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Nitroglycerin Tablets Instructions
Please read the instruction manual carefully and use under the guidance of a physician
[Drug Name]
Generic Name: Nitroglycerin Tablets
English Name:Nitroglycerin Tablets
Hanyu Pinyin:Xiaosuan Ganyou Pian
[Ingredients]
The main ingredient of this product is nitroglycerin.
The chemical name is:1,2,3-propanetriol trinitrate
The chemical structure formula is:
Molecular Formula:C3H5N3O9
Molecular weight:227.09
[Properties]
This product is a white tablet
[Indications]
For the prevention and rapid relief of angina attacks due to coronary artery disease.
[Specifications]
0.5mg
[dosage]
In acute attacks of angina pectoris, one tablet of this product should be administered sublingually or in the buccal mucosa of the mouth. This can be repeated every5 minutes until symptoms are relieved. If15minutes are administered3 tablets of chest pain that does not resolve or if the pain is worse than before, other medical measures should be taken immediately. If this product is used as prophylactic treatment, it should be administered 5to before activities that may lead to an angina attack. style=”font-family:Times New Roman”>10minute dosing.
Dosing at rest is recommended, preferably in a seated position.
Patients with renal insufficiency do not require dose adjustment.
[Adverse Reactions]
Severe and persistent headache may occur immediately after dosing. Occasionally, vertigo, dizziness, weakness, palpitations, and other symptoms of postural hypotension may occur, especially in patients in the upright position and immobile. Hypotensive reactions that are particularly sensitive to the hypotensive effects of nitrates (e.g., nausea, vomiting, weakness, sweating, pallor, and weakness) can occur at therapeutic doses. Syncope has been reported as a result of vasodilatation with nitrates. Flushing, drug rash, and exfoliative dermatitis have been reported in patients treated with nitrates.
[Contraindicated]
This product is contraindicated in persons with hypersensitivity to organic nitrates.
This product is contraindicated in early myocardial infarction, in patients with severe anemia, elevated intracranial pressure, in patients with acute circulatory failure or shock, and in those with known hypersensitivity to nitroglycerin.
Currently taking phosphodiesterase-5(PDE-5) inhibitors (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride) are contraindicated in patients with this product. This is because these compounds have been shown to potentiate the antihypertensive effects of nitrates.
This product is contraindicated in patients taking liothyronine, an activator of soluble guanylate cyclase, and the combination may cause hypotension.
[Precautions]
Warning:
The efficacy of sublingual nitroglycerin in patients with acute myocardial infarction or congestive heart failure has not been established. Considering the possibility of hypotension or tachycardia, the patient’s hemodynamic status and clinical condition must be closely monitored if this product is applied.
General Precautions:
This product is a sublingual tablet and should be administered sublingually or buccally; it should not be chewed, crushed, or swallowed.
If possible, patients should take the drug in a seated position and use caution when returning to a standing position to avoid falls due to dizziness or lightheadedness. Try to use the smallest possible dose of the drug to achieve effective relief of angina attacks. Overdose may lead to drug resistance.
A burning or tingling sensation may occur when the product is administered sublingually. However, whether or not a burning or tingling sensation is produced should not be used to judge the strength of the drug’s action.
Nitroglycerin can cause dose-related headache, especially when treatment with nitroglycerin is initiated, and the headache may be severe and persistent, but usually subsides with continued use. In patients who have a headache response, the headache may be a sign that the drug is becoming effective. Overdose of nitroglycerin can cause severe headache.
Patients on nitroglycerin may experience dizziness in the standing position, especially when first standing up from a seated or recumbent position. Dizziness occurs more frequently in patients who have consumed alcohol.
Small doses of nitroglycerin may also cause severe hypotension (especially in the upright position). Nitroglycerin should be used with caution in patients with hypovolemia or in patients who already have hypotension for whatever reason. Paradoxical bradycardia and increased levels of angina pectoris may also occur with nitroglycerin-induced hypotension.
Nitrates can worsen angina pectoris caused by hypertrophic cardiomyopathy.
When resistance to other nitrates has developed, sublingual nitroglycerin has diminished its effect, although it still improves exercise tolerance.
