PRESCRIBING INFORMATION
1. NAME OF MEDICINAL PRODUCT
NASIVION® 0.05% (Adult) Oxymetazoline Hydrochloride Nasal Solution IP (0.05%)
2.QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains
Oxymetazoline Hydrochloride IP - 0.5 mg in buffered aqueous solution.
Preservative: Benzalkonium Chloride solution 50% IP - 0.3 mg
3. PHARMACEUTICAL FORM
Nasal solution
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Nasivion® (0.05%) (Adult) /Nasivion® (0.05%) Classic adult nasal spray, is indicated for the symptomatic relief of nasal congestion in adults and in children of 6 years and older.
4.2 Posology and method of administration
Nasivion® (adult) (0.05%)/Nasivion® (Classic adult) (0.05%) nasal spray, is indicated for intranasal administration. Nasivion® (adult) (0.05%)/Nasivion® (Classic adult) (0.05%) nasal spray, may only be administered to adults and children of 6 years and older and should not be used in small children and infants. Instil/ spray 1-2 drops/1 puff of Nasivion® (adult) (0.05%)/Nasivion® (Classic adult) (0.05%) nasal spray, solution into each nostril. Apply nasal spray 2-3 times daily. Oxymetazoline-containing nasal spray should not be used for longer than 10 consecutive days. Application for more than 10 consecutive days has to under medical supervision. A treatment-free period of several days should precede any repeated use. Long-term use and overdosage must be avoided, especially in children. Dosages higher than recommended may only be used under medical supervision.
4.3 Contraindications
Rhinitis sicca,
Hypersensitivity to the active ingredient or to any of the excipients,
Children below six years of age.
4.4 Special warnings and precautions for use
This drug may only be used after carefully weighing the risk-to- benefit ratio:
Patients treated with monoamine oxidase inhibitors (MAO inhibitors, tricyclic antidepressants) and other drugs potentially increasing blood pressure,
Increased intraocular pressure, especially narrow-angle glaucoma,
Severe cardiovascular diseases (e.g. coronary heart disease, hypertension),
Phaeochromocytoma,
Metabolic disorders (e.g. hyperthyroidism, diabetes mellitus, porphyria),
Hyperplasia of the prostate.
Long-term use and overdosage are to be avoided. The efficacy of Nasal decongestant agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Medical supervision is indicated in patients with chronic rhinitis. Dosages higher than recommended may only be used under medical supervision. Benzalkonium chloride: irritant, may cause skin reactions.
4.5 Interaction with other medicinal products and other forms of interaction
The concomitant use of oxymetazoline containing nasal spray / nasal drops and of medicines with a hypertensive effect (e.g. MAO inhibitors and tricyclic antidepressants) may lead to an increase in blood pressure due to their cardiovascular activity. Overdosage or swallowing of the product and use of medicines with a hypertensive effect simultaneously or immediately prior to the administration can lead to an increase in blood pressure.
4.6 Fertility, pregnancy and lactation
Data obtained with more than 250 women exposed to oxymetazoline during the first trimester do not indicate any adverse effects of oxymetazoline on pregnancy or on the health of the foetus / new-born child. To date, no other relevant epidemiological data are available. Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonal / foetal development, birth or postnatal development. Nasivion® 0.05% (Adult) / Nasivion® (Classic Adult) 0.05% nasal spray, should only be used after the consultation with a physician during pregnancy and lactation. The recommended dosage must not be exceeded.
4.7 Effects on ability to drive and use machines
No impairment is to be expected if used as recommended. Systemic effects with involvement of the cardiovascular or central nervous system cannot be excluded after prolonged administration or intake of oxymetazoline containing cold remedies in dose higher than recommended. In these cases the ability to drive a vehicle or operate machinery can be impaired.
4.8 Undesirable effects
Adverse events from clinical trial data are both infrequent and based on small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic / recommended dose and considered attributable are listed below. As most undesirable effects are based on post-marketing spontaneous reporting, precise frequency estimation is not possible.
