CARZIN XL - Pharma Dynamics

SCHEDULING STATUS
S3
PROPRIETARY NAME AND DOSAGE FORM
CARZIN XL tablets
COMPOSITION
CARZIN XL
Each film coated tablet contains doxazosin mesylate equivalent to 4 mg doxazosin.
PHARMACOLOGICAL CLASSIFICATION
A.7.1 Vasodilators, Hypotensive Medicines.
PHARMACOLOGICAL ACTION
Doxazosin produces peripheral vasodilatation primarily through its selective blockage of
alpha1-adrenergic receptors. The result is a fall in blood pressure because of the
decreased peripheral vascular resistance.
Blockade of alpha1-adrenergic receptors may also result in a reduction in urethral
resistance and pressure, bladder outlet resistance, and urinary symptoms.
Doxazosin is well absorbed after oral administration with peak plasma concentrations for
the slow release formulation gradually reached at 8 to 9 hours after dosing. Oral
bioavailability is about 54%.
Doxazosin is extensively metabolised in the liver, and excreted in faeces as metabolites
and a small amount of unchanged drug.
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The plasma elimination of doxazosin is biphasic with the terminal elimination half-life being
22 hours.
Doxazosin is about 98% bound to plasma proteins.
INDICATIONS
CARZIN XL is indicated for:
• Treatment of mild to moderate hypertension.
• Treatment of both the urinary outflow obstruction and the symptoms associated with
benign prostatic hyperplasia (BPH). CARZIN XL may be used in normotensive or
hypertensive BPH patients.
CONTRA-INDICATIONS
CARZIN XL is contra-indicated in:
• Patients with a known hypersensitivity to doxazosin or to other quinazolines.
• Patients with a history of gastro-intestinal obstruction, oesophageal obstruction, or any
degree of decreased lumen diameter of the gastro-intestinal tract.
• Safety and efficacy have not been established in children.
WARNINGS
Caution should be used when CARZIN XL is administered to patients with coronary
insufficiency. If symptoms of angina pectoris should newly appear or worsen, CARZIN XL
should be discontinued.
Care should be taken when CARZIN XL is administered to patients with mild or moderate
impaired hepatic or renal function. These conditions may increase exposure to CARZIN
XL and may increase the hypotensive effect. Use in patients with severe hepatic
impairment is not recommended.
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There is a potential for syncope after initial dose or after an increase in dosage strength
when CARZIN XL is administered to patients with symptomatic hypotension.
Prostate cancer should be ruled out prior to commencing CARZIN XL therapy.
INTERACTIONS
The hypotensive effects of CARZIN XL may be enhanced by use with diuretics and other
antihypertensives, and by alcohol and other medicines that cause hypotension. The risk
of first-dose hypotension may be increased in patients receiving beta-blockers or calcium-
channel blockers.
The hypotensive effect of CARZIN XL may be reduced when it is used concurrently with
sympathomimetics and non-steroidal anti-inflammatory drugs (NSAIDs).
PREGNANCY AND LACTATION
Safety in pregnancy or lactation has not been established.
DOSAGE AND DIRECTIONS FOR USE
CARZIN XL can be taken with or without food. The tablets should be swallowed whole
with a sufficient amount of liquid.
Hypertension:
The usual dose is one CARZIN XL 4 mg tablet once daily. If necessary, the dosage may
be increased to 8 mg once daily according to the patient’s response.
In patients not adequately controlled on a single antihypertensive agent, CARZIN XL may
be used in combination with a thiazide diuretic or a beta-blocking agent.
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Benign Prostatic Hyperplasia:
The usual dose is one CARZIN XL 4 mg tablet once daily. Depending on the individual
patient’s urodynamics and BPH symptomatology, dosage may then be increased to 8 mg
once daily. The recommended titration interval is 1-2 weeks. Blood pressure should be
evaluated routinely in these patients.
Use in elderly:
Normal adult dosage is recommended.
Use in children:
No experience is available on usage of CARZIN XL in children.
Use in hepatically impaired patients:
CARZIN XL is wholly metabolised by the liver, and should be administered with caution to
patients with evidence of impaired hepatic function. Use in patients with severe hepatic
impairment is not recommended.
SIDE EFFECTS AND SPECIAL PRECAUTIONS
Blood and the lymphatic system disorders
The following side-effects have been reported and the frequencies are unknown:
Leucopenia and thrombocytopenia.
