SCHEDULING STATUS:
S4
Esomeprazole decreases the concentration of atazanavir and nelfinavir. Coadministration of NESOPRAM and atazanavir or nelfinavir is contra-indicated.
PROPRIETARY NAME (AND DOSAGE FORM):
Effect of other medicines on the pharmacokinetics of esomeprazole:
NESOPRAM is metabolised by CYP2C19 and CYP3A4. Concomitant
administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg
twice daily), resulted in a doubling of the exposure (AUC) to esomeprazole. Dose
adjustment of NESOPRAM is not required.
NESOPRAM® 20 (Gastro-resistant tablets)
NESOPRAM® 40 (Gastro-resistant tablets)
COMPOSITION:
NESOPRAM 20: Each gastro-resistant tablet contains
esomeprazole magnesium 20,7 mg
equivalent to esomeprazole 20 mg.
Contains sugar.
NESOPRAM 40: Each gastro-resistant tablet contains
esomeprazole magnesium 41,4 mg
equivalent to esomeprazole 40 mg.
Contains sugar.
Excipients:
crospovidone, diethlyphthalate, hydroxypropyl cellulose, hypromellose phthalate, macrogol, microcrystalline cellulose, povidone, sodium stearyl fumarate and film coating material.
PREGNANCY AND LACTATION:
Safety during pregnancy and lactation has not been established.
DOSAGE AND DIRECTIONS FOR USE:
The tablets should be swallowed whole with liquid. The tablets should not be
chewed or crushed.
The tablets can also be dispersed in half a glass of non-carbonated water. No
other liquids should be used. Stir until the tablets disintegrate and drink the liquid
with the pellets immediately or within 30 minutes. Rinse the glass with half a glass
of water and drink. The pellets must not be chewed or crushed.
PHARMACOLOGICAL CLASSIFICATION:
A 11.4.3 Medicines acting on gastro-intestinal tract. Other.
For patients who cannot swallow, the tablets can be dispersed in non-carbonated
water and administered through a gastric tube.
PHARMACOLOGICAL ACTION:
Pharmacodynamic properties:
Esomeprazole, the S-isomer of omeprazole, a proton pump inhibitor; reduces
gastric acid secretion through specific inhibition of the acid pump in the parietal
cell, where it is concentrated and converted to the active form in the acidic
environment of the secretory canaliculi and inhibits the enzyme H+K+-ATPase
– the acid pump. This effect on the final step of the gastric acid secretion is
dose-dependent and provides for effective inhibition of both basal and stimulated
acid secretion.
Gastro-oesophageal Reflux Disease (GORD):
• Treatment of erosive reflux oesophagitis: 40 mg once daily for 4 weeks. An additional 4 weeks treatment is recommended for patients in whom
oesophagitis has not healed, or who have persistent symptoms.
• Long-term management of patients with healed oesophagitis to prevent relapse: 20 mg once daily.
• Symptomatic treatment of gastro-oesophageal reflux disease (GORD):
20 mg once daily in patients without oesophagitis. If symptom control has not been achieved after 4 weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using an on demand regimen, taking 20 mg once daily, when needed.
Using AUC as a surrogate parameter for plasma concentration, a relationship
between inhibition of acid secretion and exposure has been shown.
Food intake has no significant influence on the effect of esomeprazole on
intragastric acidity.
Other effects related to acid inhibition:
During treatment with antisecretory medicines serum gastrin increases in
response to the decreased acid secretion.
During long-term treatment with antisecretory medicines gastric glandular cysts
occur. These changes are a physiological consequence of pronounced inhibition
of acid secretion, are benign and appear to be reversible.
Pharmacokinetic properties:
Absorption and distribution:
Esomeprazole is acid labile and is administered orally as enteric-coated tablets. In
vivo conversion to the R-isomer is negligible. Absorption of esomeprazole is rapid,
with peak plasma levels occurring approximately 1 – 2 hours after dose.
The absolute bioavailability is 89 % after repeated once-daily administration. The
apparent volume of distribution at steady state in healthy subjects is approximately
0,22 litres/kg body weight.
Esomeprazole is 97 % plasma protein bound.
Metabolism and excretion:
Esomeprazole is completely metabolised by the cytochrome P450 system
(CYP). The major part of the metabolism of esomeprazole is dependent on
the polymorphic CYP2C19, responsible for the formation of the hydroxy and
desmethyl metabolites of esomeprazole. The remaining part is dependent on
another specific isoform, CYP3A4, responsible for the formation of esomeprazole
sulphone, the main metabolite in plasma.
The parameters below reflect mainly the pharmacokinetics in individuals with a
functional CYP2C19 enzyme, extensive metabolisers.
Total plasma clearance is about 17 litres/hour after a single dose and about 9
litres per hour after repeated administration. The plasma elimination half-life is
about 1,3 hours after repeated once-daily dosing. The area under the plasma
concentration-time curve increases with repeated administration of esomeprazole.