Respiratory, thoracic and mediastinal disorders:
Nasal discomfort (burning of the nasal mucosa)
Nasal dryness
Sneezing (especially in sensitive patients)
After the effect has worn off increased swelling of the mucosa (reactive hyperaemia)
Epistaxis
Nervous system disorders:
Somnolence
Sedation
Headache
Cardiac disorders:
Palpitations
Tachycardia
Vascular disorders:
Hypertension
Immune system disorders:
Hypersensitivity reactions (angiooedema, rash, pruritus)
Psychiatric disorders
Insomnia
Restlessness
General disorders and administration site conditions
Fatigue
Tachyphylaxis (associated with long-term use or overdose)
4.9 Overdose
The efficacy of Nasal decongestant agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Overdosage may occur after nasal or accidental oral administration. The clinical picture following intoxication with imidazol-derivatives may be unclear due to the occurrence of episodes of hyperactivity alternated with episodes of depression of the central nervous system and of the cardiovascular and pulmonary system. Symptoms of an overdose may be: Hypertension, tachycardia, palpitations, cardiac arrhythmia, cardiac arrest, sweating, agitation, convulsion, mydriasis, nausea, vomiting, cyanosis, fever, spasms, circulatory collapse, pulmonary oedema, respiratory disorders, psychic disorders, drowsiness, paleness, miosis, decrease in body temperature, bradycardia, shock-like hypotension, apnoea and coma. In children, in particular, overdose often causes dominating central nervous effects with convulsions and coma, bradycardia, apnoea as well as hypertension possibly followed by hypotension. Therapeutic measures after overdosage: In-house intensive-care therapy is indicated in cases of severe overdose. Administration of medicinal charcoal (absorbent), sodium sulfate (laxative) or gastric lavage (in the case of large quantities) should be performed immediately as oxymetazoline may be absorbed rapidly. A non-selective alpha-blocker can be given as antidote. If required, initiate fever- lowering measures, anticonvulsive therapy and oxygen ventilation. Vasopressors are contraindicated.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic Properties ATC code: R01AA05
Pharmacotherapeutic group:
Decongestant agent and other topical rhinological agents, α-sympathomimetic
Oxymetazoline containing medicinal products for intranasal use have a sympathomimetic, vasoconstrictive and therefore a decongestant effect on mucous membranes. Application of oxymetazoline into the nostrils leads to decongestion of the inflamed nasal mucosa and thus to a normalization of nasal breathing. Also decongestion of the nasal mucosa opens and dilates the efferent ducts of the paranasal sinuses and clears the auditory tube. This facilitates the discharge of secretion and combats bacterial invasion. Antiviral effects of oxymetazoline-containing solutions were demonstrated by studies performed with cultured, virally infected cells (therapeutic approach). This causal mechanism of action was demonstrated by the inhibition of the activity of viruses, e.g. Human Rhinoviruses (HRV) and Influenza-A-Virus. Antiviral activity was demonstrated by using the plaque reduction test, determination of residual infectivity (virus titration) as well as CPE inhibition test. Anti-inflammatory and antioxidative effects of oxymetazoline have been demonstrated in various studies. The production of lipid mediators from arachidonic acid is significantly influenced by oxymetazoline in ex vivo stimulated alveolar macrophages. Particularly owing to an oxmetazoline-induced inhibition of the activity of the enzyme 5-lipoxygenase, the formation of proinflammatory signal molecules (LTB4) is suppressed while in parallel the synthesis of anti-inflammatory messenger substances (PGE2, 15-HETE) increases. Oxymetazoline also inhibits the inducible form of nitrogen monoxide synthase (iNOS) in long-term cultivated alveolar macrophages. Oxymetazoline significantly inhibits oxidative stress triggered by ultrafine carbon particles in primary alveolar macrophages. Oxymetazoline also suppresses the lipid peroxidation of microsomes in an iron / ascorbate system (antioxidative effect). Immunomodulatory effects of oxymetazoline were demonstrated in human peripheral blood mononuclear cells (PBMC). Here oxymetazoline significantly reduces the formation of inflammation-enhancing cytokines (IL1β, IL6, TNFα). In addition, oxymetazoline inhibits the immunostimulating properties of dendritic cells. Treatment with 0.05% oxymetazoline nasal spray in comparison with physiological saline solution significantly shortened the duration of colds from an average of 6 days to 4 days (p<0.001). This double-blind comparative study with parallel groups was carried out in 247 adult patients and demonstrated for oxymetazoline a faster and better improvement of the typical symptoms of acute rhinitis (blocked nose, running nose, sneezing, impaired well-being) (p< 0.05) due to the combination of vasoconstrictive, antiviral, anti-inflammatory and antioxidative effects of oxymetazoline.
5.2 Pharmacokinetic Properties
The effect of 0.05 % oxymetazoline sets in within a few seconds (onset of action was measured in an open observational study where the effect set in after an average of 20.6 seconds. This finding was verified by a double-blind placebo-controlled study including 247 patients where the mean onset of action was observed after 25 seconds). The effect of oxymetazoline persists for up to 12 hours. Relevant absorption of pharmacodynamically effective doses of oxymetazoline following the recommended topical use is regarded as uncommon but cannot be excluded. The absorption rate has been estimated at 3.5% in a study performed in humans. The maximum plasma concentration was found after 8 to 10 hours. Terminal serum half- life was 35 hours, and the excretion was measured in faeces (1.1% of the applied dose, after 48 hours) and urine (2.1% of the applied dose, after 96 hours). Oral administration to healthy subjects showed first unspecific ECG changes only after administration of 1.8 mg oxymetazoline – this is equivalent to 3.6 ml of a 0.05% solution. Neither blood pressure nor pulse rate was affected by the intake of this quantity of active substance.
5.3 Preclinical safety data
Repeated-dose toxicity studies with nasal administration of oxymetazoline in dogs did not reveal any safety risks for human beings. An in vitro mutagenicity test on bacteria proved negative. No data are available with regard to carcinogenity. No teratogenic effects were observed in rats and rabbits. Dosages exceeding the therapeutic range had embryolethal effects or led to retarded foetal growth. Milk production was inhibited in rats. There is no evidence of fertility disorders. Preclinical studies have indicated that benzalkonium chloride can trigger concentration- and time-dependent inhibitory effects on ciliary motility to the point of irreversible arrest as well as histopathological alterations of the nasal mucosa.
6. PHARMACEUTICAL PARTICULARS
6.1 Incompatibilities Not applicable.
6.2 Shelf life Please refer carton or label for expiry.
6.3 Special Precautions for storage Preserve in tight containers at a temperature not exceeding 30o C.
6.4 Nature and contents of container NASIVION® (0.05%) (Adult) : 1 x 10 ml plastic bottle NASIVION® (0.05%) (Classic Adult) : 1 x 10 ml plastic bottle 1 x 15 ml plastic bottle
6.5 Special precautions for disposal and other handling No special requirements.
INFORMATION COMPILED ON:
01st Jan 2023
For further information
Please write to:
P&G Plaza, Cardinal Gracious Road, Chakala, Andheri (East), Mumbai – 400099
® Registered Trade Mark
1. NAME OF MEDICINAL PRODUCT
NASIVION® 0.05% (Classic Adult)
Oxymetazoline Hydrochloride Nasal Solution IP (0.05%)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains
Oxymetazoline Hydrochloride IP - 0.5 mg in buffered aqueous solution.
