Page 1 of 23

PROPOSED PACKAGE INSERT

SCHEDULING STATUS

Schedule 3

PROPRIETARY NAME AND DOSAGE FORM

LYRINEL® 5 mg tablet (prolonged-release tablet)

LYRINEL® 10 mg tablet (prolonged-release tablet)

COMPOSITION

LYRINEL 5 mg prolonged-release tablet contains Oxybutynin hydrochloride 5 mg

LYRINEL 10 mg prolonged-release tablet contains Oxybutynin hydrochloride 10 mg

Contains the antioxidant, butylated hydroxytoluene.

The other ingredients are cellulose acetate, hypromellose, macrogol 3350, magnesium stearate,

polyethylene oxide, sodium chloride, black iron oxide (E172), lactose anhydrous, macrogol 400,

polysorbate 80, propylene glycol and titanium dioxide (E171).

The yellow 5 mg tablet also contains ferric oxide yellow (E172).

The pink 10 mg tablet also contains ferric oxide red (E172).

PHARMACOLOGICAL CLASSIFICATION

A 5.4 Cholinolytics (anticholinergics)

PHARMACOLOGICAL ACTION

Pharmacodynamics

Oxybutynin hydrochloride is a synthetic tertiary amine with direct spasmolytic and anticholinergic

action on the smooth musculature of the detrusor muscle of the bladder.

Pharmacokinetics

Following the first dose of oxybutynin hydrochloride in LYRINEL, oxybutynin plasma concentrations

rise for 4 to 6 hours; thereafter steady concentrations are maintained for up to 24 hours.

Page 2 of 23

The relative bioavailabilities of R-oxybutynin and S-oxybutynin from oxybutynin hydrochloride in

LYRINEL are 156% and 187% respectively, compared with oxybutynin. After a 10 mg single dose of

oxybutynin hydrochloride, the peak plasma concentrations of R-oxybutynin and S-oxybutynin,

achieved after 12,7 ± 5,4 and 11,8 ± 5,3 hours respectively, are 1,0 ± 0,6 and 1,8 ± 1,0 ng/ml, and

the plasma concentration time profiles of both enantiomers are similar in shape. The elimination

half-life is 13,2 ± 10,3 hours for R-oxybutynin and 12,4 ± 6,1 hours for S-oxybutynin.

Steady state oxybutynin plasma concentrations are achieved by day 3 of repeated oxybutynin

hydrochloride dosing with no observed medicine accumulation or change in oxybutynin and

desethyloxybutynin pharmacokinetic parameters.

The pharmacokinetic parameters of oxybutynin and desethyloxybutynin (Cmax and AUC) are dose

proportional following administration of 5 – 20 mg of oxybutynin hydrochloride.

The pharmacokinetics of oxybutynin hydrochloride was similar in all patients studied irrespective

of gender or age and are unaffected by food intake.

Limited data suggests that the pharmacokinetics of oxybutynin hydrochloride prolonged release

tablets is similar in adults and children (aged 6 years and above).

The pharmacokinetics of oxybutynin hydrochloride prolonged release tablets have not been

investigated in patients with renal or hepatic insufficiency.

Oxybutynin is extensively metabolised by the liver, primarily by the cytochrome P450 enzyme

system, particularly CYP3A4 found mostly in the liver and gut wall. Less than 0,1 % of the

administered dose is excreted unchanged in the urine. Its metabolic products include

phenylcyclohexylglycolic acid, which is pharmacologically inactive, and desethyloxybutynin, which

is pharmacologically active.

Page 3 of 23

INDICATIONS

Adults and the Elderly:

Urinary urgency, incontinence and frequency in patients with unstable bladder conditions.

Paediatrics:

LYRINEL is also indicated in the treatment of paediatric patients aged 6 years and older with

symptoms of detrusor overactivity associated with a neurological condition (e.g., spina bifida).

CONTRA-INDICATIONS

- Hypersensitivity to oxybutynin or any of the excipients

- Narrow-angle glaucoma or shallow anterior chamber

- Myasthenia gravis

- Patients with bladder outflow obstruction where urinary retention may be precipitated

- Gastrointestinal obstructive disorder, paralytic ileus or intestinal atony

- Severe ulcerative colitis

- Toxic megacolon

- Severely impaired liver/renal function.