Psychiatric disorders
Frequent: Depression.
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Nervous system disorders
Less frequent: Nervousness, restlessness or unusual irritability, somnolence, insomnia.
The following side-effects have been reported and the frequencies are unknown:
Agitation, hypoaesthesia and paraesthesia.
Eye disorders
The following side-effect has been reported and the frequency is unknown:
Blurred vision.
Cardiac disorders
Less frequent: Arrhythmias, palpitations, tachycardia.
The following side-effects have been reported and the frequencies are unknown:
Bradycardia, myocardial infarction, chest pain and angina pectoris.
Vascular disorders
Frequent: Dizziness, vertigo, headache.
Less frequent: Hypotension, orthostatic hypotension, peripheral oedema, syncope.
The following side-effects have been reported and the frequencies are unknown:
Cerebrovascular incidents and hot flushes.
Respiratory, thoracic and mediastinal disorders
Less frequent: Dyspnoea, respiratory tract infection, rhinitis.
The following side-effect has been reported and the frequency is unknown:
Aggravated bronchospasm.
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Gastrointestinal disorders
Less frequent: Abdominal pain, dyspepsia, nausea.
The following side-effects have been reported and the frequencies are unknown:
Anorexia, vomiting and diarrhoea.
Hepato-biliary disorders
The following side-effects have been reported and the frequencies are unknown:
Hepatitis, cholestatic hepatitis and jaundice.
Skin and subcutaneous tissue disorders
Less frequent: Skin rash and pruritus (allergic reaction).
The following side-effects have been reported and the frequencies are unknown:
Purpura and urticaria.
Musculoskeletal, connective tissue and bone disorders
Less frequent: Back pain, myalgia.
The following side-effects have been reported and the frequencies are unknown:
Muscle cramps or weakness.
Renal and urinary disorders
Less frequent: Urinary tract infections, dysuria.
The following side-effects have been reported and the frequencies are unknown:
Haematuria, painful urination and changes in frequency of urination, nocturia and polyuria.
Reproductive system and breast disorders
Less frequent: Priapism and impotence.
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The following side-effect has been reported and the frequency is unknown:
Gynecomastia.
General disorders and administration site conditions
Frequent: Asthenia, unusual tiredness.
The following side-effects have been reported and the frequencies are unknown:
Alopecia, fatigue and malaise.
Investigations
The following side-effects have been reported and the frequencies are unknown:
Abnormal liver function tests.
Driving/Use of Machinery
The ability to engage in activities such as operating machinery or operating a motor
vehicle may be impaired especially when initiating therapy.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Should overdosage lead to hypotension, the patient should be immediately placed in a
supine, head down position. Because doxazosin is highly protein bound, it is not removed
by dialysis.
Treatment is symptomatic and supportive.
IDENTIFICATION
White, round, slightly convex, film-coated tablet.
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PRESENTATION
CARZIN XL is available in pack sizes of 30 tablets packed in blister strips of OPA/AL/PVC
film and aluminium foil.
STORAGE INSTRUCTIONS
Store below 25°C. Protect from light and moisture.
Keep the tablets in the outer carton until required for use.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER
41/7.1/0557
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF
REGISTRATION
Pharma Dynamics (Pty) Ltd
F02 Grapevine House
Steenberg Office Park
Westlake
7945
DATE OF PUBLICATION OF THE PACKAGE INSERT
July 2009
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SKEDULERINGSTATUS
S3
EIENDOMSNAAM EN DOSEERVORM
CARZIN XL tablette
SAMESTELLING
CARZIN XL
Elke filmbedekte tablet bevat doksasosienmesilaat ekwivalent aan 4 mg doksasosien.
FARMAKOLOGIESE KLASSIFIKASIE
A.7.1 Vasodilatore, hipotensiewe middels.
FARMAKOLOGIESE WERKING
Doksasosien veroorsaak perifere vasodilatasie hoofsaaklik deur selektiewe blokkering van
alfa1-adrenergiese reseptore. Die resultaat is ‘n verlaging in bloeddruk weens die
verminderde perifere vaskulêre weerstand.
Blokkering van alfa1-adrenergiese reseptore mag ook ‘n vermindering in uretrale
weerstand en druk, blaasuitlaatweerstand en urinêre simptome tot gevolg hê.