Preservative: Benzalkonium Chloride solution 50% IP - 0.3 mg
3. PHARMACEUTICAL FORM
Nasal solution
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Nasivion® (0.05%) (Adult) /Nasivion® (0.05%) Classic adult nasal spray, is indicated for the symptomatic relief of nasal congestion in adults and in children of 6 years and older.
4.2 Posology and method of administration
Nasivion® (adult) (0.05%)/Nasivion® (Classic adult) (0.05%) nasal spray, is indicated for intranasal administration. Nasivion ®(adult) (0.05%)/Nasivion® (Classic adult) (0.05%) nasal spray, may only be administered to adults and children of 6 years and older and should not be used in small children and infants. Instil/ spray 1-2 drops/1 puff of Nasivion® (adult) (0.05%)/Nasivion® (Classic adult) (0.05%) nasal spray, solution into each nostril. Apply nasal spray 2-3 times daily. Oxymetazoline-containing nasal spray should not be used for longer than 10 consecutive days. Application for more than 10 consecutive days has to under medical supervision. A treatment-free period of several days should precede any repeated use. Long-term use and overdosage must be avoided, especially in children. Dosages higher than recommended may only be used under medical supervision. 4.3 Contraindications
Rhinitis sicca,
Hypersensitivity to the active ingredient or to any of the excipients,
Children below six years of age.
4.4 Special warnings and precautions for use
This drug may only be used after carefully weighing the risk-to- benefit ratio:
Patients treated with monoamine oxidase inhibitors (MAO inhibitors, tricyclic antidepressants) and other drugs potentially increasing blood pressure,
Increased intraocular pressure, especially narrow-angle glaucoma,
Severe cardiovascular diseases (e.g. coronary heart disease, hypertension),
Phaeochromocytoma,
Metabolic disorders (e.g. hyperthyroidism, diabetes mellitus, porphyria),
Hyperplasia of the prostate.
Long-term use and overdosage are to be avoided. The efficacy of Nasal decongestant agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Medical supervision is indicated in patients with chronic rhinitis. Dosages higher than recommended may only be used under medical supervision. Benzalkonium chloride: irritant, may cause skin reactions.
4.5 Interaction with other medicinal products and other forms of interaction
The concomitant use of oxymetazoline containing nasal spray / nasal drops and of medicines with a hypertensive effect (e.g. MAO inhibitors and tricyclic antidepressants) may lead to an increase in blood pressure due to their cardiovascular activity. Overdosage or swallowing of the product and use of medicines with a hypertensive effect simultaneously or immediately prior to the administration can lead to an increase in blood pressure.
4.6 Fertility, pregnancy and lactation
Data obtained with more than 250 women exposed to oxymetazoline during the first trimester do not indicate any adverse effects of oxymetazoline on pregnancy or on the health of the foetus / new-born child. To date, no other relevant epidemiological data are available. Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonal / foetal development, birth or postnatal development. Nasivion® 0.05% (Adult) / Nasivion® (Classic Adult) 0.05% nasal spray, should only be used after the consultation with a physician during pregnancy and lactation. The recommended dosage must not be exceeded.
4.7 Effects on ability to drive and use machines
No impairment is to be expected if used as recommended. Systemic effects with involvement of the cardiovascular or central nervous system cannot be excluded after prolonged administration or intake of oxymetazoline containing cold remedies in dose higher than recommended. In these cases the ability to drive a vehicle or operate machinery can be impaired.
4.8 Undesirable effects
Adverse events from clinical trial data are both infrequent and based on small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic / recommended dose and considered attributable are listed below. As most undesirable effects are based on post-marketing spontaneous reporting, precise frequency estimation is not possible.
