Approval date: November 09, 2007
Modification date: November 30, 2015
Modification date: December 27, 2019
Date of modification.
Year
Month
Date
Isosorbide mononitrate extended release capsule instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name
Generic name: Isosorbide Mononitrate Sustained-release Capsules
English name: Isosorbide Mononitrate Sustained-release Capsules
Hanyu Pinyin: Danxiaosuan Yishanlizhi Huanshijiaonang
Ingredients
The main ingredient of this product is isosorbide mononitrate.
Chemical name: 1,4:3,6-Dianhydro-D-sorbitol-5-mononitrate.
Chemical structure formula.
Molecular formula: C6H9NO6
Molecular weight: 191.14
【Properties】.
The contents of this product are white micro-pills.
Indications】
1.Long-term treatment of coronary heart disease.
2.Long-term treatment and prevention of angina pectoris (including after myocardial infarction).
3.Treatment of chronic congestive heart failure in combination with digitalis and / or diuretics.
Specification
40mg
Dosage and Administration
Take orally. Unless otherwise prescribed, take 1 capsule (40mg) once daily with warm water and swallow whole (do not chew). In patients with unstable circulation, the first dose may cause vascular deficiency symptoms and may produce nitrate headache. Isosorbide mononitrate in a non-long-acting formulation (20 mg/tablet) half a tablet (10 mg) in the morning and half a tablet in the evening may be given at the start of treatment to reduce these symptoms.
In severe cases, the dose may be increased to 1 capsule (40 mg) twice a day (equivalent to 80 mg of isosorbide mononitrate). For the full effect of this product, when the dose is 1 capsule (40mg) twice a day, the second dose should be taken no more than 6 hours after the first dose.
The whole capsule should be kept intact before taking and swallowed with half a glass of water, not chewed or crushed.
Isosorbide mononitrate is not suitable for immediate relief of acute attack of angina pectoris, if the above situation occurs, additional treatment with fast-acting nitrates should be prepared.
Adverse reactions]
A very common adverse reaction with this product is headache (≥1/10), but it will gradually subside with time and continued application.
Common (≥1/100 to <1/10): Upright hypotension and/or mild headache are common with the first dose or increasing dose. These symptoms may be associated with dizziness, drowsiness, reflex tachycardia, and fatigue.
Infrequently (≥1/1,000 to <1/100).
Nausea, vomiting, flushing, and allergic skin reactions (e.g., erythema), which may sometimes be severe. Individual cases have developed exfoliative dermatitis.
Severe hypotension, including nausea, vomiting, fidgeting, pallor, and excessive sweating, has been reported with organonitrate use. Circulatory collapse (often with bradycardia and syncope) is uncommon. Exacerbation of angina symptoms due to severe hypotension is uncommon.
Very rare (<1/10,000): reports of heartburn due to nitrate-induced sphincter relaxation.
During treatment with this product, temporary hypoxemia may result from increased blood supply to poorly ventilated alveoli (formation of a pulmonary “bypass”). This phenomenon may lead to myocardial hypoxia, especially in patients with coronary artery disease.
Contraindications
Hypersensitivity to any of the ingredients of this product.
Acute circulatory failure (shock, vascular deficiency).
Cardiogenic shock (except when appropriate measures are taken to ensure sufficiently high end-diastolic pressure).
Severe hypotension (systolic blood pressure below 90 mmHg)
Phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) should not be used during nitrate therapy (see [Precautions])
Soluble guanylate cyclase activator liothyronine cannot be used during nitrate therapy
Acute myocardial infarction with low filling pressures (unless used in an intensive care unit with continuous hemodynamic monitoring conditions)
Severe hypovolemia
Severe anemia
Hypertrophic obstructive cardiomyopathy
constrictive pericarditis
Acute cardiac tamponade
Precautions]
It should only be used under special supervision of a physician in the following cases.
Low filling pressures, such as acute myocardial infarction, left ventricular impairment (left ventricular failure)
Aortic and/or mitral valve stenosis
Conditions associated with increased intracranial pressure
Postural circulatory dysregulation
This product is not indicated for acute angina attacks. Although the release of this product occurs in two phases, such as the rapid release of 30% of the active ingredient after administration, it is not immediately effective in acute angina attacks.
It is resistant and has cross-resistance with other nitro compounds.
Patients on continuous use of this product should be advised not to use products containing phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil). Treatment with this product should not be interrupted by the use of phosphodiesterase inhibitor-containing products (e.g., sildenafil, tadalafil, vardenafil) because of the increased risk of angina attacks (see [Contraindications]).
Saxaparin (tetrahydrobiopterins) is a cofactor for nitric oxide synthase. Caution should be taken when combining with drugs containing salprotectin that may cause vasodilatory effects due to effects on the metabolism or action of nitric oxide, including commonly used nitric oxide donors (e.g., nitroglycerin, isosorbide nitrate, isosorbide 5-mononitrate, etc.).
