Approved on.
Date of revision.
Isosorbide Mononitrate Tablets Instructions
Please read the instructions carefully and use under the guidance of your physician
[Medication Name].
Generic Name: Isosorbide Mononitrate Tablets
Trade Name: Xinkang
English Name: Isosorbide Mononitrate Tablets
Hanyu Pinyin: Danxiaosuan Yishanlizhi Pian
[Ingredient] 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] This product is a white tablet.
[Indications] Long-term treatment of coronary heart disease; prevention of angina pectoris; treatment of persistent angina pectoris after myocardial infarction; treatment of chronic congestive heart failure in combination with digitalis and/or diuretics.
[Specifications] 20 mg.
[Dosage].
Oral: The recommended dose is 20 mg once, twice a day (7 hours between doses), or as directed by your doctor.
Drug tolerance or reduced efficacy may occur in individual patients receiving continuous treatment with long-acting nitrates. Asymmetric dosing regimens (twice daily at 7-hour intervals) may reduce the occurrence of tolerance.
[Adverse reactions].
Adverse reaction assessments were categorized based on the following frequencies.
Very common (≥1/10),common (≥1/100,<1/10); occasional (≥1/1000,<1/100); rare (≥1/10,000,<1/1000); very rare (<1/10000); unknown (estimation not possible based on available data).
Neurological disorders
Very common: Headache, especially nitrate-induced headache at the beginning of treatment, usually resolves with continued medication.
Common: Sleepiness, dizziness, drowsiness
Heart disease
Common: Tachycardia
Occasionally: exacerbation of angina pectoris
Vascular disease
Common: Decreased blood pressure and/or postural hypotension may be combined with reflex tachycardia
Occasionally: circulatory collapse, sometimes with bradycardia and syncope
Gastrointestinal disorders
Sometimes: nausea, vomiting
Very rare: Heartburn
Dermal and subcutaneous tissue disorders
Sometimes: flushing, allergic skin reactions (e.g., rash)
Very rare: Stevens-Johnson syndrome, angioneurotic edema
unknown: exfoliative dermatitis
Systemic disease and administration site conditions
Very common: Cross-resistance with other nitrates
Common: Weakness, drug tolerance
There is transient hypoxemia during use of this product due to redistribution of blood flow in the poorly ventilated alveolar region. It can lead to myocardial hypoxia especially in patients with coronary artery disease.
[Contraindications].
This product is contraindicated in patients with the following conditions.
– Hypersensitivity to the known active ingredients of this product, to nitrates, or to any of the excipient ingredients.
– Acute myocardial infarction with low filling pressures (except under conditions of continuous hemodynamic monitoring).
– Severe aortic stenosis/mitral stenosis
– hypertrophic obstructive cardiomyopathy.
– constrictive pericarditis, restrictive cardiomyopathy, pericardial tamponade.
– Acute circulatory failure (shock, vascular deficit).
– cardiogenic shock (except when appropriate measures are used to ensure sufficiently high end-diastolic pressure).
– hypotension (systolic blood pressure below 90 mmHg).
– Severe anemia.
– Increased intracranial pressure.
– closed-angle glaucoma.
– Concomitant use of phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil, vardenafil, or tadalafil, as PDE5 inhibitors may potentiate the vasodilatory effects of isosorbide mononitrate and lead to severe hypotension.
– Soluble guanylate cyclase stimulating agents (eg, liothyronine) are being used, and concomitant use can lead to hypotension.
[Caution].
1. Isosorbide mononitrate should be used with caution if.
(1) A recent history of myocardial infarction.
(2) Impaired left ventricular function (left ventricular failure).
(3) Postural circulatory dysregulation.
2. This product is not indicated for acute angina pectoris attacks.
3. A small number of patients may have an idiosyncratic reaction to nitrates, such as fainting.
4. Patients with severe cerebral atherosclerosis should be observed with caution.
5. Tolerance can occur with long-term dosing, especially when blood levels of isosorbide mononitrate are high and stable, so it is recommended that the dose be kept to a minimum and that the last dose of the day be taken no later than dinner time.
As with other nitrates, treatment with isosorbide mononitrate should not be stopped abruptly, but should be tapered.
6. Patients on maintenance therapy with isosorbide mononitrate should be advised not to use type 5 phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil). Treatment with this product should not be interrupted by the option of using a product containing a type 5 phosphodiesterase inhibitor (eg, sildenafil, tadalafil, vardenafil), as this may tend to increase the risk of angina attack.
7. The use of this product may cause transient hypoxemia due to increased blood supply to poorly ventilated alveoli (formation of a pulmonary “bypass”). This can lead to myocardial hypoxia, especially in patients with coronary artery disease.
8. Alcohol should be avoided during treatment, as it may increase the vasodilatory effect of this product.
9. Effects on driving and operating machinery.
Because dizziness may occur during treatment with this product, it should be used with caution when concentration is required, such as when driving and operating machinery.
[For pregnant and lactating women].
1. There have been no adequate, rigorously controlled trial studies in pregnant women.
2. Reproductive studies in rats and rabbits have shown that isosorbide mononitrate is not found to be harmful to the embryo at maternally toxic doses. Because animal studies do not always predict human responses, this product should be administered to pregnant women only when necessary and under strict medical supervision.