- Porphyria

WARNINGS

LYRINEL is associated with anticholinergic central nervous system (CNS) effects. Patients should be

monitored for signs of anticholinergic CNS effects, particularly in the first few months after

beginning treatment or increasing the dose. If a patient experiences anticholinergic CNS effects,

dose reduction or discontinuation of LYRINEL should be considered.

LYRINEL should be used with caution in the frail elderly who may be more sensitive to the effects

of oxybutynin, in patients with gastrointestinal motility disorders, particularly gastroesophageal

reflux, and in patients with hepatic or renal impairment.

Safety and efficacy have not been established in children younger than 6 years of age.

Page 4 of 23

LYRINEL should be used with caution in patients with pre existing dementia treated with

cholinesterase inhibitors due to the risk of aggravation of symptoms

INTERACTIONS

Care should be taken if other anticholinergic agents are used together with oxybutynin, as

potentiation of anticholinergic effects may occur.

Interaction between anticholinergics and phenothiazines, amantadine, butyrophenones, L-dopa,

digitalis and tricyclic antidepressants have been reported and care should be taken if LYRINEL is

used concurrently with such medicines. By reducing gastric motility, LYRINEL may affect the

absorption of other medicines.

Mean LYRINEL plasma concentrations were [approximately 2 fold] higher when LYRINEL was

administered with ketoconazole, a potent CYP3A4 inhibitor. Other inhibitors of the cytochrome

P450 3A4 enzyme system, such as antimycotic agents (e.g., itraconazole and miconazole) or

macrolide antibiotics (e.g., erythromycin and clarithromycin), may increase LYRINEL mean

pharmacokinetic parameters (i.e., Cmax and AUC). Caution should be used when such medicines are

coadministered.

PREGNANCY AND LACTATION

Insufficient data exists to evaluate the possible harmful effects of LYRINEL during pregnancy in

humans. LYRINEL should not be used during pregnancy.

When oxybutynin is used during lactation a small amount is excreted in the mother’s milk. Breast

feeding while using LYRINEL is therefore not recommended as oxybutynin is excreted in

breastmilk.

DOSAGE AND DIRECTIONS FOR USE

Dosage

Adults and elderly:

Starting dose: the recommended initial dosage is one 5 mg tablet once daily for at least 1 week.

Page 5 of 23

Dosage adjustment: the dosage may be increased or subsequently decreased in increments of 5

mg weekly to achieve a maintenance dose giving an optimal balance of efficacy and tolerability.

Maintenance dose: the recommended maintenance dose is 10 mg once daily for most patients.

Maximum dose: 20 mg once daily.

Children over the age of 6 years:

Initial dose, of 5 mg once a day. The dose can be increased at weekly intervals in 5 mg increments

up to a maximum of 15 mg once a day.

The safety and efficacy of LYRINEL has not been established in patients less than 6 years of age.

Method of administration

LYRINEL must be swallowed whole with the aid of liquid, and must not be chewed, divided, or

crushed.

Patients should be advised that the tablet membrane may pass through the gastrointestinal tract

unchanged. This has no bearing on the efficacy of LYRINEL.

LYRINEL may be administered with or without food.

SIDE EFFECTS AND SPECIAL PRECAUTIONS

Clinical Trial Data

Adverse events reported by subjects participating in six trials of LYRINEL for treatment of overactive

bladder are presented in Table 1. A total of 1006 subjects were treated with LYRINEL (5-30 mg/day)

from 3 to up to 23 weeks in these trials. Included in the table are adverse events, regardless of

investigator assessment of causality.