Respiratory, thoracic and mediastinal disorders:
Nasal discomfort (burning of the nasal mucosa)
Nasal dryness
Sneezing (especially in sensitive patients)
After the effect has worn off increased swelling of the mucosa (reactive hyperaemia)
Epistaxis
Nervous system disorders:
Somnolence
Sedation
Headache
Cardiac disorders:
Palpitations
Tachycardia
Vascular disorders:
Hypertension
Immune system disorders:
Hypersensitivity reactions (angiooedema, rash, pruritus)
Psychiatric disorders
Insomnia
Restlessness
General disorders and administration site conditions
Fatigue
Tachyphylaxis (associated with long-term use or overdose)
4.9 Overdose
The efficacy of Nasal decongestant agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Overdosage may occur after nasal or accidental oral administration. The clinical picture following intoxication with imidazol-derivatives may be unclear due to the occurrence of episodes of hyperactivity alternated with episodes of depression of the central nervous system and of the cardiovascular and pulmonary system. Symptoms of an overdose may be: Hypertension, tachycardia, palpitations, cardiac arrhythmia, cardiac arrest, sweating, agitation, convulsion, mydriasis, nausea, vomiting, cyanosis, fever, spasms, circulatory collapse, pulmonary oedema, respiratory disorders, psychic disorders, drowsiness, paleness, miosis, decrease in body temperature, bradycardia, shock-like hypotension, apnoea and coma. In children, in particular, overdose often causes dominating central nervous effects with convulsions and coma, bradycardia, apnoea as well as hypertension possibly followed by hypotension. Therapeutic measures after overdosage: In-house intensive-care therapy is indicated in cases of severe overdose. Administration of medicinal charcoal (absorbent), sodium sulfate (laxative) or gastric lavage (in the case of large quantities) should be performed immediately as oxymetazoline may be absorbed rapidly. A non-selective alpha-blocker can be given as antidote. If required, initiate fever- lowering measures, anticonvulsive therapy and oxygen ventilation. Vasopressors are contraindicated.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic Properties ATC code: R01AA05
Pharmacotherapeutic group: Decongestant agent and other topical rhinological agents, α-sympathomimetic
Oxymetazoline containing medicinal products for intranasal use have a sympathomimetic, vasoconstrictive and therefore a decongestant effect on mucous membranes. Application of oxymetazoline into the nostrils leads to decongestion of the inflamed nasal mucosa and thus to a normalization of nasal breathing. Also decongestion of the nasal mucosa opens and dilates the efferent ducts of the paranasal sinuses and clears the auditory tube. This facilitates the discharge of secretion and combats bacterial invasion. Antiviral effects of oxymetazoline-containing solutions were demonstrated by studies performed with cultured, virally infected cells (therapeutic approach). This causal mechanism of action was demonstrated by the inhibition of the activity of viruses, e.g. Human Rhinoviruses (HRV) and Influenza-A-Virus. Antiviral activity was demonstrated by using the plaque reduction test, determination of residual infectivity (virus titration) as well as CPE inhibition test. Anti-inflammatory and antioxidative effects of oxymetazoline have been demonstrated in various studies. The production of lipid mediators from arachidonic acid is significantly influenced by oxymetazoline in ex vivo stimulated alveolar macrophages. Particularly owing to an oxmetazoline-induced inhibition of the activity of the enzyme 5-lipoxygenase, the formation of proinflammatory signal molecules (LTB4) is suppressed while in parallel the synthesis of anti-inflammatory messenger substances (PGE2, 15-HETE) increases. Oxymetazoline also inhibits the inducible form of nitrogen monoxide synthase (iNOS) in long-term cultivated alveolar macrophages. Oxymetazoline significantly inhibits oxidative stress triggered by ultrafine carbon particles in primary alveolar macrophages. Oxymetazoline also suppresses the lipid peroxidation of microsomes in an iron / ascorbate system (antioxidative effect). Immunomodulatory effects of oxymetazoline were demonstrated in human peripheral blood mononuclear cells (PBMC). Here oxymetazoline significantly reduces the formation of inflammation-enhancing cytokines (IL1β, IL6, TNFα). In addition, oxymetazoline inhibits the immunostimulating properties of dendritic cells. Treatment with 0.05% oxymetazoline nasal spray in comparison with physiological saline solution significantly shortened the duration of colds from an average of 6 days to 4 days (p<0.001). This double-blind comparative study with parallel groups was carried out in 247 adult patients and demonstrated for oxymetazoline a faster and better improvement of the typical symptoms of acute rhinitis (blocked nose, running nose, sneezing, impaired well-being) (p< 0.05) due to the combination of vasoconstrictive, antiviral, anti-inflammatory and antioxidative effects of oxymetazoline.
5.2 Pharmacokinetic Properties
The effect of 0.05 % oxymetazoline sets in within a few seconds (onset of action was measured in an open observational study where the effect set in after an average of 20.6 seconds. This finding was verified by a double-blind placebo-controlled study including 247 patients where the mean onset of action was observed after 25 seconds). The effect of oxymetazoline persists for up to 12 hours. Relevant absorption of pharmacodynamically effective doses of oxymetazoline following the recommended topical use is regarded as uncommon but cannot be excluded. The absorption rate has been estimated at 3.5% in a study performed in humans. The maximum plasma concentration was found after 8 to 10 hours. Terminal serum half- life was 35 hours, and the excretion was measured in faeces (1.1% of the applied dose, after 48 hours) and urine (2.1% of the applied dose, after 96 hours). Oral administration to healthy subjects showed first unspecific ECG changes only after administration of 1.8 mg oxymetazoline – this is equivalent to 3.6 ml of a 0.05% solution. Neither blood pressure nor pulse rate was affected by the intake of this quantity of active substance.
5.3 Preclinical safety data
Repeated-dose toxicity studies with nasal administration of oxymetazoline in dogs did not reveal any safety risks for human beings. An in vitro mutagenicity test on bacteria proved negative. No data are available with regard to carcinogenity. No teratogenic effects were observed in rats and rabbits. Dosages exceeding the therapeutic range had embryolethal effects or led to retarded foetal growth. Milk production was inhibited in rats. There is no evidence of fertility disorders. Preclinical studies have indicated that benzalkonium chloride can trigger concentration- and time-dependent inhibitory effects on ciliary motility to the point of irreversible arrest as well as histopathological alterations of the nasal mucosa.
6. PHARMACEUTICAL PARTICULARS
6.1 Incompatibilities Not applicable.
6.2 Shelf life Please refer carton or label for expiry.
6.3 Special Precautions for storage Preserve in tight containers at a temperature not exceeding 30o C.
6.4 Nature and contents of container NASIVION® (0.05%) (Adult) : 1 x 10 ml plastic bottle NASIVION® (0.05%) (Classic Adult) : 1 x 10 ml plastic bottle 1 x 15 ml plastic bottle
6.5 Special precautions for disposal and other handling No special requirements. INFORMATION COMPILED ON:
01st Jan 2023
For further information
Please write to:
P&G Plaza, Cardinal Gracious Road, Chakala, Andheri (East), Mumbai – 400099
® Registered Trade Mark
1. NAME OF MEDICINAL PRODUCT
NASIVION® 0.025% (Pediatric)
Oxymetazoline Hydrochloride Nasal Solution IP (0.025%)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains
Oxymetazoline Hydrochloride IP - 0.25 mg in buffered aqueous solution.
