsiness. The drug is, however, rapidly metabolised and excreted in the urine.

Patients should be kept under observation and treated symptomatically.

Menthol is considered to be safe, and cases of menthol overdose are extremely rare. However, when consumed in large quantities in short span of time may cause heartburn, diarrhoea, dizziness, muscle weakness, mouth sores, skin lesions etc. Treatment should consist of gastric lavage and aspiration.

5.1 Pharmacodynamic properties

Ambroxol is a metabolic product of bromhexine and possesses mucokinetic (improvement in mucus transport) and secretolytic (liquifies secretions) properties. It promotes the removal of tenacious secretions in the respiratory tract and reduces mucostasis (arresting the secretion of mucus). The breakdown of acid mucopolysaccharide fibers makes the sputum thinner and less viscous and therefore more easily removed by coughing. Although sputum volume eventually decreases, its viscosity remains low for as long as treatment is maintained.

Terbutaline sulphate is an ethanolamine derivative with bronchodilating and tocolytic properties. It selectively binds to and activates β-2 -adrenergic receptors, leading to intracellular adenyl cyclase activation via a trimeric G protein and subsequent increase in cyclic cAMP production. Increased cAMP levels result in relaxation of bronchial and vascular smooth muscle mediated through the activation of protein kinase A (PKA), which phosphorylates proteins in control of muscle tone. cAMP also inhibits release of intracellular calcium ion, reduces calcium entry into cells and induces the sequestration of intracellular calcium. This helps in the relaxation of airway muscles. Terbutaline sulfate also increases mucociliary clearance and reduces release of inflammatory cell mediators.

Guaifenesin is a glyceryl guaiacolate with expectorant effects. It increases respiratory tract mucus secretions, acts as an irritant to gastric vagal receptors and recruits efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. This provokes cough which facilitates in flushing out tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or breathing. This agent reduces the viscosity of mucus secretion by reducing adhesiveness and surface tension as well as increasing hydration of mucus. Guaifenesin increases the efficiency of the mucociliary mechanism which is important in removing accumulated secretions from the upper and lower respiratory tract.

Guaifenesin is a glyceryl guaiacolate with expectorant effects. It increases respiratory tract mucus secretions, acts as an irritant to gastric vagal receptors and recruits efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. This provokes cough which facilitates in flushing out tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or breathing. This agent reduces the viscosity of mucus secretion by reducing adhesiveness and surface tension as well as increasing hydration of mucus. Guaifenesin increases the efficiency of the mucociliary mechanism which is important in removing accumulated secretions from the upper and lower respiratory tract.

5.2 Pharmacokinetic properties

5.3 Preclinical safety data

Not Available

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data.

Soventus Syrup is a combination of Terbutaline sulphate, Ambroxol hydrochloride and Guaiphenesin. Terbutaline sulphate is a beta-adrenergic agonist bronchodilator available as syrup for oral administration.

Terbutaline sulphate is ±-alpha-[(tert-butylamino) methyl]-3,5-dihydroxybenzyl alcohol sulphate (2:1) (salt).

The empirical formula is (C12H19NO3)2H2SO4 and the structural formula is

Guaiphenesin, a member of methoxybenzenes is an expectorant. The physiologic effect of guaifenesin is by means of decreased respiratory secretion viscosity, and increased respiratory secretions.

Chemical Name: 3-(2-methoxyphenoxy)propane-1,2-diol

Molecular formula: C₁₀H₁₄O₄

Molecular Weight: 198.22 g/mol

Ambroxol hydrochloride is an aromatic amine. A metabolite of Bromhexine that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride.

Chemical Name: 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydrochloride Molecular Formula: C13H19Br2ClN2O Molecular Weight: 414.56 g/mol

8.1 List of excipients

Disodium Edetate, Sodium Benzoate, Sucralose, Glycerol, Propylene Glycol, Liquid Sorbitol (Non Crystallising), Hydroxyethyl Cellulose, Potassium Sorbate, Colour Tartrazine Supra Soluble , Flavour Ginger RS- 2, Flavour Honey RS 80008, Flavour Lemon RS , Sodium Citrate, Citric Acid Monohydrate.

8.2 Incompatibilities

Not Applicable

8.3 Shelf life

24 MONTHS

8.4 Special precautions for storage

Protect from light.

