Numotrate
Numotrate Uses, Dosage, Side Effects, Food Interaction and all others data.
Isosorbide-5-mononitrate is an active metabolite of isosorbide dinitrate. It is a vasodilator with effects on both arteries and vein and also coronary vessels. It causes reduction of preload and afterload and redistributes coronary flow to ischemic regions.
Isosorbide mononitrate relaxes vascular smooth muscles by stimulating cyclic-GMP. It decreases left ventricular pressure (preload) and arterial resistance (afterload).
Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. The pharmacological action is mediated by the active metabolite, nitric oxide, which is released when isosorbide mononitrate is metabolized. Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload. In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness.
At therapeutic doses of isosorbide mononitrate, nitric oxide has a bigger effect on larger muscular arteries over small resistance arteries. Arterial relaxation leads to reduced systemic vascular resistance and systolic blood (aortic) pressure, decreasing to decreased cardiac afterload. The direct dilator effect on coronary arteries opposes the coronary artery spasm in variant angina or angina pectoris. At larger doses, nitric oxide causes the resistance arteries and arterioles to dilate, reducing arterial pressure via coronary vasodilatation. This leads to increased coronary blood flow. Reduced cardiac preload and afterload caused by nitric oxide causes a reduction in myocardial oxygen consumption; decreased myocardial oxygen demand, along with increased coronary blood flow, leads to an increased in the oxygen content of coronary sinus blood and the relief from ischemia.
The end effect of isosorbide mononitrate include decreased cardiac oxygen consumption, redistribution coronary flow toward ischemic areas via collaterals, and the relief of coronary spasms. Nitric oxide can also increase the rate of relaxation of cardiac muscles, which is an effect outside of vascular smooth muscles. Organic nitrates can also relax other types of smooth muscles, including esophageal and biliary smooth muscle. The anti-anginal activity of isosorbide mononitrate was observed about 1 hour after dosing, and the peak effect was achieved from 1-4 hours after dosing. The duration of anti-anginal action of at least 12 hours was observed with an asymmetrical dosing regimen.
| Trade Name | Numotrate |
| Generic | Isosorbide Mononitrate |
| Isosorbide Mononitrate Other Names | ISMN, Isosorbide 5-mononitrate, Isosorbide 5-nitrate, Isosorbide mononitrate, Isosorbidi mononitras, Mononitrate d'isosorbide, Mononitrato de isosorbida, Monosorbitrate |
| Type | Tablet |
| Formula | C6H9NO6 |
| Weight | Average: 191.1388 Monoisotopic: 191.042987025 |
| Protein binding | Isosorbide mononitrate is about 5% bound to plasma proteins. |
| Groups | Approved |
| Therapeutic Class | Nitrates: Coronary vasodilators |
| Manufacturer | Emcure Pharmaceuticals Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Isosorbide mononitrate tablets are used for-
- The prevention of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
- Long-term treatment of blood-flow disorders of the coronary vessels (coronary heart disease)
- Long-term treatment and prophylaxis of angina pectoris (chest pain due to coronary blood-flow disorders of the coronary vessels).
- Treatment of severe myocardial insufficiency (chronic heart failure)
Numotrate is also used to associated treatment for these conditions: Angina Pectoris
How Numotrate works
Isosorbide mononitrate acts as a prodrug for nitric oxide (NO), which is a potent vasodilator gas that is released when the drug is metabolized. NO activates soluble guanylyl cyclase in vascular endothelial cells, which increases the intracellular concentrations of cyclic GMP (cGMP). cGMP activates cGMP-dependent protein kinases, such as protein kinase G and I, which activates the downstream intracellular cascades. The downstream cascade results in reduced intracellular concentrations of calcium, caused by processes including inhibition of IP3-mediated pathway, phosphorylation of big calcium-activated potassium channel leading to cell hyperpolarization and reduced calcium influx, and increased calcium efflux via the Ca2+-ATPase-pump. Reduced intracellular calcium concentrations lead to the dephosphorylation of myosin light chains and the relaxation of smooth muscle cells.
Dosage
Numotrate dosage
The recommendedregimenof Numotrate tablets is 20 mg (one tablet) twice daily, with the two doses given 7 hours apart. For most patients, this can be accomplished by taking the first dose on awakening and the second dose 7 hours later. Dosage adjustments are not necessary for elderly patients or patients with alteredrenalorhepaticfunction.