Very common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to

<1/100

Rare

≥1/10,000 to

<1/1000

Not

Known

Infections and

infestations

Urinary tract

infection,

cystitis,

pharyngitis

nasopharyn-

Page 6 of 23

Very common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to

<1/100

Rare

≥1/10,000 to

<1/1000

Not

Known

gistis,upper

respiratory tract

infection,

bronchitis,

sinusitis

Blood and

Lymphatic

system

disorders

Leucopenia,

thrombocyto-

penia

Immune

System

Disorders

Hypersensitivity

Metabolism &

Nutritional

Disorders

Anorexia,

dehydration,

hyperglycaemia

Increased

appetite

Psychiatric

disorders

Insomnia,

depression,

nervousness,

confusional

state

Anxiety,

abnormal

dreams

Night terror

Nervous

System

Disorders

Somnolence,

headache,

dizziness,

dysgeusia

Paraesthesia,

vertigo

Hypertonia,

tremor,

tinnitus

Eye Disorders Blurred vision,

dry eye,

keratoconjunc-

tivitis sicca

Conjunctivitis Diplopia,

glaucoma,

photophobia

Cardiac

Disorders

Palpitations Atrial

dysrhythmia,

bradycardia,

bundle branch

block,nodal

dysrhythmia,

supraventricular

extrasystoles

Vascular Hypertension Vasodilation, Hypotension,

Page 7 of 23

Very common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to

<1/100

Rare

≥1/10,000 to

<1/1000

Not

Known

Disorders migraine phlebitis,

ecchymosis

Respiratory

thoracic and

mediastinal

disorders

Nasal dryness,

mucosal

dryness,

cough,

pharyngolaryn-

geal pain,

dry throat

Rhinitis,

hoarseness,

epistaxis,

dyspnoea

Laryngitis,

laryngeal

oedema,

respiratory

disorder,

sputum

increased

Gastrointestin

al Disorders

Dry mouth Constipation,

diarrhoea,

nausea,

dyspepsia,

abdominal

pain,

flatulence,

gastroesophag-

eal reflux

disease,

loose stools,

vomiting

Dysphagia,

mouth

ulceration,

abdominal

distension,

glossitis,

stomatitis

Aquired

oesophageal

stenosis,

gastritis,

viral

gastroenterititis ,

hernia, rectal

disorder,

gastric

atony,tongue

disorder,tongue

oedema

Skin and

subcutaneous

tissue

disorders

Dry

skin,pruritus

Acne,urticaria,

face oedema,

alopecia,

eczema,nail

disorder,skin

discolouration,

anhidrosis

Hair

disorder,rash

macula-

papular,granulo-

ma,

sweating,

increased

photosensitivity

reaction

Musculoskelet

al and

connective

tissue

disorders

Pain in

extremity,

back

pain,arthralgia

Muscle

cramps,myalgia

Arthritis

Page 8 of 23

Very common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to

<1/100

Rare

≥1/10,000 to

<1/1000

Not

Known

Renal and

urinary

disorders

Micturition

disorder,

residual urine

volume,urinary

retention,

dysuria,

urinary

hesitation

Urinary

frequency,

urinary tract

disorder,

haematuria,

nocturia,

pyuria,

micturition

urgency

Urinary

incontinence,

abnormal urine ,

urogenital

disorder

Erectile

dysfunction

Reproductive

system and

breast

disorders

Breast

pain,vaginitis

Vulvovaginal

disorder,

uterine cervical

disorder,genital

discharge

General

disorders and

administration

site

conditions

Asthenia,

peripheral

oedema,

fatigue,

chest pain

Pain, thirst,

oedema

Rigor,pyrexia,in-

fluenza-like

illness,malaise,

pelvic pain

Investigations Blood pressure

increased

Abnormal elec-

trocardiogram,

increased

blood urea,

increased

blood

creatinine

Increased blood

alkaline

phosphatase,

increased blood

lactase

deshydro-

genase,

increased blood

aspartate,

aminotrans-

ferase,

Postmarketing Data

Additional adverse drug reactions were obtained from spontaneous reports during worldwide

postmarketing surveillance of LYRINEL and are presented below.

Psychiatric Disorders

Page 9 of 23

Hallucinations

Psychotic disorder, agitation, memory impairment

Nervous System Disorders

Convulsions

Cardiac Disorders

Dysrhythmia, tachycardia

Vascular Disorders

Flushing

Skin and Subcutaneous Tissue Disorders

Rash

Renal and Urinary Disorders

Impotence

Injury, poisoning and procedural complications

Fall

Undesirable effects noted with other oxybutynin hydrochloride formulations

In addition, cyclopegia, mydriasis and suppression of lactation have been reported with the use of

other oxybutynin hydrochloride formulations.

Special precautions

LYRINEL may aggravate the symptoms of hyperthyroidism, congestive heart failure, cardiac

dysrhythmia, tachycardia, hypertension and prostatic hypertrophy.

When LYRINEL is used in high environmental temperatures this can cause heat prostration due to

decreased sweating. Because the tablets have a non-absorbable shell, caution should be used

when administering LYRINEL to patients with pre-existing gastrointestinal narrowing.

Effects on Ability to Drive and Use Machines

As LYRINEL may produce drowsiness or blurred vision, the patient should be cautioned regarding

activities requiring mental alertness such as driving, operating machinery or performing hazardous

work while taking LYRINEL.

Page 10 of 23

Lactose: Each tablet contains 0,03 mg lactose. Patients with rare hereditary problems of galactose

intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take

LYRINEL.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

The symptoms of overdosage with LYRINEL progress from an intensification of the usual CNS

disturbances (from restlessness and excitement to psychotic behaviour), circulatory changes

(flushing, fall in blood pressure, circulatory failure ext.), respiratory failure, paralysis and coma.

Measures to be taken:

1. immediate gastric lavage

2. physostigmine by slow intravenous injection:

Adults: 0,5 to 2,0 mg i.v. slowly, repeated after 5 minutes if necessary, up to a maximum of

5 mg.

Children: 30 μg/kg i.v. slowly, repeated if necessary, up to a maximum of 2 mg.

Fever should be treated symptomatically with tepid sponging or ice packs.

In pronounced restlessness or excitation, diazepam 10 mg may be given by intravenous injection.

Tachycardia may be treated with intravenous propranolol and urinary retention managed by bladder

catheterization.

In the event of progression of curare-like effects to paralysis of the respiratory muscles,

mechanical ventilation will be required.

The continuous release of oxybutynin from LYRINEL should be considered in the treatment of

overdosage. Patients should be monitored for at least 24 hours.

IDENTIFICATION

LYRINEL 5 mg: round yellow coloured tablet printed with “5XL” in black ink.

Page 11 of 23

LYRINEL 10 mg: round pink coloured tablet printed with “10XL” in black ink.

PRESENTATION

High density polyethylene bottles with child resistant closure and desiccant. Tablets are packed in

bottles containing 30 tablets.

STORAGE INSTRUCTIONS

Keep the container tightly closed. Protect from moisture and humidity.

Store below 25 °C. Keep out of reach of children.

REGISTRATION NUMBER

South Africa

LYRINEL 5 mg: A39/5.4/0212

LYRINEL 10 mg: A39/5.4/0224

Nam Reg. No.:

LYRINEL 5 mg: 09/5.4/0002

LYRINEL 10 mg: 09/5.4/0003

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION

JANSSEN PHARMACEUTICA (Pty.) Ltd.

(Reg No.: 1980/011122/07)

Building 6, Country Club Estate,

21 Woodlands Drive, Woodmead, 2191

Tel: +27 (11) 518 7000

www.janssen.co.za

DATE OF PUBLICATION OF THE PACKAGE INSERT

November 2011

Page 12 of 23

FINALE VOUBILJET

SKEDULERINGSTATUS

S3

EIENDOMSNAAM EN DOSEERVORM

LYRINEL® 5 mg tablet (langwerkende vrystellingstablet)

LYRINEL® 10 mg tablet (langwerkende vrystellingstablet)

SAMESTELLING

LYRINEL 5 mg langwerkende vrystellingstablet bevat Oksibutinienhidrochloried 5 mg

LYRINEL 10 mg langwerkende vrystellingstablet bevat Oksibutinienhidrochloried 10 mg

Bevat die antiöksidant, gebutileerde hidroksitolueen.

Die ander bestandele is: Sellulose asetaat, hipromellose, macrogol 3350, magnesiumstearaat,

poliëtileenoksied, natriumchloried, swart ysteroksied (E172), laktose anhidries, macrogol 400,

polisorbaat 80, propileenglikool, and titaandioksied (E171).

Die geel 5 mg tablet bevat ook geel ysteroksied (E172)

Die pienk 10 mg tablet bevat ook rooi ysteroksied (E172)

FARMAKOLOGIESE KLASSIFIKASIE

A 5.4 Cholinolitika (anticholinergiese middels)

FARMAKOLOGIESE WERKING

Farmakodinamika

Oksibutinienhidrochloried is ‘n sintetiese tersiêre amien met direkte spasmolitiese en

anticholinergiese werking op die gladde spierstelsel van die detrusorspier van die blaas.

Farmakokinetika

Page 13 of 23

Na die eerste dosis van oksibutinienhidrochloried in LYRINEL styg oksibutinien -

plasmakonsentrasies vir 4 tot 6 ure; daarna word bestendige konsentrasies tot 24 uur lank

gehandhaaf.

Die relatiewe biobeskikbaarheid van R-oksibutinien en S-oksibutinien uit LYRINEL is respektiewelik

156 % en 187 %, vergeleke met oksibutinien. Ná ‘n 10 mg enkeldosis oksibutinienhidrochloried, is

die piek plasmakonsentrasies van R-oksibutinien en S-oksibutinien 1,0 ± 0,6 en 1,8 ± 1,0 ng/ml,

wat respektiewelik ná 12,7 ± 5,4 en 11,8 ± 5,3 uur bereik word, en is die vorm van die

plasmakonsentrasie-tydprofiele van albei enantiomere eenders. Die eliminasie halfleeftyd is 13,2

± 10,3 uur vir R-oksibutinien en 12,4 ± 6,1 uur vir S-oksibutinien.

