Skip to Content

ISOSORBRIDE MONONITRATE 40 MG TABLETS

Active substance(s): ISOSORBIDE MONONITRATE / ISOSORBIDE MONONITRATE

View full screen / Print PDF » Download PDF ⇩

PDF Transcript

SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Isosorbide Mononitrate 40 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains diluted isosorbide mononitrate equivalent to isosorbide
mononitrate 40 mg.
Excipient(s) with known effect:
Each tablet contains 129.00mg lactose monohydrate.
For the full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
Tablet
Isosorbide mononitrate 40 mg Tablets are white to off white circular, biconvex
uncoated tablets debossed with ‘I’ and ‘40’ separated by break line on one side and
plain on other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the prophylaxis and long term management of angina pectoris.

4.2

Posology and method of administration
For oral administration
Tablet should be swallowed whole with water.
One tablet daily, twice daily, or three times daily

Adults:
One tablet to be taken asymmetrically (to allow a nitrate low period) two or three
times a day. The dosage may be increased up to 120mg per day.
Dosage regime should be designed according to the clinical response of the patient.
Tablets should be taken after meals, unchewed with water.
The lowest effective dose should be used.
In patients taking one tablet twice daily the second dose should be taken 8 hours after
the first dosage. If the dose is one three times daily, take one every 6 hours. This
provides a nitrate-free period of 6 – 8 hours.
Paediatric population: The safety and efficacy of Isosorbide Mononitrate 40mg
Tablets in children has not been established.
Older people: There is no evidence to suggest that an adjustment of the dosage is
necessary.
Treatment with Isosorbide mononitrate tablets, as with any other nitrate, should not
be stopped suddenly. Both the dosage and frequency should be tapered gradually (see
section 4.4)

4.3

Contraindications
Isosorbide mononitrate tablets should not be given to patients with a known
sensitivity to isosorbide mononitrate, the listed ingredients or other nitrates.
Isosorbide mononitrate tablets should not be used in cases of acute myocardial
infarction with low filling pressures, acute circulatory failure (shock, vascular
collapse), or very low blood pressure (systolic blood pressure below 90 mmHg),
hypertrophic obstructive cardiomyopathy (HOCM), constrictive pericarditis, cardiac
tamponade, low cardiac filling pressures, aortic/mitral valve stenosis and diseases
associated with a raised intra-cranial pressure e.g. following a head trauma and
including cerebral haemorrhage.
Isosorbide mononitrate Tablets should not be used in patients with severe anaemia,
severe hypotension, closed angle glaucoma or severe hypovolaemia.
Phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) have
been shown to potentiate the hypotensive effects of nitrates, and their coadministration with nitrates or nitric oxide donors is therefore contraindicated (see
section 4.4 and 4.5)
During nitrate therapy, the soluble guanylate cyclase stimulator riociguat must not be
used (see section 4.5).

4.4

Special warnings and precautions for use
Isosorbide mononitrate Tablets should be used with caution in patients who have
recent history of myocardial infarction, or who are suffering from hypothyroidism,
hypothermia, malnutrition and severe liver or renal disease.
Symptoms of circulatory collapse may arise after first dose, particularly in patients
with labile circulation.
This product may give rise to symptoms of postural hypotension and syncope in some
patients. Severe postural hypotension with light-headedness and dizziness is
frequently observed after the consumption of alcohol.
Hypotension induced by nitrates may be accompanied by paradoxical bradycardia and
increased angina.
Isosorbide mononitrate Tablets contain lactose and therefore should not be used in
patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption.
In the event of an acute angina attack, a sublingual treatment such as a GTN spray or
tablet should be used instead of Isosorbide mononitrate Tablets. The onset of action
of Isosorbide mononitrate Tablets is not sufficiently rapid to be useful to treat an
acute anginal attack.
If the tablets are not taken as indicated (see section 4.2), tolerance to the medication
could develop. The lowest effective dose should be used.
Treatment with Isosorbide mononitrate, as with any other nitrate, should not be
stopped suddenly. Both the dosage and frequency should be tapered gradually (see
section 4.2)
In patients with decreased gastrointestinal transit time, a decrease in release of the
active ingredient may occur.
Patients who undergo a maintenance treatment with Isosorbide mononitrate should be
informed that they must not use phosphodiesterase inhibitor-containing products (e.g.
sildenafil, tadalafil, vardenafil).
Isosorbide mononitrate therapy should not be interrupted to take phosphodiesterase
inhibitor-containing products (e.g. sildenafil, tadalafil, vardenafil), because the risk of

inducing an attack of angina pectoris could increase by doing so (see section 4.3 &
4.5).

