New Zealand - English - Medsafe (Medicines Safety Authority)
Consumer Medicine Information
What is in this leaflet
This leaflet answers somecommon
Itdoes notcontain allthe available
information. Itdoes nottake the
place of talking to your doctor or
Allmedicines have risks and
benefits. Your doctor has weighed
the risks of you having
Corangin againstthe benefitsthey
expect it will provide.
If you have any concerns about
this medicine, ask your doctor or
Keep this leaflet.
You may need to read it again.
What Corangin is
Corangin contains the active
mononitrate. Itbelongs toa class of
medicines know as organic nitrate
vasodilators, meaningthat they
cause blood vesselstowiden.
Widening the blood vesselsmeans
thatblood flow and blood pressure
isimproved, and so the heartdoes
notneed todo as much work and
does notneed as much oxygen.
Corangin isused topreventangina
pectoris andtotreat heart failure. It
is notsuitable for the treatmentof
acute attacks of angina pectoris.
Ask your doctor ifyou have any
questions about why this
medicine has been prescribed for
Your doctor mayhave prescribed it
Corangin isonlyavailable witha
doctor's prescription. Itisnot
There isnotenough information to
recommend the use of thismedicine
Before you take
When you must not take
Do not take Corangin if you have
ever had an allergic reaction to:
or anyof the other ingredients
listedat the endofthis leaflet
anyother medicine containing
nitrates or nitrites.
You have low blood pressure
You have recently had a heart
attack or other serious heart
disease, a stroke or a head
Do notuse Corangin if you are
taking Viagra, a medicine for
impotence in men.
If you use these two medicines
together your blood pressure may
fall toa dangerously low level.
mayinclude shortness of breath,
wheezing or difficulty breathing;
swelling of the face, lips, tongue or
other parts of the body;rash, itching
or hives on the skin.
Do not take Corangin after the
expiry date printed on the pack
or ifthe packaging istorn or
shows signs of tampering.
In that case, return the medicine to
Before you start to take it
Tellyour doctor ifyou are
pregnant or planning to become
There is limitedinformation
available on the use of this
medicine inpregnancy. Your doctor
can discuss withyou the benefits
and risks involved.
Tell your doctor if you are breast-
whileyou are taking Corangin. Itis
notknown ifthe active ingredient,
intothe breast milkandcouldaffect
Tellyour doctor if:
you have anycardiac or
allergies toany other
medicines, foods, dyes or
Your doctor maywanttotake
special precautions if you have any
of the above conditions.
Taking other medicines
Tellyour doctor ifyou are taking
any other medicines, including
medicines that you buy without a
prescription from a pharmacy,
supermarket or health food shop.
Somemedicines and Corangin may
interfere with each other. These
Viagra, a medicine for
impotence in men
other medicines for angina
medicines for high blood
pressure or hearttrouble
diureticmedicines, also called
water or fluid tablets
medicines used to treat
medicines for mentaldisorders
dihydroergotamine, a medicine
acetylsalicylic acid (aspirin)
medicines used to treat
inflammation called non-
You mayneed totake different
amounts of your medicines or you
mayneed totake different
medicines. Your doctor and
pharmacisthave more information.
If you have not toldyour doctor
about any of these things, tell
him/her before you take
How to take Corangin
Follow all directions given to you
by your doctor or pharmacist
information contained inthis
Yourdoctor will tell youhowmany
Corangin tablets to take each day.
Corangin ispresented inthe formof
divitabs. These are divisible slow-
relase tablets, whichallow the
dosage to be increased or decreased
stepwise, so that it can be more
How much to take
The adultdose isusuallyone tablet
of Corangin 40mg once dailyand
increased as required byadding ½
of a 40mg tablet. Tablets can be
takeneither inthe morningor
evening depending on whattime of
day the angina attacks occur.
Swallow the table witha full glass
of water or other liquid.
