Nitroglycerin lingual spray

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse reactions occurring at a frequency greater than 2% and greater than placebo included: headache, dizziness, and paresthesia.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Nitrolingual Pumpspray and other nitroglycerin drugs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or establish a causal relationship to drug exposure.

Neurologic: weakness, drowsiness

Dermatologic: cutaneous vasodilation, flushing, drug rash, exfoliative dermatitits

Gastrointestinal: nausea, vomiting

Respiratory: transient hypoxemia

Cardiovascular: tachycardia,

Read the entire FDA prescribing information for Nitrolingual Pumpspray (Nitroglycerin Lingual Spray)

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

2.1 Recommended Dosage

At the onset of an attack, one metered spray or two metered sprays should be administered on or under the tongue. A spray may be repeated approximately every 5 minutes as needed. If two sprays are used initially, the patient may only administer one more spray after waiting 5 minutes.  No more than 3 metered sprays are recommended within a 15-minute period. If chest pain persists after a total of 3 sprays, prompt medical attention is recommended. Nitroglycerin Lingual Aerosol may be used prophylactically 5 minutes to 10 minutes before engaging in activities that might precipitate an acute attack.

2.2 Priming the Container

After an initial priming of 10 sprays, each metered spray of Nitroglycerin Lingual Aerosol delivers 33 mg of solution containing 400 mcg of nitroglycerin. It will remain adequately primed for 6 weeks. If the product is not used within 6 weeks, it can be adequately re-primed with 2 sprays. Nitroglycerin Lingual Aerosol is available in either 200 metered sprays or 60 metered sprays per container, but the total number of available doses depends on the number of sprays per use (1 spray or 2 sprays), and the frequency of priming.

2.3 Administration

During use the patient should rest, ideally in the sitting position. The container should be held vertically with the valve head uppermost and the spray orifice as close to the mouth as possible. The dose should preferably be sprayed into the mouth on or under the tongue by pressing the button firmly and the mouth should be closed immediately after each dose. THE SPRAY SHOULD NOT BE INHALED. Patients should be instructed to familiarize themselves with the position of the spray orifice, which can be identified by the finger rest on top of the valve, in order to facilitate orientation for administration at night.

1. Do not shake container.
   
2. Remove plastic cap.
   
3. If this is the first time using the bottle, press actuator button 10 times to ensure proper dose priming (holding unit away from yourself and others).
   
4. Hold container upright with forefinger on top of the actuator button.
   
5. Open mouth and bring the container as close as possible.
   
6. Press the actuator button firmly with forefinger to release spray(s) onto or under the tongue.
   
7. Release button and close mouth. The medication should not be spit out or the mouth rinsed for 5 minutes to 10 minutes following administration.
   
8. If a second administration is required to obtain relief, repeat steps 4, 5, and 6. No more than 3 metered sprays can be given within a 15-minute period.
   
9. Replace plastic cover.
   
10. If the product is not used for more than 6 weeks, then it can be adequately re-primed with 2 sprays.

The level of the liquid in the container should be periodically checked. While the container is in the upright position, if the liquid reaches the top or middle of the hole on the side of the container, one should order more. When the liquid reaches the bottom of the hole, the remaining doses will have less than label content.

4.1 PDE5 Inhibitor Use

Administration of Nitroglycerin Lingual Aerosol is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), as PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use Nitroglycerin Lingual Aerosol in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension. [see DRUG INTERACTIONS (7.1)].

4.2 Severe Anemia

Nitroglycerin Lingual Aerosol is contraindicated in patients with severe anemia.

4.3 Increased Intracranial Pressure

Nitroglycerin Lingual Aerosol is contraindicated in patients with increased intracranial pressure

4.4 Hypersensitivity

Nitroglycerin Lingual Aerosol is contraindicated in patients who have shown hypersensitivity to it or to other nitrates or nitrites. Skin reactions consistent with hypersensitivity have been observed with organic nitrates.

6.1 Headache

Headache, which may be severe and persistent, may occur immediately after nitroglycerin use.

6.2 Flushing

Flushing, drug rash and exfoliative dermatitis have been reported in patients receiving nitrate therapy.

6.3 Hypotension

Postural hypotension, as manifest by vertigo, weakness, palpitation, and other symptoms, 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.

6.4 Syncope

Syncope due to nitrate vasodilatation has been reported.

7.1 PDE5 Inhibitors

Administration of Nitroglycerin Lingual Aerosol is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use Nitroglycerin Lingual Aerosol in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use may result in severe hypotension, syncope, or myocardial ischemia.

The time course and dose dependence of this interaction have not been studied, and use within a few days of one another cannot be recommended. Appropriate supportive care for the severe hypotension has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion. The use of any form of nitroglycerin during the early days of acute myocardial infarction requires particular attention to hemodynamic monitoring and clinical status.

7.2 Antihypertensives

Patients receiving antihypertensive drugs, beta-adrenergic blockers, and nitrates should be observed for possible additive hypotensive effects. Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly.

Labetolol blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. If labetolol is used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur.

7.3 Aspirin

Coadministration of aspirin and nitroglycerin has been reported to result in increased nitroglycerin maximum concentrations by as much as 67% and AUC by 73% when administered as a single dose. The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

7.4 Tissue-type Plasminogen Activator (t-PA)

Intravenous administration of nitroglycerin decreases the thrombolytic effect of tissue-type plasminogen activator (t-PA). Plasma levels of t-PA are reduced when coadministered with nitroglycerin. Therefore, caution should be observed in patients receiving nitroglycerin during t-PA therapy.

7.5 Heparin

Intravenous nitroglycerin reduces the anticoagulant effect of heparin. 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 nitroglycerin doses.

7.6 Ergotamine

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.

Nitroglycerin, an organic nitrate, is a vasodilator which has effects on both arteries and veins. The chemical name for nitroglycerin is 1,2,3-propanetriol trinitrate (C3H5N3O9). The compound has a molecular weight of 227.09. The chemical structure is:

Nitroglycerin Lingual Aerosol (nitroglycerin) lingual aerosol is a metered-dose spray containing 200 or 60 metered sprays of nitroglycerin per container. This product delivers 400 mcg of nitroglycerin per actuation in the form of spray droplets on or under the tongue. Inactive ingredients: caprylic/capric diglycerol succinate, peppermint oil, L(-)-menthol, n-butane.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal carcinogenicity studies with sublingually administered or lingual spray nitroglycerin have not been performed.

Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At the highest dose, the incidences of hepatocellular carcinomas was 52% 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 found to have reverse mutation activity in the Salmonella typhimurium strain TA1535 (Ames assay). A similar mutation in S. typhimurium strain was also reported for other NO donors. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with oral doses of up to about 363 mg/kg/day or in ex vitro cytogenic tests in rat and dog tissues. In vitro cytogenetic assay using Chinese hamster ovary cells showed no chromosomal aberrations.

In a 3-generation reproduction study, rats received dietary nitroglycerin at doses up to about 408 mg/kg/day (males) to 452 mg/kg/day (females) for 5 months (females) or 6 months (males) prior to mating of the F0 generation with treatment continuing through successive F1 and F2 generations. The highest 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 F0 generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males.

In a randomized, double-blind, single-center, single-administration, placebo-controlled, 4-period cross-over study in 30 subjects with stable angina pectoris, statistically significant dose-related increases in exercise tolerance were seen following doses of 200 mcg, 400 mcg, and 800 mcg of nitroglycerin delivered by Nitroglycerin Lingual Aerosol compared to placebo.