Resistance rarely occurs in workers who have been exposed to organic nitrates for a long time (exact dose unknown, presumably in large amounts). However, when they were suddenly not exposed to nitrates, they had experienced chest pain, acute myocardial infarction, and even sudden death, which also confirmed the existence of organic dependence. Several clinical trials in patients with angina pectoris using nitroglycerin patches or silent nitroglycerin evaluated dosing regimens at intervals of 10 to 12 hours. Some trials showed that a few patients had an increased frequency of angina attacks during the dosing interval. In one of these trials, patients experienced a decrease in exercise tolerance at the end of the dosing interval. Rebound of hemodynamic markers was rare, but on the other hand, even when rebound occurred, few trials were designed to ensure that such rebound was detected.
The possibility of drug resistance due to sublingual nitroglycerin, although not excluded, occurs only when plasma nitrate levels are consistently elevated above10or12hours. Only daily application of a large number of sublingual tablets would result in such a condition, and this usage is not recommended.
If the patient experiences blurred vision or dry mouth, the medication should be discontinued.
Nitroglycerin should be kept in the original packaging bottle and the cap must be tightened after each dose to avoid loss of effectiveness.
[For Pregnant and Lactating Women]
Pregnancy:
Animal reproductive toxicity and teratogenicity tests have not been performed with nitroglycerin tablets. However, the administration of nitroglycerin cream to rats and rabbits at doses of 80 mg/kg/day and 240mg/kg/day, teratogenic tests were performed and no toxic effects were found in mothers or fetuses.
The use of nitroglycerin in pregnant women has not been well studied. Nitroglycerin should be administered to pregnant women only when clearly needed.
Lactation:
It is not known whether nitroglycerin is secreted into human milk. Because many drugs are secreted into human milk, nitroglycerin should be used with caution in nursing women.
[Children’s medication]
No studies are available on the safety and efficacy of nitroglycerin in children.
[Geriatric use]
For age ≥65 years There is insufficient clinical trial data in the elderly to confirm the difference in clinical outcomes between elderly patients and younger patients with this product. Other clinical reports have not found differences in clinical efficacy between older and younger patients. Dose selection in elderly patients should be cautious, with dosing usually initiated at low doses due to the greater frequency of hepatic, renal, and cardiac decompensation, complications, and treatment with other medications in the elderly.
[Drug Interactions]
Coadministration of this product (nitroglycerin sublingual tablets) with soluble guanylate cyclase activators is prohibited (see [Contraindications]).
Concurrent nitrates and alcohol consumption can lead to hypotension.
Nitroglycerin with high-dose aspirin (1000mg) coadministered can increase nitroglycerin exposure.
Nitroglycerin in combination with high-dose aspirin enhances the vasodilatory and hemodynamic effects of nitroglycerin.
Tissue-type fibrinogen activator (t-PA): concurrently givent-PA and intravenous nitroglycerin have been shown to reduce plasmat-PAlevels and its thrombolytic effect. Intravenous administration of nitroglycerin reduces the thrombolytic effect of alteplasealteplase (accelerated by increasing blood flow to the liver) clearance of fibrinogen activator from plasma). Therefore, nitroglycerin tablets should be used with caution in patients treated with alteplase (alteplase).
Intravenous administration of nitroglycerin decreases the anticoagulant effect of heparin and should be monitored for activated partial thromboplastin time (APTT). It is unclear whether sublingual nitroglycerin alone would produce such an effect.
Dissolution of nitroglycerin tablets is difficult because tricyclic antidepressants (amitriptyline, desipramine, doxepin) and acetylcholine antagonists can cause dry mouth and decreased saliva production. Chewing gum to increase saliva production or using artificial saliva products can effectively aid in the dissolution of nitroglycerin tablets.
Oral nitroglycerin significantly decreases the first-pass metabolism of dihydroergotamine and therefore improves its oral bioavailability. Ergotamine is known to induce angina pectoris and ergotamine and similar drugs should be avoided in patients with sublingual nitroglycerin. If it cannot be avoided, symptoms of ergot toxicity should be noted.
Being on phosphodiesterase-5(PDE-5) inhibitors (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride) are contraindicated in patients with this product. These compounds have been shown to potentiate the antihypertensive effects of organic nitrates.
Taking long-acting nitrate preparations can lead to reduced efficacy of nitroglycerin tablets.
Drug/Laboratory Interactions examined:
Nitrates can interfere withZlatkis-Zakchromogenic reaction and a false appearance of low serum cholesterol.