Stabiele-staat oksibutinien plasmakonsentrasies word teen Dag 3 van herhaaldelike LYRINEL

doserings bereik, met geen waarneembare geneesmiddel akkumulasie of verandering in

oksibutinien en desetieloksibutinien farmakokinetiese parameters nie.

Die farmakokinetiese parameters van oksibutinien en desetieloksibutinien (Kmaks en AOK) is

proporsioneel tot die dosis na toediening van 5 – 20 mg oksibutinienhidrochloried.

Die farmakokinetika van oksibutinien was eenders onder alle pasiënte wat bestudeer was, ongeag

geslag of ouderdom en was nie deur voedselinname beïnvloed nie.

Beperkte data dui daarop dat die farmakokinetika van oksibutinienhidrochloried langwerkende

vrystellingstablette dieselfde is by volwassenes as by kinders (6 jaar en ouer).

Die farmakokinetika van oksibutinienhidrochloried langwerkende vrystellingstablette is nie

ondersoek by patiente met nier- of lewerontoereikendheid nie.

Oksibutinien word uitgebreid deur die lewer gemetaboliseer, hoofsaaklik deur die sitochroom

P450 ensiemstelsel, veral CYP3A4, wat hoofsaaklik in die lewer en dermwand aangetref word.

Minder as 0,1 % van die toegediende dosis word onveranderd in die urine uitgeskei. Metaboliese

Page 14 of 23

produkte sluit in fenielsikloheksielglikoolsuur, wat farmakologies onaktief is, en

desetieloksibutinien, wat farmakologies aktief is.

INDIKASIES

Volwassenes en bejaardes:

Urinêre drang, inkontinensie en frekwensie by pasiënte met onstabiele blaastoestande.

Pediatrie

LYRINEL word ook aangedui by die behandeling van pediatriese pasiënte van 6 jaar en ouer met

simptome van ’n ooraktiewe detrusor, geassosieer met ’n neurologiese toestand (bv. spina bifida).

KONTRA-INDIKASIES

Hipersensitiwiteit vir oksibutinien of enige van die mengmiddels

Nouhoek - gloukoom of vlak anterior kamer

Myasthenia gravis

Pasiënte met blaas uitvloei obstruksie waar urienretensie gepresipiteer kan wees

Gastroïntestinale obstruktiewe aandoening, paralitiese ileus of intestinale atonie

Erge ulseratiewe kolitis

Toksiese megakolon

Ernstig belemmerde lewer/nierfunksie.

Porfirie

WAARSKUWINGS

LYRINEL word geassosieer met anticholinergiese sentrale senuweestelsel (SSS) effekte. Pasiënte

moet gemoniteer word vir tekens van anticholinergiese SSS-effekte, veral tydens die eerste paar

maande vandat behandeling begin is, of die dosis verhoog is. Indien ’n pasiënt anticholinergiese

SSS-effekte ervaar, moet dosis vermindering of staking van die geneesmiddel oorweeg word.

Oksibutinien moet met omsigtigheid gebruik word by verswakte bejaardes wat meer gevoelig kan

wees vir die effekte van oksibutinien, by pasiënte met gastroïntestinale motiliteitsaandoenings,

Page 15 of 23

veral gastroësofageale refluks, en by pasiënte met lewer- of nierinkorting. Die veiligheid en

doeltreffendheid is nog nie by kinders onder 6 jaar oud vasgestel nie.

As gevolg van die risiko om die simptome te vererger, moet LYRINEL met omsigtigheid gebruik

word by pasiënte met reeds bestaande demensie, wat behandel word met cholienesterase

remmers.

INTERAKSIES

Versigtigheid moet aan die dag gelê word indien ander anticholinergiese middels tesame met

LYRINEL gebruik word, aangesien potensiëring van anticholinergiese effekte kan voorkom.

Gevalle van interaksie tussen anticholinergika en fenotiasiene, amantadien, butirofenone, L-dopa,

digitalis en trisikliese antidepressante is aangemeld en sorg moet geneem word indien LYRINEL

gelyktydig met dergelike middels gebruik word. Deur verlaging van gastriese motiliteit kan

LYRINEL die absorpsie van ander geneesmiddels affekteer.