This product can affect the reaction speed to some extent, such as the ability to drive and operate machinery, and this can be more pronounced if alcohol is consumed at the same time.
Pregnant women and nursing mothers
This product is contraindicated in the first trimester of pregnancy (within 3 months) and should only be used during pregnancy unless clearly necessary and under medical supervision.
Use in Children
The safety and efficacy of this product in children have not been established.
Geriatric Use
There is no evidence that dose adjustment is required in the elderly.
Drug Interactions
1.Concurrent use of drugs with hypotensive effects, such as beta-blockers, calcium channel blockers, vasodilators and/or alcohol, psychostimulants, tricyclic antidepressants may enhance the hypotensive effect of this product.
2.The combination with sildenafil for the treatment of erectile dysfunction will increase the hypotensive effect of this product, which may cause fatal cardiovascular complications, so sildenafil should not be used when using this product.
3. It has been reported that if dihydroergotamine is taken at the same time, this product may increase the blood concentration of the former and enhance its antihypertensive effect.
Drug overdose]
Mice and rats were given 1965 and 2581mg/kg of isosorbide mononitrate by gavage respectively, and obvious death was seen.
Clinical signs of overdose in humans include: blood pressure ≤90mmHg, pallor, sweating, weak pulse, tachycardia, mild dizziness when upright, headache, weakness, dizziness, nausea, vomiting, diarrhea, and methemoglobinemia previously reported in patients using other organonitrate drugs. Isosorbide mononitrate biotransforms to release nitroso ions, which may cause methemoglobinemia and cyanosis, shortness of breath, anxiety, loss of consciousness, and cardiac arrest. Very high doses may cause brain symptoms due to increased intracranial pressure.
Routine measures.
Discontinuation of the drug.
Management of nitrate-induced hypotension.
Patients should be maintained in a horizontal position with head down and feet elevated
administer oxygen
Increasing blood volume (e.g., fluid infusion)
Treatment for shock (patient should be closely monitored)
Special measures
If blood pressure is very low, raise it and give sympathomimetic drugs such as norepinephrine or epinephrine.
Treatment of methemoglobinemia.
Use vitamin C, methylene blue or toluidine blue
Oxygen administration (if necessary)
Artificial ventilation
Dialysis (if necessary)
Resuscitation
If respiratory and circulatory arrest occurs, use resuscitation immediately.
[Pharmacology and Toxicology
Pharmacological effects
Isosorbide mononitrate is the main active metabolite of isosorbide nitrate. It can reduce myocardial oxygen consumption by dilating peripheral blood vessels, especially by increasing venous blood volume, reducing the amount of return blood and lowering the cardiac anterior and posterior loads; at the same time, it can also improve the blood supply in the ischemic area by promoting the redistribution of myocardial blood flow, and may exert anti-myocardial ischemic effects through these two aspects.
Toxicity studies
Isosorbide mononitrate was administered to rats and dogs for 78 and 52 weeks, and toxic reactions were observed at 405 and 90 mg/kg levels, respectively.
Pharmacokinetics]
The literature shows that isosorbide mononitrate is rapidly and completely absorbed orally, and the bioavailability is 90-100%. There is no hepatic first pass effect. The apparent volume of distribution is about 50L, and the plasma half-life is 4~5 hours. Isosorbide mononitrate is almost completely metabolized in the liver. The metabolites are mainly excreted by the kidneys, and only about 2% of the dose is excreted in its original form by the kidneys. Food has no effect on absorption. The clinical effect of nitrate may be diminished despite relatively stable blood levels. Drug tolerance may diminish within 24 hours after discontinuation of therapy, and intermittent dosing may prevent the development of drug tolerance. The pharmacokinetic profile is similar in healthy volunteers and patients with chronic stable angina pectoris.
This product is an extended-release formulation of isosorbide mononitrate. The absorption period and duration of action of the extended-release formulation are longer than those of the regular tablets.
Storage
Keep sealed.
Package
Aluminum-plastic packaging. 10 capsules per plate, 1 plate per box; 12 capsules per plate, 1 plate per box; 10 capsules per plate, 2 plates per box; 10 capsules per plate, 3 plates per box.
[Expiration date
24 months
【Execution standard
【Approval number】
State Drug Administration H20073915
[Drug Marketing Licensee
Holder’s name: Zhuhai Rundu Pharmaceutical Co.
Address of the holder: No. 6, Airport North Road, Sanzao Town, Jinwan District, Zhuhai
Postal Code: 519041
Telephone number: 0756-7630088 0756-7630122
Fax number: 0756-7630678 0756-7630123
Manufacturer
Company name: Zhuhai Rundu Pharmaceutical Co.
Address: No. 6, Airport North Road, Sanzao Town, Jinwan District, Zhuhai
Postal Code: 519041
Telephone number: 0756-7630088 0756-7630122
Fax number: 0756-7630678 0756-7630123
Web
Address: http://www.rdpharma.cn
Adverse reaction feedback telephone and mailbox: telephone: 13702329078; mailbox:
Box: [email protected]