8.5 Nature and contents of container

1x100ml, PET Bottle

8.6 Special precautions for disposal and other handling

No special requirements for disposal.

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

• Take this medicine in the dose and duration as advised by your doctor.
• Check the label for directions before use.
• Measure it with a measuring cup and take it by mouth. Shake well before use.
• Soventus Syrup may be taken with or without food, but it is better to take it at a fixed time.
• It may cause dizziness and sleepiness. Do not drive or do anything that requires mental focus until you know how it affects you.
• If you are diabetic, monitor your blood glucose regularly while taking this medicine.
• Inform your doctor if you have a history of thyroid or heart disease.
• Stop taking Soventus Syrup and inform your doctor if your cough persists for more than 1 week, tends to recur, or is accompanied by a fever, rash or persistent headache.

18th Oct. 2023

Oxymetazoline Hydrochloride Nasal Spray

Oxymetazoline Hydrochloride IP 0.05% w/v

Benzalkonium Chloride IP 0.02% w/v

(As preservative)

In buffered aqueous solution q.s

Nasal Spray

Oxymetazoline (0.05%w/v)

4.1 Therapeutic Indication

For the relief of stuffy, running nose associated with cold and influenza, also post nasal drip, sinusitis.

4.2 Posology and method of administration

Adults and children over 12 years: 1 – 2 sprays up each nostril maximum 2 – 3 times daily. The preparation should not be used for more than 5 – 7 days in a row. Method of administration: Nasal use

4.3 Contraindications

Maxtra-O Nasal Spray should not be used in the following conditions:

In case of hypersensitivity to the active substance or to any of the excipients listed in the formulation.

Patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs in the previous two weeks.

In patients with narrow-angle glaucoma. Maxtra-O nasal spray should not be used by patients after trans-sphenoidal hypophysectomy.

Children under 12 years of age.

Inflammation of the skin and mucosa of the nasal vestibule and encrustation (rhinitis sicca).

Patients with acute coronary disease or cardiac asthma.

4.4 Special warnings and precautions for use

• Caution should be exercised in case of hypertension, cardiac diseases including angina, hyperthyroidism, diabetes mellitus and prostatic hypertrophy.
• Do not exceed the recommended dose.
• If symptoms worsen or do not improve after 3 days, physician should re-evaluate clinical situation.
• Maxtra-0 Nasal Spray should be used for a maximum of 7 consecutive days to avoid rebound-effect and drug induced rhinitis.
• The preservative (benzalkonium chloride) contained Maxtra-0 Nasal Spray can cause swelling of the nasal mucosa, especially during long-term use. If such a reaction (persistent nasal congestion) is suspected, a product for nasal administration which contains no preservative should be used if possible. If such products for nasal administration are not available without preservative, the use of another dosage form should be considered.

4.5 Drugs interactions

• This product should not be used in combination with MAOIs, or for up to 2 weeks after taking MAOIs as there is a risk of interactions leading to hypertension.
• This product is known to interact with tricyclic antidepressants with a possible increased risk of hypertension and arrhythmias.
• The effects of beta-blockers or other antihypertensive drugs e.g. methyl dopa, bethanidine, debrisoquine and guanethidine may be antagonised.
• Possible additive cardiovascular toxicity may occur when sympathomimetics are given with anti-parkinsonian drugs such as bromocriptine.

4.6 Use in special populations

Pregnancy

For oxymetazoline no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Breast Feeding

It is unknown whether oxymetazoline hydrochloride is excreted into breast milk. The recommended dose should not be exceeded because overdosing can decrease placental blood flow and reduce milk production. Caution should be exercised during pregnancy and lactation as oxymetazoline may be systemically absorbed

4.7 Effects on ability to drive and use machines

Maxtra-0 Nasal Spray has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories, very common (≥1/10); common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

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 email to:medico@zuventus.com

Website: https://www.zuventus.co.in/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Symptoms of Overdose

Symptoms of moderate or severe overdose can be mydriasis, nausea, cyanosis, fever, spasms, tachycardia, cardiac arrhythmia, cardiac arrest, hypertension, oedema of the lungs, dyspnoea, psychic disturbance. The inhibition of functions of the central nervous system such as somnolence, lowering of the body temperature, bradycardia, shock like hypotension, apnoea and loss of consciousness is also possible.