4.5

Interaction with other medicinal products and other forms of interaction
Concurrent administration of drugs with blood pressure lowering properties, e.g. betablockers, calcium channel blockers, vasodilators, alprostadil, aldesleukin, angiotensin
II receptor antagonists etc. and/or alcohol may potentiate the hypotensive effects of
Isosorbide mononitrate Tablets. This may occur with neuroleptics and tricyclic
antidepressants.
Any blood pressure lowering effect of Isosorbide mononitrate tablets will be
increased if used together with phosphodiesterase type-5- inhibitors, which are used
for erectile dysfunction (see special warning and contraindications). This may lead to
life threatening cardiovascular complications. Patients who are on Isosorbide
mononitrate therapy therefore must not use phosphodiesterase type-5 inhibitors. (e.g.
sildenafil, tadalafil, vardenafil).
The use of isosorbide mononitrate with riociguat, a soluble guanylate cyclase
stimulator, is contraindicated (see section 4.3) since concomitant use can cause
hypotension.
Reports suggest that concomitant administration of Isosorbide mononitrate tablets
may increase the blood levels of dihydroergotamine and its hypertensive effects.
Sapropterine (Tetrahydrobiopterine, BH4) is a cofactor for nitric oxide synthetase.
Caution is recommended during concomitant use of sapropterine-containing medicine
with all agents that cause vasodilation by affecting nitric oxide (NO) metabolism or
action, including classical NO donors (e.g. glyceryl trinitrate (GTN), isosorbide
dinitrate (ISDN), isosorbide 5-mononitrate (5-ISMN) and others).

4.6

Fertility, pregnancy and lactation
Pregnancy
Safety in pregnancy has not been established for isosorbide mononitrate. There is data
that nitrates are excreted in breast milk and may cause methemoglobinemia in infants.
Therefore Isosorbide mononitrate tablets should only be used in pregnancy and
during lactation if, in the opinion of the physician, the possible benefits of treatment
outweigh the hazards.
Breast-feeding

The extent of excretion of isosorbide mononitrate in human breast milk has not been
determined. Therefore caution should be exercised when administered to nursing
women.
Fertility
There is no data available on the effect of isosorbide mononitrate on fertility in
humans.

4.7

Effects on ability to drive and use machines
Dizziness, tiredness or blurred vision might occur at the start of the treatment.
The patient should therefore be advised that if affected, they should not drive or
operate machinery. This effect may be increased by alcohol.

4.8

Undesirable effects
Frequency categories are defined according to the following convention:
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)
During administration of Isosorbide Mononitrate Tablets the following undesirable
effects may be observed:
Nervous system disorders:


very common: headache



common: dizziness (including dizziness postural), somnolence

Cardiac disorders:


common: tachycardia



uncommon: angina pectoris aggravated

Vascular disorders:


common: orthostatic hypotension



uncommon: circulatory collapse (sometimes accompanied by
bradyarrhythmia and syncope)



not known: hypotension

Gastrointestinal disorders:


uncommon: nausea, vomiting



very rare: heartburn

Skin and subcutaneous tissue disorders:


uncommon: allergic skin reactions (e.g. rash), flushing



not known: dermatitis exfoliative

Immune system disorders:


not known: angioedema

General disorders and administration site conditions:


common: asthenia.

Severe hypotensive responses have been reported for organic nitrates and include
nausea, vomiting, restlessness, pallor and excessive perspiration.
During treatment with Isosorbide Mononitrate Tablets, a temporary hypoxemia may
occur due to a relative redistribution of the blood flow in hypoventilated alveolar
areas. Particularly in patients with coronary artery disease this may lead to a
myocardial hypoxia.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Animal experience:
In rats and mice, significant lethality at oral doses of 1965 mg/kg and 2581 mg/kg,
respectively, was observed.
Human experience:
Symptoms:
- Fall of blood pressure ≤ 90 mmHg

