(Verbena herb, Hops strobiles, Valerian root, Passion flower herb

UKPAR Goodnight
THR 00904/0003
Goodnight
THR 00904/0003
UKPAR
TABLE OF CONTENTS
Lay Summary
Page 2
Scientific discussion
Page 3
Steps taken for assessment
Page 12
Steps taken after authorisation
Page 13
Summary of Product Characteristics
Page 14
Product Information Leaflets
Page 18
Labelling
Page 22
1
UKPAR Goodnight
THR 00904/0003
Goodnight
THR 00904/0003
LAY SUMMARY
On 16th November 2010, the Medicines and Healthcare products Regulatory Agency
(MHRA) granted Kerbina Limited (trading as Bio-Health) a Traditional Herbal
Registration Certificate for the traditional herbal medicinal product, Goodnight
(Traditional Herbal Registration number: THR 00904/0003). This is a medicine
available on the General Sales List (GSL), and can be purchased at pharmacies and
other retail outlets without the supervision of a pharmacist.
Goodnight is a traditional herbal medicinal product used for the temporary relief of
sleep disturbances based on traditional use only.
Each tablet of Goodnight contains the stated quantities of the following active herbal
ingredients (botanical names are given in brackets):
•
•
•
•
•
60mg Verbena herb (Verbena officinalis L.)
30mg Hops strobiles (Humulus lupulus L.)
36mg extract from Valerian root (Valeriana officinalis L) (5:1)
30mg extract from Passion flower herb (Passiflora incarnata L) (3:1)
18mg extract from Wild lettuce herb (Lactuca virosa L) (5:1)
This registration is based exclusively upon evidence of the use of Verbena herb, Hops
strobiles, Valerian root, Passion flower herb and Wild lettuce herb as traditional
herbal medicines and not upon data generated from clinical trials. There is no
requirement under the Traditional Herbal Registration scheme to prove scientifically
that the product works.
No new or unexpected safety concerns arose from this application and it was,
therefore, decided that a Traditional Herbal Registration Certificate could be granted.
2
UKPAR Goodnight
THR 00904/0003
Goodnight
THR 00904/0003
SCIENTIFIC DISCUSSION
TABLE OF CONTENTS
Introduction
Page 4
Pharmaceutical assessment
Page 5
Non-clinical assessment
Page 9
Clinical assessment
Page 10
Overall conclusion and risk assessment
Page 11
3
UKPAR Goodnight
THR 00904/0003
INTRODUCTION
The MHRA granted Kerbina Limited (trading as Bio-Health) a Traditional Herbal
Registration Certificate for the traditional herbal medicinal product, Goodnight
(Traditional Herbal Registration number: THR 00904/0003), on 16th November 2010.
This is a medicine available on the General Sales List (GSL).
A product licence of right (PLR) was granted to Kerbina Limited (trading as BioHealth) for this product (PL 00904/5060R) in 1972. The PLR was reviewed and a
product licence was granted on 17th March 1988. The PL 00904/5060 will be
cancelled after the THR is granted.
This THR application was made under Article 16.c of Directive 2001/83 EC in
accordance with arrangements to transfer certain herbal products with a marketing
authorisation (product licence) to a THR (according to MHRA Guidance dated
January 2009). The application falls within the simplified THR application Category
A as no changes have been made to the formulation of the product. No new data were
submitted, nor was it necessary for this application, as the data are essentially
identical to those of the existing product.
Goodnight is a traditional herbal medicinal product used for the temporary relief of
sleep disturbances based on traditional use only.
The product contains 5 herbal ingredients. Each coated tablet contains:
•
60mg Verbena herb (Verbena officinalis L.)
•
30mg Hops strobiles (Humulus lupulus L.)
•
36mg of extract (as dry extract) from Valerian root (Valeriana officinalis L.)
(5:1) Extraction solvent: Ethanol 60% v/v
•
30mg of extract (as dry extract) from Passion flower herb (Passiflora incarnata
L.) (3:1) Extraction solvent: Ethanol 60% v/v
•
18mg of extract (as dry extract) from Wild Lettuce herb (Lactuca virosa L.)
(5:1) Extraction solvent: Water
4
UKPAR Goodnight
THR 00904/0003
PHARMACEUTICAL ASSESSMENT
HERBAL SUBSTANCE: VERBENA HERB
Scientific name of the plant:
Parts of the plant used:
Verbena officinalis L.
Whole or fragmented, dried aerial parts
The herbal substance complies with its European Pharmacopoeia (Ph. Eur.)
monograph; it is, therefore, acceptable.