Treatment of overdose

Symptomatic treatment of overdose is required. A nonselective alpha-lytic such as phentolamine may be administered to depress the increased blood pressure, Intubation and artificial respiration may be necessary in serious cases. In the case of moderate or severe inadvertent oral consumption, the administration of activated carbon (adsorbent) and sodium sulphate (laxative) or perhaps gastro-lavage in the case of large amounts should be undertaken. Further treatment is supportive and symptomatic. Vasopressor drugs are contraindicated.

5.1 Pharmacodynamic properties

Oxymetazoline is a direct-acting sympathomimetic amine. It acts on alpha-adrenergic receptors in the blood vessels of the nasal mucosa producing vasoconstriction and decongestion. Onset of action is within minutes and lasts up to 12 hours.

5.2 Pharmacokinetic properties

Absorption

With local use on the nasal mucosa, there is no clinically relevant absorption of oxymetazoline hydrochloride

6.1 Animal Toxicology or Pharmacology

Preclinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity or toxicity to reproduction. Oxymetazoline Hydrochloride Nasal Spray has not been tested for genotoxicity or carcinogenicity. Preclinical data suggest that benzalkonium chloride can produce a concentration- and time-dependant toxic effect on cilia, including irreversible immobility, and can induce histopathological changes in the nasal mucosa.

Oxymetazoline is a member of the class of phenols that is 2,4-dimethylphenol which is substituted at positions 3 and 6 by 4,5-dihydro-1H-imidazol-2-ylmethyl and tert-butyl groups, respectively. A direct-acting sympathomimetic with marked alpha-adrenergic activity, it is a vasoconstrictor that is used (generally as the hydrochloride salt) to relieve nasal congestion. It has a role as an alpha-adrenergic agonist, a sympathomimetic agent, a nasal decongestant and a vasoconstrictor agent.

Oxymetazoline

Chemical Name: 6-tert-butyl-3-(4,5-dihydro-1H-imidazol-2-ylmethyl)-2,4-dimethylphenol. Molecular formula: C₁₆H₂₄N₂O Molecular weight: 260.37 g/mol Structural formula:

8.1 Incompatibilities

None

8.2 Shelf-life

Refer on the pack

8.3 Packaging information

A bottle of 10 ml.

8.4 Storage and handing instructions

Preserve in tight container at a temperature not exceeding 30°C.

Keep out of reach of children.

Do not accept the pack if cap seal is broken on the bottle.

Close the cap tightly after use.

Zuventus healthcare Ltd.

Plot Y2, CTS No: 358/A2, Near

Nahur Railway Station, Nahur

(West), Mumbai - 400 078, India

Acebrophylline Capsules 100 mg

Each hard gelatin capsule contains

Acebrophylline 100 mg

Excipients q.s.

Capsule 100 mg

4.1 Therapeutic indication

For the treatment of chronic obstructive pulmonary disease, bronchial asthma and bronchitis.

4.2 Posology and method of administration

Adults

The usually recommended dose of acebrophylline for adults is one Brophyle Capsules twice daily. Acebrophylline capsules are not recommended for use in children (who may find difficulty in swallowing capsules).

In elderly patients dosage may be adjusted if required.

4.3 Contraindications

• Hypersensitivity to ambroxol, acebrophylline, theophylline or any other xanthine derivative
• Patients suffering from acute myocardial infarction
• Patients with hypotension, hemodynamic instability, and arrhythmias
• Patients with renal disease or liver disorder

4.4 Special warnings and precautions for use

Careful monitoring is recommended for patients with congestive heart failure, chronic alcoholism, hepatic dysfunction, or viral infections. Caution should be exercised in patients with cardiac arrhythmias, other cardiovascular diseases, hyperthyroidism or hypertension, gastric and duodenal ulceration or convulsive disorders. Patients with hepatic and renal insufficiency should take it with caution.

4.5 Drugs interactions

The following reduce clearance and a reduced dosage may therefore be necessary to avoid side-effects: allopurinol, cimetidine, ciprofloxacin, corticosteroids, diltiazem, erythromycin, frusemide, isoprenaline, oral contraceptives, thiabendazole and verapamil, doxycycline, amoxicillin etc.

Xanthines can potentiate hypokalaemia resulting from beta2-agonist therapy, steroids, diuretics and hypoxia. Particular caution is advised in severe asthma. It is recommended that serum potassium levels are monitored in such situations.

