Monoket

Name: Monoket

How supplied

Monoket® (isosorbide mononitrate, USP) 10 mg tablets are white, round, scored and engraved “10” on one side and engraved “SCHWARZ 610” on the other. They are supplied as follows:

Bottles of 100 .............NDC 62175-3610-1

Monoket ® (isosorbide mononitrate, USP) 20 mg tablets are white, round, scored and engraved “20” on one side and engraved “SCHWARZ 620” on the other. They are supplied as follows:

Bottles of 100 .............NDC 62175-3620-1

Store at 20°-30°C (68°-86°F) [See USP] Keep tightly closed.

Distributed by: Kremers Urban Pharmaceuticals Inc. Princeton, NJ 08540. Rev. Oct 2014

Overdose

Hemodynamic Effects

The ill effects of isosorbide mononitrate overdose are generally the results of isosorbide mononitrate'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; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and 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.

Laboratory determinations of serum levels of isosorbide mononitrate and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of isosorbide mononitrate overdose.

There are no data suggesting what dose of isosorbide mononitrate is likely to be life-threatening in humans. In rats and mice, there is significant lethality at oral doses of 1965 mg/kg and 2581 mg/kg, respectively.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of isosorbide mononitrate. Isosorbide mononitrate is significantly removed from the blood during hemodialysis.

No specific antagonist to the vasodilator effects of isosorbide mononitrate is known, and no intervention has been subject to controlled study as a therapy of isosorbide mononitrate overdose. Because the hypotension associated with isosorbide mononitrate overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward an 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 isosorbide mononitrate overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Methemoglobinemia has been reported in patients receiving other organic nitrates, and it probably could also occur as a side effect of isosorbide mononitrate. Certainly nitrate ions liberated during metabolism of isosorbide mononitrate can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moiety of isosorbide mononitrate is quantitatively applied to oxidation of hemoglobin, about 2 mg/kg of isosorbide mononitrate should be required before any of these patients manifests clinically significant ( ≥ 10%) methemoglobinemia. In patients with normal reductase function, significant production of methemoglobin should require even larger doses of isosorbide mononitrate. In one study in which 36 patients received 2-4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 7.8-11.1 mg of isosorbide mononitrate per hour), the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.

Notwithstanding these observations, there are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusually susceptible.

Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial p02. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1-2 mg/kg intravenously.

Side effects

Headache is the most frequent side effect and was the cause of 2% of all dropouts from controlled-clinical trials. Headache decreased in incidence after the first few days of therapy.

The following table shows the frequency of adverse reactions observed in 1% or more of subjects in 6 placebo-controlled trials, conducted in the United States and abroad. The same table shows the frequency of withdrawal for these adverse reactions. In many cases the adverse reactions were of uncertain relation to drug treatment.

Frequency Of Adverse Reactions (Discontinuations)*

Dose 6 Placebo-Controlled Studies
Placebo 5 mg 10 mg 20 mg
Patients 160 54 52 159
Headache 6% (0%) 17% (0%) 13% (0%) 35% (5%)
Fatigue Upper Respiratory 2% (0%) 0% (0%) 4% (0%) 1% (0%)
Infection < 1% (0%) 0% (0%) 4% (0%) 1% (0%)
Pain < 1% (0%) 4% (0%) 0% (0%) < 1% (0%)
Dizziness 1% (0%) 0% (0%) 0% (0%) 4% (0%)
Nausea Increased < 1% (0%) 0% (0%) 0% (0%) 3% (2%)
Cough < 1% (0%) 0% (0%) 2% (0%) < 1% (0%)
Rash Abdominal 0% (0%) 2% (2%) 0% (0%) < 1% (0%)
Pain Allergic < 1% (0%) 0% (0%) 2% (0%) 0% (0%)
Reaction Cardiovascular 0% (0%) 0% (0%) 2% (0%) 0% (0%)
Disorder 0% (0%) 2% (0%) 0% (0%) 0% (0%)
Chest Pain < 1% (0%) 0% (0%) 2% (0%) < 1% (0%)
Diarrhea 0% (0%) 0% (0%) 2% (0%) 0% (0%)
Flushing Emotional 0% (0%) 0% (0%) 2% (0%) 0% (0%)
Lability 0% (0%) 2% (0%) 0% (0%) 0% (0%)
Pruritus 1% (0%) 2% (2%) 0% (0%) 0% (0%)
*Some individuals discontinued for multiple reasons.

