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Microsoft word - cetirizine hydrochloride 10mg film-coated tablets pl 08137_0269.doc

UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
CETIRIZINE HYDROCHLORIDE 10MG FILM-COATED
TABLETS (PL 08137/0269)
TABLE OF CONTENTS
Scientific discussion Steps taken for assessment Steps taken after authorisation – summary Summary of Product Characteristics Product Information Leaflet UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
CETIRIZINE HYDROCHLORIDE 10MG FILM-COATED
TABLETS (PL 08137/0269)
LAY SUMMARY
On 13 October 2009, the MHRA granted Neolab Limited a Marketing Authorisation (licence) for the medicinal product Cetirizine Hydrochloride 10mg Film-Coated Tablets (PL 08137/0269). This is a pharmacy medicine (P) for the relief of symptoms of seasonal allergic rhinitis (e.g. hay fever), perennial allergic rhinitis (e.g. year round allergies often due to dust mites or animal allergies) and urticaria (itchy, red, swollen skin). These symptoms include itchy skin rashes; sneezing; itchy, runny or blocked nose; red, itchy and watering eyes. The active ingredient is cetirizine hydrochloride, which belongs to a group of medicines called antihistamines. No new or unexpected safety concerns arose from these applications and it was, therefore, judged that the benefits of taking Cetirizine Hydrochloride 10mg Film-Coated Tablets outweigh the risks, hence a Marketing Authorisation has been granted. UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
CETIRIZINE HYDROCHLORIDE 10MG FILM-COATED
TABLETS (PL 08137/0269)
SCIENTIFIC DISCUSSION
TABLE OF CONTENTS
Pharmaceutical assessment Preclinical assessment Clinical assessment (including statistical assessment) Overall conclusions and risk benefit assessment UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269

Based on the review of the data on quality, safety and efficacy, the UK granted a
marketing authorisation for the medicinal product Cetirizine Hydrochloride 10mg
Film-Coated Tablets (PL 08137/0269) on 13th October 2009. The product is a
Pharmacy medicine (P).

The application was submitted as simple abridged application according to article
10.1(c) of Directive 2001/83/EC, cross-referring to Cetirizine Hydrochloride 10mg
Film-Coated Tablets (PL 08137/0053) granted to Neolab Limited on 17th June 2002.
No new data were submitted nor was it necessary for this simple application, as the
data is identical to that of the previously granted cross-reference product. As the
cross-reference product was granted prior to the introduction of current legislation, no
PAR was generated.

Cetirizine Hydrochloride 10mg Film-Coated Tablets are indicated for the
symptomatic treatment of allergic rhinitis (seasonal and perennial) associated allergic
conjunctivitis (adults over 12 only), and chronic idiopathic urticaria.
The product contains the active substance cetirizine hydrochloride, which is one of a
group of medicines called antihistamines.

UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
PHARMACEUTICAL ASSESSMENT
LICENCE NO: PL 08137/0269
PROPRIETARY NAME: Cetirizine Hydrochloride 10mg Film-Coated Tablets
ACTIVE(S): Cetirizine hydrochloride
COMPANY NAME:
Neolab Limited
E.C. ARTICLE:
Article 10c (formerly 10.1(a)(i)) of Directive 2001/83/EC
LEGAL STATUS: P
1.
This is a simple, piggy back application for Cetirizine Hydrochloride 10mg Film-
Coated Tablets submitted under Article 10c (formerly 10.1(a)(i)) of Directive
2001/83/EC. The proposed MA holder is Neolab Limited, 57 High Street, Odiham,
Hants, RG29 1LF.
This application cross refers to Marketing Authorisation application for Cetirizine
Hydrochloride 10mg Film-Coated Tablets (PL 08137/0053), which is currently
registered in the UK. This application is considered valid.
2. MARKETING
AUTHORISATION APPLICATION FORM
2.1 Name(s)
The proposed name of the products is Cetirizine Hydrochloride 10mg Film-Coated
Tablets. The product has been named in line with current requirements.

2.2 Strength, pharmaceutical form, route of administration, container and pack
sizes
The product contains cetirizine hydrochloride, equivalent to 10mg. They are to be
stored in polyvinylchloride/aluminium foil blister packs contained in cardboard
cartons in pack sizes of 7 and 14 tablets.
The proposed shelf-life of 3 years, with no specific storage instructions is consistent
with the cross-reference product.