Multiple studies oforganicnitrates have shown that maintenance of continuous 24-hourplasmalevels results inrefractorytolerance. The dosing regimen for Numotrate tablets provides a daily nitrate-free interval to avoid the development of this tolerance. Well-controlled studies have shown that tolerance to Numotrate tablets is avoided when using the twice-daily regimen in which the two doses are given 7 hours apart. This regimen has been shown to have antianginal efficacy beginning 1 hour after the first dose and lasting at least 5 hours after the second dose. The duration (if any) of antianginal activity beyond 12 hours has not been studied; large controlled studies with other nitrates suggest that no dosing regimen should be expected to provide more than about 12 hours of continuous antianginal efficacy per day.
Inclinical trials, Numotrate tablets have been administered in a variety of regimens. Single doses less than 20 mg have not been adequately studied, while single doses greater than 20 mg have demonstrated no greater efficacy than doses of 20 mg.
Side Effects
Hypotension, tachycardia, flushing, headache, dizziness, palpitation, syncope, confusion. Nausea, vomiting, abdominal pain. Restlessness, weakness and vertigo. Dry mouth, chest pain, back pain, oedema, fatigue, abdominal pain, constipation, diarrhoea, dyspepsia and flatulence.
Toxicity
The oral LD50 is 2010 mg/kg in rats and 1771 mg/kg in mice.
The symptoms of overdose from isosorbide mononitrate is associated with vasodilatation, venous pooling, reduced cardiac output, and hypotension. These symptoms can be accompanied by several manifestations, including increased intracranial pressure (possibly along with persistent throbbing headache, confusion, and moderate fever), vertigo, palpitations, visual disturbances, nausea and vomiting (possibly along with colic and bloody diarrhea), syncope (especially in the upright posture), air hunger and dyspnea (later followed by reduced ventilatory effort), diaphoresis (with flushed or cold and clammy skin), heart blocks and bradycardia, paralysis, coma, seizures, and death.
There is limited clinical information on the management of isosorbide mononitrate overdose; it is advised that venodilatation and arterial hypovolemia from overdose are responded with therapy aimed to increase in central fluid volume. However, this method may be potentially hazardous in patients with renal disease or congestive heart failure: invasive monitoring may be required in these patients. The patient's legs should be passively elevated, and intravenous infusion of normal saline or similar fluid is recommended. Isosorbide mononitrate was shown to be significantly removed from the systemic circulation via hemodialysis. The use of epinephrine or other arterial vasoconstrictors is not recommended.
Precaution
Severe renal or severe hepatic impairment, hypothyroidism, malnutrition, or hypothermia. Caution in patients who are already hypotensive. May aggravate angina caused by hypertrophic cardiomyopathy. Tolerance may develop after long-term treatment. Lactation.
Interaction
Hypotensive effects may be increased when used with alcohol or vasodilators. Concurrent use with calcium channel blockers may lead to marked orthostatic hypotension.
Food Interaction
- Take with or without food. The absorption is unaffected by food.
Volume of Distribution
The volume of distribution is approximately 0.6 L/kg, which is approximately the volume of total body water.
Elimination Route
Upon oral administration, isosorbide mononitrate is rapidly and completely absorbed from the gastrointestinal tract. Isosorbide mononitrate has a dose-linear kinetics and the absolute bioavailability is nearly 100%. The Cmax is reached within 30 to 60 minutes following administration.
Half Life
The elimination half-life of isosorbide mononitrate is about 5 hours. The elimination half-life of its metabolites, isosorbide and 2-glucuronide of mononitrate, are 8 hours and 6 hours, respectively.
Clearance
The total body clearance is 115-120 mL/min.
Elimination Route
In a human radio-labelled drug study, about 93% of the total dose was excreted in the urine within 48 hours. Following oral administration of 20 mg, only 2% of isosorbide mononitrate was excreted unchanged in the urine within 24 hours. Among the excreted dose, nearly half of the dose was found de-nitrated in urine as isosorbide and sorbitol: approximately 30% is excreted as isosorbide and about 17% is the 2-glucuronide of mononitrate. These metabolites were not vasoactive or pharmacologically active. Renal excretion was complete after 5 days, and fecal excretion accounted for only 1% of drug elimination.
Pregnancy & Breastfeeding use
There are no adequate and controlled studies to date with Isosorbide-5-mononitrate in pregnant women, and the drug should be used during pregnancy only when the potential benefit justified possible risks to the fetus. Execration of Isosorbide-5-mononitrate into human milk is unknown, so precaution should be taken when it is administered to a nursing mother.
Contraindication
It is contraindicated in patients who have shown hypersensitivity or idiosyncratic reactions to other nitrates or nitrites.