If you forgettotake a dose of this
medicine, butremember todo so
within2 hours, take the missed dose
rightaway witha full glass ofwater
or other liquid. Then go back to
your regular dosing schedule.
However, if you do notremember
until later, skipthe misseddose and
then go back toyour regular dosing
schedule. Do notdouble the doses.
If you take too much
Tellyour doctor ifyou have any
of the following symptoms, which
may point to possible signs of
feeling of extreme pressure in
dizziness or faintness
shortness of breath, rapid
blueness around the mouth and
at extremities due tolackof
weak and unusuallyfast
While you are taking
Things you must do
Follow your doctor's instructions
carefully and keep all
Tell your doctor immediately if
you become pregnant while
having treatment with Corangin.
Your doctor can discuss withyou
the risks oftakingit while youare
If you are about to be started on
any new medicine, remind your
doctor and pharmacist that you
are taking Corangin.
Tellany other doctor, dentist or
pharmacist who treats you that
you are taking Corangin.
Things you must not do
Donot givethis medicine to
symptoms seem to be the same as
Do not use it to treat any other
complaints unless your doctor
tells you to.
Things to be careful of
Be careful driving, operating
machinery or doing jobs that
require you to be alert until you
know how Corangin affects you.
Be careful when drinking alcohol
while youare usingCorangin
If you drink alcoholwhileyou are
using it,your blood pressure may
drop, making you feeldizzyor
Tell your doctor or pharmacist as
soon as possible ifyou do not feel
well while youare taking
Allmedicines can have side effects.
Sometimes they are serious, most of
the time they are not. You may need
of the side effects.
If you are over 65 years old, you
should be especially careful and
report any side effects promptly
to your doctor.
As people grow older, theyare
more likely toget side effects from
Do not be alarmed by these lists
of possible side effects. You may
not experience any of them. Ask
your doctor or pharmacist to
answer any questions you may
Tellyour doctor ifyou notice any
of the following side effects and
they worry you:
lightheadedness upon standing
flushing – these normallyoccur
at the start of treatment
headache – these normally
occur at the start of treatment
allergic skinreactions suchas
Tell your doctor immediately or
go to the Accident and
Emergency Department at your
nearest hospitalifyou notice any
of the following:
signs of allergy such as rash,
itching or hives on the skin;
swelling of the face, lips,
tongue or other partof the
body;shortness of breath,
wheezing or troubled breathing
symptomsof angina getworse
The above side effects maybe
serious. You mayneed urgent
Tellyour doctor ifyou notice
anything else that ismaking you
Somepeople mayhave other side
effects notyetknown or mentioned
inthis leaflet. Some side effects can
onlybe found bylaboratorytesting.
After taking Corangin
Store the medicine ina cooldry
Do notstore Corangin or any
other medicine inthe bathroom
or near a sink.
Do not leave it in the car or on
Keep the medicine where children
cannot reach it.
A locked cupboard atleastone-and-
a-halfmetres above the ground isa
good place to store medicines.
If you no longer need Corangin
or it has passed its expiry date,
return any unused medicine to
What it looks like
Corangin is a white capsule shaped
divisible (scored) slow-release
tablet with convex faces imprinted
withCG/CG on one side and
EDE/EDE on the other. Packs
containing 30 tablets
Corangin tablets contain 40mg
isosorbide-5-mononitrate of the
active ingredientincluding the
Polyvinylpyrrolidon K 30
Corangin issupplied inNew
NovartisNew Zealand Limited
NovartisNew Zealand Limited
Private Bag 65904
BuildingG, 5Orbit Drive
Telephone 0800 652 422
®= Registered Trademark
This leaflet was prepared on 23
June 2009 based on the currently
approved datasheetfor thisproduct
NEW ZEALAND DATA SHEET
CORANGIN ® 40 mg and 60 mgslow release divisible tablets
Description and composition
Slow-release tablets ,divisible (Divitabs ®
), containing 40 or 60 mgisosorbide-5-mononitrate.