HERBAL SUBSTANCE: HOPS STROBILES
Scientific name of the plant:
Parts of the plant used:
Humulus lupulus L.
Dried, generally whole, female inflorescences
The herbal substance complies with its European Pharmacopoeia (Ph. Eur.)
monograph; it is, therefore, acceptable.
HERBAL SUBSTANCE: VALERIAN ROOT
Scientific name of the plant:
Family:
Synonyms of the herbal substance:
Part of the plant used:
Valeriana officinalis L.
Valerianaceae
Valerian
root
The herbal substance complies with its European Pharmacopoeia (Ph. Eur.)
monograph; it is, therefore, acceptable.
HERBAL PREPARATION: VALERIAN ROOT DRY EXTRACT (5:1)
Herbal preparation:
Extraction solvent:
Valerian root dry extract (5:1)
Ethanol 60% v/v
The herbal preparation specification is in line with that applied to the herbal
preparation used in the already licensed product. It is, therefore, acceptable.
HERBAL SUBSTANCE: PASSION FLOWER HERB
Scientific name of the plant:
Parts of the plant used:
Passiflora incarnata L.
Fragmented or cut, dried aerial parts
The herbal substance complies with satisfactory in-house specifications and is
acceptable.
5
UKPAR Goodnight
THR 00904/0003
HERBAL PREPARATION: PASSION FLOWER HERB DRY EXTRACT (3:1)
Herbal preparation:
Extraction solvent:
Passion flower herb dry extract (3:1)
Ethanol 60% v/v
The herbal preparation specification is in line with that applied to the herbal
preparation used in the already licensed product. It is, therefore, acceptable.
HERBAL SUBSTANCE: WILD LETTUCE HERB
Scientific name of the plant:
Lactuca virosa L.
The herbal substance complies with satisfactory in-house specifications and is
acceptable.
HERBAL PREPARATION: WILD LETTUCE HERB DRY EXTRACT (5:1)
Herbal preparation:
Extraction solvent:
Wild lettuce herb dry extract (5:1)
water
The herbal preparation specification is in line with that applied to the herbal
preparation used in the already licensed product. It is, therefore, acceptable.
6
UKPAR Goodnight
THR 00904/0003
HERBAL PRODUCT: GOODNIGHT
Description and Composition of the Herbal Product
The medicinal product, Goodnight, is presented as grey, biconvex, sugar-coated
tablets, each containing 60mg Verbena herb, 30mg Hops strobiles, 36mg of extract (as
dry extract) from Valerian root (5:1), 30mg of extract (as dry extract) from Passion
flower herb (3:1) and 18mg of extract (as dry extract) from Wild Lettuce herb (5:1).
All excipients used comply with their respective European Pharmacopoeia
monographs. Satisfactory Certificates of Analysis have been provided for all
excipients.
The formulation is identical to that of the already licensed product. It is, therefore,
acceptable.
The magnesium stearate has been confirmed as being of vegetable origin. The only
excipient used that contains material of animal or human origin is lactose. The
applicant has provided a declaration that milk used in the production of lactose is
sourced from healthy animals under the same conditions as that for human
consumption. None of the excipients are sourced from genetically modified
organisms.
Manufacture
The manufacturing process is identical to that of the already licensed product and is
satisfactory.
Finished Product Specification
The finished product specification is in line with that of the already licensed product
and is satisfactory.
Container Closure System
The tablets are licensed for marketing in 100ml high-density polyethylene (HDPE)
plastic containers with tamper-evident caps, in a pack size of 50 tablets. The HDPE
containers are packaged with the Patient Information Leaflet (PIL) into cardboard
outer cartons.
This type of packaging has been used to store the already licensed product and is
satisfactory.
Stability
The product shelf-life of 3 years was applied to the already licensed product and is
appropriate. Storage instructions are ‘Store below 25°C. Store in the original
package’.
7
UKPAR Goodnight
THR 00904/0003
Summary of Product Characteristics (SmPC), label and Patient Information
Leaflet (PIL)
All product literature is in line with that of the already licensed product, with some
details amended in line with other valerian-containing products for sleep registered
under the THR scheme.
The Patient Information Leaflet (PIL) is in line with the SmPC and is satisfactory. The
package leaflet for the existing product licence has been evaluated via a user
consultation study in accordance with the requirements of Articles 59(3) and 61(1) of
Directive 2001/83/EC, as amended. The results showed that the package leaflet met
the criteria for readability as set out in the Guideline on the readability of the label and
package leaflet of medicinal products for human use. The text, content and layout of
the proposed leaflet are considered essentially identical to the approved leaflet for the
existing product, and bridging of the PIL user testing to the existing product is
therefore accepted.
