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
o Patients should be kept horizontal with the head lowered and legs raised
o Supply oxygen
o Expand plasma volume (i.v. fluids)
o 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
o Reduction therapy of choice with vitamin C, methylene-blue or toluidine-blue
o Administer oxygen (if necessary)
o Initiate artificial ventilation
o Hemodialysis (if necessary)
- Resuscitation measures
In case of signs of respiratory and circulatory arrest, initiate resuscitation measures immediately.
5 years
None Known
Core:
Lactose monohydrate
Purified Talc
Ethyl cellulose
Macrogol 20000
Hydroxypropyl cellulose
Sucrose
Corn starch
Capule shell:
Gelatin
Titanium dioxide
Iron oxide red (E172)
Iron oxide black (E172)
Undesirable effects frequencies are defined as: very common (>1/10), common (>1/100 <1/10), uncommon (>1/1,000 <1/100), rare (>1/10,000 <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
During administration of Elantan LA 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 Elantan LA, 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 products 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, oncogenicity and toxicity to reproduction.
ATC Code: C01D A14 Vasodilator 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 afterload and especially preload of the heart.
Isosorbide mononitrate influences the oxygen supply to the 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 requirement 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.
Isosorbide mononitrate is a vasodilator, which is rapidly absorbed following oral administration. These capsules have a bioavailability of 84 (±7)% when compared to the immediate release isosorbide mononitrate tablets. There is no effect of food on bioavailability.
The capsules contain pellets which are formulated to release 30% of the dose immediately whilst 70% of the dose is released slowly.
Time to peak plasma levels (Tmax) is 5.0 (±3) hrs; with a half life (T½) of 5.02 (±0.68) hrs.
Isosorbide mononitrate is extensively metabolised to nitric oxide (NO-which is the active ingredient) and isosorbide (inactive). In patients with cirrhotic disease or cardiac failure or renal failure, parameters were similar to those obtained in healthy volunteers.
August 2016
Merus Labs Luxco II S.Ã r.l.
26-28, rue Edward Steichen
L-2540 Luxembourg
Do not store above 30°C.
Cartons of blister strips of PVC and aluminium or of PP and aluminium.
Aluminium foil thickness 20 μm or 16 μm.
Pack size: 28 capsules.
PL 44374/0015
Dizziness, tiredness or blurred vision may occur at the start of treatment. The patient should therefore be advised that if affected, they should not drive or operate machinery. This effect may be increased by alcohol.
None
28 February 2008