Isosorbide-5-mononitrate. One tablet contains 40 mg or 60 mg.
Tablets(40 mg, 60 mg): silicagel, aerosil 200, lactose, magnesium stearate, Methocel
K 100 M premium (hydroxypropyl-methylcellulose), polyethylenglycol 4000,
polyvinylpyrrolidon K 30.
Corangin is indicated for:
Long termtreatment of ischemic heart disease,
Prevention of angina pectoris attacks,and also in cases wheresymptomsof angina pectoris
persist after myocardial infarction. Corangin may be used either as monotherapy or in
combination with other antianginal agents(e.g. beta-blockers orcalciumantagonists).
Treatment for chronic heart failure, in combination with digitalis or other positive-inotropic
agents and/or diuretics.
Dosage and administration
Corangin is not intended for the immediate relief ofacute attacks ofangina pectoris; ifthey
occur, the additional use ofrapid-acting nitrate preparationsis indicated.
Development of tolerance or attenuation of effect may occur withall long-acting nitrates in
individual patients on continuoustreatment. This can be reversed with low-nitrate blood
levels (as observed with Corangin atthe end of thedosing interval).
The starting dose should be 1tablet of Corangin 40 mgonce dailyand increased asrequired,
either by adding one-half of a 40mg tablet or changing to the 60 mgtablet. Depending on the
time of day at which the angina pectoris attacks occur in the individual patient, the slow-
release tablet can be taken eitherin the morning or in the evening.
Iftreatment with Corangin in angina pectorispatients isto bediscontinued, an abrupt
cessation should be avoided: if a change toanother product is envisaged, a period of
overlapping treatment should be considered.
Chronic heart failure
In chronic heart failure, it is recommended thattreatment be started in hospital and the
patient’s hemodynamic status monitored; treatment should also be continued in hospital until
the required maintenance dose has been established. The optimal dose should be determined
based on the clinical response and tolerability,with careful monitoring for signs of
overdosage such as hypotension and tachycardia.
Dosage and administrationin special populations
No information is available on the use of Corangin in children.
Geriatrics(aged 65 years or above)
In elderly patients, Corangin should be startedat a low dose and with caution due to the
higher likelihood of orthostatic or postural hypotension.
No dose adjustment of Corangin is requiredinpatients with renal impairment (see Clinical
No dose adjustment of Corangin is requiredin patients with hepatic impairment (see Clinical
Method of administration
Corangin is taken orally and can be administered with or without food (see Clinical
Corangin is presented in the formof Divitabs.These are divisible slow-release tablets, which
allow the dosage to beincreased or decreased stepwise, so that it can bemore closely adapted
to individual requirements. Even ifthe two halves of the tablet are ingested separately, the
prolonged duration of action remains unchanged.
Known hypersensitivity to nitrates.
Acute circulatory failure associated with marked hypotension(shock, states of collapse).
Conditions associated with elevated intracranial pressure.
Myocardial insufficiency due to obstruction (e.g. in the presence of aortic or mitral valve
stenosis or of constrictive pericarditis).
Concomitant use of Corangin and phosphodiesterase type 5 (PDE5) inhibitors such as
sildenafil is contraindicated, because PDE5 inhibitors may amplify the vasodilatory effects
of Corangin resulting insevere hypotension.
Warnings and precautions
Cardiac and vascular disorders
In cases of recent myocardial infarction or acute heart failure, Corangin should only be used
cautiously under strict medical surveillance and/or hemodynamic monitoring.
Patients with angina pectoris,myocardial infarction, or cerebral ischemia frequently suffer
fromabnormalities of the small airways (especially alveolar hypoxia). Under these
circumstances vasoconstriction occurs within thelung to shift perfusion fromareas of alveolar
hypoxia to better ventilated regions of the lung. As a potentvasodilator, isosorbide-5-
mononitrate could reverse this protective vasoconstriction and thus result in increased
perfusion of poorly ventilated areas, worsening ofthe ventilation/perfusion imbalance, and a
further decrease in the arterial partial pressure of oxygen.