Preservative: Benzalkonium Chloride solution 50% IP - 0.3 mg
3. PHARMACEUTICAL FORM
Nasal solution.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Nasivion® Pediatric nasal spray/drops 0.025%, is indicated for the symptomatic relief of nasal congestion in children aged between one and six years.
4.2 Posology and method of administration
Nasivion® Pediatric 0.025%, is indicated for intranasal administration.
Nasivion® Pediatric 0.025%, may only be administered to children aged between one and six years or as directed by physician and should not be used in infants under 1 year of age. Instil 1-2 spray/drops of the 0,025 % solution into each nostril 2-3 times daily. Oxymetazoline-containing nasal spray/drops should not be used for longer than 10 consecutive days. Application for more than 10 consecutive days has to beunder medical supervision. A treatment-free period of several days should precede any repeated use. Long-term use and overdosage must be avoided, especially in children. Dosages higher than recommended may only be used under medical supervision.
4.3 Contraindications
Rhinitis sicca,
Hypersensitivity to the active ingredient or to any of the excipients,
Infants and small children below 1 year of age.
4.4 Special warnings and precautions for use
In the following cases this drug may only be used after carefully weighing the risk-to- benefit ratio:
patients treated with monoamine oxidase inhibitors (MAO inhibitors, tricyclic antidepressants) and other drugs potentially increasing blood pressure,
increased intraocular pressure, especially narrow-angle glaucoma,
severe cardiovascular diseases (e.g. coronary heart disease, hypertension),
phaeochromocytoma,
metabolic disorders (e.g. hyperthyroidism, diabetes mellitus, porphyria),
hyperplasia of the prostate.
Long-term use and overdosage are to be avoided. The efficacy of decongestant rhinological agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis.Medical supervision is indicated in patients with chronic rhinitis. Dosages higher than recommended may only be used under medical supervision. Benzalkonium chloride: irritant, may cause skin reactions.
4.5 Interaction with other medicinal products and other forms of interaction
The concomitant use of oxymetazoline containing nasal spray/drops and of medicines with a hypertensive effect (e.g. MAO inhibitors and tricyclic antidepressants) may lead to an increase in blood pressure due to their cardiovascular activity. Overdosage or swallowing of the product and use of medicines with a hypertensive effect simultaneously or immediately prior to the administration can lead to an increase in blood pressure.
4.6 Fertility, pregnancy and lactation
Data obtained with more than 250 women exposed to oxymetazoline during the first trimester do not indicate any adverse effects of oxymetazoline on pregnancy or on the health of the foetus/new-born child. To date, no other relevant epidemiological data are available. Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonal/foetal development, birth or postnatal development. Nasivion® Pediatric 0.025%, should only be used after the consultation with a physician during pregnancy and lactation. The recommended dosage must not be exceeded.
4.7 Effects on ability to drive and use machines
No impairment is to be expected if used as recommended. Systemic effects with involvement of the cardiovascular or central nervous system cannot be excluded after prolonged administration or intake of oxymetazoline containing cold remedies in dose higher than recommended. In these cases the ability to drive a vehicle or operate machinery can be impaired.
4.8 Undesirable effects
Adverse events from clinical trial data are both infrequent and based on small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/recommended dose and considered attributable are listed below. As most undesirable effects are based on post-marketing spontaneous reporting, precise frequency estimation is not possible.
Respiratory, thoracic and mediastinal disorders:
Nasal discomfort (burning of the nasal mucosa)
Nasal dryness
Sneezing (especially in sensitive patients)
After the effect has worn off increased swelling of the mucosa (reactive hyperaemia)
Epistaxis
Nervous system disorders:
Somnolence
Sedation
Headache
Hallucinations (especially in children)
Convulsions (especially in children)
Cardiac disorders:
Palpitations
Tachycardia
Vascular disorders:
Hypertension
Immune system disorders:
Hypersensitivity reactions (angioedema, rash, pruritus) Psychiatric disorders
Insomnia
Restlessness
General disorders and administration site conditions
Fatigue
Tachyphylaxis (associated with long-term use or overdose)
4.9 Overdose
The Efficacy of decongestant rhinological agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Overdosage may occur after nasal or accidental oral administration. The clinical picture following intoxication with imidazol-derivatives may be unclear due to the occurrence of episodes of hyperactivity alternated with episodes of depression of the central nervous system and of the cardiovascular and pulmonary system.
Symptoms of an overdose may be: Hypertension, tachycardia, palpitations, cardiac arrhythmia, cardiac arrest, sweating, agitation, convulsion, mydriasis, nausea, vomiting, cyanosis, fever, spasms, circulatory collapse, pulmonary oedema, respiratory disorders, psychic disorders, drowsiness, paleness, miosis, decrease in body temperature, bradycardia, shock-like hypotension, apnoea and coma. In children, in particular, overdose often causes dominating central nervous effects with convulsions and coma, bradycardia, apnoea as well as hypertension possibly followed by hypotension.
Therapeutic measures after overdosage: In-house intensive-care therapy is indicated in cases of severe overdose. Administration of medicinal charcoal (absorbent), sodium sulfate (laxative) or gastric lavage (in the case of large quantities) should be performed immediately as oxymetazoline may be absorbed rapidly. A non-selective alpha-blocker can be given as antidote. If required, initiate fever- lowering measures, anticonvulsive therapy and oxygen ventilation. Vasopressors are contraindicated.
