100 mg/100 ml, 10 mg/10 ml
For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
Each ml contains :
Isosorbide Dinitrate 1 mg
Sodium Chloride B.P. 9 mg
Water for Injections B.P. q.s.
Contains no preservatives.
PHARMACEUTICAL DOSAGE FORM :
1. Intravenous : ISOBID is indicated in the treatment of unresponsive left ventricular failure secondary to acute myocardial infarction, unresponsive left ventricular failure of various aetiology and severe or unstable angina pectoris.
2. Intra-coronary : ISOBID is indicated during percutaneous transluminal coronary angioplasty to facilitate prolongation of balloon inflation and to prevent or relieve coronary spasm.
ISOBID is a concentrated solution and must be diluted prior use. The diluted solution should never be injected directly in the form of a bolus except via the intra-coronary route prior to balloon inflation. A dilution of 50 % is advocated for intracoronary administration. ISOBID can be administered as an intravenous admixture with a suitable vehicle such as Sodium Chloride Injection B.P. or Dextrose Injection B.P.
Prepared ISOBID admixtures should be given by intravenous infusion or with the aid of a syringe pump incorporating a glass or rigid plastic syringe. During administration the patient’s blood pressure and pulse should be closely monitored.
INSTRUCTION FOR USE OF AMPOULE (for 10 ml Ampoule) :
The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
Adults, including the elderly :
Intravenous route :
A dose of between 2 mg and 12 mg per hour is usually satisfactory. However, dosages up to 20 mg per hour administered should be adjusted to the patient response.
Intra-coronary Route :
The usual dose is 1 mg given as a bolus injection prior to balloon inflation. Further doses may be given not exceeding 5 mg within a 30 minute period.
The safety and efficacy of ISOBID has not yet been established in children.
Dosage chart :
1 ml = 60 paediatric microdrops ≡ 20 standard drops.
The dosage chart shows the infusion rate necessary to achieve a certain ISOBID dosage in mg/hour, using a concentration of either 100 µg/ml or 200 µg/ml.
Dosage is very simple to calculate. With a concentration of 100 µg/ml the patient requiring 6 mg ISDN per hour would need a drip rate of 60 paediatric microdrops per minute (which is the same as 60 ml per hour) or 20 standard drops per minute. If it is necessary to restrict the fluid intake the same dose (6 mg/hour) could be achieved using a concentration of 200 µg/ml and a drip rate of 30 paediatric microdrops per minute (30 ml per hour) or 10 standard drops per minute. A dilution of 50 % is advocated to produce a solution containing 0.5 mg/ml where fluid intake is strictly limited.
Admixtures are stable for approximately 24 hours at room temperature in the recommended containers. Open ampoules or vials should be used immediately and any unused drug discarded.
Contraindicated in patients hypersensi-tive to Isosorbide Dinitrate. ISOBID should not be used in patients with severe anaemia, recent head trauma or cerebral haemorrhage, severe renal or hepatic impairment, or in patients with increased intracranial pressure, hypovolaemia and severe hypotension. Use in circulatory collapse or low filling pressure is also contraindicated. ISOBID should not be used in the treatment of cardiogenic shock, unless some means of maintaining an adequate diastolic pressure is undertaken. Sildenafil has been shown to potentiate the hypotensive effects of nitrates and its co-administration with nitrates or nitric oxide donors is therefore contraindicated.
ISOBID should be used with caution in patients who are suffering from hypothyroidism, malnutrition, severe liver or renal disease or hypothermia. Close attention to pulse and blood pressure is necessary during administration of ISOBID infusions.
Haemolysis may occur in glucose-6-de-hydrogenase deficient patients. Hypotension induced by Isosorbide Dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris. Nitrate therapy may aggravate the angina caused by hypertonic cardiomyopathy. Nitrate therapy should be discontinued if methaemoglobinaemia occurs, if blurred vision or dry mouth continues or is severe. When this medicine is to be discontinued following high dose or long term administration, dosage should be reduced gradually to prevent possible withdrawal rebound angina.