2.3 Legal status

On approval, the product will be subject to sale in a pharmacy only (P).
2.4 Marketing authorisation holder/Contact Persons/Company
The proposed Marketing Authorisation holder is Neolab Limited, 57 High Street,
Odiham, Hants, RG29 1LF.
The QP responsible for pharmacovigilance is stated and their CV is included.

2.5
Manufacturers
The proposed manufacturing sites are consistent with those registered for the
cross-reference product and evidence of GMP compliance has been provided.

2.6 Qualitative and quantitative composition
The proposed composition is consistent with the details registered for the
cross-reference product.
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
2.7 Manufacturing process
The proposed manufacturing process is consistent with the details registered for the
cross-reference product and the maximum batch size is stated.

2.8 Finished product/shelf-life specification

The proposed finished product specification is in line with the details registered for
the cross-reference product.
2.9 Drug substance specification
The proposed drug substance specification is consistent with the details registered for
the cross-reference product.
2.10 TSE Compliance
With the exception of lactose monohydrate, none of the excipients are sourced from
animal or human origins. The suppliers of lactose monohydrate have stated that the
lactose is sourced from healthy animals under the same conditions as milk for human
consumption.
3.

EXPERT REPORTS
The applicant has included detailed expert reports in Module 2 of the application.
Signed declarations and copies of the experts' CVs are enclosed in Module 1.4 for the
quality, non-clinical and clinical experts. All are considered to have sufficient
experience for their responsibilities.
4.

PRODUCT NAME & APPEARANCE
See 2.1 for details of the proposed product name. The appearance of the product is
identical to the cross-reference product.

5.

SUMMARY OF PRODUCT CHARACTERISTICS (SPC)
The proposed SPC is consistent with the details registered for the cross-reference
product.
6.

PATIENT INFORMATION LEAFLET/CARTON
PIL
The patient information leaflet has been prepared in-line with the details registered for
the cross-reference product.
Carton and blister
The proposed artwork is comparable to the artwork registered for the cross-reference
product and complies with statutory requirements. In line with current legislation the
applicant has also included sufficient space for a standard UK pharmacy dispensing
label.

7. CONCLUSIONS

The data submitted with the application are acceptable. The grant of a Marketing Authorisation is recommended. UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
PRECLINICAL ASSESSMENT
No new preclinical data have been supplied with this application and none are required for an application of this type. UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
CLINICAL ASSESSMENT
No new clinical data have been supplied with this application and none are required for an application of this type. UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
OVERALL CONCLUSION AND RISK-BENEFIT ASSESSMENT

QUALITY
The data for this application are consistent with that previously assessed for the
cross-reference product and as such have been judged to be satisfactory.
PRECLINICAL
No new preclinical data were submitted and none are required for an application of
this type.
EFFICACY
Cetirizine hydrochloride is a well-known drug and has been used as an antihistamine
for many years. This application is identical to a previously granted application for
Cetirizine Hydrochloride 10mg Film-Coated Tablets (PL 08137/0053), granted to
Neolab Limited on 17th June 2002.
No new or unexpected safety concerns arise from these applications.
The SPC, PIL and labelling are satisfactory and consistent with that for the
cross-reference product.
RISK BENEFIT ASSESSMENT
The quality of the product is acceptable and no new preclinical or clinical safety
concerns have been identified. The applicant's product is identical to the
cross-reference product. Extensive clinical experience with cetirizine hydrochloride is
considered to have demonstrated the therapeutic value of the compound. The
risk-benefit is, therefore, considered to be positive.
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
CETIRIZINE HYDROCHLORIDE 10MG FILM-COATED
TABLETS (PL 08137/0269)
STEPS TAKEN FOR ASSESMENT
The MHRA received the marketing authorisation applications on 21st January 2009 Following standard checks and communication with the applicant the MHRA considered the applications valid on 19th February 2009 Following assessment of the applications the MHRA requested further information on 17th April 2009 and 29th June 2009. The applicant responded to the MHRA's requests, providing further information on 6th May 2009 and 17th August 2009 The applications were determined on 13th October 2009 UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
CETIRIZINE HYDROCHLORIDE 10MG FILM-COATED
TABLETS (PL 08137/0269)
STEPS TAKEN AFTER AUTHORISATION - SUMMARY
Application Scope Outcome
submitted type

UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
NAME OF THE MEDICINAL PRODUCT
Cetirizine hydrochloride 10 mg film-coated tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains cetirizine hydrochloride 10 mg.
Each tablet contains 100.20 mg of lactose monohydrate.
For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL
Film-coated tablet. White, round tablets with a break line on one side and embossed with A on the other.
4 CLINICAL
PARTICULARS
4.1 Therapeutic
indications
Adults and adolescents over 12 years of age: Symptomatic treatment of allergic rhinitis (seasonal and perennial) associated allergic conjunctivitis, and chronic idiopathic urticaria. Children 6-12 years: Symptomatic treatment of allergic rhinitis (seasonal and perennial), and chronic idiopathic urticaria. Posology and method of administration
Adults and adolescents over 12 years of age: 1 tablet (10 mg) once daily.
If drowsiness occurs, the tablet can be administered in the evening.
Children 6-12 years:
1 tablet (10 mg) once daily or ½ tablet (5mg) taken twice daily (morning and evening)
For children weighing less than 30 kg:
½ tablet (5mg) taken once daily.
Clinical trials in children have not exceeded four weeks.
Cetirizine is contraindicated in patients with severe renal impairment. In patients with
moderate renal impairment the dose should be adjusted to 5 mg (½ tablet a day). Caution
should be exercised in patients with mild to moderate renal impairment or impaired liver
function.(see 4.4 Special warning and precautions for use).
There is no evidence that the dose needs to be modified for healthy elderly patients.
The duration of the treatment may vary depending on the symptoms.

4.3 Contraindications
Cetirizine hydrochloride 10 mg film coated tablets are contraindicated in - patients with hypersensitivity to cetirizine hydrochloride or to any of the excipients - In children under six years of age - Patients with severe renal impairment Special warnings and precautions for use
In some patients, long term treatment with cetirizine tablets may lead to an increased risk of
caries due to mouth dryness. The patients should therefore be informed about the importance
of oral hygiene.
At impaired hepatic function and renal function, the elimination of cetirizine may be impaired.
Caution should be exercised when administering cetirizine to these patients. (see section 4.2
posology and section 4.3 contraindications).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
Cetirizine may potentiate the effects of alcohol. Therefore caution is recommended at concomitant use of alcohol. Caution is recommended with concomitant use of CNS depressants. Interaction with other medicinal products and other forms of interaction
Allergy testing: Use of cetirizine must be discontinued three days before allergy tests.
Cetirizine may potentiate the effects of alcohol. Therefore caution is recommended at
concomitant use of alcohol. Caution is recommended with the concomitant use of CNS
depressants.

4.6 Pregnancy
lactation
Data on limited number of exposed pregnancies indicate no adverse effects of cetirizine on pregnancy or on health of foetus/new born child. To date no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / foetal development, parturition or post natal development (see section 5.3). Caution should be exercised when prescribing to pregnant women. Breast feeding No data concerning the excretion of cetirizine into human milk are available. Cetirizine should be avoided during lactation. Effects on ability to drive and use machines
Cetirizine may have minor or moderate influence on the patient's ability to drive and use
machines.
This should be considered when extra alertness is required e.g. when driving. Cetirizine may
potentiate the effects of alcohol and CNS depressants.