5. PHARMACOLOGICAL PROPRIETES
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Decongestant agent and other topical rhinological agents, α-sympathomimetic ATC code: R 01 AA 05 Oxymetazoline containing medicinal products for intranasal use have a sympathomimetic, vasoconstrictive and therefore a decongestant effect on mucous membranes. Application of oxymetazoline into the nostrils leads to decongestion of the inflamed nasal mucosa and thus to a normalization of nasal breathing. Also, decongestion of the nasal mucosa opens and dilates the efferent ducts of the paranasal sinuses and clears the auditory tube. This facilitates the discharge of secretion and combats bacterial invasion.
Antiviral effects of oxymetazoline-containing solutions were demonstrated by studies performed with cultured, virally infected cells (therapeutic approach). This causal mechanism of action was demonstrated by the inhibition of the activity of viruses, e.g. Human Rhinoviruses (HRV) and Influenza-A-Virus. Antiviral activity was demonstrated by using the plaque reduction test, determination of residual infectivity (virus titration) as well as CPE inhibition test. Anti-inflammatory and antioxidative effects of oxymetazoline have been demonstrated in various studies. The production of lipid mediators from arachidonic acid is significantly influenced by oxymetazoline in ex vivo stimulated alveolar macrophages. Particularly owing to an oxmetazoline-induced inhibition of the activity of the enzyme 5-lipoxygenase, the formation of proinflammatory signal molecules (LTB4) is suppressed while in parallel the synthesis of anti-inflammatory messenger substances (PGE2, 15-HETE) increases. Oxymetazoline also inhibits the inducible form of nitrogen monoxide synthase (iNOS) in long-term cultivated alveolar macrophages. Oxymetazoline significantly inhibits oxidative stress triggered by ultrafine carbon particles in primary alveolar macrophages. Oxymetazoline also suppresses the lipid peroxidation of microsomes in an iron/ascorbate system (antioxidative effect). Immunomodulatory effects of oxymetazoline were demonstrated in human peripheral blood mononuclear cells (PBMC). Here oxymetazoline significantly reduces the formation of inflammation-enhancing cytokines (IL1β, IL6, TNFα). In addition, oxymetazoline inhibits the immunostimulating properties of dendritic cells. Treatment with 0.05% oxymetazoline nasal spray in comparison with physiological saline solution significantly shortened the duration of colds from an average of 6 days to 4 days (p<0.001). This double-blind comparative study with parallel groups was carried out in 247 adult patients and demonstrated for oxymetazoline a faster and better improvement of the typical symptoms of acute rhinitis (blocked nose, running nose, sneezing, impaired well-being) (p< 0.05) due to the combination of vasoconstrictive, antiviral, anti-inflammatory and antioxidative effects of oxymetazoline.
5.2 Pharmacokinetic Properties
The effect of oxymetazoline sets in within a few minutes. The effect of oxymetazoline persists for up to 12 hours. Relevant absorption of pharmacodynamically effective doses of oxymetazoline following the recommended topical use is regarded as uncommon but cannot be excluded. The absorption rate has been estimated at 3.5% in a study performed in humans. The maximum plasma concentration was found after 8 to 10 hours. Terminal serum half-life was 35 hours, and the excretion was measured in faeces (1.1% of the applied dose, after 48 hours) and urine (2.1% of the applied dose, after 96 hours). Oral administration to healthy subjects showed first unspecific ECG changes only after administration of 1.8 mg oxymetazoline – this is equivalent to 3.6 ml of a 0.05% solution. Neither blood pressure nor pulse rate was affected by the intake of this quantity of active substance.
5.3 Preclinical safety data
Repeated-dose toxicity studies with nasal administration of oxymetazoline in dogs did not reveal any safety risks for human beings. An in vitro mutagenicity test on bacteria proved negative. No data are available with regard to carcinogenity. No teratogenic effects were observed in rats and rabbits. Dosages exceeding the therapeutic range had embryolethal effects or led to retarded foetal growth. Milk production was inhibited in rats. There is no evidence of fertility disorders. Preclinical studies have indicated that benzalkonium chloride can trigger concentration- and time-dependent inhibitory effects on ciliary motility to the point of irreversible arrest as well as histopathological alterations of the nasal mucosa.
6. PHARMACEUTICAL PARTICULARS
6.1 Incompatibilities
Not applicable.
6.2 Shelf life
Please refer carton or label for expiry
6.3 Special Precautions for storage
Preserve in tight containers at a temperature not exceeding 30° C.
6.4 Nature and contents of container
1 x 10 ml Plastic bottle
6.5 Special precautions for disposal and other handling
Do not use if seal is broken, Keep out of reach children.
6.6 Manufacturing site.
Refer carton or label
INFORMATION COMPILED ON:
01st Jan 2023 For further information
Please write to:
P&G Plaza, Cardinal Gracious Road, Chakala, Andheri (East), Mumbai – 400099
® Registered Trade Mark
1. NAME OF MEDICINAL PRODUCT
NASIVION® 0.01% (Mini) Oxymetazoline Hydrochloride Nasal Solution IP (0.01%)
2. COMPOSITION
Each ml contains :
Oxymetazoline Hydrochloride IP - 0.1 mg in buffered aqueous solution.
