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Nitrostat

Nitrostat is essentially a regional brand with a narrow registered footprint. Its marketing authorisation extends to five countries — the United States, Canada, China, Taiwan, and Egypt — and the active ingredient is nitroglycerin, one of the oldest and most widely recognised molecules in cardiovascular medicine.

Nitroglycerin is classified within the vasodilator and antianginal categories, and is also described in pharmacological references as having hypotensive, antispasmodic, vasoprotective, and cardiac-therapy roles. Nitrostat's registered indications cover the management of angina pectoris and angina prophylaxis, alongside associated cardiovascular conditions including coronary heart disease, heart failure, and pulmonary hypertension. The structured indication list further down this page sets out each registered use in detail.

Travellers familiar with Nitrostat from North America or from the Chinese-speaking markets are unlikely to encounter the same brand in Europe, Latin America, or much of Asia. The active ingredient itself, however, has a global presence: nitroglycerin is available in essentially every regulated pharmaceutical market under a variety of different brand names and presentations, ranging from sublingual tablets and sprays to transdermal and intravenous formulations.

A local pharmacist is well-placed to act as a translator between brand names and to identify which nitroglycerin-containing product is stocked regionally. Other molecules in the broader vasodilator and antianginal classes are also distributed internationally, although they are not interchangeable on a one-to-one basis with nitroglycerin and the choice between them is a clinical one. Anyone using Nitrostat, or trying to identify a comparable product abroad, should treat substitution as a decision for a healthcare provider familiar with their cardiovascular history rather than something resolved at a pharmacy counter.

Countries
Canada China Egypt Taiwan USA
Diseases
Pulmonary Hypertension Angina Pectoris Seizure Prophylaxis Heart Failure Coronary Heart Disease Angina pectoris prophylaxis
Ingredients
Nitroglycerin
Drug Actions
Hypotensive Antianginal Antispasmodic Vasodilator Cardiac therapy Vasoprotective Coronary deglutating

Drugs with the same active ingredients

Dauxona Enetege Niglinar Nitroderm tts Nitrodom Dbl glyceryl trinitrate Nitro-dur G t n Nitro pohl Nitrolingual Angicard Angist sr Anril Anril sr Deponit Diafusor Minitran Minitran (antianginal) Nitroderm Rectogesic

Overdose

Hemodynamic Effects

The effects of nitroglycerin overdose are generally the results of nitroglycerin's capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; tachycardia; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death.

No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Methemoglobinemia has been rarely reported in association with organic nitrates. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial PO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

If methemoglobinemia is present, intravenous administration of methylene blue, 1 to 2 mg/kg of body weight, may be required.

Contraindications

Allergic reactions to organic nitrates are extremely rare, but they do occur. Nitroglycerin is contraindicated in patients who are allergic to it.

Sublingual nitroglycerin therapy is contraindicated in patients with early myocardial infarction, severe anemia, increased intracranial pressure, and those with a known hypersensitivity to nitroglycerin.

Administration of NITROSTAT is contraindicated in patients who are using a phosphodiesterase-5 (PDE-5) inhibitor (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride) since these compounds have been shown to potentiate the hypotensive effects of organic nitrates.

Undesirable effects

Headache that may be severe and persistent may occur immediately after use. Vertigo, dizziness, weakness, palpitation, and other manifestations of postural hypotension may develop occasionally, particularly in erect, immobile patients. Marked sensitivity to the hypotensive effects of nitrates (manifested by nausea, vomiting, weakness, diaphoresis, pallor, and collapse) may occur at therapeutic doses. Syncope due to nitrate vasodilatation has been reported. Flushing, drug rash, and exfoliative dermatitis have been reported in patients receiving nitrate therapy.

Therapeutic indications

Nitroglycerin is indicated for the acute relief of an attack or acute prophylaxis of angina pectoris due to coronary artery disease.

Date of revision of the text

March 2014

Qualitative and quantitative composition

NITROSTAT is supplied as white, round, flat-faced tablets in 3 strengths (0.3 mg, 0.4 mg, and 0.6 mg) in bottles containing 100 tablets each, with color-coded labels, and in color-coded Patient Convenience Packages of 4 bottles of 25 tablets each.

0.3 mg: Coded “N” on one side and “3” on the other.

NDC 0071-0417-24—Bottle of 100 tablets

0.4 mg: Coded “N” on one side and “4” on the other.