This increase is dose-dependent and results in a non-linear dose-AUC
relationship after repeated administration. This time and dose dependency is due
to a decrease of first pass metabolism and systemic clearance probably caused
by an inhibition of the CYP2C19 enzyme by esomeprazole and/or its sulphone
metabolite. Esomeprazole is completely eliminated from plasma between doses
with no tendency for accumulation during once-daily administration.
The major metabolites of esomeprazole have no effect on gastric acid secretion.
Almost 80 % of an oral dose of esomeprazole is excreted as metabolites in the
urine, the remainder in the faeces. Less than 1 % of the parent compound is
found in urine.
Special patient populations:
Approximately 1 – 2 % of the population lack a functional CYP2C19 enzyme and
are called poor metabolisers. In these individuals the metabolism of esomeprazole
is probably mainly catalysed by CYP3A4. After repeated once-daily administration
of 40 mg esomeprazole, the mean area under the plasma concentration-time
curve was approximately 100 % higher in poor metabolisers than in subjects
having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak
plasma concentrations were increased by about 60 %.
The metabolism of esomeprazole is not significantly changed in elderly subjects
(71 – 80 years of age).
Following a single dose of 40 mg esomeprazole the mean area under the plasma
concentration-time curve is approximately 30 % higher in females than in males.
No gender difference is seen after repeated once-daily administration. These
findings have no implications for the dosage of esomeprazole.
The metabolism of esomeprazole in patients with mild to moderate liver
dysfunction may be impaired. The metabolic rate is decreased in patients with
severe liver dysfunction resulting in a doubling of the area under the plasma
concentration-time curve of esomeprazole. Therefore, a maximum of 20 mg
should not be exceeded in patients with severe dysfunction. Esomeprazole or
its major metabolites do not show any tendency to accumulate with once daily
dosing.
No studies have been performed in patients with decreased renal function. Since
the kidney is responsible for the excretion of the metabolites of esomeprazole, but
not for the elimination of the parent compound, the metabolism of esomeprazole is
not expected to be changed in patients with impaired renal function.
INDICATIONS:
NESOPRAM tablets are indicated for:
Gastro-oesophageal Reflux Disease (GORD):
• Treatment of erosive reflux oesophagitis.
• Long-term management of patients with healed oesophagitis to prevent
relapse.
• Symptomatic treatment of gastro-oesophageal reflux disease (GORD).
Patients requiring continued NSAID therapy:
• Prevention of gastric and duodenal ulcers associated with non-steroidal
anti-inflammatory drug (NSAID) therapy in patients at risk.
In combination with appropriate antibacterial therapeutic regimens for the
eradication of Helicobacter pylori:
• Healing of Helicobacter pylori associated duodenal ulcer.
• Prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcer disease.
CONTRA-INDICATIONS:
• Known hypersensitivity to NESOPRAM, substituted benzimidazoles or any other constituents of the formulation.
• Co-administration with atazanavir and nelfinavir (see ʺINTERACTIONSʺ).
WARNINGS:
NESOPRAM is not indicated for mild gastro-intestinal complaints such as nervous
dyspepsia.
Prior to treatment or in the presence of any alarm symptom (e.g. significant
unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or
melaena) and when gastric ulcer is suspected or present, the possibility of
malignancy of gastric ulcer or a malignant disease of the oesophagus should
be excluded as the treatment with NESOPRAM may alleviate the symptoms of
malignant ulcers and can thus delay diagnosis.
Patients on long-term treatment (particularly those treated for more than a year)
should be kept under regular surveillance.
INTERACTIONS:
Interaction with other medicinal products and other forms of interaction:
Effects of NESOPRAM on the pharmacokinetics of other medicines:
The decreased intragastric acidity during treatment with NESOPRAM, might
increase or decrease the absorption of medicines if the mechanism of absorption
is influenced by gastric acidity. The absorption of ketoconazole and itraconazole
can decrease during treatment with NESOPRAM.
NESOPRAM inhibits CYP2C19, the major esomeprazole metabolising enzyme.
Concomitant administration of 30 mg esomeprazole resulted in a 45 % decrease
in clearance of the CYP2C19 substrate diazepam. This interaction is unlikely to
be of clinical relevance.
Concomitant administration of 40 mg esomeprazole resulted in a 13 % increase
in trough plasma levels of phenytoin in epileptic patients; dose adjustment was
not required.
Concomitant administration of 40 mg esomeprazole to warfarin-treated patients
showed that, despite a slight elevation in the trough plasma concentration of
the less potent R-isomer of warfarin, the coagulation times were within the
accepted range. However, as with all patients receiving warfarin, monitoring is
recommended during concomitant treatment with NESOPRAM.
In healthy volunteers, concomitant administration of 40 mg esomeprazole resulted
in a 32 % increase in area under the plasma concentration-time curve (AUC) and
a 31 % prolongation of elimination half-life (t1/2) but no significant increase in peak
plasma levels of cisapride. This interaction did not alter the influence of cisapride
on cardiac electrophysiology.