Preservative : Benzalkonium Chloride solution 50% IP - 0.2 mg
3. PHARMACEUTICAL FORM
Nasal solution.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Nasivion® 0.01% (Mini) nasal spray/drops, is indicated for the symptomatic relief of nasal congestion in infants and small children. 4.2 Posology and method of administration Nasivion® 0.01% (Mini) nasal spray/drops is indicated for intranasal administration. Nasivion® 0.01% (Mini) nasal spray/drops is intended for infants and small children. Recommended for use in babies between 0.1 year. Up to the age of 4 weeks instil 1 spray/ drop of the 0.01% solution into each nostril 2-3 times daily. From the 5th week of life until the age of 1 year, instil 1-2 spray/ drops into each nostril 2-3 times daily. Oxymetazoline-containing nasal spray/drops should not be used for longer than 10 consecutive days. A treatment-free period of several days should precede any repeated use. Medical supervision is indicated in premature or underweight newborns to avoid the risk of overdosage. Long-term use and overdosage must be avoided, especially in children. Dosages higher than recommended may only be used under medical supervision.
4.3 Contraindications
Rhinitis sicca,
Hypersensitivity to the active ingredient or to any of the excipients.
4.4 Special warnings and precautions for use
In the following cases this drug may only be used after carefully weighing the risk-to- benefit ratio:
Patients treated with monoamine oxidase inhibitors (MAO inhibitors, tricyclic antidepressants) and other drugs potentially increasing blood pressure,
Increased intraocular pressure, especially narrow-angle glaucoma,
Severe cardiovascular diseases (e.g. coronary heart disease, hypertension),
Phaeochromocytoma,
Metabolic disorders (e.g. hyperthyroidism, diabetes mellitus, porphyria),
Hyperplasia of the prostate.
The efficacy of Nasal decongestant agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Special attention should be paid during application to avoid overdosage. Medical supervision is indicated in premature or underweight newborns to avoid the risk of overdosage. Medical supervision is indicated in patients with chronic rhinitis. Dosages higher than recommended may only be used under medical supervision. Benzalkonium chloride: irritant, may cause skin reactions.
4.5 Interaction with other medicinal products and other forms of interaction
The concomitant use of oxymetazoline containing nasal spray/drops and of medicines with a hypertensive effect (e.g. MAO inhibitors and tricyclic antidepressants) may lead to an increase in blood pressure due to their cardiovascular activity. Overdosage or swallowing of the product and use of medicines with a hypertensive effect simultaneously or immediately prior to the administration can lead to an increase in blood pressure. 4.6 Fertility, pregnancy and lactation
Data obtained with more than 250 women exposed to oxymetazoline during the first trimester do not indicate any adverse effects of oxymetazoline on pregnancy or on the health of the foetus/new-born child. To date, no other relevant epidemiological data are available. Animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonal/foetal development, birth or postnatal development. Nasivion® 0.01% (Mini) nasal spray/drops, should only be used after the consultation with a physician during pregnancy and lactation. The recommended dosage must not be exceeded.
4.7 Effects on ability to drive and use machines
No impairment is to be expected if used as recommended. Systemic effects with involvement of the cardiovascular or central nervous system cannot be excluded after prolonged administration or intake of oxymetazoline containing cold remedies in dose higher than recommended. In these cases the ability to drive a vehicle or operate machinery can be impaired.
4.8 Undesirable effects
Adverse events from clinical trial data are both infrequent and based on small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/recommended dose and considered attributable are listed below. As most undesirable effects are based on post-marketing spontaneous reporting, precise frequency estimation is not possible.
Respiratory, thoracic and mediastinal disorders:
Nasal discomfort (burning of the nasal mucosa)
Nasal dryness
Sneezing (especially in sensitive patients)
After the effect has worn off increased swelling of the mucosa (reactive hyperaemia)
Epistaxis
Apnoea in newborns and in young infants (especially in case of overdosage)
Nervous system disorders:
somnolence
sedation
headache
hallucinations (especially in children)
convulsions (especially in children)
Cardiac disorders:
palpitations
tachycardia
Vascular disorders:
hypertension
Immune system disorders:
hypersensitivity reactions (angioedema, rash, pruritus)
Psychiatric disorders:
insomnia
restlessness
General disorders and administration site conditions:
fatigue
tachyphylaxis (associated with long-term use or overdose)
4.9 Overdose
The efficacy of Nasal decongestant agents may be reduced (tachyphylaxis) with long-term use or overdose. This may lead to use of higher doses or to more frequent usage which, in turn, can result in permanent use. If long term use or overdose occurs, treatment should be discontinued immediately. Continuous use may cause nasal congestion due to reactive hyperaemia of the nasal mucosa (rebound effect) and chronic swelling of the nasal mucosa (rhinitis medicamentosa) as well as mucosal atrophy or rhinitis sicca. Rebound effects and tachyphylaxis should stop once use of the product is discontinued. Patients are advised to use for a maximum of 10 consecutive days to avoid rebound effect and drug induced rhinitis. Overdosage may occur after nasal or accidental oral administration. The clinical picture following intoxication with imidazol-derivatives may be unclear due to the occurrence of episodes of hyperactivity alternated with episodes of depression of the central nervous system and of the cardiovascular and pulmonary system.
Symptoms of an overdose may be: Hypertension, tachycardia, palpitations, cardiac arrhythmia, cardiac arrest, sweating, agitation, convulsion, mydriasis, nausea, vomiting, cyanosis, fever, spasms, circulatory collapse, pulmonary oedema, respiratory disorders, psychic disorders, drowsiness, paleness, miosis, decrease in body temperature, bradycardia, shock-like hypotension, apnoea and coma. In children, in particular, overdose often causes dominating central nervous effects with convulsions and coma, bradycardia, apnoea as well as hypertension possibly followed by hypotension.