Die gemiddelde LYRINEL plasmakonsentrasies was [ongeveer twee keer] hoër wanneer LYRINEL

saam met ketokonasool, ’n kragtige CYP2A4-remmer, toegedien is. Ander remmers van die

sitochroom P450 3A4 ensiemstelsel, soos swambestrydende middels (bv. itrakonasool en

mikonasool), of makroliede antibiotika (bv. eritromisien en klaritromisien), kan die gemiddelde

farmakokinetiese parameters (d.i. Kmaks en AOK) van LYRINEL verhoog. Versigtigheid moet aan die

dag gelê word as sulke geneesmiddels saam toegedien word.

SWANGERSKAP EN LAKTASIE

Daar bestaan nie voldoende data om die moontlike skadelike effekte van LYRINEL gedurende

swangerskap in mense te bepaal nie. LYRINEL moet nie tydens swangerskap gebruik word nie.

Wanneer oksibutinien gedurende swangerskap gebruik word, word ‘n klein hoeveelheid in die

moedersmelk uitgeskei. Borsvoeding word dus nie aanbeveel terwyl oksibutinien gebruik word

nie.

Page 16 of 23

DOSIS EN GEBRUIKSAANWYSINGS

Dosis

Volwassenes en bejaardes

Aanvangsdosis: die aanbevole aanvanklike dosis is een 5 mg tablet een keer per dag vir ten minste

1 week.

Dosisaanpassing: die dosis kan verhoog of daarna verlaag word met inkremente van 5 mg per

week om ‘n onderhoudsdosis te bereik wat optimale balans tussen doeltreffendheid en

verdraagbaarheid bied.

Onderhoudsdosis: die aanbevole onderhoudsdosis is 10 mg een keer per dag by die meeste

pasiënte.

Maksimumdosis: 20 mg een keer per dag.

Kinders ouer as 6 jaar:

Die aanvangsdosis is 5 mg een keer per dag. Hierdie dosis kan met weeklikse intervalle

inkrementeel met 5 mg verhoog word tot by ’n maksimum van 15 mg een keer per dag.

Die veiligheid en doeltreffenfheid van LYRINEL is nog nie by kinders jonger as 6 jaar oud vasgestel

nie.

Metode van toediening

LYRINEL moet heel ingesluk word met behulp van vloeistof en moet nie gekou, verdeel of

fyngemaak word nie.

Pasiënte moet geadviseer word dat die tabletmembraan onveranderd deur die maagdermkanaal

kan gaan. Dit het geen betrekking op die doeltreffendheid van LYRINEL nie.

LYRINEL kan met of sonder voedsel toegedien word.

NEWE-EFFEKTE EN SPESIALE VOORSORGMAATREËLS

Kliniese proef data

Page 17 of 23

Ongunstige reaksies wat deur proefpersone in ses proewe met LYRINEL vir behandeling van

ooraktiewe blaas aangemeld is, word in Tabel 1 weergegee. Daar is tydens hierdie proewe

altesaam 1006 proefpersone behandel met LYRINEL (5-30 mg/dag) vanaf 3 tot en met 23 weke.

Ongunstige reaksies, ongeag die navorser se bepaling van die oorsaak, is by hierdie tabel ingesluit .

