1. Name Of The Medicinal Product
RINATEC 21 micrograms per metered dose, Nasal Spray solution.
2. Qualitative And Quantitative Composition
RINATEC is an aqueous formulation (adjusted to pH 4.0 - 5.0) available as a 15 ml (180 metered doses) and 30 ml (380 metered doses) pump spray.
Each valve actuation delivers 70 µl of solution containing 21 micrograms of ipratropium bromide.
3. Pharmaceutical Form
Nasal Spray, solution
4. Clinical Particulars
4.1 Therapeutic Indications
RINATEC is indicated for the symptomatic relief of rhinorrhoea in allergic and non-allergic rhinitis.
4.2 Posology And Method Of Administration
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Administration
To obtain the best results from your nasal spray follow the simple instructions given below. If you are unclear about how to use the nasal spray ask your doctor or pharmacist to explain.
1. Remove the dust cap.
2. The nasal spray pump must be primed before RINATEC is used for the first time. To prime the pump, hold the bottle with your thumb at the base and your index and middle fingers on the white shoulder area. Make sure the bottle points upright and away from your eyes. Press your thumb firmly and quickly against the bottle seven times. The pump is now primed and can be used. Your pump will hold its prime for up to 24 hours. If you have not used your pump for more than 24 hours, you will need to prime it again before use. Reprime the pump as before, but this time only two sprays are required. If you have not used your pump for more than 7 days reprime using 7 sprays.
3. Blow your nose to clear your nostrils if necessary.
4. Close one nostril by gently placing your fingers against the side of your nose. Tilt your head slightly forward and, keeping the bottle upright, insert the nasal tip into the other nostril. Point the tip toward the back and outer side of the nose.
Press firmly and quickly upwards with the thumb at the base while holding the white shoulder portion of the pump between your index and middle fingers. Following each spray, sniff deeply and breathe out through the mouth.
After spraying the nostril and removing the unit, tilt your head backwards for a few seconds to let the spray spread over the back of the nose.
5. Repeat step 4 in the other nostril.
6. Replace the cap.
Avoid spraying RINATEC in or around your eye. Should this occur, immediately flush your eye with cold tap water for several minutes. If you accidently spray RINATEC in your eyes, you may experience a temporary blurring of vision and increased sensitivity to light, which may last a few hours. Follow your doctor's instructions about when and how to take your medicine and always read the label.
If the nasal tip becomes clogged, remove the clear plastic dust cap. Hold the nasal tip under warm running water for about a minute. Dry the nasal tip, reprime the nasal spray pump and replace the plastic dust cap.
4.3 Contraindications
RINATEC is contraindicated in patients known to be hypersensitive to atropine or its derivatives or to any other component of the product.
4.4 Special Warnings And Precautions For Use
Caution is advocated in the use of anticholinergic agents in patients with narrow-angle glaucoma, or with prostatic hyperplasia or bladder-outflow obstruction.
As patients with cystic fibrosis may be prone to gastro-intestinal motility disturbances, RINATEC, as with other anticholinergics, should be used with caution in these patients.
Immediate hypersensitivity reactions following the use of RINATEC have been demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.
There have been isolated reports of ocular complications (i.e. mydriasis, increased intraocular pressure, narrow-angle glaucoma, eye pain) when aerosolised ipratropium bromide, either alone or in combination with an adrenergic beta2-agonist, has come into contact with the eyes. Thus, patients must be instructed in the correct administration of RINATEC.
Eye pain or discomfort, blurred vision, visual halos or coloured images in association with red eyes from conjunctival congestion and corneal oedema may be signs of acute narrow-angle glaucoma. Should any combination of these symptoms develop, treatment with miotic drops should be initiated and specialist advice sought immediately.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
The concomitant use of RINATEC with other drugs commonly prescribed for perennial rhinitis i.e. antihistamines, decongestants or nasal steroids does not increase the incidence of nasal or non-nasal side-effects.
Ipratropium bromide is minimally absorbed into the systemic circulation; nonetheless, there is some potential for additive interaction with other concomitantly administered anticholinergic medications, including ipratropium bromide-containing aerosols for oral inhalation.
4.6 Pregnancy And Lactation
The safety of RINATEC during human pregnancy has not been established. The benefits of using RINATEC during a confirmed or suspected pregnancy must be weighed against the possible hazards to the unborn child. Preclinical studies have shown no embryotoxic or teratogenic effects following inhalation or intranasal application at doses considerably higher than those recommended in man.
It is not known whether ipratropium bromide is excreted into breast milk. It is unlikely that ipratropium bromide would reach the infant to an important extent, however caution should be exercised when RINATEC is administered to nursing mothers.
4.7 Effects On Ability To Drive And Use Machines
No studies on the effects on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as dizziness, accommodation disorder, mydriasis and blurred vision during treatment with Rinatec. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery.
4.8 Undesirable Effects
The most frequent local undesirable effects reported are nasal reactions including epistaxis, dryness of the nose and nasal irritation. These effects may necessitate reduced frequency of administration. Pharyngitis and sinusitis may also occur.