When transferring the patient on long-termtherapy to another formof medication,Corangin
should be gradually withdrawn and overlapping treatment should be started to avoid the risk
of angina pectoris.
Driving and using machines
As syncope and dizziness are the known adversedrug reactions associated with the use of
Corangin, patients should not drive a vehicle or operate a machine or performtasks that
require alertness if they experience these symptoms.
Adverse drug reactions
Table 7.1 presents adverse drug reactions observed frommixed sources including clinical
trials and post-marketing spontaneous reports.
Table 0-1 Tabulated summaryof adverse drugreactions
Syncope, orthostatic hypotension, tachycardia, dizziness, flushing
Nervous system disorders
Like other nitrate preparations,Corangin may frequently give rise to headache, which is due
to cerebral vasodilatation and is dose dependent. Headaches, however, usually regress after a
few days despite continuation of the therapy.Flushing, syncope, dizziness, and orthostatic
hypotension, which may be associated with reflex-induced tachycardia, have rarely been
Interactionsresultingin a contraindication
Concomitant use of Corangin and PDE5 inhibitors suchas sildenafil is contraindicated;
because sildenafil may amplifythe vasodilatory effects of Corangin resulting in severe
hypotension (see Contraindications ).
Interactionsto be considered
Concomitant treatment with other vasodilators, calciumantagonists, ACE inhibitors, beta-
blockers, diuretics, antihypertensives, may potentiate the blood-pressure-lowering effect of
Tricyclic antidepressants,or major tranquilizers, as wellas the consumption of alcohol, may
potentiate the blood-pressure-lowering effect of Corangin.
Concurrent administration of Coranginwith dihydroergotamine may increase the
bioavailability of dihydroergotamine. This warrants special attention inpatients with coronary
artery disease, because dihydroergotamine antagonizes the effect of nitrates and may lead to
Non-steroidal anti-inflammatory drugs (NSAIDS)
The possibility that acetylsalicylic acid andNSAIDS might diminish the therapeutic response
to Corangin cannot be excluded.
Women of child bearing potential, pregnancy,breast-feeding and
Women of child bearing potential
There is nodata supportinganyspecialrecommendations in women of child-bearing
There is a limited amount ofdatafromtheuse of isosorbide-5-mononitrate in pregnant
patients. Limited animalstudies do not indicate director indirectharmful effects with respect
to reproductive toxicity. Corangin should be given to a pregnantwoman only if clearly needed
and the benefit outweighs the risk.
Itis not known whether the active substance passes into the breast milk. Thebenefitsforthe
mother must be weighed against the risks for the child.
There is no data available on the effect ofisosorbide-5-mononitrate on fertility in humans.
Signs and symptoms
High doses of isosorbide-5-mononitrate may leadto more pronounced systemic side effects,
e.g. to a marked hypotension or to syncope. Excessive dosage of all nitrates may, on rare
occasions, provoke methemoglobinemia.
Overdosage should be treated symptomatically.
Pharmacotherapeutic group, ATC
Pharmaco therapeutic group: Vasodilator (ATC code C01DA14)
Mechanism of action
Nitrates are prodrugs that are sources of nitric oxide (NO). NO activatesthe soluble isoform
of guanylyl cyclase,thereby increasing intracellular levels of cyclic guanosine
monophosphate (cGMP). In turn, cGMP promotesthe dephosphorylation ofthe myosin light
chain and the reductionof cytosolic calciumwhich leads to the relaxation of smooth muscle
cells, ultimately leading to vasodilation .