Studies in healthy subjects have shown that concomitant use of esomeprazole
and clopidogrel resulted in reduced plasma concentrations of the active metabolite
of clopidogrel and a reduction in platelet inhibition. An increase in cardiovascular
events has also been reported. Concomitant use of NESOPRAM and clopidogrel
should be avoided.
Patients requiring continued NSAID therapy:
• Prevention of gastric and duodenal ulcers associated with NSAID therapy in patients at risk: 20 mg or 40 mg once daily.
In combination with appropriate antibacterial therapeutic
regimens for the eradication of Helicobacter pylori:
• Healing of Helicobacter pylori associated duodenal ulcer.
• Prevention of relapse of peptic ulcers in patients with Helicobacter pylori associated ulcer disease: 20 mg NESOPRAM with 1 g amoxicillin and 500 mg clarithromycin, all twice daily for 7 days.
Children:
There is no experience with NESOPRAM in children.
Impaired renal function:
Dose adjustment is not required in patients with impaired renal function. Due to
limited experience in patients with severe renal insufficiency, such patients should
be treated with caution.
Impaired hepatic function:
Dose adjustment is not required in patients with mild to moderate liver impairment.
For patients with severe liver impairment, a maximum daily dose of 20 mg
NESOPRAM should be used.
Elderly:
Dose adjustment is not required in the elderly.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Infections and infestations:
Less frequent: Clostridium difficile associated diarrhoea.
Blood and the lymphatic system disorders:
Less frequent: Agranulocytosis, leucopenia, thrombocytopenia.
Immune system disorders:
Less frequent: Hypersensitivity reactions e.g. angioedema,
anaphylactic reaction.
Nervous system disorders:
Frequent: Headache.
Less frequent: Dizziness, somnolence, paraesthesia.
Psychiatric disorders:
Less frequent: Insomnia, reversible confusional state,
agitation, hallucinations, depression.
Eye disorders:
Less frequent: Blurred vision.
Ear and labyrinth disorders:
Less frequent: Vertigo.
Vascular disorders:
Less frequent: Peripheral oedema.
Gastro-intestinal disorders:
Frequent: Abdominal pain, diarrhoea, flatulence,
nausea/vomiting, constipation.
Less frequent: Dry mouth, stomatitis, taste disturbances.
Hepato-biliary disorders:
Less frequent: Increased liver enzymes, hepatitis with or without jaundice.
Frequency unknown: Hepatic encephalopathy.
Skin and subcutaneous tissue disorders:
Frequent: Skin rashes.
Less frequent: Dermatitis, pruritus, urticaria, alopecia,
bullous eruption, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity.
Musculoskeletal, connective tissue and bone disorders:
Less frequent: Arthralgia, myalgia.
Renal and urinary system disorders:
Less frequent: Interstitial nephritis.
Reproductive system and breast disorders:
Less frequent: Impotence, gynaecomastia.
General disorders and administrative site conditions:
Less frequent: Fatigue, increased sweating, malaise.
Special Precautions:
Clostridium difficile associated diarrhoea:
Published observational studies suggest that PPI therapy like esomeprazole may
be associated with an increased risk of Clostridium difficile associated diarrhoea,
especially in hospitalised patients. This diagnosis should be considered for
diarrhoea that does not improve. Patients should use the lowest dose and shortest
duration of NESOPRAM therapy appropriate to the condition being treated.
Effects on the ability to drive and use machines:
NESOPRAM may cause somnolence, dizziness and blurred vision. As
concentration may be impaired, patients should be advised to exercise caution
when driving or operating machinery.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS
TREATMENT:
The symptoms described in connection with deliberate NESOPRAM overdose
(limited experience of doses in excess of 240 mg/day) are transient. Single
doses of 80 mg esomeprazole were uneventful. No specific antidote is known.
Esomeprazole is extensively plasma protein bound and is, therefore, not readily
dialysable. As in any case of overdose, treatment should be symptomatic and
general supportive measures should be utilised.
IDENTIFICATION:
NESOPRAM 20: Light brick red to brown coloured, oval, biconvex, film coated
tablets with ‘E5’ debossed on one side and plain on the other side.
NESOPRAM 40: Light brick red to brown coloured, oval, biconvex, film coated
tablets with ‘E6’ debossed on one side and plain on the other side.
PRESENTATION:
Carton contains 14, 28 or 30 tablets packed in cold form blister strips or desiccant
embedded cold form blister strips. Each blister strip contains 7 or 10 tablets.
Carton contains white opaque HDPE bottle with screw cap closure containing
30 tablets.
Description of desiccant embedded cold form blister pack:
Cold forming laminate composed of aluminium foil of one side bright, soft
tempered, plain, dull side lacquer laminated to oriented polyamide film; other side
extrusion coated with desiccant embedded polyethylene and further having an
outer layer of HDPE with lidding foil.
