NitroMist

Tell your doctor if you are pregnant. 

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

NitroMist falls into category C. There are no adequate and well controlled studies in pregnant women. NitroMist should be given to a pregnant woman only if clearly needed.

Use NitroMist exactly as prescribed.

NitroMist comes in a spray and is administered on or under the tongue at the first sign of chest pain. 

Patients must prime the pump before using NitroMist for the first time.

To Prime NitroMist spray, follow the steps below:

• Do not shake the container.
• Remove the plastic cap from the container
• While holding the container away from yourself and others, press the actuator button 10 times
• Your NitroMist spray is now primed. You are ready to give your first dose.
• If you do not use your NitroMist spray for more than 6 weeks, you will need to prime again by pressing the nozzle button 2 times.

Giving a Dose:

• Hold your NitroMist spray upright with your index finger on top of the actuator button.
• Open your mouth and bring the NitroMist spray as close as possible to your mouth.
• Press the actuator button firmly to release the NitroMist spray(s) onto or under your tongue at the beginning of angina or to prevent an angina attack. 
• Release the actuator button and close your mouth. Do not spit out NitroMist or rinse your mouth for 5 to 10 minutes after using NitroMist.
• If a second dose is needed, repeat steps 1-4.
• Replace the plastic cap

Treatment with nitroglycerin products such as NitroMist may be associated with lightheadedness on standing, especially just after rising from a laying or seated position. To help avoid feeling lightheadedness on standing, patients should be seated when taking NitroMist. This reduces the likelihood of falling due to lightheadedness or dizziness.

If you use too much NitroMist, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of nitroglycerin in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of nitroglycerin in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving nitroglycerin.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Avanafil
• Riociguat
• Sildenafil
• Tadalafil
• Vardenafil

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alteplase, Recombinant

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetylcysteine
• Aspirin
• Dihydroergotamine
• Pancuronium

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia, severe or
• Brain tumor or
• Circulatory failure or shock or
• Heart attack, acute (already occurring) or
• Head injury, severe with increased pressure in the head—Should not be used in patients with these conditions.

• Congestive heart failure or
• Heart attack, recent or
• Heart disease (eg, hypertrophic cardiomyopathy, constrictive pericarditis, aortic or mitral stenosis) or
• Hypotension (low blood pressure) or
• Hypovolemia (low amount of blood)—Use with caution. May make these conditions worse.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how NitroMist affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have your blood pressure checked often. Talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Talk with your doctor before you drink alcohol.
• Taking more of NitroMist or taking it more often than you have been told may cause it to not work as well. This is known as tolerance. Talk with your doctor if this medicine stops working well. Do not take more than ordered.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using NitroMist while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Very bad headache.
• Fast or slow heartbeat.
• Flushing.
• Blurred eyesight.
• Dry mouth.
• Sweating a lot.
• Pale skin.
• Very upset stomach or throwing up.
• A heartbeat that does not feel normal.
• Restlessness.
• Feeling very tired or weak.

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. NitroMist 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 NitroMist 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. NitroMist is available in either 230 metered sprays or 90 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 NitroMist 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 NitroMist 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

NitroMist is contraindicated in patients with severe anemia.

4.3 Increased Intracranial Pressure

NitroMist is contraindicated in patients with increased intracranial pressure.

4.4 Hypersensitivity

NitroMist 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.

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.

Each box of NitroMist contains one glass bottle coated with red/orange transparent plastic which assists in containing the glass and medication should the bottle be shattered. NitroMist is available as an 8.5 g (Net Content) of nitroglycerin lingual aerosol that will deliver 230 metered sprays containing 400 mcg of nitroglycerin per actuation or as a 4.1 g (Net Content) of nitroglycerin lingual aerosol that will deliver 90 metered sprays containing 400 mcg of nitroglycerin per actuation.

230 metered sprays: NDC 76299-430-08 
90 metered sprays: NDC 76299-430-04

• Storage
  Store at room temperature (25oC, 77oF); excursions permitted to 15oto30oC (59o to 85 oF)
  
• Handling
  NitroMist contains a highly flammable propellant (butane). Do not forcefully open a NitroMist bottle, do not have the container burned after use, and do not spray directly toward flames.