RiteMED Isosorbide-5-Mononitrate

RiteMED Isosorbide-5-Mononitrate

isosorbide mononitrate

Manufacturer:

RiteMED

Distributor:

United Lab
Full Prescribing Info
Contents
Isosorbide-5-mononitrate.
Description
Each sustained-release tablet contains 60 mg Isosorbide-5-mononitrate.
Action
Pharmacology: Pharmacodynamics: Mechanism of action: Isosorbide mononitrate has a direct relaxing effect on the smooth muscles and leads to vasodilation.
Postcapillary capacitance vessel and the great arteries - especially the still reagible coronary arteries are thereby more affected than resistance vessels. Vasodilation in the current path leads to an increase in venous capacity ("pooling"), reflux to the heart is decreased, ventricular volumes and filling pressures go down ("preload" reduction). Reduced ventricular radius and decreased systolic wall tension lower myocardial energy or oxygen requirements.
The decrease in the cardiac filing pressures favours the perfusion of ischaemically endangered, subendocardial wall layers, regional wall movement and stroke volume can be improved.
The dilation of the great arteries near the heart leads to a decrease in the systemic ("afterload reduction") as well as in the pulmonary ejection resistance.
Isosorbide mononitrate causes a relaxation of the bronchial musculature, of the efferent urinary tract, the musculature of the gall bladder, the bile duct as well as the oesophagus, the small and large intestines including the sphincter muscles.
On a molecular level, the nitrates most probably act on the formation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), which is regarded as mediator of relaxation.
Pharmacokinetics: Isosorbide-5-monononitrate is rapidly and completely absorbed after oral administration. The systemic bioavailability is 90-100%. Isosorbide mononitrate is almost completely metabolised in the liver. The resulting metabolites are inactive. The plasma half-life is 4-5 hours. Isosorbide mononitrate is excreted via the kidneys almost exclusively in the form of its metabolites. Only approximately 2% is excreted via the kidneys in unchanged form.
Tolerance: Despite constant dose and constant nitrate levels, a decrease in efficacy was observed. An existing tolerance subsides within 24 hours after discontinuing therapy.
No tolerance development was observed in case of accordingly intermittent administration.
Toxicology: Preclinical safety data: Chronic Toxicity: Chronic toxicity studies in rats did not provide any evidence of toxic effects. A rise in methaemoglobin concentration by 2.6% compared to the baseline value was measured in dogs after oral administration of 191 mg isosorbide mononitrate/kg. The serum nitrite concentration after oral administration of 191 mg isosorbide mononitrate/kg bordered on the detection limit (less than 0.02 mg/L); alkaline phosphatase and GPT were unchanged.
Mutagenic and tumorinogenic potential: Long-term studies in rats did not yield any evidence of a tumorinogenic potential of isosorbide-5-mononitrate. Mutagenicity studies in several test systems (in vitro and in vivo) demonstrated negative results.
Reproductive toxicity: Animal studies did not give any evidence of teratogenic effects of isosorbide-5-mononitrate.
Studies of perinatal/postnatal toxicity showed foetotoxic effects only after very high doses in the maternal-toxic range.
No sufficient experience is available regarding use in human pregnancy and lactation. When used by pregnant women, it is advisable to observe the infants for pharmacologic effects of isosorbide mononitrate.
Indications/Uses
Prophylaxis and long-term treatment of angina pectoris.
Dosage/Direction for Use
One sustained-release tablet of isosorbide-5-mononitrate 60mg is taken once daily.
General rules: Isosorbide mononitrate is not intended for the immediate relief of acute attacks of angina pectoris; if they occur, the additional use of rapid-acting nitrate preparations is indicated.
Development of tolerance or attenuation of effect may occur with all long-acting nitrates in individual patients on continuous treatment. This can be reversed with low-nitrate blood levels.
One sustained-release tablet of isosorbide-5-mononitrate 60mg is taken once daily.
Method and duration of administration: The sustained-release tablets are to be taken whole with some liquid (e.g. 1 glass of water).
Therapy should be started with low dosage and increased slowly up to the dosage required.
The duration of administration is determined by the attending physician.
Overdosage
Symptoms of overdose: Isosorbide monohydrate overdose may lead to the following symptoms: Orthostatic hypotension, reflex-tachycardia and headaches, weakness, dizziness, somnolence, flush, sweating, palor, weak pulse, nausea, vomiting and diarrhoea.
At high doses (>20 mg/kg/bodyweight), cyanosis, methaemoglobinaemia, dyspnoea and tachypnoea must be anticipated owing to nitrite ions liberated during metabolism of isosorbide mononitrate. With chronic overdose, increased methaemoglobin levels have been observed.
At very high doses, an increase in intracranial pressure with cerebral symptoms may occur.
Treatment in the event of overdose: Besides general measures such as supine position of the patient with raised logs, oxygen supply, and administration of activated charcoal or gastric lavage, the vital signs must be monitored under intensive care conditions and corrected, if necessary.
In the event of marked hypotension and/or shock volume expansion should occur; in exceptional cases, norepinephrine (noradrenaline) and/or dopamine can be administered. Vasopressors should only be used in patients with inadequate response to volume expansion.
