Isorey

Clear colorless to slightly yellow solution.
Each mL contains: Isosorbide Dinitrate, BP 1 mg.

Pharmacotherapeutic group: Vasodilators used in cardiac diseases, organic nitrates. ATC Code: CO1D A08.
Pharmacology: Pharmacodynamics: Mechanism of Action and Pharmacodynamic effects: Isosorbide dinitrate is an organic nitrate and vasodilator. It decreases left and right ventricular end-diastolic pressures to a greater extent than systemic arterial pressure, resulting in reduced cardiac afterload and, particularly, preload.
Isosorbide dinitrate enhances oxygen delivery to ischemic myocardium by promoting redistribution of blood flow through collateral channels and from epicardial to endocardial regions via selective dilation of large epicardial vessels.
Isosorbide dinitrate reduces myocardial oxygen demand by increasing venous capacitance, leading to peripheral venous pooling and a consequent reduction in ventricular volume and myocardial wall tension.
Pharmacokinetics: Metabolism and Elimination: Isosorbide dinitrate (ISDN) is eliminated from plasma with a short half-life of approximately 0.7 hours. Its metabolic degradation, similar to that of other organic nitrates, occurs primarily through denitration and glucuronidation. The rate constants for metabolite formation are approximately 0.57 h^-1 for isosorbide-5-mononitrate (IS-5-MN), 0.27 h^-1 for isosorbide-2-mononitrate (IS-2-MN), and 0.16 h^-1 for isosorbide (IS).
Both IS-5-MN and IS-2-MN are pharmacologically active primary metabolites. IS-5-MN undergoes further metabolism to isosorbide-5-mononitrate-2-glucuronide (IS-5-MN-2-GLU), which has a shorter half-life (approximately 2.5 hours) compared to IS-5-MN (approximately 5.1 hours). Among these compounds, ISDN has the shortest half-life, while that of IS-2-MN (approximately 3.2 hours) is intermediate.

Isosorbide dinitrate is indicated for the management and treatment of: Severe or unstable angina pectoris; Left ventricular failure unresponsive to conventional therapy secondary to acute myocardial infarction; Left ventricular failure of various etiologies unresponsive to standard treatment; Adjunctive use during percutaneous transluminal coronary angioplasty (PTCA) to facilitate prolonged balloon inflation and to prevent or relieve coronary spasm.

Adults: Intravenous: A dose between 2 mg and 12 mg per hour is usually effective. Doses up to 20 mg per hour may be given and should be adjusted based on the patient's response.
Intra-coronary: The typical dose is 1 mg as a bolus injection before balloon inflation. Additional doses may be given if needed, but the total should not exceed 5 mg within 30 minutes.
Children: The safety and efficacy of Isosorbide Dinitrate Injection have not yet been established in children.
Elderly: No dose adjustment is necessary.
Renal and Hepatic Impairment: Isosorbide Dinitrate Injection should be used with caution in patients with severely impaired renal or hepatic function.
Method of administration: Isosorbide Dinitrate Injection is a concentrated solution and must be diluted before use. It should not be given as a direct bolus injection, except via the intra-coronary route before balloon inflation. A 50% dilution is recommended for intra-coronary use.
Isosorbide Dinitrate Injection can be administered by intravenous infusion using a compatible solution. Prepared admixtures should be given via infusion pump or syringe pump with a glass or rigid plastic syringe. Blood pressure and pulse should be closely monitored during administration and the dose adjusted according to clinical response.
For intravenous or intracoronary use only.

Symptoms: Symptoms may include a fall in blood pressure to ≤90 mmHg, pallor, sweating, weak pulse, tachycardia, postural dizziness, headache, asthenia, dizziness, nausea, vomiting, and diarrhea. Methaemoglobinemia has been reported in patients receiving other organic nitrates; during isosorbide dinitrate biotransformation, nitrite ions are released, which may induce methaemoglobinemia and cyanosis, potentially leading to tachypnoea, anxiety, loss of consciousness, and cardiac arrest. Although rare, an overdose of Isosorbide Dinitrate may cause this adverse reaction. At very high doses, increased intracranial pressure may occur, potentially resulting in cerebral symptoms.
Treatment: If nitrate-related adverse effects occur, the first step is to stop the delivery of the drug. General management includes laying the patient down with the head lowered and legs raised, supplying oxygen, expanding plasma volume through intravenous fluids, and providing specific shock treatment, which may require admission to an intensive care unit. If blood pressure remains very low, it should be raised carefully. Vasopressors are reserved for patients who do not respond adequately to fluid resuscitation, with noradrenaline or other vasoconstrictors used as needed. In cases of methaemoglobinemia, treatment involves reduction therapy with agents such as vitamin C, methylene blue, or toluidine blue, along with oxygen administration and, if necessary, artificial ventilation. Should respiratory or circulatory arrest occur, resuscitation measures must be initiated immediately.