Description of cold form blister pack:
Cold form blister pack comprise of cold form blister laminate composed of
aluminium foil (one side bright, soft tempered, plain; dull side lacquer laminated
to oriented polyamide film; bright side lacquer laminated to PVC film), PVC and
polyamide with a backing of aluminium foil coated with heat seal lacquer.
Description of HDPE bottle pack:
The bottle is a white, opaque HDPE bottle with white opaque polypropylene screw
cap closure having induction seal liner. Bottle also contains desiccant sachet (1 g).
STORAGE INSTRUCTIONS:
Store at or below 25 ºC, protected from moisture.
Do not remove the blisters from the carton until required for use.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBERS:
NESOPRAM 20: 45/11.4.3/0123
NESOPRAM 40: 45/11.4.3/0124
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE
OF REGISTRATION:
RANBAXY (SA) (PTY) LTD
Ground Floor, Tugela House, Riverside Office Park, 1303 Heuwel Avenue,
Centurion, South Africa
Marketed by CIPLA MEDPRO (PTY) LTD.
DATE OF PUBLICATION OF THE PACKAGE INSERT:
2 October 2014
CM482A/SA
Effect on gastric acid secretion:
After oral dosing with esomeprazole 20 mg and 40 mg the onset of effect occurs
within 1 hour. After repeated administration with esomeprazole 20 mg once daily
for 5 days, mean peak acid output after pentagastrin stimulation is decreased by
90 % when measured 6 – 7 hours after dosing on day 5.
After 5 days of oral dosing with 20 mg and 40 mg of esomeprazole, intragastric pH
above 4 was maintained for a mean time of 13 hours and 17 hours, respectively
over 24 hours in symptomatic Gastro-oesophageal Reflux Disease (GORD)
patients.
SKEDULERINGSTATUS:
S4
’n Toename in die kardiovaskulêre voorvalle is ook aangemeld.
Gelyktydige gebruik van NESOPRAM en klopidogrel behoort vermy te word.
EIENDOMSNAAM (EN DOSEERVORM):
Esomeprasool verlaag die konsentrasie van atasanavir en nelfinavir. Gelyktydige
toediening van NESOPRAM en atasanavir of nelfinavir is teenaangedui.
SAMESTELLING:
NESOPRAM 20: Elke gastries-weerstandbiedende tablet bevat 20,7 mg magnesiumesomeprasool ekwivalent aan 20 mg esomeprasool.
Bevat suiker.
NESOPRAM 40: Elke gastries-weerstandbiedende tablet bevat 41,4 mg magnesiumesomeprasool ekwivalent aan 40 mg esomeprasool.
Bevat suiker.
Bymiddels:
krospovidoon, dietielftalaat, hidroksipropielsellulose, hipromelloseftalaat, makrogol, mikrokristallyne sellulose, povidoon, natriumstearielfumaraat en filmbedekkingsmateriaal.
FARMAKOLOGIESE KLASSIFIKASIE:
A 11.4.3 Middels met ’n uitwerking op die maagdermkanaal. Ander.
FARMAKOLOGIESE WERKING:
Farmakodinamiese eienskappe:
Esomeprasool, die S-isomeer van omeprasool, ’n protonpompinhibeerder; verlaag
maagsuurafskeiding deur spesifieke inhibering van die protonpomp in die pariëtale
sel, waar dit in die suuromgewing van die afskeidende kanaaltjies gekonsentreer
en na die aktiewe vorm omgeskakel word, en dit rem die ensiem H+K+-ATPase –
die protonpomp. Hierdie effek op die finale stap van suurafskeiding in die maag
is dosisafhanklik en bied effektiewe remming van beide basale en gestimuleerde
suurafskeiding.
Effek op maagsuurafskeiding:
Na orale dosering van 20 mg en 40 mg esomeprasool kan die aanvanklike
uitwerking daarvan binne 1 uur plaasvind. Na herhaalde toediening van 20 mg
esomeprasool, een maal per dag vir 5 dae, word die gemiddelde piek suuruitset
na pentagastriese stimulasie met 90 % verminder as dit 6 – 7 ure na toediening
op dag 5 gemeet word.
Na 5 dae van orale dosering met 20 mg en 40 mg esomeprasool, is ’n pH bo 4
oor 24 uur in die maag gehandhaaf vir ’n gemiddelde tydperk van 13 uur en 17
uur, onderskeidelik in simptomatiese Gastro-esofageale reflukssiekte (GERS)pasiënte.
Die AOK word gebruik as ’n surrogaatparameter vir plasmakonsentrasie en toon ’n
verband tussen inhibering van suurafskeiding en blootstelling.
Voedselinname het geen beduidende invloed op die uitwerking van esomeprasool
op maagsuur nie.
Ander effekte verwant aan suurinhibering:
Tydens behandeling met anti-afskeidingsmiddels verhoog serumgastrien in
respons tot die verminderde suurafskeiding.
Tydens langtermynbehandeling met anti-afskeidingsmiddels kom gastriese
klieragtige siste voor. Hierdie veranderings is ’n fisiologiese resultaat van
uitgesproke inhibering van suurafskeiding, is goedaardig en skynbaar omkeerbaar.