Likeother nitrates, isosorbide-5-mononitrateissuitable forthe chronic treatment ofischemic
heart disease and heart failure.In angina pectoris, its fundamental mechanismof action is
primarily based on an increasein venous capacitance (venous pooling) leading to a decreased
return of blood to the heart. Owing to this phenomenon, left-ventricularend-diastolic pressure
(preload) and hence filling volume diminishes, resultingin a decreased myocardial oxygen
requirement at rest andespeciallyduring exercise, with an improvementin exercisecapacity
in patients with angina pectoris. In the coronary arterial circulation,isosorbide-5-mononitrate
dilates both extramural conductance and small resistance vessels.The drug appears to cause a
redistribution of coronary blood flow to theischemic subendocardiumby selectively dilating
large epicardial vessels.It also produces relaxation of vasospasm,whether spontaneous or
induced by ergometrine.
In addition, isosorbide-5-mononitrate exerts a dose-dependent dilating effect on the arteriolar
vascular bed, as a result of which systemic vascular resistance (afterload) and left-ventricular
systolic wall tension decrease, leading toa reduction in myocardial oxygen consumption.
In chronic heart failure the dilating action exerted by isosorbide-5-mononitrate on the veins
lowers the elevated left-ventricular filling pressure, while atthe sametime cardiacoutput
either remains unchanged or increases slightly.
Isosorbide-5-mononitrate proves effective especially in patients with severe heart failure
showing prominent signs and symptomsof venous pulmonary congestion due to a pronounced
increase inleft-ventricular fillingpressure. If an increase in cardiac output is desired,
combined treatment with an arterial vasodilator is recommended.
The duration of action of isosorbide-5-mononitrate is longer than thatof its parent compound.
A therapeutic efficacysimilar tothat of isosorbide dinitrate may be achieved with
approximately half the dose.
Isosorbide-5-mononitrate is rapidly and completely absorbed fromthe conventional dosage
forms. Unlike isosorbide dinitrate, isosorbide-5-mononitrate isfree fromfirst-pass
metabolism in theliver, anditsbioavailabilitytherefore showslower inter-individual
variability. AUC values assessed byreferenceto the plasma levels increase linearlywith the
With Corangin, the peakconcentrations attainedare approximately 60% lower than after
administration of the samedose in conventional dosage forms. Peak concentrations are
reached 4-8 hours after ingestion of Corangin and in less than 1 hour after administration of
conventional formulations. The amount absorbedfromsustained-release formulations such as
Corangin is slightly reduced (by 10-20%) in comparison with conventional formulations. No
accumulation of isosorbide-5-mononitrate was seenafter repeated once-daily administration
in normal volunteers or in patients. The results of pharmacokinetic studies suggest that no
alterations ofthe dosage should be necessary inpatients with coronaryheart disease, renal
failure, or hepatic cirrhosis. Ingestion of food has been reported to have only a negligible
effect on the absorption of isosorbide-5-mononitrate.
The volume of distribution of isosorbide mononitrate is approximately 0.6 L/kg, which is
close to the total body water. The plasmaprotein binding of isosorbide mononitrate is
Isosorbide mononitrate is almost completelymetabolized in the liver. The resulting
metabolites are inactive.
Isosorbide mononitrate is excreted via the kidneys almostexclusively in the formof
metabolites.Approximately 2% is excreted via the kidneys in unchanged form. Mean half-
lives of isosorbide-5-mononitrate calculated after administration of conventional formulations
range between 4.0 and 4.8 hours.
No recent clinical trials have been conducted with Corangin.
Non- clinical safetydata
Several in vitro and in vivo test systems revealed no evidence of mutagenic activity of
isosorbide-5-mononitrate. A dietary carcinogenicity study in rats gave no evidence of a
carcinogenic potential of isosorbide-5-mononitrate. The effect of Corangin on reproduction
and embryonic, fetal and/or postnatal development has been insufficiently investigated in
Special precautions for storage
Store at below 25°C. Protect frommoisture.
Corangin should be kept out of the reach of children.
Instructions for use and handling
PVC/PE/PVDC blisters of30 tablets
Name and address
Novartis New Zealand Limited
Private Bag 65904
Building G, 5 Orbit Drive
Telephone: 09 361 8100
Date of preparation
21 October 2011