- Paleness
- Sweating
- Weak pulse
- Tachycardia
- Light-headedness on standing
- Headache
- Weakness
- Dizziness
- Nausea
- Vomiting
- Diarrhoea
Methaemoglobinaemia has been reported in patients receiving other organic nitrates.
During isosorbide mononitrate biotransformation nitrite ions are released, which may
induce methaemoglobinaemia and cyanosis with subsequent tachypnoea, anxiety, loss
of consciousness and cardiac arrest. It cannot be excluded that an overdose of
isosorbide mononitrate may cause this adverse reaction.
In very high doses the intracranial pressure may be increased. This might lead to
cerebral symptoms.
General procedure:
• Stop intake of the drug
• General procedures in the event of nitrate-related hypotension
- Patients should be kept horizontal with the head lowered and legs raised
- Supply oxygen
- Expand plasma volume (i.v. fluids)
- Specific treatment for shock (admit patient to intensive care unit)
Special procedure:
• Raising the blood pressure if the blood pressure is very low.
• Treatment of methaemoglobinaemia
- Reduction therapy of choice with vitamin C, methylene-blue or toluidine-blue
- Administer oxygen (if necessary)
- Initiate artificial ventilation
- Hemodialysis (if necessary)
• Resuscitation measures
In case of signs of respiratory and circulatory arrest, initiate resuscitation measures
immediately.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC code: C01D A14 Vasodilatator used in cardiac diseases
Isosorbide mononitrate is an organic nitrate, which, in common with other
cardioactive nitrates, is a vasodilator. It produces decreased left and right ventricular
end-diastolic pressures to a greater extent than the decrease in systemic arterial
pressure, thereby reducing after load and especially the preload of the heart.
Isosorbide mononitrate influences the oxygen supply to ischaemic myocardium by
causing the redistribution of blood flow along collateral channels and from epicardial
to endocardial regions by selective dilation of large epicardial vessels.
It reduces the requirements of the myocardium for oxygen by increasing venous
capacitance, causing a pooling of blood in peripheral veins, thereby reducing
ventricular volume and heart wall distension.

5.2

Pharmacokinetic properties
Isosorbide-5-mononitrate is rapidly absorbed and peak plasma levels occur approx. 1
hour following oral dosing.
Isosorbide-5-mononitrate is completely bioavailable after oral doses and is not subject
to pre-systemic elimination processes.
Isosorbide-5-mononitrate is eliminated from the plasma with a half-life of about 5.1
hours. It is metabolised to Isosorbide-5-mn-2-glucoronide, which has a half-life of
approximately 2.5 hours. As well as being excreted unchanged in the urine.
After multiple oral dosing plasma concentrations are similar to those that can be
predicted from single dose kinetic parameters.

Characteristics in patients:
Evidence was provided that the plasma profiles in healthy volunteers and patients
suffering from chronic stable angina are similar.
Isosorbide mononitrate is dialysable.

5.3

Preclinical safety data
Acute toxicity:
Studies on acute toxicity in mice and rats with different routes of administration
indicate a low acute toxicity (LD50 oral approximately 2,000 - 2,500 mg/kg b.w.).

Chronic toxicity:
Long term toxicity has been tested in rats for 78 weeks and in dogs for 52 weeks.
First toxic reactions occurred in dosages of 90 mg/kg (dog) and 405 mg/kg (rat),
respectively. Thus taking into account the recommended dosage of 20 to 30 mg/d in
humans, the therapeutic index can be stated as high.

Reproduction studies:
These studies included a fertility and breeding study over two generations in rats;
teratology studies in rats and rabbits; and a rat peri-postnatal study. The dosage levels
used were generally high and produced maternal toxic effects at the highest dose. No
teratogenic effects of isosorbide mononitrate were observed.

Mutagenicity:
Isosorbide mononitrate was tested in different studies both in vitro and in vivo (Ames
test, Human peripheral lymphocytes, Bone marrow of rats and hamsters, V 79 test,
SCE test) on possible mutagenic effects. As all tests were negative the mutagenic risk
in humans is considered low.

Carcinogenicity:
Neither the long term toxicity studies in rats and dogs nor a special carcinogenicity
study, performed in rats over 125 weeks (males) and 138 weeks (females), indicated
neoplastic properties of isosorbide mononitrate. Therefore, it can be concluded that
the carcinogenic risk in humans is low.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Microcrystalline cellulose (E460),
Lactose monohydrate,
Colloidal silicon dioxide (E551),
Talc
Stearic acid

6.2

Incompatibilities
Not Applicable.

6.3

Shelf life
24 months

6.4

Special precautions for storage
This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container
Child resistant Aluminium-PVC blister packs of 28s, 56s tablets
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Not Applicable.

7

MARKETING AUTHORISATION HOLDER
Flamingo Pharma UK Ltd.
Ist floor, Kirkland House,
11-15 Peterborough Road,
Harrow, Middlesex,
HA12AX, United Kingdom.

8

MARKETING AUTHORISATION NUMBER(S)
PL 43461/0012

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
15/06/2017

10

DATE OF REVISION OF THE TEXT
15/06/2017

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide