The prophylaxis and treatment of seasonal allergic rhinitis (including hay fever) and perennial rhinitis.
Fluticasone propionate has potent anti-inflammatory activity but when used topically on the nasal mucosa has
no detectable systemic activity.

Rhinase Aqueous Nasal Spray is for administration by the intranasal route only.
Contact with the eyes should be avoided.
Adults and children over 12 years of age:
For the prophylaxis and treatment of seasonal allergic rhinitis and perennial rhinitis. Two sprays into each
nostril once a day, preferably in the morning. In some cases, two sprays into each nostril twice daily may be
required. Once symptoms are under control a maintenance dose of one spray per nostril once a day may be
used. If symptoms recur the dosage may be increased accordingly. The minimum dose should be used at
which effective control of symptoms is maintained. The maximum daily dose should not exceed four sprays into
each nostril.
Elderly patients:
The normal adult dosage is applicable.

Children under 12 years of age:
For the prophylaxis and treatment of seasonal allergic rhinitis and perennial rhinitis in children aged 4-11 years
a dose of one spray into each nostril once daily preferably in the morning is recommended. In some cases, one
spray into each nostril twice daily may be required. The maximum daily dose should not exceed two sprays into
each nostril. The minimum dose should be used at which effective control of symptoms is maintained.
For full therapeutic benefit regular usage is essential. The absence of an immediate effect should be explained
to the patient, as maximum relief may not be obtained until after 3 to 4 days of treatment.

Local infections: infections of the nasal airways should be appropriately treated but do not constitute a specific
contraindication to treatment with Rhinase Aqueous Nasal Spray.
The full benefit of Rhinase Aqueous Nasal Spray may not be achieved until treatment has been administered
for several days.
Care must be taken while transferring patients from systemic steroid treatment to Rhinase Aqueous Nasal
Spray if there is any reason to suppose that their adrenal function is impaired.
Although Rhinase Aqueous Nasal Spray will control seasonal allergic rhinitis in most cases, an abnormally
heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy.
Systemic effects of nasal corticosteroids may occur particularly at high doses prescribed for prolonged periods.
These effects are much less likely to occur than with oral corticosteroids preparation and may vary in individual
patients and between different corticosteroids preparations. (please refer to Sections 5.1 and 5.2). Potential
systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth
retardation in children and adolescents and more rarely, a range of psychological or behavioral effects
including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in
children).
Growth retardation has been reported in children receiving some nasal corticosteroids at licensed doses. It is
recommended that the height 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. In addition,
consideration should be given to referring the patient to a pediatric specialist.
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 (see Section 5.1
for data on intranasal fluticasone propionate).
The full benefit of fluticasone propionate aqueous nasal spray may not be achieved until treatment has been
administered for several days.
Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant
use should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid
side effects. There is also an increased risk of systemic side effects when combining fluticasone propionate
with other potent CYP3A inhibitors (see 4.5 Interaction with Other Medicinal Products and Other Forms of
Interaction).
Visual disturbance
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents 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.

Rhinase Aqueous Nasal Spray contains benzalkonium chloride which may cause bronchospasm.
Benzalkonium chloride may cause irritation or swelling inside the nose, especially if used for a long period of
time.

Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled
dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4
in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are
unlikely.
In an interaction study in healthy subjects with intranasal fluticasone propionate, ritonavir (a highly potent
cytochrome P450 3A4 inhibitor) 100 mg b.i.d. increased the fluticasone propionate plasma concentrations
several hundred-fold, resulting in markedly reduced serum cortisol concentrations. Cases of Cushing's
syndrome and adrenal suppression have been reported. The combination should be avoided unless the benefit
outweighs the increased risk of systemic glucocorticoid side-effects.
In a small study using inhaled fluticasone propionate in healthy volunteers, the slightly less potent CYP3A
inhibitor ketoconazole increased the exposure of fluticasone propionate after a single inhalation by 150%. This
resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate alone. Co-treatment
with other potent CYP3A inhibitors, such as itraconazole, is also expected to increase the systemic fluticasone
propionate exposure and the risk of systemic side-effects. Caution is recommended and long-term treatment
with such drugs should if possible be avoided.
Co-treatment with other potent CYP3A inhibitors, including cobicistat-containing products, is expected to
increase the risk of systemic side-effects.
Other inhibitors of CYP3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic
exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Combinations
should be avoided unless the benefit outweighs the potential increased risk of systemic corticosteroid sideeffects,
in which case patients should be monitored for systemic corticosteroid side-effects.

There is inadequate evidence of safety in human pregnancy. Administration of corticosteroids to pregnant
animals can cause abnormalities of foetal development, including cleft palate and intra-uterine growth
retardation. There may therefore be a very small risk of such effects in the human foetus. It should be noted,
however, that the foetal changes in animals occur after relatively high systemic exposure; direct intranasal
application ensures minimal systemic exposure.
As with other drugs the use of Rhinase Aqueous Nasal Spray during human pregnancy requires that the
possible benefits of the drug be weighed against the possible hazards.
The secretion of fluticasone propionate in human breast milk has not been investigated. Subcutaneous
administration of fluticasone propionate to lactating laboratory rats produced measurable plasma levels and
evidence of fluticasone propionate in the milk. However, following intranasal administration to primates, no drug
was detected in the plasma, and it is therefore unlikely that the drug would be detectable in milk. When
Rhinase Aqueous Nasal Spray is used in breast feeding mothers the therapeutic benefits must be weighed
against the potential hazards to mother and baby.