NDC 0071-0418-13—Convenience Package
NDC 0071-0418-24—Bottle of 100 tablets

0.6 mg: Coded “N” on one side and “6” on the other.

NDC 0071-0419-24—Bottle of 100 tablets

Store at Controlled Room Temperature 20°–25°C (68°–77°F) .

Distributed by: Parke-Davis, Division of Pfizer Inc., NY, NY 10017. Revised: March 2014

Special warnings and precautions for use

WARNINGS

The benefits of sublingual nitroglycerin in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use nitroglycerin in these conditions, careful clinical or hemodynamic monitoring must be used because of the possibility of hypotension and tachycardia.

PRECAUTIONS General

Only the smallest dose required for effective relief of the acute anginal attack should be used. Excessive use may lead to the development of tolerance. NITROSTAT tablets are intended for sublingual or buccal administration and should not be swallowed.

Severe hypotension, particularly with upright posture, may occur with small doses of nitroglycerin. This drug should therefore be used with caution in patients who may be volume-depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

As tolerance to other forms of nitroglycerin develops, the effects of sublingual nitroglycerin on exercise tolerance, although still observable, is blunted.

In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance rarely occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence.

Several clinical trials of nitroglycerin patches or infusions in patients with angina pectoris have evaluated regimens that incorporated a 10- to 12-hour nitrate free interval. In some of these trials, an increase in the frequency of anginal attacks during the nitrate free interval was observed in a small number of patients. In one trial, patients had decreased exercise tolerance at the end of the nitrate interval. Hemodynamic rebound has been observed only rarely; on the other hand, few studies were so designed that rebound, if it had occurred, would have been detected.

Nitrate tolerance as a result of sublingual nitroglycerin administration is probably possible, but only in patients who maintain high continuous nitrate levels for more than 10 or 12 hours daily. Such use of sublingual nitroglycerin would entail administration of scores of tablets daily and is not recommended.

The drug should be discontinued if blurring of vision or drying of the mouth occurs. Excessive dosage of nitroglycerin may produce severe headaches.

Information For Patients

NITROSTAT is a sublingual tablet and should not be chewed, crushed, or swallowed.

If possible, patients should sit down when taking NITROSTAT tablets and should use caution when returning to a standing position. This eliminates the possibility of falling due to lightheadedness or dizziness.

One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5 minutes until relief is obtained.

If chest pain persists after a total of 3 tablets in a 15-minute period, or if the pain is different than is typically experienced, prompt medical attention is recommended.

NITROSTAT may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.

Nitroglycerin may produce a burning or tingling sensation when administered sublingually; however, the ability to produce a burning or tingling sensation should not be considered a reliable method for determining the potency of the tablets.

Headaches can sometimes accompany treatment with nitroglycerin. In patients who get these headaches, the headaches may be a marker of the activity of the drug.

Treatment with nitroglycerin may be associated with lightheadedness upon standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol.

Nitroglycerin should be kept in the original glass container and must be tightly capped after each use to prevent loss of tablet potency.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Animal carcinogenesis studies with sublingually administered nitroglycerin have not been performed.

Carcinogenicity potential of nitroglycerin was evaluated in rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years. Rats developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At high dose, the incidences of hepatocellular carcinomas in males was 48% and in females was 33%, compared to 0% in untreated controls. Incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice.

Nitroglycerin was mutagenic in Ames tests performed in 2 different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, PO, or in ex vivo cytogenetic tests in rat and dog cells.

In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for 6 months prior to mating of the F generation, with treatment continuing through successive F and F generations. The high dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males. In this 3- generation study, there was no clear evidence of teratogenicity.

Pregnancy Category B

Animal reproduction and teratogenicity studies have not been conducted with nitroglycerin sublingual tablets. However, teratology studies conducted in rats and rabbits with topically applied nitroglycerin ointment at dosages up to 80 mg/kg/day and 240 mg/kg/day, respectively revealed no toxic effects on dams or fetuses.

There are no adequate and well-controlled studies in pregnant women. Nitroglycerin should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when nitroglycerin is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of nitroglycerin in pediatric patients have not been established.

Geriatric Use

Clinical studies of NITROSTAT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Dosage (Posology) and method of administration

One tablet should be dissolved under the tongue or in the buccal pouch at the first sign of an acute anginal attack. The dose may be repeated approximately every 5 minutes until relief is obtained. If the pain persists after a total of 3 tablets in a 15-minute period, or if the pain is different than is typically experienced, prompt medical attention is recommended. NITROSTAT may be used prophylactically 5 to 10 minutes prior to engaging in activities that might precipitate an acute attack.