[Drug overdose]
Hemodynamic effects:
The response to nitroglycerin overdose is due to the vasodilatory effects of nitroglycerin, venodilation, decreased cardiac transfusion bleeding, and hypotension. Hemodynamic changes manifest in a variety of ways, including increased intracranial pressure, which may be accompanied by persistent pulsating headache, confusion or moderate fever, and vertigo; palpitations; tachycardia; visual disturbances; nausea and vomiting (which may include abdominal cramps or even bloody diarrhea); syncope (especially in the upright position); dyspnea followed by decreased ventilation; sweating, flushed or clammy skin; heart block and bradycardia; paralysis Coma; seizures; death.
There are no antagonists for nitroglycerin vasodilation and no controlled studies for the treatment of nitroglycerin overdose. Because hypotension due to nitroglycerin overdose is caused by venodilatation and arterial hypovolemia, treatment should be directed at expanding central blood volume, which may be effective by elevating the patient’s lower extremities, but may also require intravenous saline or similar fluids.
If an excessive amount of nitroglycerin is swallowed in a short period of time, gastric lavage may be used.
The application of epinephrine or other arterial vasoconstrictor drugs may do more harm than good.
Expansion of central blood volume may be dangerous in patients with concomitant renal disease or congestive heart failure. Management of nitroglycerin overdose is more difficult at this time and may require invasive hemodynamic monitoring.
Hyperferritinemia:
Hyperferritinemia associated with organonitrates has been reported relatively rarely. The diagnosis of methemoglobinemia should be considered in patients presenting with signs of inadequate oxygenation when both cardiac output and arterialPO2are adequate. Typically, the blood of a patient with methemoglobinemia is chocolate in color and does not change color when exposed to air.
If methemoglobinemia is present, it should be given1-2 mg/kgmethylene blue intravenous treatment.
[Pharmacology and Toxicology]
Nitroglycerin is an organic nitrate drug whose primary action is vasodilation.
Mechanism:
Nitroglycerin produces nitric oxide (NO) radicals, which activate guanylate cyclase,
increases smooth muscle and other tissues in 3’5’Guanosine monophosphate (cGMP) dephosphorylates the light chain of myosin, which regulates the contractile state of smooth muscle, leading to vasodilation.
Clinical pharmacology:
The primary pharmacologic effect of nitroglycerin is relaxation of vascular smooth muscle. Despite its predominant action on venous vessels, nitroglycerin produces a dose-dependent dilating effect on both arterial and venous vascular beds. After dilatation of postcapillary vessels (including large veins), peripheral blood volume increases, venous return blood volume decreases, and left ventricular end-diastolic pressure (preload) decreases. After arterial dilatation, peripheral vascular resistance decreases and arterial pressure (afterload) decreases. Nitroglycerin also dilates large coronary arteries in the epicardium, but the contribution of this mechanism of action to the angina-relieving effect of nitroglycerin is unclear.
Therapeutic doses of nitroglycerin lower systolic, diastolic, and mean arterial pressures. In general, it ensures that the effective coronary perfusion pressure is not affected. However, if the drop in blood pressure is too significant or if the increased heart rate affects the ventricular diastolic filling time, the perfusion pressure in the coronary arteries may be reduced.
Nitroglycerin also reduces elevated central venous pressure and pulmonary capillary wedge pressure, as well as pulmonary vascular resistance and systemic vascular resistance. The heart rate is usually mildly accelerated, primarily as a compensatory response by the body to a decrease in blood pressure. The cardiac index may increase, decrease, or remain unchanged. Myocardial oxygen consumption or oxygen demand (measured as the product of blood pressure-heart rate, tension-time index, and beat -work done index measures) decreases and a more favorable supply and demand balance is achieved. If a patient has high left ventricular filling pressures and high systemic vascular resistance with concomitant low cardiac index, nitroglycerin may increase the cardiac index; conversely, if left ventricular filling pressures and systemic vascular resistance are normal, nitroglycerin administration may result in a mild decrease in the cardiac index.
Pharmacodynamics:
Consistent with the relief of angina symptoms, digital volumetric tracing showed that sublingual nitroglycerin was approximately1~3 minutes after administration of the drug. 5minutes after dosing to achieve maximum effect. The effect lasts for at least 25minutes.
Carcinogenic effects, mutagenic effects, effects on fertility:
Sublingual nitroglycerin in animals to assess its carcinogenicity has not been tested.