None reported.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very
common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and
<1/1000) and very rare (<1/10,000) including isolated reports and not known (cannot be estimated from the
available data). Very common, common and uncommon events were generally determined from clinical trial
data. Rare and very rare events were generally determined from spontaneous data. In assigning adverse event
frequencies, the background rates in placebo groups were not taken into account.

As with other nasal sprays, unpleasant taste and smell and headache have been reported.
As with other nasal sprays, dryness and irritation of the nose and throat, and epistaxis have been reported.
Nasal septal perforation has also been reported following the use of intranasal corticosteroids.
Systemic effects of some nasal corticosteroids may occur, particularly when prescribed at high doses for
prolonged periods.

Reporting of suspected adverse reactions
To report any side effect(s):
Saudi Arabia:

The National Pharmacovigilance Centre (NPC)
o SFDA call center: 19999
o E-mail: npc.drug@sfda.gov.sa
o Website: https://ade.sfda.gov.sa

• Other GCC States:

Please contact the relevant competent authority

There are no data from patients available on the effects of acute or chronic overdosage with Rhinase Aqueous
Nasal Spray. Intranasal administration of 2 mg fluticasone propionate twice daily for seven days to healthy
human volunteers has no effect on hypothalamo-pituitary-adrenal (HPA) axis function.
Inhalation or oral administration of high doses of corticosteroids over a long period may lead to suppression of
HPA axis function.
Treatment
Administration of doses higher than those recommended over a long period of time may lead to temporary
suppression of adrenal function.
In these patients, treatment with fluticasone propionate should be continued at a dose sufficient to control.

Pharmacotherapeutic group: Decongestants and other nasal preparations for topical use Corticosteroids.
ATC Code: R01AD08
Fluticasone propionate causes little or no hypothalamic-pituitary-adrenal axis suppression following intranasal
administration.
Following intranasal dosing of fluticasone propionate, (200mcg/day) no significant change in 24h serum cortisol
AUC was found compared to placebo (ratio1.01, 90%CI 0.9-1.14).
In a 1-year randomised, double-blind, placebo-controlled, parallel group growth study in pre-pubescent children
aged 3 to 9 years (56 patients receiving intranasal fluticasone propionate and 52 receiving placebos,) no
statistically significant difference in growth velocity was observed in patients receiving intranasal fluticasone
propionate (200 micrograms per day nasal spray) compared to placebo. The estimated growth velocity over
one year of treatment was 6.20 cm/year (SE=0.23) in the placebo group and 5.99 cm/year (SE=0.23) in the
fluticasone propionate group; the mean difference between treatments in growth velocity after one year was
0.20 cm/year (SE=0.28, 95% CI= -0.35, 0.76). No evidence of clinically relevant changes in HPA axis function
or bone mineral density was observed as assessed by 12-hour urinary cortisol excretion and dual-energy x-ray
absorptiometry, respectively.

Absorption: Following intranasal dosing of fluticasone propionate, (200mcg/day) steady-state maximum plasma
concentrations were not quantifiable in most subjects (<0.01ng/mL). The highest Cmax observed was
0.017ng/mL. Direct absorption in the nose is negligible due to the low aqueous solubility with the majority of the
dose being eventually swallowed. When administered orally the systemic exposure is <1% due to poor
absorption and pre-systemic metabolism. The total systemic absorption arising from both nasal and oral
absorption of the swallowed dose is therefore negligible.
Distribution: Fluticasone propionate has a large volume of distribution at steady-state (approximately 318L).
Plasma protein binding is moderately high (91%).
Metabolism: Fluticasone propionate is cleared rapidly from the systemic circulation, principally by hepatic
metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450 enzyme CYP3A4. Swallowed
fluticasone propionate is also subject to extensive first pass metabolism. Care should be taken when co-administering potent CYP3A4 inhibitors such as ketoconazole and ritonavir as there is potential for increased
systemic exposure to fluticasone propionate.
Elimination: The elimination rate of intravenous administered fluticasone propionate is linear over the 250-
1000mcg dose range and are characterized by a high plasma clearance (CL=1.1L/min). Peak plasma
concentrations are reduced by approximately 98% within 3-4 hours and only low plasma concentrations were
associated with the 7.8h terminal half-life. The renal clearance of fluticasone propionate is negligible (<0.2%)
and less than 5% as the carboxylic acid metabolite. The major route of elimination is the excretion of
fluticasone propionate and its metabolites in the bile.

There are no preclinical data of relevance to the prescriber which are additional to that already included in other
sections of the SPC.

Dispersible cellulose
Phenylethyl Alcohol
Benzalkonium Chloride
Glycerin
Polysorbate 80
Purified water

Not applicable.

Store between 4°C and 30°C

Rhinase Aqueous Nasal Spray is supplied in an amber glass bottle fitted with a metering, atomising pump.
Pack size of 120 metered sprays.

Shake gently before use.