Doksasosien word goed geabsorbeer na orale toediening, met piek plasmakonsentrasies
wat geleidelik teen 8 tot 9 ure na dosering bereik word vir die stadige vrystelling
formulasie. Orale biobeskikbaarheid is ongeveer 54%.
Doksasosien word ekstensief in die lewer gemetaboliseer en in die feses uitgeskei as
metaboliete en ‘n klein hoeveelheid van die onveranderde middel.
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Die plasma-eliminasie van doksasosien is bi-fasies, met ʼn terminale eliminasie half-leeftyd
van 22 ure.
Doksasosien bind ongeveer 98% aan plasmaproteïene.
INDIKASIES
CARZIN XL word aangedui vir:
• Behandeling van ligte tot matige hipertensie.
• Behandeling van sowel die urinêre uitvloei-obstruksie, as die simptome geassosieer
met goeddaardige prostaat hiperplasie (BPH). CARZIN XL kan gebruik word by
normotensiewe of hipertensiewe BPH pasiënte.
KONTRA-INDIKASIES
CARZIN XL word teenaangedui in:
• Pasiënte wat hipersensitief is vir doksasosien of ander kinasoliene.
• Pasiënte met ‘n geskiedenis van gastro-intestinale obstruksie, esofageale obstruksie,
of enige mate van verminderde lumendeursnee van die gastro-intestinale weg.
• Veiligheid en effektiwiteit in kinders is nie bepaal nie.
WAARSKUWINGS
Versigtigheid moet aan die dag gelê word wanneer CARZIN XL aan pasiënte met
koronêre ontoereikendheid toegedien word. Indien simptome van angina pectoris vir die
eerste keer verskyn of vererger, moet CARZIN XL gestaak word.
CARZIN XL moet met sorg toegedien word aan pasiënte met ligte of matige ingekorte
lewer- of nierfunksie. Hierdie toestande mag blootstelling aan CARZIN XL laat toeneem
en mag die hipotensiewe effek vergroot. Die gebruik by pasiënte met erge
lewerontoereikendheid word nie aanbeveel nie.
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Daar is ‘n moontlikheid van sinkopee (floute) na die aanvanklike dosering of na ‘n
verhoging in dosissterkte, wanneer CARZIN XL aan pasiënte met simptomatiese
hipotensie toegedien word.
Die moontlikheid van prostaatkanker moet uitgeskakel word voordat terapie met CARZIN
XL begin word.
INTERAKSIES
Die hipotensiewe effekte van CARZIN XL mag versterk word indien dit saam met diuretika
en ander antihipertensiewe middels gebruik word, sowel as deur alkohol en ander
medisyne wat hipotensie veroorsaak. Die risiko van hipotensie met die eerste dosering
mag verhoog word by pasiënte wat beta-blokkeerders of kalsiumkanaalblokkeerders
ontvang.
Die hipotensiewe effek van CARZIN XL mag verminder word wanneer dit gelyktydig met
simpatomimetiese en nie-steroïed anti-inflammatoriese middels (NSAIMs) gebruik word.
SWANGERSKAP EN BORSVOEDING
Veiligheid tydens swangerskap en borsvoeding is nie bepaal nie.
DOSIS EN GEBRUIKSAANWYSINGS
CARZIN XL kan met of sonder kos geneem word. Die tablette moet heel ingesluk word,
met ‘n voldoende hoeveelheid vloeistof.
Hipertensie:
Die gewone dosis is een CARZIN XL 4 mg tablet daagliks. Indien nodig, mag die
dosering verhoog word na 8 mg eenmaal per dag, na gelang van die pasiënt se reaksie.
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By pasiënte wie nie voldoende beheer ervaar met ‘n enkele antihipertensiewe middel nie,
mag CARZIN XL in kombinasie met ‘n tiasieddiuretikum of ‘n beta-blokker gebruik word.
Goedaardige Prostaat Hiperplasie:
Die gewone dosis is een CARZIN XL 4 mg tablet daagliks. Afhangende van die
individuele pasiënt se urodinamika en BPH simptomatologie, mag dosering verhoog word
na 8 mg eenmaal per dag. Die aanbevole titrasie-interval is 1-2 weke. Bloeddruk moet
roetinegewys geëvalueer word by hierdie pasiënte.
Gebruik by bejaardes:
Die normale dosering vir volwassenes word aanbeveel.
Gebruik by kinders:
Daar is geen ondervinding met die gebruik van CARZIN XL by kinders nie.
