Dalman

Off-white, opaque, homogenous aqueous suspension.
Each actuation contains: Fluticasone propionate 50 mcg (0.05% w/w).

Pharmacotherapeutic group: Corticosteroids. ATC Code: R01AD08.
Pharmacology: Pharmacodynamics: Fluticasone propionate has strong anti-inflammatory activity but does not produce detectable systemic activity when administered topically to the nasal mucosa.
Fluticasone propionate causes little or no hypothalamic-pituitary-adrenal axis suppression following intranasal administration.
Following intranasal dosing of fluticasone propionate, (200 mcg/day) no significant change in 24h serum cortisol AUC was found compared to placebo (ratio 1.01, 90% CI 0.9-1.14).
Pharmacokinetics: Absorption: Following intranasal dosing of fluticasone propionate, (200 mcg/day) steady-state maximum plasma concentrations were not quantifiable in most subjects (<0.01 ng/mL). The highest Cmax observed was 0.017 ng/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 318 L). 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 250-1000 mcg dose range and are characterized by a high plasma clearance (CL=1.1 L/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.
Toxicology: Preclinical Safety Data: The toxicology appears only in the type of effects that potent corticosteroids have when administered at higher doses than recommended. No new effects were identified in repeated dose toxicity studies, reproductive toxicity studies, or teratology studies.
Fluticasone propionate did not show mutagenic activity in vitro and in vivo and did not show tumorigenic activity in rodents. Not irritating or sensitizing on animal models.

Indicated for the symptomatic treatment and prophylaxis of seasonal allergic rhinitis and perennial rhinitis including hay fever. Fluticasone propionate has a strong anti-inflammatory effect, but does not produce a noticeable systemic effect when applied topically to the nasal mucosa.

Adults and children over 12 years of age: 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.
The maximum daily dose should not exceed four sprays into each nostril.
Pediatric population: Children 4-11 Years: One spray in each nostril once daily preferably in the morning is recommended. In some cases, the patient may need to do 2 times a day 1 spray in each nostril. The maximum daily dose should not exceed 2 sprays in each nostril. Or as prescribed by the physician.

There are no data on the effect of acute or chronic overdose of intranasal fluticasone propionate. Intranasal administration of 2 mg fluticasone propionate twice daily for 7 days to healthy volunteers had no effect on hypothalamic-pituitary-adrenal (HPA) axis functions.
Long-term administration of higher than recommended doses may cause temporary suppression of adrenal function.
In these patients, fluticasone propionate treatment should be continued at a dose sufficient to control symptoms; adrenal function will return to normal within a few days and this can be monitored by measuring the plasma cortisol level.

Hypersensitivity to any of its ingredients.

Local infection: Although the presence of infection in the nasal airways does not constitute a specific contraindication for intranasal fluticasone propionate therapy, this infection should be treated appropriately.
Caution should be exercised in patients who discontinue systemic steroid therapy and initiate intranasal fluticasone propionate therapy, especially if there is a reason to think that adrenal function is impaired.
Systemic effects of nasal corticosteroids, especially in high doses and long-term use, have been reported. These effects are much less likely to occur than with oral corticosteroids and may differ between patients and different corticosteroid preparations.
Growth retardation has been reported in children using certain nasal corticosteroids at approved doses. Regular monitoring of the height of children receiving long-term nasal corticosteroid therapy is recommended. In the event of growth retardation, treatment should be reviewed to reduce the nasal corticosteroid dose and, whenever possible, the lowest dose to control symptoms should be used. In addition, referral to a pediatrician should be considered.
During post-marketing use, clinically significant drug interactions have been reported in patients receiving fluticasone propionate and ritonavir; this has led to systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefits to the patient outweigh the risk of systemic corticosteroid side effects.
Full benefit may not be achieved unless treatment with Fluticasone Propionate Nasal Spray suspension is continued for several weeks.
Glaucoma and increased intraocular pressure have been reported rarely following intranasal administration of corticosteroids.

Pregnancy: Pregnancy category is C.
Women with childbearing potential/Contraception: Studies on animals are insufficient in terms of the effects on pregnancy or embryonal/fetal development and/or postnatal and/or postnatal development. The potential risk for humans is unknown.
Pregnancy Period: There are insufficient data regarding its safety in human pregnancy. In animal reproduction studies, adverse effects typical of potent corticosteroids were seen only at high systemic exposure levels; direct intranasal administration provides minimal systemic exposure.
As with other drugs, the benefits of intranasal fluticasone propionate use during pregnancy and lactation should outweigh the possible risks that may arise from using the product or alternative treatment methods.
Lactation Period: It has not been studied whether fluticasone propionate is excreted in breast milk. In lactating laboratory rats, fluticasone propionate was seen in milk when measurable plasma levels were achieved following subcutaneous administration. However, plasma levels are low following intranasal administration of fluticasone propionate at recommended doses.