Headache and nausea may occur as nonspecific reactions in association with use of RINATEC. Potential systemic anticholinergic effects are dry mouth and dry throat. Ocular side effects (see Special Warnings and Special Precautions for Use), increase of heart rate and palpitations, urinary retention and gastrointestinal motility disturbances have been reported in isolated patients in association with use of ipratropium bromide either intranasally or after oral inhalation.
Allergic-type reactions such as skin rash, angioedema of tongue, lips and face, urticaria, laryngospasm and anaphylactic reactions may occur.
After oral inhalation of ipratropium bromide in patients suffering from COPD/Asthma supraventricular tachycardia and atrial fibrillation have been reported.
4.9 Overdose
No symptoms specific to overdosage have been encountered. In view of the wide therapeutic window and topical administration of RINATEC, no serious anticholinergic symptoms are to be expected. As with other anticholinergics, dry mouth, visual accommodation disturbances and tachycardia would be the expected symptoms and signs of overdose.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Ipratropium bromide, a quaternary ammonium derivative of atropine is an anticholinergic drug. Ipratropium bromide administered intranasally has a localised parasympathetic blocking action, which reduces watery hypersecretion from mucosal glands in the nose.
5.2 Pharmacokinetic Properties
Absorption
The therapeutic effect of ATROVENT is produced by a local action in the airways. Time courses of bronchodilation and systemic pharmacokinetics do not run in parallel.
Following inhalation, 10 to 30% of a dose is generally deposited in the lungs, depending on the formulation, device and inhalation technique. The major part of the dose is swallowed and passes through the gastro-intestinal tract.
The portion of the dose deposited in the lungs reaches the circulation rapidly (within minutes).
Cumulative renal excretion (0-24 hrs) of parent compound is approximated to 46% of an intravenously administered dose, below 1% of an oral dose and approximately 3 to 13% of an inhaled dose. Based on these data the total systemic bioavailability of oral and inhaled doses of ipratropium bromide is estimated at 2% and 7 to 28% respectively.
Taking this into account, swallowed dose portions of ipratropium bromide do not contribute significantly to systemic exposure.
Distribution
The drug is minimally (less than 20%) bound to plasma proteins. The quarternary amine of the ipratropium ion does not cross the blood-brain barrier.
Biotransformation
Ipratropium has a mean total clearance of 2.3 L/min and a renal clearance of 0.9 L/min. After intravenous administration approximately 60% of the dose is metabolised, mainly by conjugation (40%), wheras after inhalation about 77% of the systemically available dose is metabolised by ester hydrolysis (41%) and conjugation (36%).
Elimination
After inhalation of ipratropium bromide either with HFA 134a or CFC propellant, cumulative renal excretion over 24 hours was approximately 12% and 10%, respectively.
In an excretion balance study cumulative renal excretion (6 days) of drug-related radioactivity (including parent compound and all metabolites) accounted for 72.1% after intravenous administration, 9.3% after oral administration and 3.2% after inhalation. Total radioactivity excreted via the faeces was 6.3% following intravenous application, 88.5% following oral dosing and 69.4% after inhalation. Regarding the excretion of drug-related radioactivity after intravenous administration, the main excretion occurs via the kidneys. The half-life for elimination of drug-related radioactivity (parent compound and metabolites) is 3.2 hours. The main urinary metabolites bind poorly to the muscarinic receptor and have to be regarded as ineffective.
5.3 Preclinical Safety Data
The toxicity of ipratropium bromide has been investigated extensively in the following types of studies: acute, subchronic and chronic toxicity, carcinogenicity, reproductive toxicity and mutagenicity via oral, intravenous, subcutaneous, intranasal and/or inhalation routes. Based on these toxicity studies, the probability of systemic anticholinergic side effects decreases in the following order:
intravenous> subcutaneous> oral> inhalation> intranasal.
Pre-clinically, ipratropium bromide was found to be well-tolerated. Two-year carcinogenicity studies in rats and mice have revealed no carcinogenic activity at doses up to approximately 1,200 times the maximum recommended human daily dose for RINATEC. Results of various mutagenicity tests were negative.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Sodium chloride
Benzalkonium chloride
Disodium edetate
Purified water
Hydrochloric acid and sodium hydroxide are used for pH adjustment.
6.2 Incompatibilities
None known
6.3 Shelf Life
2 years
In-use: 6 months
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
RINATEC is a clear colourless aqueous solution adjusted to the optimum pH 4.0-5.0. The solution is filled into either 15 ml or 30 ml amber glass bottles (Type I glass) fitted with 70µL manually activated nasal pump/closures.
6.6 Special Precautions For Disposal And Other Handling
No special requirements
Administrative Data
7. Marketing Authorisation Holder
Boehringer Ingelheim Limited
Ellesfield Avenue
Bracknell
Berkshire
RG12 8YS
8. Marketing Authorisation Number(S)
PL 00015/0196
9. Date Of First Authorisation/Renewal Of The Authorisation
20 March 1996
10. Date Of Revision Of The Text
July 2011
11. LEGAL CATEGORY
POM
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