Farmakokinetiese eienskappe:
Absorpsie en verspreiding:
Esomeprasool is suurlabiel en word oraal toegedien as enteriesbedekte tablette.
In vivo-omsetting na die R-isomeer is onbeduidend. Absorpsie van esomeprasool
is vinnig, met piekplasmavlakke wat ongeveer 1 – 2 uur na dosering bereik word.
Die absolute biobeskikbaarheid is 89 % na herhaalde toediening van een keer per
dag. Die skynbare volume van verspreiding by gelykvlak in gesonde pasiënte is
ongeveer 0,22 liter/kg liggaamsmassa.
Esomeprasool is 97 % aan plasmaproteïen gebonde.
Metabolisme en uitskeiding:
Esomeprasool word volledig deur die sitochroom P450-stelsel (CYP)
gemetaboliseer. Die belangrikste deel van die metabolisme van esomeprasool
is afhanklik van die polimorfiese CYP2C19, verantwoordelik vir die vorming van
die hidroksi- en desmetielmetaboliete van esomeprasool. Die oorblywende deel
is afhanklik van ’n ander spesifieke isovorm, CYP3A4, verantwoordelik vir die
vorming van esomeprasoolsulfoon, die hoofmetaboliet in die plasma.
Die onderstaande parameters toon hoofsaaklik die farmakokinetika in individue
met ’n funksionele CYP2C19-ensiem wat ekstensiewe metaboliseerders is.
Die totale plasma-opruiming is ongeveer 17 liter/uur na ’n enkele dosering
en ongeveer 9 liter per uur na herhaaldelike dosering. Die plasma eliminasiehalfleeftyd is ongeveer 1,3 uur na herhaaldelike dosering van een keer per dag.
Die area onder die plasmakonsentrasie-tydkurwe neem toe met herhaaldelike
toediening van esomeprasool. Die toename is dosisafhanklik en lei na
herhaalde toediening tot ’n nie-lineêre dosis-AOK-verwantskap. Hierdie tyd- en
dosisafhanklikheid is die gevolg van ’n afname van eerstedeurgangsmetabolisme
en sistemiese opruiming, waarskynlik veroorsaak deur ’n remming van die
CYP2C19-ensiem deur esomeprasool en/of die sulfoonmetaboliet. Esomeprasool
word in die geheel tussen doserings uit die plasma uitgeskei, met geen
geneigdheid tot akkumulering tydens toediening van een maal per dag nie.
Die hoofmetaboliete van esomeprasool het geen invloed op gastriese
suurafskeiding nie. Bykans 80 % van die orale dosis van esomeprasool word as
metaboliete in die uriene uitgeskei, en die res in die feses. Minder as 1 % van die
moederverbinding word in die uriene gevind.
Spesiale pasiëntbevolkings:
Ongeveer 1 – 2 % van die bevolking ervaar ’n funksionele tekort aan die
CYP2C19-ensiem en word as swak metaboliseerders beskryf. In hierdie individue
word die metabolisme van esomeprasool waarskynlik hoofsaaklik deur CYP3A4
gekataliseer. Na herhaalde toediening van 40 mg esomeprasool een keer per dag,
was die gemiddelde area onder die plasmakonsentrasie-tydkurwe ongeveer
100 % hoër in swak metaboliseerders as in persone met ’n funksionele
CYP2C19-ensiem (ekstensiewe metaboliseerders). Gemiddelde
piekplasmakonsentrasies was ongeveer 60 % hoër.
Die metabolisme van esomeprasool is nie beduidend anders in bejaarde persone
nie (71 – 80 jariges).
Ná ’n enkele 40 mg-dosis esomeprasool is die gemiddelde area onder die
plasmakonsentrasie-tydkurwe by vroue nagenoeg 30 % hoër as by mans. Geen
geslagsverskille is waargeneem ná herhaalde een maal daaglikse toediening nie.
Hierdie bevindings hou geen implikasie in vir die dosering van esomeprasool nie.
Die metabolisme van esomeprasool by pasiënte met ligte tot matige
lewerdisfunksie kan ingekort wees. Die metabolismetempo is stadiger by
pasiënte met erge lewerdisfunksie, en het ’n verdubbeling van die area onder die
plasmakonsentrasie-tydkurwe van esomeprasool tot gevolg. By pasiënte met erge
disfunksie moet ’n maksimum van 20 mg dus nie oorskry word nie. Esomeprasool
of sy hoofmetaboliete toon geen neiging om te akkumuleer tydens dosering van
een maal per dag nie.
Geen studies by pasiënte met verswakte nierfunksie is gedoen nie. Aangesien die
nier verantwoordelik is vir die uitskeiding van die metaboliete van esomeprasool,
maar nie vir die eliminering van die moederverbinding nie, word daar nie verwag
dat die metabolisme van esomeprasool by pasiënte met verswakte nierfunksie
anders sal wees nie.