Assessor’s Overall Conclusions on Quality
The grant of a Traditional Herbal Registration is acceptable.
8
UKPAR Goodnight
THR 00904/0003
NON-CLINICAL ASSESSMENT
No new non-clinical data have been supplied with this application and none are
required for applications of this type. Tests on reproductive toxicity, genotoxicity and
carcinogenicity have not been performed. The results of genotoxicity testing will be
provided before the THR is renewed.
All product literature is satisfactory from a non-clinical point of view.
It is recommended that a Traditional Herbal Registration can be granted from a nonclinical perspective.
9
UKPAR Goodnight
THR 00904/0003
CLINICAL ASSESSMENT
The clinical particulars for Goodnight are identical to those for the already licensed
product. This is satisfactory. No new clinical data have been supplied with this
application and none are required.
All product literature is satisfactory from a clinical point of view.
It is recommended that a Traditional Herbal Registration can be granted from a
clinical perspective.
10
UKPAR Goodnight
THR 00904/0003
OVERALL CONCLUSION AND RISK ASSESSMENT
QUALITY
Goodnight is identical to an already licensed product. It is, therefore,
pharmaceutically satisfactory.
NON-CLINICAL
No new non-clinical data were submitted and none are required for an application of
this type.
EFFICACY
No clinical efficacy data are required for registration of Traditional Herbal Medicinal
Products (THMP).
SAFETY
No new or unexpected safety concerns arose from this application.
PRODUCT LITERATURE
The approved Summary of Product Characteristics (SmPC) is satisfactory.
PIL user testing has been accepted, based on a bridging statement provided by the
applicant making reference to the successful user-testing of the PIL for the existing
product licence. The bridging is accepted.
Mock-ups of the labelling have been provided and are satisfactory. The approved
labelling artwork complies with statutory requirements. In line with current
legislation, the name of the product in Braille appears on the outer packaging.
RISK BENEFIT ASSESSMENT
The quality of the product is acceptable and no new non-clinical or clinical safety
concerns have been identified. The proposed product is identical to the already
licensed product.
11
UKPAR Goodnight
THR 00904/0003
Goodnight
THR 00904/0003
STEPS TAKEN FOR ASSESSMENT
1
The MHRA received the Traditional Herbal Registration application on 25th
May 2010
2
Following standard checks and communication with the applicant the MHRA
considered the application valid on 8th June 2010
3
Following assessment of the application, a THR was granted on 16th November
2010
12
UKPAR Goodnight
THR 00904/0003
Goodnight
THR 00904/0003
STEPS TAKEN AFTER AUTHORISATION
Not applicable
13
UKPAR Goodnight
THR 00904/0003
SUMMARY OF PRODUCT CHARACTERISTICS
1
NAME OF THE MEDICINAL PRODUCT
Goodnight
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each coated tablet contains:
60mg Verbena herb (Verbena officinalis L.).
30mg Hops strobiles (Humulus lupulus L.)
36mg of extract (as dry extract) from Valerian root (Valeriana officinalis L.) (5:1) Extraction
solvent: Ethanol 60% v/v
30mg of extract (as dry extract) from Passion flower herb (Passiflora incarnata L.) (3:1)
Extraction solvent: Ethanol 60% v/v
18mg of extract (as dry extract) from Wild Lettuce herb (Lactuca virosa L.) (5:1) Extraction
solvent: Water
Excipients: each coated tablet contains: 222mg of sucrose, 30mg lactose
For full list of excipients see section 6.1
3
PHARMACEUTICAL FORM
Coated tablet.
Grey, biconvex sugar coated tablet.
4
CLINICAL PARTICULARS
4.1
Therapeutic indications
A traditional herbal medicinal product used for the temporary relief of sleep disturbances
based on traditional use only.
4.2
Posology and method of administration
For oral short term use only.
Adults and the elderly.
For the relief of sleep disturbances take two tablets 30 minutes before bedtime.
As treatment effects may not be apparent immediately, GOODNIGHT should be taken for 2-4
weeks continuously.
Duration of use:If symptoms persist or worsen after 4 weeks of using the product, a doctor or qualified
healthcare practitioner should be consulted.
The use in children or adolescents under 18 years of age is not recommended (see Section 4.4.