During administration the patient should rest, preferably in the sitting position.

No dosage adjustment is required in patients with renal failure.

Interaction with other medicinal products and other forms of interaction

SIDE EFFECTS

Headache that may be severe and persistent may occur immediately after use. Vertigo, dizziness, weakness, palpitation, and other manifestations of postural hypotension may develop occasionally, particularly in erect, immobile patients. Marked sensitivity to the hypotensive effects of nitrates (manifested by nausea, vomiting, weakness, diaphoresis, pallor, and collapse) may occur at therapeutic doses. Syncope due to nitrate vasodilatation has been reported. Flushing, drug rash, and exfoliative dermatitis have been reported in patients receiving nitrate therapy.

DRUG INTERACTIONS

Concomitant use of nitrates and alcohol may cause hypotension.

The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

Intravenous administration of nitroglycerin decreases the thrombolytic effect of alteplase. Therefore, caution should be observed in patients receiving sublingual nitroglycerin during alteplase therapy.

Intravenous nitroglycerin reduces the anticoagulant effect of heparin and activated partial thromboplastin times (APTT) should be monitored in patients receiving heparin and intravenous nitroglycerin. It is not known if this effect occurs following single sublingual nitroglycerin doses.

Tricyclic antidepressants (amitriptyline, desipramine, doxepin, others) and anticholinergic drugs may cause dry mouth and diminished salivary secretions. This may make dissolution of sublingual nitroglycerin difficult. Increasing salivation with chewing gum or artificial saliva products may prove useful in aiding dissolution of sublingual nitroglycerin.

Oral administration of nitroglycerin markedly decreases the first-pass metabolism of dihydroergotamine and subsequently increases its oral bioavailability. Ergotamine is known to precipitate angina pectoris. Therefore, patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs or be monitored for symptoms of ergotism if this is not possible.

Administration of nitroglycerin is contraindicated in patients who are using PDE-5 inhibitors (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride). These compounds have been shown to potentiate the hypotensive effects of organic nitrates.

A decrease in therapeutic effect of sublingual nitroglycerin may result from use of long-acting nitrates.

Drug/Laboratory Test Interactions

Nitrates may interfere with the Zlatkis-Zak color reaction, causing a false report of decreased serum cholesterol.

Frequently asked questions

What conditions does Nitrostat treat?

Nitrostat is prescribed in the management of angina pectoris and for angina prophylaxis, and is also associated in its registered indications with conditions including coronary heart disease, heart failure, and pulmonary hypertension. The active ingredient belongs to the vasodilator and antianginal categories. The structured indication block further down this page lists each registered use as recognised by the regulators in the markets where Nitrostat is sold.

Which active substance is in Nitrostat?

Nitrostat contains nitroglycerin, a vasodilator with antianginal and hypotensive properties. Nitroglycerin is one of the longest-established molecules in cardiovascular medicine and circulates internationally under a number of different brand names and formulations. The same active ingredient appears in products with quite different presentations from one country to another, even where the underlying molecule is identical.

In how many countries is Nitrostat available?

Nitrostat is registered in five countries: the United States, Canada, China, Taiwan, and Egypt. The brand itself is not broadly internationalised, though nitroglycerin as an active ingredient is available in essentially every regulated pharmaceutical market in the world. If your country is not on this short list, a local pharmacist can usually identify a nitroglycerin-containing product available regionally.

Are there other medications with the same active ingredient as Nitrostat?

Nitroglycerin is sold under a wide variety of brand names worldwide and in several different presentations, reflecting its long-established role in cardiovascular care. Other molecules in the broader vasodilator and antianginal categories are also available internationally, although they are not freely interchangeable with nitroglycerin. To identify a regional equivalent, search the active ingredient on Pill2Trip or ask a local pharmacist.

Is Nitrostat a prescription medication?

Nitrostat is a prescription medication, and nitroglycerin therapy is calibrated closely to a patient's cardiovascular status, concurrent treatments, and individual circumstances. For travellers and people relocating between countries, prescription requirements, available formulations, and brand names vary considerably between regulatory systems. Any decision to start, stop, or substitute a nitroglycerin product should be made together with a healthcare provider familiar with the patient's history.

Nitrostat

Available in 5 countries