Beipackzettel, Nebenwirkungen, Wirkung, Anwendungsgebiete - Nebivolol Lannacher 5 mg Tabletten
Lannacher Heilmittel Ges.m.b.H.
Publication:
10.02.2023
This module reflects the scientific discussion for the approval of the above-mentioned procedure. The procedure was finalised on 03.12.2008.
TABLE OF CONTENTS
ADMINISTRATIVE INFORMATION
| Proposed name of the medicinal product in the RMS | Nebivolol Lannacher 5 mg Tabletten |
| INN (or common name) of the active substance(s): | Nebivolol Hydrochlorid |
| Pharmaco-therapeutic group (ATC Code): | C07AB12 |
| Pharmaceutical form(s) and strength(s): | tablet |
| Reference Number for the Decentralised Procedure | DE/H/1454/001/DC |
| Reference Member State: | DE |
| Member States concerned: | AT; BG; CZ; EE; HU; LT; LV; PL; RO; SK |
| Applicant (name and address) | Lannacher Heilmittel Ges.m.b.H. Schlossplatz 1 8502 Lannach Austria |
| Names and addresses of manufacturers responsible for batch release in the EEA | Lannacher Heilmittel Ges.m.b.H. Schlossplatz 1 8502 Lannach Austria |
I.
INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the RMS considers that the application for Nebivolol Lannacher 5 mg Tabletten , in the treatment of
-
■ essential hypertension
-
■ stable mild and moderate chronic heart failure in addition to standard therapies in elderly patients > 70 years
is approved.
-
II. EXECUTIVE SUMMARY
-
II.1 Problem statement
-
This decentralized procedure concerns a generic version of nebivolol, under the trade name Nebivolol Lannacher 5 mg Tabletten.
The originator product is Nebilet® 5 mg tablet (5 mg, tablet) by Menarini International Operations, registered since 19.10.1995.
With Germany as the Reference Member State in this Decentralised Procedure, Lannacher Heilmittel Ges.m.b.H., Austria applied for the Marketing Authorisations Nebivolol Lannacher 5 mg Tabletten in AT; BG; CZ; EE; HU; LT; LV; PL; RO and SK.
-
II.2 About the product
Nebivolol is a long-acting, cardioselective beta-blocker Nebivolol consists of a racemic mixture of two enantiomers: D-Nebivolol and L-Nebivolol. Both enantiomers are rapidly resorbed following oral administration, regardless of the absence or presence of food. Nebivolol is extensively metabolized, partly to active hydroxy-metabolites. The metabolism of nebivolol via aromatic hydroxylation is highly dependent on CYP2D6 status. The oral bioavailability of nebivolol is on average 12% in CYP2D6 extensive metabolizers and nearly complete in poor metabolizers. Steady state plasma concentrations of unchanged nebivolol is 23 times higher in poor metabolizers than in extensive metabolizers. The aromatic hydroxyl metabolites have comparable pharmacological and binding features as nebivolol. Other metabolites have no (clinical significant) pharmacological activity. When administered alone only D-nebivolol but not L-nebivolol has blood-pressure lowering activity. However, the antihypertensive action of D-nebivolol is enhanced by the presence of L-nebivolol.
-
II.3 General comments on the submitted dossier
The dossier is of acceptable quality.
-
II.4 General comments on compliance with GMP, GLP, GCP and agreed ethical principles.
The RMS has been assured that acceptable standards of GMP are in place for these product types at all sites responsible for the manufacture and assembly of this product.
-
III. SCIENTIFIC OVERVIEW AND DISCUSSION
-
III.1 Quality aspects
Drug substance
-
Nebivolol HCl is neither described in the European Pharmacopoeia nor in the USP. The ASMF procedure is used. The synthesis has been described sufficiently. All relevant specifications have been provided. The analytical methods are well validated. The retest period can be accepted. A storage condition is not required. Regarding the quality of the drug substance all points for clarification have been resolved.
Drug Product
The composition of the medicinal products, pharmaceutical development and route of manufacture of the finished products are described sufficiently. In process controls, which cover the critical steps of manufacture are described. Process validation data have been submitted. The release specification contains the relevant quality characteristics to describe the finished product, dissolution testing has been updated. Batch analysis data are provided, the results meet the specified requirements.
Stability studies of the finished product are performed by long term and accelerated studies in the proposed package material PVC/aluminium blister. Based upon the submitted stability data of 12 months the extrapolation of the shelf life to 3 years can be accepted. The establishment of a storage condition is not required.
-
III.1 Nonclinical aspects
Pharmacology
The pharmacology of nebivolol is well known. No new data has been submitted and none is required.
Pharmacokinetics
The pharmacokinetics of nebivolol is well known. No new data has been submitted and none is required.
Toxicology
The toxicological properties of nebivolol are well known. No new data has been submitted and none is required.
-
III.2 Clinical aspects
No specific clinical studies have been performed, as the application is submitted in accordance with Article 10(1) of Directive 2001/83/EC as amended.
An open label, randomized, two-treatment, two-sequence, two-period, single-dose, crossover bioequivalence study was performed under fasting conditions in order to compare the rate and the extent of absorption of the generic product and the originator product.
Based on the submitted bioequivalence study Nebivolol Lannacher 5 mg Tabletten is considered bioequivalent with Nebilet® 5 mg. Moreover, tolerability of the test product is acceptable and not significantly different from reference product.
Common Renewal Date
A proposed common renewal date of 5 years after finalisation of the procedure was accepted.
Legal Status
Medicinal product subject to medical prescription.
User Testing
User testing has been performed. The results of the test indicate that the PL is adequately structured and written in a comprehensible manner.
-
IV. BENEFIT RISK ASSESSMENT