Therapeutic measures after overdosage:
In-house intensive-care therapy is indicated in cases of severe overdose. Administration of medicinal charcoal (absorbent), sodium sulfate (laxative) or gastric lavage (in the case of large quantities) should be performed immediately as oxymetazoline may be absorbed rapidly. A non-selective alpha-blocker can be given as antidote. If required, initiate fever- lowering measures, anticonvulsive therapy and oxygen ventilation. Vasopressors are contraindicated.
5. PHARMACOLOGICAL PROPRIETES
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Decongestant agent and other topical rhinological agents, α-sympathomimetic
ATC code: R 01 AA 05
Oxymetazoline containing medicinal products for intranasal use have a sympathomimetic, vasoconstrictive and therefore a decongestant effect on mucous membranes. Application of oxymetazoline into the nostrils leads to decongestion of the inflamed nasal mucosa and thus to a normalization of nasal breathing. Also, decongestion of the nasal mucosa opens and dilates the efferent ducts of the paranasal sinuses and clears the auditory tube. This facilitates the discharge of secretion and combats bacterial invasion. Antiviral effects of oxymetazoline-containing solutions were demonstrated by studies performed with cultured, virally infected cells (therapeutic approach). This causal mechanism of action was demonstrated by the inhibition of the activity of viruses, e.g. Human Rhinoviruses (HRV) and Influenza-A-Virus. Antiviral activity was demonstrated by using the plaque reduction test, determination of residual infectivity (virus titration) as well as CPE inhibition test. Anti-inflammatory and antioxidative effects of oxymetazoline have been demonstrated in various studies. The production of lipid mediators from arachidonic acid is significantly influenced by oxymetazoline in ex vivo stimulated alveolar macrophages. Particularly owing to an oxmetazoline-induced inhibition of the activity of the enzyme 5-lipoxygenase, the formation of proinflammatory signal molecules (LTB4) is suppressed while in parallel the synthesis of anti-inflammatory messenger substances (PGE2, 15-HETE) increases. Oxymetazoline also inhibits the inducible form of nitrogen monoxide synthase (iNOS) in long-term cultivated alveolar macrophages. Oxymetazoline significantly inhibits oxidative stress triggered by ultrafine carbon particles in primary alveolar macrophages. Oxymetazoline also suppresses the lipid peroxidation of microsomes in an iron/ascorbate system (antioxidative effect). Immunomodulatory effects of oxymetazoline were demonstrated in human peripheral blood mononuclear cells (PBMC). Here oxymetazoline significantly reduces the formation of inflammation-enhancing cytokines (IL1β, IL6, TNFα). In addition, oxymetazoline inhibits the immunostimulating properties of dendritic cells. Treatment with 0.05% oxymetazoline nasal spray in comparison with physiological saline solution significantly shortened the duration of colds from an average of 6 days to 4 days (p<0.001). This double-blind comparative study with parallel groups was carried out in 247 adult patients and demonstrated for oxymetazoline a faster and better improvement of the typical symptoms of acute rhinitis (blocked nose, running nose, sneezing, impaired well-being) (p< 0.05) due to the combination of vasoconstrictive, antiviral, anti-inflammatory and antioxidative effects of oxymetazoline.
5.2 Pharmacokinetic Properties
The effect of oxymetazoline sets in within a few minutes. The effect of oxymetazoline persists for up to 12 hours. Relevant absorption of pharmacodynamically effective doses of oxymetazoline following the recommended topical use is regarded as uncommon but cannot be excluded. The absorption rate has been estimated at 3.5% in a study performed in humans. The maximum plasma concentration was found after 8 to 10 hours. Terminal serum half-life was 35 hours, and the excretion was measured in faeces (1.1% of the applied dose, after 48 hours) and urine (2.1% of the applied dose, after 96 hours). Oral administration to healthy subjects showed first unspecific ECG changes only after administration of 1.8 mg oxymetazoline – this is equivalent to 3.6 ml of a 0.05% solution. Neither blood pressure nor pulse rate was affected by the intake of this quantity of active substance.
5.3 Preclinical safety data
Repeated-dose toxicity studies with nasal administration of oxymetazoline in dogs did not reveal any safety risks for human beings. An in vitro mutagenicity test on bacteria proved negative. No data are available with regard to carcinogenity. No teratogenic effects were observed in rats and rabbits. Dosages exceeding the therapeutic range had embryolethal effects or led to retarded foetal growth. Milk production was inhibited in rats. There is no evidence of fertility disorders. Preclinical studies have indicated that benzalkonium chloride can trigger concentration- and time-dependent inhibitory effects on ciliary motility to the point of irreversible arrest as well as histopathological alterations of the nasal mucosa.
6. PHARMACEUTICAL PARTICULARS
6.1 Incompatibilities
Not applicable.
6.2 Shelf life
Please refer carton or label for expiry
6.3 Special Precautions for storage
Preserve in tight containers at a temperature not exceeding 30° C.
6.4 Nature and contents of container
1 x 10 ml Plastic bottle
6.5 Special precautions for disposal and other handling
Do not use if seal is broken, Keep out of reach children.
6.6 Manufacturing site.
Refer carton or label
INFORMATION COMPILED ON:
01st Jan 2023
For further information
Please write to:
P&G Plaza, Cardinal Gracious Road, Chakala, Andheri (East), Mumbai – 400099
® Registered Trade Mark