Safety in pregnancy and lactation has not been established.
ISOBID should only be used in pregnancy and during lactation if, in the opinion of the physician, the possible benefits of treatment outweigh the possible hazards.
Paediatric Use :
Safety and effectiveness in paediatric patients has not been established.
The relationship of age to the effects of nitrates has not been studied in geriatrics. However elderly patients may be more sensitive to the hypotensive effects of nitrates and are more likely to have age related renal function impairment, which may require caution in patients receiving nitrates.
EFFECTS ON ABILITY TO DRIVE AND OPERATE MACHINE :
The effects of norepinephrine, acetylcholine, histamine and many other agents may be decreased when used concurrently with nitrates. Concurrent use of sympathomimetics may reduce the anti-anginal effects of nitrates. Alcohol, antihypertensives or other hypotension producing medication, opioid analgesics or vasodilators may intensify the orthostatic hypotensive effects of nitrates. Dosage adjustment may be necessary. The hypotensive effect of nitrates is potentiated by concurrent administration of Sildenafil. This might also occur with neuroleptics and tricyclic antidepressants.
Laboratory/Physiology values :
Serum cholesterol determination by the Zlatkis-Zak colour reaction method may be falsely decreased. Methaemoglobin concentration in blood may be increased by excessive doses of nitrate.
SIDE EFFECTS :
Cutaneous vasodilatation with facial flushing, tachycardia, oedema and coldness of the skin. Rarely cyanosis and methaemoglobinaemia may occur. Impairment of respiration and bradycardia may ensue. Headache, which usually decreases after a few days, is common but may be severe and persistent. Headaches may often be controlled by decreasing the dose. Transient episodes of dizziness and weakness as well as other signs of cerebral ischaemia associated with postural hypotension, and syncope may occasionally develop. Cresendo angina and rebound hypertension have also been reported but are uncommon. Patients with normal or low pulmonary capillary wedge pressure may be unusually sensitive to hypotensive effects. An occasional individual exhibits a marked sensitivity to the hypotensive effects of nitrate, and severe responses (laryngeal oedema, blurred vision, dryness of the mouth, nausea, vomiting, weakness, restlessness, pallor, perspiration and collapse) can occur even with the usual therapeutic dose. Alcohol antihypertensives or other hypotension producing medication, opioid analgesics or vasodilators may enhance this effect. Dosage adjustments may be necessary. Drug rash and/or exfoliative dermatitis may occasionally occur. A slight increase and decrease in intra-ocular pressure has been found in patients with closed angle glaucoma.
Hemodynamic effects :
The ill-effects of Isosorbide Dinitrate overdose are generally the results of its metabolite Isosorbide mononitrate’s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifesttions, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo, palpitations, visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhoea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures and death.
Methaemoglobinemia has been reported in patients receiving other organic nitrates, and it probably could also be a side effect of Isosorbide Dinitrate. Certainly nitrate ions liberated during metabolism of Isosorbide Dinitrate can oxidize haemoglobin into methaemoglobin. Notwithstanding these observations, there are case reports of significant methaemoglobinemia in association with moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusually susceptible. Methaemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial po2. Classically, methaemoglobinemic blood is described as chocolate brown, without colour change or exposure to air.
TREATMENT OF OVERDOSAGE :
In general, treatment should be symptomatic and supportive. When methaemoglobinemia is diagnosed, the treatment of choice is Methylene Blue, 1-2 mg / kg intravenously.
PHARMACEUTICAL PRECAUTIONS :
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Store below 30°C (86°F),
Do not refrigerate.
SHELF LIFE :
36 months from the date of manufacture.
ISOBID is supplied as per below table.
|1 mg/ml (0.1%)
|10 ml Ampoule||5 Ampoules|
|1 mg/ml (0.1%)
|50 ml Vial||1 Vial|
|1 mg/ml (0.1%)
|100 ml Vial||1 Vial|
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.