3. It is not known whether isosorbide mononitrate is secreted from breast milk, and because many drugs can be secreted from breast milk, isosorbide mononitrate should be taken with caution by nursing women.
[Medication for Children].
Studies of these drugs have been conducted in adults, and there is no information comparing pediatric and adult use, so it is not possible to determine the safety and effectiveness of isosorbide mononitrate in pediatric patients.
[Medication in the Elderly].
Clinical studies of isosorbide mononitrate have not included sufficient numbers of subjects aged 65 years and older to determine whether they respond differently than younger subjects. Other clinical experiences that have been reported have not identified differences in response between older and younger patients. In general, older patients may be more sensitive to this class of drugs and more likely to experience reactions such as dizziness. Therefore, dose selection in elderly patients should be cautious, usually starting at the lower dose of the dosing range.
[Drug interactions].
1. Combination with any form of phosphodiesterase inhibitor is prohibited (see [Contraindications]).
2. Soluble guanylate cyclase agonists (eg, liothyronine) should not be used in combination with this product (see [Contraindications]).
3. The vasodilatory effects of isosorbide mononitrate may be superimposed on the vasodilatory effects of other vasodilators, and alcohol in particular has been found to exhibit varying degrees of superimposed effects.
4. Significant symptoms of upright hypotension have been reported with the combination of calcium channel blockers and organonitrates, which may require dose adjustment for administration.
[Drug overdose].
The following symptoms may occur with overdose.
Upright hypotension, reflex tachycardia and headache, weakness, dizziness, drowsiness, flushing, sweating, pallor, weak pulse, nausea, vomiting, and diarrhea.
High doses (>20 mg/kg body weight) can cause cyanosis, methemoglobinemia, dyspnea, and shortness of breath due to the release of nitrite from isosorbide mononitrate metabolism. Chronic drug overdose can lead to elevated methemoglobin levels.
Increased intracranial pressure combined with cerebral symptoms may occur at ultra-high doses.
Treatment of overdose.
1. General measures such as supine, elevated legs, oxygen, activated charcoal, gastric lavage, and close monitoring and correction of vital signs.
2. For significant hypotension and/or shock, blood volume needs to be replenished and shock targeted; in exceptional cases, norepinephrine may be given. Vasopressin should only be used in patients who are not responding adequately to volume expansion therapy.
3. Depending on the severity of methemoglobinemia, treatment with vincristine C, methylene blue (recommended dosage is methylene blue 1 to 2 mg/kg by sedation), and toluidine blue may be given. For severe methemoglobinemia, oxygenation, artificial ventilation, hemodialysis, and blood replacement may be given.
4. Resuscitation: If there are signs of respiratory and circulatory arrest, resuscitation should be administered immediately.
[Pharmacology and Toxicology].
Carcinogenicity and mutagenicity have not been observed in animal studies.
[Pharmacokinetics].
Isosorbide mononitrate is rapidly absorbed orally with no hepatic first pass effect and bioavailability of up to 100%. The blood concentration peaked about 30-60 minutes after administration. It has a linear pharmacokinetic profile over the recommended dosing range. Food has no significant effect on drug absorption. The pharmacokinetic profile of the drug is not affected by the combination of metoprolol. The volume of distribution of isosorbide mononitrate was approximately 0.6 L/kg, and plasma protein binding was less than 5%.
Radiolabeling tests showed that about 50% of the prodrug was denitrated and excreted renally as isosorbide and sorbitol, and about 25% was excreted in the urine as prodrug conjugates; none of the metabolites had vasodilating activity, and only 2% was excreted in the prodrug form.
Isosorbide mononitrate has an elimination half-life of approximately 5 hours. The in vivo clearance was the same in healthy young subjects as in older subjects with varying degrees of hepatic, renal, or cardiac impairment. Approximately 93% was excreted in the urine 48 hours after oral administration, and renal excretion was complete after 5 days, with fecal excretion accounting for 1% of the administered dose.
Isosorbide mononitrate has no significant effect on hepatic or renal function. No dose adjustment was required in patients with varying degrees of renal failure, and in patients with cirrhosis, pharmacokinetic parameters after single-dose administration were similar to those in healthy subjects.
Blood clearance of isosorbide mononitrate during hemodialysis was significant, but no additional supplemental dose was required. In patients receiving continuous peritoneal dialysis, blood drug concentrations were similar to those of non-dialysis patients.
[Storage] Protect from light and keep sealed.
[Packaging】Packaged in aluminum and plastic. 28 tablets/box, 36 tablets/box, 48 tablets/box.
[Expiration date] 24 months.
[Executive Standard].
[Approval Number] State Drug Certificate H10940039
[Manufacturer]
Marketing license holder: Lunanbetter Pharmaceutical Co.
Registered address: No. 209 Hongqi Road, Linyi City, Shandong Province
Manufacturer’s name: Lunanbetter Pharmaceutical Co.
Manufacturing Address: No. 243 Yinqishan Road, Linyi City, Shandong Province
Postal code: 276006
Tel: 0539-8336336 (Sales Department) 8336169 (Quality Control Department)
Fax number: 0539-8336338
Website: www.LUNAN.com.cn