Isosorbide dinitrate is contraindicated in patients with known hypersensitivity to the active substance, to any of the excipients, or to other nitrates or nitrites. It must not be used in conditions associated with low filling pressure, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, or cardiogenic shock, unless measures are in place to maintain adequate diastolic pressure. The use of isosorbide dinitrate is also contraindicated in circulatory collapse, severe aortic or mitral valve stenosis, severe hypotension (systolic blood pressure <90 mmHg), head trauma, cerebral hemorrhage, or diseases associated with increased intracranial pressure.
Isosorbide dinitrate should not be administered to patients with marked anemia, hypovolemia, or closed-angle glaucoma. Concomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) or with the soluble guanylate cyclase stimulator riociguat is contraindicated.

Use with caution: Isosorbide dinitrate should be used with caution and under medical supervision in patients with hypothyroidism, hypothermia, malnutrition, severe liver or renal disease, and in those with orthostatic hypotension.
Tolerance: The development of tolerance (reduced efficacy) and cross-tolerance to other nitrate-type drugs has been reported. To prevent a decrease or loss of effect, continuously high dosages should be avoided.
Monitoring of blood pressure and pulse: Blood pressure and pulse should be regularly monitored, and the dose adjusted according to the patient's clinical response.
Hypoxemia: Caution is advised in patients with hypoxemia or ventilation/perfusion imbalance due to lung disease or ischemic heart failure. As a potent vasodilator, isosorbide dinitrate may increase perfusion to poorly ventilated areas, potentially worsening the ventilation/perfusion imbalance and further reducing arterial oxygen partial pressure.
Alcohol: Alcohol should be avoided during treatment, as it may potentiate the hypotensive and vasodilatory effects of isosorbide dinitrate.
Phosphodiesterase inhibitors: Patients receiving maintenance therapy with isosorbide dinitrate must not use phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil). Therapy should not be interrupted to take these products, as this may increase the risk of angina attacks. Acute therapy with isosorbide dinitrate must not be administered to patients who have recently taken phosphodiesterase inhibitors-24 hours for sildenafil or vardenafil, and 48 hours for tadalafil. Patients should be warned not to take phosphodiesterase inhibitor-containing products during treatment.

Pregnancy: Studies in animals have not shown evidence of harm to the fetus. However, there is limited experience in pregnant women, and animal data may not reliably predict human response. Isosorbide dinitrate should only be used during pregnancy if clearly necessary and under medical supervision.
Lactation: Available evidence is insufficient to determine the risk to the breastfed infant. Nitrates are known to be excreted in breast milk and may cause methemoglobinemia in infants. The extent of excretion of isosorbide dinitrate and its metabolites in human breast milk has not been established. Therefore, caution should be exercised when administering isosorbide dinitrate to lactating women.

Undesirable effects frequencies are defined as very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000), and not known when the frequency cannot be estimated from available data. During administration of Isosorbide Dinitrate, the following undesirable effects may be observed: See table.

Click on icon to see table/diagram/image

Phosphodiesterase-5 inhibitors: Concomitant use of isosorbide dinitrate with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) may lead to pronounced hypotension and potentially life-threatening cardiovascular events. Therefore, isosorbide dinitrate must not be administered to patients receiving these agents. Acute therapy with isosorbide dinitrate must not be given within 24 hours of sildenafil or vardenafil intake, or within 48 hours of tadalafil intake.
Blood pressure-lowering agents: The hypotensive effect of isosorbide dinitrate may be potentiated by concurrent use of other blood pressure-lowering drugs, such as beta-blockers, calcium channel blockers, ACE inhibitors, vasodilators, monoamine oxidase inhibitors, neuroleptics, or tricyclic antidepressants, as well as by alcohol. Co-administration with ACE inhibitors or arterial vasodilators may be therapeutically desirable; however, if excessive hypotension occurs, dose adjustment of one or both agents should be considered.
Dihydroergotamine: Concomitant administration of isosorbide dinitrate may increase plasma concentrations of dihydroergotamine, potentially enhancing its hypertensive effects.
Riociguat: The use of isosorbide dinitrate with riociguat, a soluble guanylate cyclase stimulator, is contraindicated due to the risk of pronounced hypotension (see Contraindications).
Sapropterin: Sapropterin (tetrahydrobiopterin, BH4) is a cofactor for nitric oxide synthase. Caution is advised when sapropterin-containing medicines are used concomitantly with agents that induce vasodilation via nitric oxide pathways, including classical NO donors such as glycerol trinitrate, isosorbide dinitrate, or isosorbide 5-mononitrate.

Store at temperatures not exceeding 30°C.
Shelf-Life: 36 months.

Anti-Anginal Drugs

C01DA08 - isosorbide dinitrate ; Belongs to the class of organic nitrate vasodilators. Used in the treatment of cardiac disease.

Rx