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Information about the initial procedure:
Application type/Legal basis Bibliographic application Art.10a Dir.2001/83/EC
Name of the product
Active substance
OLYNTH HA 1 mg/ml nasal spray without preservatives, solution
Xylometazoline hydrochloride
Pharmaceutical form, strength Nasal spray, solution 1 mg/ml
Pharmacotherapeutic group
ATC code
Applicant’s name and address
Nasal decongestants
R01AA07
McNeil Products Limited, c/o Johnson Johnson,
Foundation Park, Roxborough Way, Maidenhead,
Berkshire SL6 3UG, United Kingdom
EU-procedure number
Reference Member State
Member States Concerned
LV/H/0103/001/MR
Latvia
CY, DK, ES, EL, FI, IE, IS, IT, NO, PT, SE
End of procedure 20 October 2010
1.
INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the State Agency of Medicines
(SAM) considered that the application for Olynth HA 1 mg/ml nasal spray without preservatives, solution, indicated for temporary symptomatic treatment of nasal congestion due to rhinitis or sinusitis could be approvable.
National marketing authorisation for the above mentioned product was granted on February 2
2006.
Xylometazoline hydrochloride can be considered as being well known with respect to its clinical properties and a number of preparations have already been approved and marketed in several European countries. It has been marketed in the EU since 1961. The first registration was in Belgium in 1961, originally marketed as Sinutab® and since that time has been in widespread use for all over the world.
The active component xylometazoline hydrochloride is an imidazole derivate, αadrenoreceptor agonist with local vasoconstrictive properties resulting in decongestion of mucous membrane of the nose. The vasoconstriction induced by xylometazoline hydrochloride is likely transmitted via the direct stimulative effect on the postsynaptic alpha receptors. It produces a rapid and prolonged vasoconstriction lasting a period of 8 hours as a result of which nasal congestion reduces.
The use of topical vasoconstrictors in the treatment of sinusitis is based on the xylometazoline hydrochloride congestion-reducing effect that also improves the ventilation of the sinuses and makes it easier to empty them.
Xylometazoline hydrochloride is not known to have much effect on adrenergic beta receptors.
The active substance is not considered a new active substance. It concerns a bibliographical application with reference to Directive 2001/83/EC Article 10a (well established use application).
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The product is rather old and its use for the applied application is well-established for over several decades. This bibliographical application is considered acceptable. The clinical efficacy of Olynth HA 1 mg/ml nasal spray without preservatives, solution for the indications stated in the Summary of Product Characteristics may be concluded without any reasonable doubt.
The safety profile of xylometazoline hydrochloride is well known through its extensive use in clinical practice. The adverse events that can be expected are listed in the SmPC.
The pharmacological effects of the active substance can be regarded as general knowledge.
2.
QUALITY ASPECTS
The chemical-pharmaceutical documentation and Quality Overall Summary in relation to
Olynth HA 1mg/ml nasal spray without preservatives, solution, are of sufficient quality in view of the present European regulatory requirements.
Drug substance
The drug substance xylometazoline hydrochloride is known substance described in a Ph. Eur. monograph. Drug substance is sourced from BASF PharmaChemikalien GmbH & Co.KG,
Germany. Ph. Eur. Certificate of suitability (CEP) is available for the manufacturer.
Applicant’s specification has been developed according to the Ph. Eur. requirements. The proposed retest period of 4 years is justified and stated in the CEP.
Medicinal product
The development of the product has been described, the choice of excipients is justified and their functions explained.
The manufacturing process is adequately described. The used in-process controls and the performed validation studies are considered as sufficient to guarantee an appropriate quality of the drug product.
The product specifications cover appropriate parameters for this dosage form. Validation of the analytical methods has been presented . Specifications and tests are described adequately.
Batch analysis has been performed on 3 production batches. The batch analysis results show that the finished product meet the specification proposed.
The conditions used in the stability studies are according to the ICH stability guideline. The control tests and specifications for drug product are adequately drawn up.
The proposed shelf-life of 36 months with storage conditions “The medicinal product does not require any special storage conditions” for the drug product is considered acceptable.
3.
NON CLINICAL ASPECTS
Due to the long term experience with the compound in human medicine the cited literature is sufficient.