No clinically relevant unfavourable interactions with other medications have been reported.

4.6 Use in special populations

Pregnancy

Acebrophylline is not recommended in pregnancy as well as during parturition.

Lactation

The safety of acebrophylline is not established during lactation period. Hence the use of acebrophylline is not advisable in lactating mothers.

4.7 Effects on ability to drive and use machines

No studies on the effect on the ability to drive and use machines have been performed.

4.8 Undesirable effects

Transient nausea and dizziness may occur on taking this drug, but these effects are reversible. On cessation of therapy, these symptoms tend to disappear.

The commonly reported adverse effects with acebrophylline include abdominal discomfort, stomach/abdominal distension, vomiting, abdominal pain, diarrhea, constipation, heart burn, loss of appetite, esophageal bleeding, rashes, urticaria, itching, drowsiness, difficulty in breathing, leukocytosis, and nasal inflammation. If chills and fevers occur, the drug should be immediately discontinued.

Other rarely reported adverse events include headache, occasional numbness including numbness in arm, insomnia, tachycardia, fatigue, hypertension, albuminuria, glycosuria, hypotension and occasionally hyperglycemia.

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 email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting&nbsp;

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Nausea, vomiting (which is often severe), epigastric pain and haematemesis. Pancreatitis if abdominal pain persists. Restlessness, hypertonia, exaggerated limb reflexes and convulsions. Tachycardia is common.

Symptomatic treatment should be provided.

5.1 Mechanism of Action

Acebrophylline is a compound which has been found to act as a bronchodilating, mucoregulating and anti-inflammatory drug due to its components theophylline-7-acetate and ambroxol.

Theophylline-7-acetate, as with other xanthinic derivatives, has a bronchodilator effect due to inhibition of the intracellular phosphodiesterases, followed by an increase of adenosine monophosphate cyclic levels, which promote the relaxation of bronchial muscles.

Ambroxol modifies the mucous gel phase of secretions by decreasing the viscosity and increasing the serous gel phase. It increases the mucociliary clearance by stimulating cilia motility.

5.2 Pharmacodynamic properties

Acebrophylline inhibits phospholipase A2 and phosphatidylcholine leading to lesser production of the powerful pro-inflammatory substances like leukotrienes and tumor necrosis factor. By inhibiting the synthesis and release of these inflammatory mediators, acebrophylline reduces inflammation, a key factor in airway obstruction, especially in chronic forms.

5.3 Pharmacokinetic properties

In healthy volunteers, given 200 mg oral acebrophylline, the two components of the molecule ambroxol and theophylline-7 acetic acid are released in the stomach and absorbed in the intestine, reaching optimal concentrations of ambroxol within 2 hours and of theophylline-7 acetic acid after 1 hour. The plasma half-life varies from 4 to 9 hours after oral administration. The drug is metabolized in the liver and eliminated renally.

6.1 Animal Toxicology or Pharmacology

Negative interference has been reported between theophylline and erythromycin and in animal’s simultaneous administration of theophylline together with erythromycin estolate at doses that alone are non-toxic enhanced the toxicity of the former, as indicated by the drastic drop in the LD50, i.e. the dose causing the death of half the animals. In similar experimental conditions, acebrophylline was not affected by simultaneous use of erythromycin, and not only was there no reduction in the LD50 but in some cases it was actually higher, indicating the safety of the two components as regards their potential tolerability in patients.

Acebrophylline, an airway mucoregulator and anti-inflammatory agent is a combination product of ambroxol and theophylline 7 acetic acid.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on pack

8.3 Packaging information

8.4 Storage and handing instructions

Store below 30°C. Protect from light & moisture.

• You have been prescribed Acebrophylline for prevention and treatment of asthma and chronic obstructive pulmonary disease (COPD).
• It should be taken at the same time each day, preferably in the evening after food.
• It does not work right away and should not be used to relieve sudden breathing problems. Always keep a fast-acting (rescue) inhaler with you.
• Your doctor may take regular blood test to monitor potassium level and the level of this medicine in your body.
• Notify your doctor if you have ever been diagnosed with kidney, liver or heart disease, or if you have a smoking history. Your dose may need to be adjusted.
• Do not discontinue use without consulting your doctor, even if you feel better.

18.05.2022