Acute Overdose
Symptoms : Most common symptoms are hypotension, throbbing headache, tachycardia, and flushing. Methemoglobinemia may occur with massive doses.
Treatment: Treatment consists of placing patients in recumbent position and administering fluids; alpha-adrenergic vasopressors may be required. Methemoglobinemia should be treated with methyline blue at a dose of 1-2 mg/kg IV slowly.
Storage Condition
Store at 20-25° C.
Innovators Monograph
You find simplified version here Numotrate
Numotrate contains Isosorbide Mononitrate see full prescribing information from innovator Numotrate Monograph, Numotrate MSDS, Numotrate FDA label
FAQ
What is Numotrate used for?
Numotrate is used to prevent angina (chest pain) caused by coronary artery disease (heart disease). Numotrate is a medication used for heart-related chest pain, heart failure, and esophageal spasms. It can be used both to treat and to prevent heart-related chest pain.
How safe is Numotrate?
Do not take more or less of it or take it more often than prescribed by your doctor. Numotrate chest pain but does not cure coronary artery disease. Continue to take Numotrate even if you feel well. Do not stop taking isosorbide without talking to your doctor.
How does Numotrate work?
Numotrate works by relaxing the blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload.
What are the common side effects of Numotrate?
Common side effects of Numotrate are include:
- low blood pressure.
- dizziness.
- temporary redness of face and neck.
- headache.
- nervousness.
- a feeling of pins and needles on skin.
Is Numotrate safe during pregnancy?
Numotrate should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby. No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Numotrate should be given to a pregnant woman only if clearly needed.
Is Numotrate safe during breastfeeding?
Use is not recommended. Caution is recommended and this Numotrate should be used only if the benefits outweigh the risks.
Can I drink alcohol with Numotrate ?
Do not drink alcohol. It could increase the effect of Numotrate Tablets and lower your blood pressure too much. If this happens, you may feel dizzy or faint.
Can I drive after taking Numotrate ?
Do not drive, use machinery, or do anything that needs alertness until you can do it safely.
When is the best time to take Numotrate?
You should take this medicine first thing in the morning and follow the same schedule each day. This medicine works best if you have a "drug-free" period of time every day when you do not take it. Your doctor will schedule your doses during the day to allow for a drug-free time.
Should Numotrate be taken with food?
Take this Numotrate on an empty stomach, at least 30 minutes before or 2 hours after food. Do not take with food. Take your medicine at regular intervals. Do not take your medicine more often than directed.
What happens if I take Numotrate with food?
Taking Numotrate with high fat containing foods may increase the absorption of the drug.
Can I take Numotrate at night?
You may need to take the medicine only once daily, in the morning after getting out of bed.
How long does Numotrate take to work?
After oral administration, Numotrate has a quick onset of action (30 minutes) and effects are evident for up to 17 hours.
How often can I take Numotrate?
Take this medication by mouth as directed by your doctor, usually twice a day. Each day, take the first dose when you wake up, then take the second dose 7 hours later. It is important to take the Numotrate at the same times each day.
Can I take Numotrate for a long time?
Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This form of nitrate is used to reduce the number of angina attacks over a long time.
Is Numotrate bad for kidneys?
Numotrate is not known to affect the kidneys. People with kidney problems should be able to take the usual dose of Numotrate.
What does Numotrate do to the heart?
Numotrate works by relaxing the blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload.
What happen if I stop Numotrate suddenly?
Stopping suddenly could cause a severe angina attack. Numotrate can cause severe headaches, especially when you first start using it. These headaches may gradually become less severe as you continue to use the medication. Do not stop taking Numotrate.
Who should not take Numotrate?
You should not take erectile dysfunction medicine while you are taking Numotrate. Taking these medicines together can cause a sudden and serious decrease in blood pressure. Seek emergency medical attention if you have early symptoms of a heart attack (chest pain or pressure, pain spreading to your jaw or shoulder, sweating, general ill feeling).
What happens if I miss a dose?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
What happen if I overdose on Numotrate?
Seek emergency medical attention. An overdose of isosorbide mononitrate can be fatal.
Overdose symptoms may include a severe throbbing headache, fever, confusion, severe dizziness, fast or pounding heartbeats, vision problems, nausea, vomiting, stomach pain, bloody diarrhea, trouble breathing, sweating, cold or clammy skin, fainting, and seizure (convulsions).
Does Numotrate cause anxiety?
Numotrate can causes anxiety also with other side effects.