INDIKASIES:
NESOPRAM tablette is aangedui vir:
Gastro-esofageale reflukssiekte (GERS):
• Behandeling van eroderende refluksesofagitis.
• Langtermynbehandeling van pasiënte met geneesde esofagitis om ’n terugval te voorkom.
• Simptomatiese behandeling van gastro-esofageale reflukssiekte (GERS).
Pasiënte wat voortgesette NSAIM-behandeling benodig:
• Voorkoming van gastriese en duodenale ulkusse geassosieer met nie-
steroïedale anti-inflammatoriese middel (NSAIM)-terapie by risiko-pasiënte.
In kombinasie met toepaslike antibakteriële terapeutiese regimens vir die
uitwissing van Helicobacter pylori:
• Genesing van duodenale ulkus vanweë Helicobacter pylori.
• Voorkoming van terugkeer van ’n peptiese ulkus vanweë Helicobacter pylori by pasiënte met sodanige siekte.
KONTRA-INDIKASIES:
• Bekende hipersensitiwiteit teenoor NESOPRAM, gesubstitueerde bensimidasole of enige ander bestanddele van die formulering.
• Gelyktydige toediening met atasanavir en nelfinavir (sien ʺINTERAKSIESʺ).
WAARSKUWINGS:
NESOPRAM word nie vir ligte gastro-intestinale klagtes soos nerveuse dispepsie
aangedui nie.
Voor behandeling van of in die teenwoordigheid van enige waarskuwingsimptoom
(bv. beduidende onbeplande gewigsverlies, herhaalde braking, disfagie,
hematemese of melena) en as ’n maagseer vermoed word of teenwoordig is,
behoort die moontlikheid van maligniteit van ’n gastriese ulkus of ’n maligne siekte
van die esofagus uitgesluit te word aangesien behandeling met NESOPRAM die
simptome van maligne ulkusse kan verlig en sodoende diagnose kan vertraag.
Pasiënte op langtermynbehandeling (veral diegene wat vir meer as ’n jaar onder
behandeling is), moet onder gereelde observasie gehou word.
INTERAKSIES:
Interaksie met ander medisinale produkte en ander vorme van interaksie:
Effekte van NESOPRAM op die farmakokinetika van ander middels:
Die afname in die intragastriese suurgehalte tydens behandeling met
NESOPRAM kan die absorpsie van ander middels verhoog of verlaag indien die
absorpsiemeganisme deur gastriese suurgehalte beïnvloed word. Die absorpsie
van ketokonasool en itrakonasool kan laer wees tydens behandeling met
NESOPRAM.
NESOPRAM inhibeer CYP2C19, die hoof esomeprasool-metaboliserende
ensiem. Gelyktydige toediening van 30 mg esomeprasool het ’n 45 % afname in
die opruiming van die CYP2C19-substraat van diasepaam tot gevolg gehad. Dit is
onwaarskynlik dat hierdie interaksie enige kliniese waarde inhou.
Gelyktydige toediening van 40 mg esomeprasool het ’n toename van 13 %
in trogplasmavlakke van fenitoïen in epileptiese pasiënte tot gevolg gehad;
dosisaanpassing was nie nodig nie.
Gelyktydige toediening van 40 mg esomeprasool aan pasiënte wat met
warfarien behandel word, het getoon dat, ondanks ’n effense verhoging in die
trogplasmakonsentrasie van die minder potente R-isomeer van warfarien, die
stoltye binne aanvaarde perke was. Soos in die geval van alle pasiënte wat
warfarien ontvang, word monitoring gedurende gesamentlike behandeling met
NESOPRAM egter aanbeveel.
In gesonde vrywilligers het gelyktydige toediening van 40 mg esomeprasool ’n
toename van 32 % veroorsaak in die area onder die plasmakonsentrasie-tydkurwe
(AOK) en ’n verlenging van 31 % in die eliminasie-halfleeftyd (t1/2), maar geen
beduidende toename in piekplasmavlakke van sisapried nie. Hierdie interaksie het
nie die invloed van sisapried op die kardiale elektrofisiologie verander nie.
Studies in gesonde vrywilligers het getoon dat gelyktydige gebruik van
esomeprasool en klopidogrel verlaagde plasmakonsentrasies van die aktiewe
metaboliet van klopidrogrel tot gevolg gehad het en ’n afname in plaatjie-inhibisie.
Effek van ander middels op die farmakokinetika van esomeprasool:
NESOPRAM word deur CYP2C19 en CYP3A4 gemetaboliseer. Gelyktydige
toediening van esomeprasool en ’n CYP3A4-inhibeerder, klaritromisien
(500 mg twee maal per dag), het tot ’n verdubbeling van die blootstelling (AOK)
aan esomeprasool gelei. Dosisaanpassing van NESOPRAM is nie nodig nie.
SWANGERSKAP EN LAKTASIE:
Veiligheid tydens swangerskap en laktasie is nie vasgestel nie.