Special warnings and precautions for use).
4.3
Contraindications
Hypersensitivity to the active substances Verbena, Hops, Valerian, Passion flower, Wild
Lettuce or any of the excipients.
14
UKPAR Goodnight
4.4
THR 00904/0003
Special warnings and precautions for use
Do not exceed stated dose
The use of this product in children or adolescents under 18 years of age is not recommended
because data are not sufficient and medical advice should be sought.
This product contains sucrose and lactose. One coated tablet contains a maximum of 222mg of
sucrose and a maximum of 30mg of lactose.
Patients with rare hereditary problems of fructose intolerance, galactose intolerance, the Lapp
lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should
not take this medicine.
If symptoms persist or worsen after 4 weeks of using the product, a doctor or qualified
healthcare practitioner should be consulted.
4.5
Interaction with other medicinal products and other forms of interaction
Only limited data on pharmacological interactions with other medicinal products are
available. Clinically relevant interactions with drugs metabolised by the CYP 2D6, CYP
3A4/5, CYP1A2 or CYP 2E1 pathway has not been observed. Additive effects with
hypnotics and other sedatives cannot be excluded and therefore co-medication is not
recommended as a general precaution.
The effect of GOODNIGHT may be potentiated by alcohol. Excessive concomitant
consumption of alcohol should therefore be avoided.
4.6
Pregnancy and lactation
The safety of the product during pregnancy and lactation has not been established. In the
absence of sufficient data, the use during pregnancy and lactation is not recommended.
4.7
Effects on ability to drive and use machines
GOODNIGHT may impair ability to drive and use machines. Patients who are affected should
not drive or operate machinery
4.8
Undesirable effects
Gastrointestinal symptoms (eg nausea, abdominal cramps) may occur after ingestion of
Valerian root preparations. The frequency is not known.
One case of hypersensitivity (vasculitis) and one case of nausea and tachycardia have been
reported with Passion flower. The frequency is not known.
There are no known adverse reactions with the other active ingredients.
If other adverse reactions not mentioned above occur, a doctor or qualified healthcare
practitioner should be consulted.
4.9
Overdose
Valerian root at a dose of approximately 20g (equivalent to 100 tablets) caused benign
symptoms (fatigue, abdominal cramp, chest tightness, light headedness, hand tremor and
mydriasis) which disappeared within 24 hours.
If symptoms arise, treatment should be supportive.
After intake of very high doses of Valerian root over several years (daily consumption
corresponding to approximately 30 g of the drug) withdrawal symptoms (delirium) have been
reported.
15
UKPAR Goodnight
THR 00904/0003
No cases of overdose have been reported for the other active ingredients.
Symptomatic and supportive measures should be taken as appropriate.
5
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Not required as per Article 16 c (1) (a) (iii) of Directive 2001/83/EC as amended.
5.2
Pharmacokinetic properties
Not required as per Article 16 c (1) (a) (iii) of Directive 2001/83/EC as amended.
5.3
Preclinical safety data
Tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed.
6
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Excipients of the herbal preparations:
Calcium hydrogen phosphate, maltodextrin.
Tablet core:
Sucrose, lactose, sodium starch glycollate, magnesium stearate, talc.
Tablet coating: Sucrose, talc, ferric oxide, titanium oxide
6.2
Incompatibilities
Not applicable.
6.3
Shelf life
3 years
6.4
Special precautions for storage
Store below 25°C. Store in the original package.
6.5
Nature and contents of container
100ml HDPE plastic container and tamper evident cap.
Pack contains 50 tablets
6.6
Special precautions for disposal
There are no special precautions for disposal. When the container is empty the label should be
removed and the container placed in a recycling bin
7
MARKETING AUTHORISATION HOLDER
Kerbina Limited
T/A Bio-Health
Culpeper Close
Medway City Estate
Rochester
Kent
ME2 4HU
8
MARKETING AUTHORISATION NUMBER(S)
THR 00904/0003
16
UKPAR Goodnight
9
THR 00904/0003
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
16/11/2010
10
DATE OF REVISION OF THE TEXT
16/11/2010
17
UKPAR Goodnight
THR 00904/0003
PRODUCT INFORMATION LEAFLET
18
UKPAR Goodnight
THR 00904/0003
19
UKPAR Goodnight
THR 00904/0003
20
UKPAR Goodnight
THR 00904/0003
21
UKPAR Goodnight
THR 00904/0003
LABELLING
Bottle label
Braille
22
UKPAR Goodnight
THR 00904/0003
Carton
23