Nitrolingual.com

220370026_3.qxp 13.12.2010 10:05 Uhr Seite 1 How to Use Nitrolingual® Pumpspray
Pumpspray
Before using this product for the first
5. Press the button firmly with the forefinger to (nitroglycerin lingual spray)
time, the pump must be sprayed 5 times
release the spray onto or under the tongue.
400 mcg per spray, 60 or 200 Metered Sprays
P into the air (this is known as priming).
The pump should be primed every
6. Release button and close mouth. Avoid swallowing Before using your Nitrolingual® Pumpspray THE 6 weeks to remain ready for use. If the
immediately after administering the spray. The (nitroglycerin lingual spray) 400 mcg per product has not been used for 6 weeks,
medication should not be expectorated or the mouth spray, 60 or 200 metered sprays, read careful- FOR a prime of 1 spray is necessary.
rinsed for 5 to 10 minutes following administration.
ly the following directions for use.
7. If you require a second administration to obtain TION 2. DO NOT SHAKE.
containing 400 mcg of nitroglycerin with each spray. Nitroglycerin is absorbed from the forefinger on top of the grooved button.
tongue and surrounding mucosa producing a DO NOT SHAKE
prompt therapeutic effect. It is best to use 4. Open the mouth and bring the container Nitrolingual® Pumpspray in a sitting position.
HOLD CONTAINER UPRIGHT
CLINICAL PHARMACOLOGY: The principal pharmacological action of nitroglycerin
In a pharmacokinetic study when a single 0.8 mg dose of Nitrolingual® Pumpspray Nitrate therapy may aggravate the angina caused by hypertrophic cardi- is relaxation of vascular smooth muscle, producing a vasodilator effect on both was administered to healthy volunteers (n = 24), the mean Cmax and tmax were peripheral arteries and veins with more prominent effects on the latter. Dilation of 1,041pg/mL · min and 7.5 minutes, respectively. Additionally, in these subjects the Pumpspray
the post-capillary vessels, including large veins, promotes peripheral pooling of Tolerance to this drug and cross-tolerance to other nitrates and nitrites may mean area-under-the-curve (AUC) was 12,769 pg/mL · min.
HERE blood and decreases venous return to the heart, thereby reducing left ventricular occur. Tolerance to the vascular and anti-anginal effects of nitrates has been In a randomized, double-blind single-dose, 5-period cross-over study in 51 patients end-diastolic pressure (pre-load). Arteriolar relaxation reduces systemic vascular demonstrated in clinical trials, experience through occupational exposure, and with exertional angina pectoris significant dose-related increases in exercise in isolated tissue experiments in the laboratory.
400 mcg per spray, 60 or 200 Metered Sprays resistance and arterial pressure (after-load).
tolerance, time to onset of angina and ST-segment depression were seen following TEAR The mechanism by which nitroglycerin relieves angina pectoris is not fully doses of 0.2, 0.4, 0.8 and 1.6 mg of nitroglycerin delivered by metered pumpspray In industrial workers continuously exposed to nitroglycerin, tolerance clearly occurs. Moreover, physical dependence also occurs since chest pain, acute DESCRIPTION: Nitroglycerin, an organic nitrate, is a vasodilator which has
understood. Myocardial oxygen consumption or demand (as measured by the myocardial infarction, and even sudden death have occurred during temporary effects on both arteries and veins. The chemical name for nitroglycerin is pressure-rate product, tension-time index, and stroke-work index) is decreased by Additionally the drug was well tolerated as evidenced by a profile of generally mild withdrawal of nitroglycerin from the workers. In various clinical trials in both the arterial and venous effects of nitroglycerin and presumably, a more favorable supply-demand ratio is achieved.
angina patients, there are reports of anginal attacks being more easily weight of 227.09. The chemical structure is: While the large epicardial coronary arteries are also dilated by nitroglycerin, the INDICATIONS AND USAGE: Nitrolingual® Pumpspray is indicated for acute relief of
provoked and of rebound in the hemodynamic effects soon after nitrate an attack or prophylaxis of angina pectoris due to coronary artery disease.
extent to which this action contributes to relief of exertional angina is unclear.
withdrawal. The relative importance of these observations to the routine, Nitroglycerin is rapidly metabolized in vivo, with a liver reductase enzyme CONTRAINDICATIONS: Allergic reactions to organic nitrates are rare. Nitroglycerin
clinical use of nitroglycerin is not known.