DOSIS EN GEBRUIKSAANWYSINGS:
Die tablette moet heel met vloeistof ingesluk word. Die tablette moet nie gekou of
fyngemaak word nie.
Die tablette kan ook in ’n halwe glas nie-gekarboneerde water opgelos word.
Geen ander vloeistowwe moet gebruik word nie. Roer totdat die tablette
disintegreer en drink die vloeistof met die korrels daarin onmiddellik of binne 30
minute. Spoel die glas met ’n halwe glas water uit, en drink. Die korrels moet nie
gekou of fyngemaak word nie.
Vir pasiënte wat nie kan sluk nie, kan die tablette in nie-gekarboneerde water
opgelos en met behulp van ’n gastriese buis toegedien word.
Gastro-esofageale reflukssiekte (GERS):
• Behandeling van eroderende refluksesofagitis: 40 mg een maal per dag vir
4 weke. ’n Bykomende 4 weke van behandeling word aanbeveel vir pasiënte in wie esofagitis nog nie genees is nie, of wat volgehoue simptome toon.
• Langtermynbehandeling van pasiënte met geneesde esofagitis om ’n terugval te voorkom: 20 mg een maal per dag.
• Simptomatiese behandeling van gastro-esofageale reflukssiekte (GERS):
20 mg een maal per dag by pasiënte sonder esofagitis. Indien simptoombeheer nie bereik kan word na 4 weke nie, moet die pasiënt verder ondersoek word. Sodra simptome opgeklaar het, kan dit dan beheer word deur, wanneer nodig, 20 mg daagliks te neem.
Pasiënte wat voortgesette NSAIM-behandeling benodig:
• Voorkoming van gastriese en duodenale ulkusse geassosieer met
NSAIM-terapie by risiko-pasiënte: 20 mg of 40 mg een maal per dag.
In kombinasie met toepaslike antibakteriële terapeutiese regimens vir die
uitwissing van Helicobacter pylori:
• Genesing van duodenale ulkus vanweë Helicobacter pylori.
• Voorkoming van terugkeer van ’n peptiese ulkus vanweë Helicobacter pylori by pasiënte met sodanige siekte: 20 mg NESOPRAM met 1 g amoksisillien en 500 mg klaritromisien, gelyktydig toegedien, twee maal per dag vir 7 dae.
Kinders:
Daar is geen ervaring met NESOPRAM in kinders nie.
Ingekorte nierfunksie:
Dosisaanpassing is nie nodig by pasiënte met ingekorte nierfunksie nie. Vanweë
beperkte ervaring by pasiënte met ernstige ingekorte nierfunksie, moet sulke
pasiënte met versigtigheid behandel word.
Ingekorte lewerfunksie:
Dosisaanpassing is nie nodig by pasiënte met ligte tot matige ingekorte
lewerfunksie nie. By pasiënte met ernstige lewerinkorting, behoort ’n maksimum
daaglikse dosis van 20 mg NESOPRAM gebruik te word.
Bejaardes:
Dosisaanpassing is nie nodig by bejaardes nie.
NEWE-EFFEKTE EN SPESIALE VOORSORGMAATREËLS:
Newe-effekte:
Infeksies en infestasies:
Minder dikwels: Clostridium difficile wat met diaree verband hou.
Bloed- en die limfatiese stelselversteurings:
Minder dikwels: Agranulositose, leukopenie, trombositopenie.
Immuunstelselversteurings:
Minder dikwels: Hipersensitiwiteitsreaksies bv. angio-edeem, anafilaktiese reaksie.
Senuweestelselversteurings:
Dikwels: Hoofpyn.
Minder dikwels: Duiseligheid, slaperigheid, parestesie.
Psigiatriese versteurings:
Minder dikwels: Slaaploosheid, omkeerbare verwarde toestand, agitasie, hallusinasies, depressie.
Oogversteurings:
Minder dikwels: Belemmerde sig.
Oor- en labirintversteurings:
Minder dikwels: Vertigo.
Vaskulêre versteurings:
Minder dikwels: Periferale edeem.
Gastro-intestinale versteurings:
Dikwels: Abdominale pyn, diaree, opgeblasenheid, naarheid/braking, hardlywigheid.
Minder dikwels: Droë mond, stomatitis, smaakversteurings.
Hepato-biliêre versteurings:
Minder dikwels: Verhoogde lewerensieme, hepatitis met of sonder geelsug.
Voorkoms onbekend: Hepatiese enkefalopatie.
Vel- en subkutane weefselversteurings:
Dikwels: Veluitslae.
Minder dikwels: Dermatitis, pruritus, urtikarie, alopesie, blaserige veluitslag, veelvuldige eriteem, Stevens-Johnson-sindroom, toksiese epidermale nekrolise, fotosensitiwiteit.
Muskuloskeletale, bindweefsel- en beenversteurings:
Minder dikwels: Artralgie, mialgie.
Renale en urinêre stelselversteurings:
Minder dikwels: Interstisiële nefritis.