Depending on the severity of methaemoglobinaemia, vitamin C, methylene blue or toluidine blue may be administered. In case of severe methaemoglobinaemia, oxygen therapy, initiation of artificial ventilation, haemodialysis, and blood exchange should occur.
Contraindications
Known hypersensitivity to the active substance, nitrates or to any of the excipients; low cardiac filing pressures (e.g. in acute myocardial infarction); aortic/mitral valve stenosis; marked hypotension (systolic blood pressure <90 mmHg); acute circulatory failure (shock, circulatory collapse); cardiogenic shock; severe hypovolaemia; severe anaemia; diseases associated with a raised intracranial pressure (e.g. following a head trauma, cerebral haemorrhage); hypertrophic obstructive cardiomyopathy; constrictive pericarditis, cardiac tamponade; closed angle glaucoma.
Concomitant use of phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil, vardenafil or tadalafil because PDE5 inhibitors may amplify the vasodilatory effects of isosorbide mononitrate resulting in severe hypotension (see Interactions).
Concomitant use of isosorbide mononitrate with riociguat, a soluble guanylate cyclase stimulator, is contraindicated.
Special Precautions
Isosorbide mononitrate should be used with caution in case of: recent history of myocardial infarction; low filing pressures e.g. in acute myocardial infarction; impaired left ventricular function (left ventricular failure); orthostatic dysfunction.
Treatment with isosorbide mononitrate, as with any other nitrate, should not be stopped suddenly, but tapered gradually.
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 on attack of angina pectoris could increase by doing so (see Contraindications and Interactions).
Effects on ability to drive and use machines: While driving or operating machinery it must be considered that hypotension, dizziness or fatigue may occur, especially at the start of treatment or with concomitant use of alcohol.
Use In Pregnancy & Lactation
Pregnancy: There are no or limited amount of data from the use of isosorbide mononitrate in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foeto-/neonatal development, birth or postnatal development. Isosorbide mononitrote should be given to a pregnant woman only if clearly indicated.
Breast-feeding: It is not known whether isosorbide mononitrate passes into the breast milk. Therefore, breastfeeding should be discontinued before starting treatment.
There is no data available on the effect of isosorbide mononitrate on fertility in humans.
Adverse Reactions
The evaluation of undesirable effects is based on the following frequency definitions: 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).
Nervous system disorders: Very common: Headaches, in particular at the beginning of treatment ("nitrate headache"), which commonly improves on treatment continuation.
Common: Drowsiness, dizziness, somnolence.
Cardiac disorders: Common: Tachycardia.
Uncommon: Angina pectoris aggravated.
Vascular disorders: Common: Drop in blood pressure and/or orthostatic hypotension that may be associated with reflex tachycardia.
Uncommon: Circulatory collapse, sometimes accompanied by bradyarrhythmia and syncope.
Gastrointestinal disorders: Uncommon: Nausea, vomiting.
Very rare: Heartburn.
Skin and subcutaneous tissue disorders: Uncommon: Flush, allergic skin reactions (e.g. rash).
Very rare: Steven-Johnson syndrome, angioneurotic oedema.
Not known: Exfoliative dermatitis.
General disorders and administration site conditions: Very common: Cross-tolerance to other nitrates.
Common: Asthenia, development of tolerance.
During treatment with isosorbide mononitrate, temporary hypoxia 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.
Drug Interactions
Concurrent administration of other vasodilators, antihypertensives (e.g. beta-blockers, calcium channel blockers, diuretics, ACE inhibitors), neuroleptics and tricyclic antidepressants as well as alcohol maycpotentiate the hypotensive effect of isosorbide-5-mononitrate.
Concomitant use of isosorbide mononitrote and PDE5 inhibitors such as sildenafil, vardenafil and tadalafil may potentiate the vasodilatory effects of isosorbide mononitrate resulting in life-threatening cardiovascular complications. Patients on isosorbide mononitrate therapy therefore must not use phosphodiesterase type-5 inhibitors (see Contraindications).
Concurrent administration of isosorbide mononitrate with dihydroergotamine may increase dihydroergotamine blood levels and its hypertensive effects.
Acetylsalicylic acid may reduce the efficacy of isosorbide mononitrate.
Sapropterine (tetrahydrobiopterine, BH4) is a cofactor for nitric oxide synthetase. Caution is recommended during concomitant use of sapropterine-containing medicinal products with all agents that cause vasodilation by affecting nitric oxide (NO metabolism or action, including classical NO donors (e.g. glyceryl trinifrate (GTN), isosorbide dinitrate (ISDN), isosorbide mononitrate and others).
Concomitant use of isosorbide mononitrate and riociguat, a soluble guanylate cyclase stimulator, is contraindicated, as simultaneous use may induce hypotension (see Contraindications).
Caution For Usage
Incompatibilities: Not applicable.
Storage
Store at temperatures not exceeding 30°C.
Store in the original pack in order to protect the contents from moisture.
MIMS Class
ATC Classification
C01DA14 - isosorbide mononitrate ; Belongs to the class of organic nitrate vasodilators. Used in the treatment of cardiac disease.
Presentation/Packing
SR tab 60 mg (white, round, flat on both sides with slight beveled edges; scored on one side and plain on the other side) x 50's.
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