Baie

algemee

n

≥1/10

Algemeen

≥1/100 to <1/10

Ongewoon

≥1/1,000 to

<1/100

Skaars

≥1/10,000 to

<1/1000

Onbekend

Infeksies en

infestasies

Urienweg-

infeksie,

Sistitis,

Faringitis

Nasofaringitis

Boonste

lugweginfeksie,

Brongitis,

Sinusitis

Bloed- en

limfstelsel

versteurings

Leukopenie,

Trombosito-

penie

Immuunstelsel

versteurings

Hipersensiti-

witeit

Metabolisme- en

voedingsver-

steurings

Anoreksie,

Dehidrasie,

hiperglukemie

Eetlus

verhoog

Psigiatriese

versteurings

Slaaploosheid

Depressie,

Senuweeagtigheid,

Verwarde toestand

Angs,

Abnormale

drome

Nag-angs

Senuweestel-

selversteurings

Lomerigheid,

Hoofpyn,

Duiseligheid,

Disgeusie

Parestesie,

vertigo

Hipertonie,

Tremor,

tinnitus

Oogversteurings Dowwe visie,

Droë oog,

Keratokonjunktivitis

sicca

Konjunktivitus Diplopie,

Gloukoom,

fotofobie

Page 18 of 23

Baie

algemee

n

≥1/10

Algemeen

≥1/100 to <1/10

Ongewoon

≥1/1,000 to

<1/100

Skaars

≥1/10,000 to

<1/1000

Onbekend

Hartversteurings Palpitasies Atriale

disritmie,

Bradikardie,

Takbondel-

blok,

knoop

aritmie,

supra-

ventrikulêre

ekstrasistolie

Vaskulêre

versteurings

Hipertensie Vasodilatasie,

migraine

Hipotensie,

Flebitis,

Ekchimose

Respiratoriese-,

bors- en

mediastinum-

versteurings

Droogheid van

neus,

Slymvlies

droogheid,

Hoes,

Faringolaringeale

pyn,

Droë keel

Rinitis,

Heesheid,

epistakse,

dispnee

Laringitis,

laringeale

edeem,

respiratoriese

versteuring,

sputum

vermeerder

Gastroïntestinale

versteurings

Droë

mond

Hardlywigheid,

Diarree,

Naarheid,

Dispepsie,

Buikpyn,

Winderigheid,

Gastroësofageale

refluks siekte,

Los stoelgang,

Braking

Disfagie,

Mondsere,

Opgesette buik

Glossitis,

Stomatitis

Esofageale

stenose -

verworwe,

Gastritis,

Gastroënteriti

tis viraal,

Hernia,

rektale

versteuring,

Gastriese

atonie, Tong

versteuring,

Tong edeem

Page 19 of 23

Baie

algemee

n

≥1/10

Algemeen

≥1/100 to <1/10

Ongewoon

≥1/1,000 to

<1/100

Skaars

≥1/10,000 to

<1/1000

Onbekend

Vel- en

onderhuidse

weefsel

versteurings

Droë vel,

Pruritis

Aknee,urtikaria,

Gesigsedeem,

Alopesie,

Ekseem, Nael

siekte, Vel

verkleuring,

Anhidrose

Haar

versteuring,

Uitslag

makulo-

papulêr,

Granuloom,

Sweet meer,

Fotosensitiwit

eitsreaksie

Skeletspier- en

bindweefsel

versteurings

Pyn in ledemate,

Rugpyn,

Artralgie

Spierkrampe,

Mialgie

Artritis

Nier- en

urienweg

versteurings

Mikturisie

versteuring,

Residuele urinêre

volume, Urinêre

retensie,

Disurie,

Urinêre huiwering

Urinêre

frekwensie,

Urienweg

versteuring,

Hematurie,

Nokturie,

Piurie,

Dwangurie

Urinêre

inkontinensie,

Uriene

abnormaal,

Urogenitale

versteuring

Ereksie

disfunksie

Voortplantingstel

sel en

borsversteuring

Borspyn,

vaginitis

Vulvovaginale

versteuring,

Uterus-

serviks

versteuring,

Genitale

afskeiding

Algemene - en

toedieningsplek

versteurings

Astenie,

Perifere edeem,

Moegheid,

Borspyn

Pyn, Dors,

Edeem

Rigor,

Griepagtige

ongesteldheid

, Onwel

gevoel,

Bekken pyn

Page 20 of 23

Baie

algemee

n

≥1/10

Algemeen

≥1/100 to <1/10

Ongewoon

≥1/1,000 to

<1/100

Skaars

≥1/10,000 to

<1/1000

Onbekend

Ondersoeke Bloeddruk verhoog Elektrokardio-

gram

abnormaal,

Bloed ureum

verhoog,

Bloed kreatinien

verhoog

Bloed

alkaliese

fosfatase

verhoog,

Bloed laktase

deshidro-

genase

verhoog,

Bloed

aspartaat,

Aminotrans-

ferase

verhoog,

Na-bemarkingsdata:

Addisionele ongunstige reaksies is verkry uit spontane berigte tydens wêreldwye na-

bemarkingstoesig oor LYRINEL en word hieronder weergegee.

Psigiatriese versteurings

Hallusinasies

Sielkundige afwyking, opgewondenheid, geheue inkorting

Senuweestelsel versteurings

Konvulsies

Hartversteurings

Disritmie; tagikardie

Vaskulêre versteurings

Gloede

Vel- en onderhuidse weefselversteurings

Uitslag

Nier- en urienweg versteurings

Page 21 of 23

Impotensie

Besering, vergiftiging en komplikasies met prosedures

Val

Ongewenste effekte wat met ander oksibutinienhidrochloried formulerings ondervind is:

Daarbenewens is sikloplegie, midriase en onderdrukking van laktasie aangemeld met die gebruik

van ander oksibutinienhidrochloried formulerings.