Voortplantingstelsel en borsversteurings:
Minder dikwels: Impotensie, ginekomastie.
Algemene versteurings en toedienplekversteurings:
Minder dikwels: Moegheid, verhoogde sweet, ongesteldheid.
Spesiale Voorsorgmaatreëls:
Clostridium difficile geassosieerde diaree:
Gepubliseerde waarnemingstudies dui daarop dat PPI-terapie soos met
esomeprasool geassosieer mag word met verhoogde risiko van Clostridium
difficile-geassosieerde diaree, veral by gehospitaliseerde pasiënte. Hierdie
diagnose behoort oorweeg te word by diaree wat nie verbeter nie. Pasiënte
behoort die laagste dosis en kortste tydperk van NESOPRAM-terapie te gebruik
wat geskik is vir die toestand wat behandel word.
Effekte op die vermoë om te bestuur en masjinerie te gebruik:
NESOPRAM kan slaperigheid, duiseligheid en belemmerde visie veroorsaak.
Pasiënte word aangeraai om versigtigheid aan die dag te lê wanneer hul motor
bestuur of masjinerie gebruik aangesien konsentrasie belemmer mag wees.
BEKENDE SIMPTOME VAN OORDOSERING EN BESONDERHEDE VAN DIE
BEHANDELING DAARVAN:
Die simptome wat in verband met doelbewuste NESOPRAM-oordosering
(beperkte ervaring van dosisse wat 240 mg/dag oorskry) beskryf word, is van
verbygaande aard. Enkeldosisse van 80 mg esomeprasool was sonder enige
voorval. Geen spesifieke teenmiddel is bekend nie. Esomeprasool is tot ’n
groot mate aan plasmaproteïene gebonde en is dus nie geredelik dialiseerbaar
nie. Soos in die geval van enige oordosering, moet behandeling simptomaties
plaasvind en moet algemene ondersteunende maatreëls toegepas word.
IDENTIFIKASIE:
NESOPRAM 20: Ligte baksteenkleurige rooi tot bruin, ovaal, bikonvekse,
filmbedekte tablette met ‘E5’ gepers op een kant en skoon op die ander kant.
NESOPRAM 40: Ligte baksteenkleurige rooi tot bruin, ovaal, bikonvekse,
filmbedekte tablette met ‘E6’ gepers op een kant en skoon op die ander kant.
AANBIEDING:
Karton bevat 14, 28 of 30 tablette verpak in kouevorm-stulpstroke of droogmiddelingelegde kouevorm-stulpstroke. Elke stulpstrook bevat 7 of 10 tablette.
Karton bevat ’n wit ondeursigtige HDPE-bottel met ’n skroefprop bevattende 30
tablette.
Beskrywing van die droogmiddel-ingelegde kouevorm-stulpverpakking:
Kouevorm-laminaat bestaande uit aluminiumfoelie waarvan die een kant helder,
saggetemper, effe, dowwe kant lakgelamineer aan geörienteerde poliamiedfilm is;
die ander kant uitgepers bedek met droogmiddel-ingelegde poli-etileen en verder
het dit ’n buitenste laag van HDPE met ’n foeliebedekking.
Beskrywing van die kouevorm-stulpverpakking:
Die kouevorm-stulpverpakking bestaan uit kouevorm-stulpstrooklaminaat
bestaande uit aluminiumfoelie (een kant helder, saggetemper, effe; dowwekant
lakgelamineer aan geörienteerde poliamiedfilm; helderkant lakgelamineer aan
PVC-film), PVC en poliamied met ’n rugkant van aluminiumfoelie bedek met
hitteseëllak.
Beskrywing van HDPE-bottelverpakking:
Die bottel is ’n wit, ondeursigtige HDPE-bottel met ’n wit ondeursigtige
polipropileen skroefdeksel met ’n induksieseël-voering. Die bottel bevat ook ’n
droogmiddelsakkie (1 g).
BEWARINGSINSTRUKSIES:
Bewaar by of benede 25 ºC, beskerm teen vog.
Moenie die stulpstroke uit die karton verwyder tot benodig vir gebruik nie.
HOU BUITE BEREIK VAN KINDERS.
REGISTRASIENOMMERS:
NESOPRAM 20: 45/11.4.3/0123
NESOPRAM 40: 45/11.4.3/0124
NAAM EN BESIGHEIDSADRES VAN DIE HOUER VAN DIE
REGISTRASIESERTIFIKAAT:
RANBAXY (SA) (PTY) LTD
Grondvloer, Tugela House, Riverside Office Park, Heuwellaan 1303,
Centurion, Suid-Afrika
Bemark deur CIPLA MEDPRO (EDMS) BPK.
DATUM VAN PUBLIKASIE VAN DIE VOUBILJET:
2 Oktober 2014
CM482A/SA
NESOPRAM® 20 (Gastries-weerstandbiedende tablette)
NESOPRAM® 40 (Gastries-weerstandbiedende tablette)