having primary importance in the formation of glycerol nitrate metabolites and is contraindicated in patients who are allergic to it. Nitrolingual® Pumpspray is PRECAUTIONS: (INFORMATION FOR PATIENTS)
inorganic nitrate. Two active major metabolites, 1,2- and 1,3-dinitroglycerols, the contraindicated in patients taking certain drugs for erectile dysfunction (phospho- Physicians should discuss with patients that Nitrolingual® Pumpspray should products of hydrolysis, although less potent as vasodilators, have longer diesterase inhibitors), as their concomitant use can cause severe hypotension. The not be used with certain drugs taken for erectile dysfunction (phosphodi- plasma half-lives than the parent compound. The dinitrates are further metabolized time course and dose-dependency of this interaction are not known.
esterase inhibitors) because of the risk of lowering their blood pressure to mononitrates (considered biologically inactive with respect to cardiovascular WARNINGS: Amplification of the vasodilatory effects of Nitrolingual® Pumpspray
effects) and ultimately glycerol and carbon dioxide.
by certain drugs (phosphodiesterase inhibitors) used to treat erectile dysfunction Nitrolingual® Pumpspray (nitroglycerin lingual spray 400 mcg) is a Therapeutic doses of nitroglycerin may reduce systolic, diastolic and mean arterial can result in severe hypotension. The time course and dose dependence of this DRUG INTERACTIONS: Alcohol may enhance sensitivity to the hypotensive
metered dose spray containing nitroglycerin. This product delivers nitro- interaction have not been studied. Appropriate supportive care has not been effects of nitrates. Nitroglycerin acts directly on vascular muscle. Therefore, v.09/10 blood pressure. Effective coronary perfusion pressure is usually maintained, but glycerin (400 mcg per spray, 60 or 200 metered sprays) in the form of spray can be compromised if blood pressure falls excessively or increased heart rate studied, but it seems reasonable to treat this as a nitrate overdose, with elevation any other agents that depend on vascular smooth muscle as the final common droplets onto or under the tongue. Inactive ingredients: medium-chain of the extremities and with central volume expansion. The use of any form of nitro- path can be expected to have decreased or increased effect depending upon triglycerides, dehydrated alcohol, medium-chain partial glycerides, pep- Elevated central venous and pulmonary capillary wedge pressures, pulmonary vas- glycerin during the early days of acute myocardial infarction requires particular cular resistance and systemic vascular resistance are also reduced by nitroglycerin attention to hemodynamic monitoring and clinical status.
Marked symptomatic orthostatic hypotension has been reported when calcium therapy. Heart rate is usually slightly increased, presumably a reflex response PRECAUTIONS: (General)
channel blockers and oral controlled-release nitroglycerin were used in to the fall in blood pressure. Cardiac index may be increased, decreased, or Severe hypotension, particularly with upright posture, may occur even with small combination. Dose adjustments of either class of agents may be necessary.
unchanged. Patients with elevated left ventricular filling pressure and systemic doses of nitroglycerin. The drug, therefore, should be used with caution in Concomitant use of nitric oxide donors (like Nitrolingual® Pumpspray) and vascular resistance values in conjunction with a depressed cardiac index are likely subjects who may have volume depletion from diuretic therapy or in patients who certain drugs for the treatment of erectile dysfunction (phosphodiesterase to experience an improvement in cardiac index. On the other hand, when filling have low systolic blood pressure (e.g., below 90 mm Hg). Paradoxical bradycardia inhibitors) can amplify their vasodilatory effects, resulting in severe hypoten- pressures and cardiac index are normal, cardiac index may be slightly reduced.
and increased angina pectoris may accompany nitroglycerin-induced hypotension.
220370026_3.qxp 13.12.2010 10:05 Uhr Seite 2 NOTE: To familiarize yourself with the product and while priming the container, actuate the spray into the air (away Precaution
from yourself and others). Get the feel of your finger resting on the grooved button so that you can use the Your physician has determined that this product is likely to help your personal health.
spray in the dark. DO NOT SHAKE the container before use. You may wish to keep additional pumpspray USE THIS PRODUCT AS DIRECTED, BY YOUR PHYSICIAN.
containers handy in convenient locations.
If you have any questions about alternatives, consult with your physician.
Do not share or give your medication to others, particularly those who may appear to be having chest discomfort similar to yours.
Nitrolingual® Pumpspray should be used during an episode of chest pain or may be used 5 to 10 minutes prior to engaging in During an anginal attack, one or two sprays should be administered into your mouth, preferably onto or under activities which might provoke an acute attack.
the tongue. Do not inhale spray. The medication should not be expectorated or the mouth rinsed for 5 to 10 minutes Nitrolingual® Pumpspray is available in a clear glass bottle with a red plastic coating on the exterior. This plastic coating is following administration. A spray may be repeated approximately every 3-5 minutes as needed. No more than designed to contain the glass and medication should the bottIe be shattered.