4.8 Undesirable
Frequency estimates: Common (>1/100, <1/10); Uncommon (>1/1,000, <1/100); Rare (>1/10,000, <1/1,000); Very rare (<1/10,000): Blood and lymphatic system disorders: Very rare: thrombocytopenia Immune system disorders: Rare: Allergic reactions (see Skin and subcutaneous disorders) Very rare: Anaphylactic shock Psychiatric disorders: Uncommon : Agitation Rare: Aggression, confusion, depression, hallucination, insomnia Nervous system: Common: Somnolence, drowsiness Uncommon: Headache, dizziness, paraesthesia. Rare: Convulsions, movement disorders Very rare : Dysgeusia, syncope Eye disorders: Very rare: Accommodation disorder, blurred vision Cardiac disorders: Rare: Tachycardia Gastrointestinal disorders: UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
Common: dry mouth Uncommon: gastrointestinal disorders (nausea, diarrhoea, abdominal pain, dyspepsia) Hepatobiliary disorders: Rare: Abnormal hepatic function (increased transaminases, alkaline phosphatase, gamma-GT, bilirubin) Skin and subcutaneous tissue disorders: Uncommon : Skin rash, pruritus Rare: Urticaria Very rare: Angioedema, erythema multiforme Renal and urinary disorders: Very rare: Dysuria, enuresis, micturition difficulties General disorders: Uncommon: asthenia, malaise Rare: Oedema, weight increase
4.9 Overdose
There is limited experience of overdosing. 20 mg to a 2-year-old, 30 mg to a 3-year-old and 40 mg to an 11-year-old did not give any symptoms. 60 mg to a 4-year-old gave mild intoxication, 400 mg to a 14-year-old gave mild symptoms, while 400 to 500 mg to an adult gave no symptoms at all. a) Symptoms Cetirizine has a low sedative and anticholinergic effect. Adverse events reported after intake of at least five times the recommended daily dose are confusion, diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, restlessness, sedation, somnolence, stupor, tachycardia, tremor and urinary retention. b) Management Should overdose occur, symptomatic or supportive measures are recommended. The patient should be kept under clinical observation for at least four hours after ingestion, and the blood pressure, heart rate and vital signs monitored until stable. In symptomatic cases, ECG should be performed. The benefit of gastric lavage is uncertain. Oral activated charcoal (50 g for an adult, 10-15 g for a child) should be considered if more than 2.5 mg/kg cetirizine has been ingested within one hour, There is no specific antidote. Cetririzine is not effectively removed by dialysis 5 PHARMACOLOGICAL
PROPERTIES
5.1 Pharmacodynamic
properties
ATC code: R06AE07 Pharmacotherapeutic group: Antihistamine for systemic use, piperazine derivative Cetirizine hydrochloride is a racemate and an anti-allergic with specific histamine H1-receptor blocking characteristics. Cetirizine inhibits cutaneous reactions in allergic individuals by VIP (Vasoactive Intestinal Polypeptide) and the P substance, neuropeptides that are considered involved in the allergic reaction. Effect is reached within 2 hours with a maximum effect after 4 hours, and remains for at least 24 hours. In allergic individuals, cetirizine inhibits the recruitment of eosinophiles after simulation with allergens and unselective histamine liberators, by a mechanism that is not primarily explained by the H1-receptor blocking characteristics of the pharmaceutical. UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
5.2 Pharmacokinetic
properties
Cetirizine is absorbed with small inter-individual variations. Cetirizine has not been given intravenously, therefore the bioavailability, clearance and distribution volume (Vd) are unknown. Maximum plasma concentration is achieved within 1 hour and the terminal half-life is about 10 hours in adults and 6 hours in children between ages of 6-12 years. The grade of protein binding in plasma is about 93%. Cetirizine is metabolised to a small extent with a known inactive main metabolite. Cetirizine is eliminated to 60% in unchanged form via the kidneys within 96 hours. At repeated administration there is no accumulation at hand, nor is absorption or elimination affected. With impaired kidney function, the elimination is slower and the half-life is prolonged. Elimination will also be decreased in cases of hepatic impairment. There is no evidence that the pharmacokinetics of cetirizine is altered in elderly patients unless renal or hepatic function is reduced. Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, toxicity to reproduction, genotoxicity or
carcinogenicity.

6 PHARMACEUTICAL
PARTICULARS
List of excipients
Tablet core
Lactose monohydrate
Microcrystalline cellulose
Colloidal anhydrous silica
Maize starch
Talc
Magnesium stearate
Coating
Titanium dioxide (E171)
Hypromellose
Lactose monohydrate
Macrogol
Sodium citrate

6.2 Incompatibilities

6.3 Shelf
Special precautions for storage
No special precautions for storage.
Nature and contents of container
Blister comprising of PVC/Aluminium foil with 7, and 14 tablets.
Not all packs may be marketed.
Special precautions for disposal
No special requirements.

7 MARKETING
AUTHORISATION HOLDER
Neolab Limited 57 High Street Odiham Hants RG29 1LF UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
8 MARKETING
AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
DATE OF REVISION OF THE TEXT
13/10/2009
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269
UKPAR Cetirizine Hydrochloride 10mg Film-Coated Tablets
PL 08137/0269

Source: http://www.kentpharmaco.com/www.mhra.gov.uk/home/groups/par/documents/websiteresources/con062894.pdf

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