Spesiale voorsorgmaatreëls

LYRINEL kan die simptome van hipertireose, kongestiewe hartversaking, hart-disritmieë,

tagikardie, hipertensie en prostaathipertrofie vererger.

Wanneer LYRINEL by hoë omgewingstemperature gebruik word, kan dit hitte-uitputting

veroorsaak, as gevolg van ‘n afname in sweetafskeiding. Soos met ander tablette met ‘n nie-

absorbeerbare dop, moet versigtigheid uitgeoefen word as LYRINEL aan pasiënte met reeds

bestaande erge maagdermkanaalvernouing toegedien word.

Effek op vermoë om te bestuur of masjinerie te gebruik

Aangesien LYRINEL lomerigheid of dowwe visie kan veroorsaak, moet die pasiënt gewaarsku word

oor aktiwiteite wat verstandelike wakkerheid vereis, soos bestuur, hantering van masjinerie of

uitvoering van gevaarlike werk terwyl LYRINEL geneem word.

Laktose: Elke tablet bevat 0,3 mg lactose. Pasiënte met die seldsame oorerflikheidsprobleem,

galaktose-intoleransie, die Lapp-laktasetekort of glukose-galaktose wanabsorpsie moenie

LYRINEL neem nie.

BEKENDE SIMPTOME VAN OORDOSERING EN BESONDERHEDE VAN DIE BEHANDELING

DAARVAN

Die simptome van oordosering met LYRINEL ontwikkel uit die intensifikasie van die gewone SSS

versteurings (van rusteloosheid en opgewondenheid tot psigotiese gedrag), sirkulatoriese

veranderings (gloede, val in bloeddruk, sirkulatoriese ineenstoring ens.), respiratoriese versaking,

paralise en koma.

Page 22 of 23

Maatreëls om te neem:

1. onmiddellike maagspoeling

2. fisostigmien met stadige intraveneuse inspuiting:

Volwassenes: 0,5 tot 2,0 mg intraveneus, stadig; herhaal na 5 minute indien nodig, tot by ‘n

maksimum van 5 mg.

Kinders: 30 μg/kg intraveneus, stadig; herhaal indien nodig, tot by ‘n maksimum van 2 mg.

Koors moet simptomaties, met louwarm afsponsing of yspakke, behandel word.

Met duidelike rusteloosheid of eksitasie kan 10 mg diasepam intraveneus toegedien word.

Tagikardie kan met intraveneuse propranolol behandel word en urinêre retensie deur blaas -

kateterisasie hanteer word.

In geval van vordering van kurare-agtige effekte tot paralise van die respiratoriese spiere sal

meganiese ventilasie benodig word.

Die volgehoue vrystelling van oksibutinien uit LYRINEL moet in ag geneem word by die

behandeling van oordosering. Pasiënte moet vir ten minste 24 uur gemoniteer word.

IDENTIFIKASIE

LYRINEL 5 mg: ronde geelkleurige tablet met “5XL” in swart ink daarop gedruk.

LYRINEL 10 mg: ronde pienk gekleurde tablet met “10XL” in swart ink daarop gedruk.

AANBIEDING

Hoë - digtheid poliëtileenbottels met kinderbestande deksel en desikkant. Tablette word verpak in

bottels met 30 tablette.

BERGINGSAANWYSINGS

Bewaar die houer deeglik toe. Beskerm teen vog en klammigheid. Bewaar onder 25 °C. Hou buite

bereik van kinders.

Page 23 of 23

REGISTRASIENOMMERS

LYRINEL 5 mg: A39/5.4/0212

LYRINEL 10 mg: A39/5.4/0224

NAAM EN BESIGHEIDSADRES VAN DIE HOUER VAN DIE REGISTRASIESERTIFIKAAT

JANSSEN PHARMACEUTICA (Pty.) Ltd.

(Reg No.: 1980/011122/07)

Building 6, Country Club Estate,

21 Woodlands Drive, Woodmead, 2191

Tel: +27 (11) 518 7000

www.janssen.co.za

DATUM VAN PUBLIKASIE VAN HIERDIE VOUBILJET

November 2011