three metered sprays are recommended within a 15-minute period. If chest pain persists, prompt medical attention is recommended. Nitrolingual® Pumpspray may be used 5 to 10 minutes prior to engaging in activities The transparent container can be used for continuous monitoring of the consumption. The end of the pump should be covered
which might provoke an acute attack.
by the fluid level. Once fluid falls below the level of the center tube, sprays will not be adequate and the container should be
replaced. As with all other sprays, there is a residual volume of fluid at the bottom of the bottle which cannot be used. Nitrolingual® Pumpspray contains 20% alcohol. Do not forcefully open or burn container. Do not spray toward flames. Keep in a safe place and
There are approximately 60 or 200 metered sprays of nitroglycerin per Nitrolingual® Pumpspray bottle. However, the number out of the reach of chiIdren.
of times the medication may be used is dependent on the number of sprays per use (1 or 2 sprays), and frequency of Store at 25 °C (77 °F); excursions permitted to 15-30 °C (59-86 °F) [see USP Controlled Room Temperature].
repriming. Each metered spray of Nitrolingual® Pumpspray delivers 400 mcg of nitroglycerin after an initial priming of The following trademarks are either registered trademarks or trademarks of Pohl-Boskamp in the United States and/or other 5 sprays. The container will remain adequately primed for 6 weeks. If the medication is not used within 6 weeks, it can be countries: Pohl-Boskamp word mark; Pohl-Boskamp logo; Nitrolingual word mark; Peppermint flavor of nitroglycerin; Peppermint adequately reprimed with 1 spray. Longer storage periods without use may require up to 5 repriming sprays.
scent of nitroglycerin; Nitrolingual Pumpspray shapes, Nitrolingual Pumpspray colors, and the sound of Nitrolingual Pumpspray.
Manufactured for Arbor Pharmaceuticals, Inc. Raleigh, North Carolina 27609
by G. Pohl-Boskamp GmbH & Co. KG, 25551 Hohenlockstedt, Germany.
The concomitant use of these drugs is contraindicated (see CONTRAINDICA-
PEDIATRIC USE: Safety and effectiveness of nitroglycerin in pediatric patients have
the case of genetic abnormalities of hemoglobin that favor methemoglobin onto the tongue by pressing the button firmly and the mouth should be closed TIONS) and alternative therapies should be used to treat acute angina
formation, even conventional doses of organic nitrates could produce harmful immediately after each dose. THE SPRAY SHOULD NOT BE INHALED. The ADVERSE REACTIONS: Adverse reactions to oral nitroglycerin dosage forms,
medication should not be expectorated or the mouth rinsed for 5 to 10 minutes CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Animal
particularly headache and hypotension, are generally dose-related. In clinical trials following administration. Patients should be instructed to familiarize carcinogenesis studies with sublingual nitroglycerin have not been performed.
at various doses of nitroglycerin, the following adverse effects have been themselves with the position of the spray orifice, which can be identified by Keep the patient recumbent in a shock position and comfortably warm. the finger rest on top of the valve, in order to facilitate orientation for Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years Passive movement of the extremities may aid venous return. Administer developed dose-related fibrotic and neoplastic changes in liver, including Headache, which may be severe and persistent, is the most commonly oxygen and artificial ventilation, if necessary. If methemoglobinemia is present, carcinomas, and interstitial cell tumors in testes. At high dose, the incidences reported side effect of nitroglycerin with an incidence on the order of about 50% in administration of methylene blue (1% solution), 1-2 mg per kilogram of body HOW SUPPLIED: Each box of Nitrolingual® Pumpspray contains one glass
of hepatocellular carcinomas in both sexes were 52% vs. 0% in controls, and some studies. Cutaneous vasodilation with flushing may occur. Transient episodes weight intravenously, may be required. If an excessive quantity of Nitrolingual® bottle coated with red transparent plastic which assists in containing the incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary of dizziness and weakness, as well as other signs of cerebral ischemia associated Pumpspray has been recently swallowed gastric lavage may be of use.
glass and medication should the bottle be shattered. Each bottle contains administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in with postural hypotension, may occasionally develop. Occasionally, an individual 4.9 g or 12 g (Net Content) of nitroglycerin lingual spray which will deliver mice. Nitroglycerin was weakly mutagenic in Ames tests performed in two may exhibit marked sensitivity to the hypotensive effects of nitrates and severe WARNING: Epinephrine is ineffective in reversing the severe hypotensive events
60 or 200 metered sprays containing 400 mcg of nitroglycerin per spray after different laboratories. Nevertheless, there was no evidence of mutagenicity in responses (nausea, vomiting, weakness, restlessness, pallor, perspiration and associated with overdosage. It and related compounds are contraindicated in this an in vivo dominant lethal assay with male rats treated with doses up to about collapse) may occur even with therapeutic doses. Drug rash and/or exfoliative Nitrolingual® Pumpspray is available as: 363 mg/kg/day, p.o., or in in vitro cytogenic tests in rat and dog tissues.