Data from large clinical studies have been used to determine the incidence of adverse events, from very common to rare. Frequencies of other adverse events (<1/10,000) were determined from post-marketing data and are based on the reporting rate rather than an actual frequency.
The frequency classification is as follows: Very common ≥1/10; Common ≥1/100 and <1/10; Uncommon ≥1/1000 and <1/100; Rare ≥1/10,000 and <1/1000; Very rare <1/10,000; Unknown (it cannot be predicted on the basis of available data).
Immune system diseases: Very rare: Hypersensitivity reactions, anaphylaxis/anaphylactic reactions, bronchospasm, skin rash, edema of the face or tongue.
Nervous System Disorders: Common: Headache, bad taste in mouth, bad odour.
As with other nasal sprays, bad taste in the mouth, bad odor and headache have been reported.
Eye diseases: Very rare: Glaucoma, increased intraocular pressure, cataract.
Few spontaneous reports have been described following long-term therapy. However, clinical studies lasting up to one year have shown that intranasal fluticasone propionate is not associated with an increased incidence of eye events such as cataracts, increased intraocular pressure, or glaucoma.
Diseases of the respiratory system: Very common: Epistaxis.
Common: Nasal dryness, nasal irritation, dry throat, throat irritation.
As with other intranasal medications, dryness, irritation and epistaxis of the nose and throat have been reported.
Very rare: Nasal septal perforation.
Cases of nasal septal perforation have been reported following the use of intranasal corticosteroids.

Allergic reactions which can develop into a more serious, even life-threatening problem if not treated.
Symptoms include: becoming very wheezy, coughing or having difficulty with breathing; suddenly feeling weak or light-headed (which may lead to collapse or loss of consciousness); swelling around the face, mouth or tongue; skin rashes or redness.
Very common side effects are nose bleeds.
Common are headache, unpleasant taste and smell, dry or painful nose or throat.
Very rare are skin reaction, eye pain or blurred vision and damage to the nose.

Under normal conditions, very low plasma concentrations of fluticasone propionate are achieved following intranasal dosing, due to extensive first-pass metabolism in the liver and intestine and high systemic clearance mediated by cytochrome P450 3A4. Therefore, clinically significant drug interactions mediated by fluticasone propionate are not expected.
In a drug interaction study in healthy volunteers, ritonavir (a highly potent cytochrome P450 3A4 inhibitor) was shown to greatly increase the plasma concentrations of fluticasone propionate, leading to a significant decrease in serum cortisol concentrations. Clinically significant drug interactions have been reported in patients receiving intranasal or inhaled fluticasone propionate and ritonavir during post-marketing use; this has led to systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefits to the patient outweigh the risk of systemic corticosteroid side effects.
Studies have shown negligible (erythromycin) and insignificant (ketoconazole) increases in systemic exposure of other cytochrome P450 3A4 inhibitors with no discernible decrease in serum cortisol concentrations of fluticasone propionate. However, caution should be exercised when co-administering potent cytochrome P450 3A4 inhibitors (eg. ketoconazole) because of the potential for increased systemic exposure to fluticasone propionate.

Instructions for Use and Handling: Shake gently before use.
Before using the product, wash hands and remove dust cap.
Each spray has a dust cap which protects the nozzle and keeps it clean. Remember to take this off before using the spray.
Preparing the spray: A new spray (or one that has not been used for a few days), may not work first time. The patient needs to "prime" the spray by pumping the spray a few times until a fine mist is produced.
1. Hold the bottle and make sure it is pointed away from the patient.
2. Put forefinger and middle finger on the collar either side of the nozzle or put the thumb underneath the bottle.
3. Keep the thumb still, and press down with fingers to pump the spray.
If the spray does not work and the patient thinks it may be blocked, they will need to clean it. See the section as follows, Cleaning the spray.
Never try to unblock or enlarge the tiny spray hole with a pin or other sharp object. This will damage the way the spray works.
Using the spray: 1. Shake the bottle and take off the dust cap.
2. Blow nose gently.
3. Close one nostril with a finger, and put the nozzle in the other nostril. Tilt head forward slightly and keep the bottle upright.
4. Start to breathe in slowly through nose. While the patient is breathing in press down firmly on the collar with the fingers. A spray of fine mist will go into the nostril.
5. Breathe out through the mouth.
6. Repeat step 4 to use a second spray in the same nostril.
7. Remove the nozzle from this nostril and breathe out through the mouth.
8. Repeat steps 3 to 6 for the other nostril.
9. After using the spray, wipe the nozzle carefully with a clean tissue or handkerchief, and replace the dust cap.
Cleaning the spray: Clean the spray at least once a week, or more often if it gets blocked.
1. Take the dust cap off by gently squeezing the ribbed sides between a finger and thumb and lifting it off. Do not twist it off.
2. Pull upwards on the white collar to remove the nozzle.
3. Soak the nozzle and dust cap in warm water for a few minutes.
4. Then rinse under a running tap.
5. Shake off the excess water and let them dry in a warm place.
6. Put the nozzle back on the spray.
7. "Prime" the bottle, preparing the spray.

Store at temperatures not exceeding 30°C.
Protect from heat and light.
Do not put in a refrigerator.

Nasal Decongestants & Other Nasal Preparations

R01AD08 - fluticasone ; Belongs to the class of topical corticosteroids used for prophylaxis and treatment of allergic rhinitis.

Rx