No new preclinical, pharmacology, or pharmacokinetics studies were performed on this formulation.
Due to the well-established use, no additional non-clinical studies were considered necessary. Information on pharmacokinetics is comprehensively presented in the clinical section. The proposed Summary of Product Characteristics adequately reflects the toxicological properties of Olynth HA 1mg/ml nasal spray without preservatives, solution and is considered satisfactory.
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4.
CLINICAL ASPECTS
In accordance with Article 10a of Directive 2001/83/EC, instead of results of pharmacological or clinical trials bibliographical scientific literature is provided. Data obtained so far are adequately summarised by the clinical expert. This application is based on well-established use of the medicinal product.
During years of experience and in several clinical investigations, xylometazoline hydrochloride has shown statistically significant effect compared with 0.9% sodium chloride solution (placebo) and it is as efficacious and well tolerated nasal decongestant as other widely used imidazoline derivates, such as oxymetazoline, naphazoline.
The use of topical vasoconstrictors in the treatment of sinusitis is based on the pharmaceutical ingredients' congestion-reducing effect that also improves the ventilation of the sinuses and makes it easier to empty them.
The safety profile of xylometazoline hydrochloride is well known through its extensive use in clinical practice.
Several published clinical studies have shown that xylometazoline hydrochloride used at recommended doses is usually well tolerated due to its local mechanism of action with none or few side effects. The most relevant adverse side effects are slight transient irritations (burning sensation or dryness) of the nasal mucosa.
If incorrect or excessive dosing occurs, it is possible that some of the drug may be absorbed from the nasal mucosa or from the gastrointestinal tract (through swallowing) and systemic effects may occur, especially in the elderly or children. The following systemic side effects have been shown: hypertension, tachycardia, palpitation, headache, insomnia.
Long-term or frequent use of xylometazoline hydrochloride can lead to tachyphylaxis, rebound congestion of the nasal mucosa and drug-induced rhinitis ( rhinitis medicamentosa ).
This may be due to inhibition of the release of noradrenaline from vasomotor adrenergic nerve endings through an action on the presynaptic α2- receptors. With vasoconstrictors, the rebound symptoms normally occur after 2 to 3 weeks of continuous treatment, but xylometazoline hydrochloride has been given to healthy test subjects for up to 6 weeks without mucosal swelling or tachyphylaxis occurring. However xylometazoline hydrochloride generally should not be used for longer than 7 days.
Xylometazoline hydrochloride is not known to have much effect on adrenergic beta receptors.
Olynth HA 1 mg/ml nasal spray without preservatives, solution contains hyaluronic acid which provides the moisturizing effect on the mucous membrane of the nose. As hyaluronic acid is an endogenous, naturally occurring molecule no safety issue is expected or has been identified.
The side effects of xylometazoline hydrochloride are well known. The SPC adequately reflects current knowledge on the safety of xylometazoline hydrochloride and provides details of precautions and possible side effects. Safety data obtained so far are adequately summarised in the clinical expert report.
Pharmacokinetics
Clinical pharmacokinetic studies of xylometazoline hydrochloride nasal decongestants have been investigated in many studies.
Applied topically in the nose xylometazoline hydrochloride produces a rapid and prolonged vasoconstriction lasting a period of 8 hours and the maximum effect of decongestion reaches after 10 minutes. Xylometazoline hydrochloride induces constriction of dilated nasal mucosal blood vessels which decreases swelling of the mucous membranes and reduces mucous secretion, hence providing an improvement in nasal ventilation. There are no data on the distribution, metabolism or excretion of xylometazoline hydrochloride in humans.
5.
BENEFIT RISK ASSESSMENT
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Review of published clinical data is provided in the application document.
The available data reported in the literature confirm a positive risk/benefit ratio for Xylometazoline hydrochloride and is considered to be favourable for the claimed indications .
Based on the review of the data on quality, safety and efficacy the SAM considered that the benefit risk balance could be favourable for Olynth HA 1 mg/ml nasal spray without preservatives, solution. No additional toxicological or clinical studies were deemed necessary for this application.
The Summary of Product Characteristics, Patient Leaflet and Labelling were presented according to the agreed template.
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