Dosing up to434 mg/kg/day at feedingThe potential carcinogenicity of nitroglycerin was evaluated in rats given nitroglycerin for two years. Rats developed dose-related fibrotic or neoplastic changes in the liver, including carcinomas, and testicular mesenchymal cell tumors. The incidence of hepatocellular carcinoma was 48% in male rats and in females at high doses -family:Times New Roman”>33% and controls0%. The incidence of testicular tumors was 52%, compared to 8%. Lifetime administration of1058 mg/kg/daynitroglycerin was not carcinogenic in mice.
In two different laboratoriesAmesassay showed that nitroglycerin is mutagenic. However, both in vivo experiments in male rats at oral doses up to 363 mg/kg/day, and in vitro cytogenetic experiments in rat and dog cells There was no evidence of mutagenicity in these experiments.
In a three-generation rat reproductive toxicity assay,F0F0 family:equinox”>generation rats for 6months before mating ingested doses as high as434 mg/kg/day of nitroglycerin, the resultingF1F1 span>generation and F2generation rats were similarly administered nitroglycerin. Both sexes showed reduced feeding and weight gain during all mating seasons. No specific effects on fertility were found in the F0generation. However, sterility was found in the offspring, which was attributed to increased mesenchymal cell organization and lack of spermatogenesis in male rats. There was no evidence of teratogenicity of this product in this experiment.
[Pharmacokinetics] (Foreign research literature)
Absorption: Nitroglycerin is rapidly absorbed after sublingual administration. On average6 to 7 minutes after administration nitroglycerin plasma concentration peaks (see table below). CmaxandAUCwith dose from0.3mg to0.6mgincreased proportionally. The absolute bioavailability of this product is approximately 40%, but may vary with factors affecting drug absorption such as sublingual hydration and mucosal metabolism.
Table
Pharmacokinetic parameters of sublingual nitroglycerin tablets
Pharmacokinetics
ParametersDosing2´0.3mg1´0.6mgCmax (ng/ml)2.3(1.7)2.1(1.5)Tmax(min)6.4(2.5)7.2(3.2)AUC(0-¥) (min)14.9(8.2)14.9(11.4)t½(min)2.8(1.1)2.6(0.6)Distribution: The volume of distribution of intravenously administered nitroglycerin is3.3L/kg and plasma concentrations of50 to 500ng/mlat plasma protein binding rates of about 60%, and And1, 2-glyceryl dinitrate and1,3-dinitrate, respectively, 60% and 30% respectively .
Metabolism: A hepatic reductase enzyme plays a major role in the metabolism of nitroglycerin to glyceryl dinitrate and glyceryl mononitrate and ultimately to glycerol and organic nitrates. Known extrahepatic sites of metabolism include blood red blood cells and the vessel wall. In addition to nitroglycerin, its two major active metabolites are found in plasma1,,2-dinitrate and11, 3-dinitroglycerin, with peak mean plasma concentrations occurring approximately after dosing 15minutes after dosing, with elimination half-lives of 3636min and 32min respectively. minutes. It was reported that1,,2-dinitrate and12%and10%. The higher plasma concentration of the dinitro metabolite and the nearly10fold longer half-life of nitroglycerin may play an important role in maintaining the duration of action. The metabolite of nitroglycerin, glycerol mononitrate, is inactive in terms of cardiovascular effects.
Excretion: The mean half-life of nitroglycerin is 2 to 3minutes, so its plasma concentration decreases rapidly. The half-life time range is 1.5 to 7.5minutes. The clearance rate (13.6 L/min) greatly exceeds the hepatic blood flow rate. Metabolism is the major route of drug excretion.
[storage
Holding
Blackout, sealed, at25°CSave below.
[package
Package
Packaged in pharmaceutical brown glass bottles,24tablets/bottle,48pieces/bottle,100pieces/bottle,50pieces/bottle,15pieces/bottles.
[Expiration date]
[Execution Standard]
[Approval number]
H11021022
[Drug Marketing Authorization Holder]
Company Name: Beijing Yimin Pharmaceutical Co.
Registered Address: North of Nongjun Road, Shunyi District, Beijing
Postal Code:101300
Phone number: (010)69442334
Fax Number: (010)69440455
Net
Address:http://www. bjyimin.com.cn
[Manufacturer]
Company Name: Beijing Yimin Pharmaceutical Co.
Manufacturing Address: Guangming South Street, Shunyi District, Beijing14 family:equal line”>No. 14 (North of Congjun Road, Shunyi District, Beijing)
Postal Code:101300
Phone number: (010)69442334
Fax Number: (010)69440455
Net
Address:http://www. bjyimin.com.