Gebruik by pasiënte met lewerinkorting:
CARZIN XL word in geheel deur die lewer gemetaboliseer en moet met omsigtigheid
toegedien word aan pasiënte met tekens van ingekorte lewerfunksie. Die gebruik daarvan
by pasiënte met erge hepatiese ontoereikendheid word nie aanbeveel nie.
NEWE-EFFEKTE EN SPESIALE VOORSORGMAATREËLS
Bloed- en die limfatiese sisteemversteurings
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Leukopenie en trombositopenie.
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Psigiatriese versteurings
Dikwels: Depressie.
Senuweestelselversteurings
Minder dikwels: Senuweeagtigheid, rusteloosheid of ongewone geïrriteerdheid,
slaperigheid, slaaploosheid.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Agitasie, hipo-estesie en parestesie.
Oogversteurings
Die volgende newe-effek is aangemeld en die frekwensie is onbekend:
Troebelvisie.
Kardiale versteurings
Minder dikwels: Aritmieë, palpitasies, tagikardie.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Bradikardie, miokardiale infarksie, borskaspyn en angina pectoris.
Vaskulêre versteurings
Dikwels: Duiseligheid, lighoofdigheid, hoofpyn.
Minder dikwels: Hipotensie, ortostatiese hipotensie, perifere edeem, sinkopee.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Serebrovaskulêre insidente en warm gloede.
Respiratoriese, toragiese en mediastinale versteurings
Minder dikwels: Dispnee, respiratoriese-weginfeksie, rinitis.
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Die volgende newe-effek is aangemeld en die frekwensies is onbekend:
Verergerde brongospasma.
Gastro-intestinale versteurings
Minder dikwels: Abdominale pyn, dispepsie, naarheid.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Anoreksie, braking en diarree.
Hepatobiliêre versteurings
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Hepatitis, cholestatiese hepatitis en geelsug.
Vel- en subkutane weefselversteurings
Minder dikwels: Veluitslag en pruritus (allergiese reaksie).
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Purpura en urtikaria.
Muskuloskeletale, bindweefsel- en beenversteurings
Minder dikwels: Rugpyn, mialgie.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Spierkrampe of -swakheid.
Nier- en urinêre versteurings
Minder dikwels: Urienweginfeksies, disurie.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Hematurie, pynlike urinering en veranderings in urienfrekwensie, nokturie en poliurie.
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Reproduktiewe sisteem en borsversteurings
Minder dikwels: Priapisme en impotensie.
Die volgende newe-effek is aangemeld en die frekwensies is onbekend:
Ginekomastie.
Algemene versteurings en toestande by die plek van toediening
Dikwels: Astenie, ongewone moegheid.
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Alopesie, uitputting en malaise.
Ondersoeke
Die volgende newe-effekte is aangemeld en die frekwensies is onbekend:
Abnormale lewerfunksietoetse.
Bestuur/Gebruik van Masjinerie
Die vermoë om masjinerie te hanteer of ‘n motorvoertuig te bestuur mag ingekort wees,
veral wanneer terapie geïnisieer word.
BEKENDE SIMPTOME VAN OORDOSERING EN BESONDERHEDE VIR DIE
BEHANDELING DAARVAN
Indien oordosering lei tot hipotensie, moet die pasiënt laat lê word, met die kop na onder.
Aangesien doksasosien hoogs proteïengebonde is, word dit nie deur dialise verwyder nie.
Behandeling is simptomaties en ondersteunend.
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IDENTIFIKASIE
Wit, ronde, effens konvekse, filmbedekte tablet.
AANBIEDING
CARZIN XL is beskikbaar in verpakkingsgroottes van 30 tablette, verpak in stulpstroke
van OPA/AL/PVC film en aluminiumfoelie.
BEWARINGSINSTRUKSIES
Bewaar onder 25°C. Beskerm teen lig en vog.
Hou die tablette in die buitenste karton tot nodig vir gebruik.
HOU BUITE BEREIK VAN KINDERS.
REGISTRASIENOMMER
41/7.1/0557
NAAM EN BESIGHEIDSADRES VAN DIE HOUER VAN DIE
REGISTRASIESERTIFIKAAT
Pharma Dynamics (Edms) Bpk.
F02 Grapevine House
Steenberg Office Park
Westlake
7945
DATUM VAN PUBLIKASIE VAN HIERDIE VOUBILJET
Julie 2009
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