dermatitis have been reported in patients receiving nitrate therapy. Nausea and DOSAGE AND ADMINISTRATION: At the onset of an attack, one or two metered
In a three-generation reproduction study, rats received dietary nitroglycerin at sprays should be administered onto or under the tongue. No more than three doses up to about 434 mg/kg/day for six months prior to mating of the F0 Nitrolingual® Pumpspray given to 51 chronic stable angina patients in single doses metered sprays are recommended within a 15-minute period. If the chest pain Store at 25 °C (77 °F); excursions permitted to 15-30 °C (59-86 °F) [see USP generation with treatment continuing through successive F1 and F2 of 0.4, 0.8 and 1.6 mg as part of a double-blind, 5-period single-dose cross-over persists, prompt medical attention is recommended. Nitrolingual® Pumpspray may generations. The high dose was associated with decreased feed intake and study exhibited an adverse event profile that was generally mild to moderate.
be used prophylactically five to ten minutes prior to engaging in activities which Note: Nitrolingual® Pumpspray contains 20% alcohol. Do not forcefully open or body weight gain in both sexes at all matings. No specific effect on the Adverse events occurring at a frequency greater than 2% included: headache, burn container after use. Do not spray toward flames.
fertility of the F0 generation was seen. Infertility noted in subsequent dizziness, and paresthesia. Less frequently reported events in this trial included generations, however, was attributed to increased interstitial cell tissue and (≤2%): dyspnea, pharyngitis, rhinitis, vasodilation, peripheral edema, asthenia, and Each metered spray of Nitrolingual® Pumpspray delivers 48 mg of solution aspermatogenesis in the high-dose males. In this three-generation study there containing 400 mcg of nitroglycerin after an initial priming of 5 sprays. The following trademarks are either registered trademarks or trademarks of was no clear evidence of teratogenicity.
OVERDOSAGE: Signs and Symptoms:
It will remain adequately primed for 6 weeks. If the product is not used within Pohl-Boskamp in the United States and/or other countries: Pohl-Boskamp Nitrate overdosage may result in: severe hypotension, persistent throbbing 6 weeks it can be adequately reprimed with 1 spray. Longer storage periods word mark; Pohl-Boskamp logo; Nitrolingual word mark; Peppermint flavor of PREGNANCY: Pregnancy Category C – Animal teratology studies have not
headache, vertigo, palpitation, visual disturbance, flushing and perspiring skin without use may require up to 5 repriming sprays. There are 60 or 200 metered nitroglycerin; Peppermint scent of nitroglycerin; Nitrolingual Pumpspray been conducted with nitroglycerin-pumpspray. Teratology studies in rats and (later becoming cold and cyanotic), nausea and vomiting (possibly with colic and sprays per bottle. The total number of available doses is dependent, however, on shapes, Nitrolingual Pumpspray colors, and the sound of Nitrolingual rabbits, however, were conducted with topically applied nitroglycerin ointment even bloody diarrhea), syncope (especially in the upright posture), methemo- the number of sprays per use (1 or 2 sprays), and the frequency of repriming.
at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively. No toxic effects globinemia with cyanosis and anorexia, initial hyperpnea, dyspnea and slow The transparent container can be used for continuous monitoring of the on dams or fetuses were seen at any dose tested. There are no adequate and breathing, slow pulse (dicrotic and intermittent), heart block, increased intracranial consumption. The end of the pump should be covered by the fluid level. Once
well-controlled studies in pregnant women. Nitroglycerin should be given to pressure with cerebral symptoms of confusion and moderate fever, paralysis and fluid falls below the level of the center tube, sprays will not be adequate and the pregnant women only if clearly needed.
coma followed by clonic convulsions, and possibly death due to circulatory container should be replaced. As with all other sprays, there is a residual volume NURSING MOTHERS: It is not known whether nitroglycerin is excreted in
of fluid at the bottom of the bottle which cannot be used.
Manufactured for
human milk. Because many drugs are excreted in human milk, caution should During application the patient should rest, ideally in the sitting position. The Arbor Pharmaceuticals, Inc. Raleigh, North Carolina 27609
be exercised when Nitrolingual® Pumpspray is administered to a nursing Case reports of clinically significant methemoglobinemia are rare at conventional container should be held vertically with the valve head uppermost and the spray by G. Pohl-Boskamp GmbH & Co. KG,
doses of organic nitrates. The formation of methemoglobin is dose-related and in orifice as close to the mouth as possible. The dose should preferably be sprayed 25551 Hohenlockstedt, Germany.

Source: http://www.nitrolingual.com/sites/default/files/pdf/NLPS_PI.pdf