Other adverse reactions, each reported by fewer than 1% of exposed patients, and in many cases of uncertain relation to drug treatment, were:

Cardiovascular: acute myocardial infarction, apoplexy, arrhythmias, bradycardia, edema, hypertension, hypotension, pallor, palpitations, tachycardia.

Dermatologic: sweating.

Gastrointestinal: anorexia, dry mouth, dyspepsia, thirst, vomiting, decreased weight.

Genitourinary: prostatic disorder.

Miscellaneous: amblyopia, back pain, bitter taste, muscle cramps, neck pain, pares thesia, susurrus aurium.

Neurologic: anxiety, impaired concentration, depression, insomnia, nervousness, nightmares, restlessness, tremor, vertigo.

Respiratory: asthma, dyspnea, sinusitis.

Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients; for further discussion of its diagnosis and treatment see OVERDOSAGE.

Read the entire FDA prescribing information for Monoket (Isosorbide Mononitrate, USP)

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What is the most important information I should know about Monoket (isosorbide mononitrate)?

You should not take erectile dysfunction medicine (Viagra, Cialis, Levitra, Stendra, Staxyn, sildenafil, avanafil, tadalafil, vardenafil) while you are taking isosorbide mononitrate. Taking these medicine together can cause a sudden and serious decrease in blood pressure.

Seek emergency medical attention if you have early symptoms of a heart attack (chest pain or pressure, pain spreading to your jaw or shoulder, sweating, general ill feeling).

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Monoket (isosorbide mononitrate) side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • a light-headed feeling, like you might pass out;

  • worsening angina pain;

  • fast or slow heart rate; or

  • pounding heartbeats or fluttering in your chest.

Isosorbide mononitrate can cause severe headaches. These headaches may gradually become less severe as you continue to use nitroglycerin. Do not stop taking this medicine to avoid headaches. Ask your doctor before using any headache pain medication.

Common side effects may include:

  • headache; or

  • flushing (warmth, redness, or tingly feeling).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Uses For Monoket

Isosorbide mononitrate is used to prevent angina (chest pain) caused by coronary artery disease (heart disease). It does not work fast enough to relieve the pain of an angina attack that has already started.

Isosorbide mononitrate belongs to the group of medicines called nitrates. It works by relaxing the blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload. When used regularly on a long-term basis, this helps prevent angina attacks from occurring.

This medicine is available only with your doctor's prescription.

Precautions While Using Monoket

If you will be taking this medicine for a long time, it is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Do not take riociguat (Adempas®), sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®) while you are using this medicine. Using these medicines together may lower your blood pressure and cause blurred vision, dizziness, lightheadedness, or fainting. If you are taking these medicines and you experience an angina attack, you must go to the hospital right away.

This medicine may cause headaches. These headaches are a sign that the medicine is working. Do not stop using the medicine or change the time you use it in order to avoid the headaches. If you have severe pain, talk with your doctor.

Dizziness, lightheadedness, or faintness may occur, especially when you get up quickly from a lying or sitting position. Getting up slowly may help.

Dizziness, lightheadedness, or fainting is also more likely to occur if you drink alcohol, stand for long periods of time, exercise, or if the weather is hot. While you are taking this medicine, be careful to limit the amount of alcohol you drink. Also, use extra care during exercise or hot weather or if you must stand for long periods of time.

Do not stop using this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before you have medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Contraindications

Isosorbide mononitrate is contraindicated in patients who are allergic to it.

Do not use Monoket® in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil.  Concomitant use can cause severe hypotension, syncope, or myocardial ischemia.

Overdosage

Hemodynamic Effects

The ill effects of isosorbide mononitrate overdose are generally the results of isosorbide mononitrate'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; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and 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.

Laboratory determinations of serum levels of isosorbide mononitrate and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of isosorbide mononitrate overdose.

There are no data suggesting what dose of isosorbide mononitrate is likely to be life-threatening in humans. In rats and mice, there is significant lethality at oral doses of 1965 mg/kg and 2581 mg/kg, respectively.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of isosorbide mononitrate. Isosorbide mononitrate is significantly removed from the blood during hemodialysis.

No specific antagonist to the vasodilator effects of isosorbide mononitrate is known, and no intervention has been subject to controlled study as a therapy of isosorbide mononitrate overdose. Because the hypotension associated with isosorbide mononitrate overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward an 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 isosorbide mononitrate overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Methemoglobinemia has been reported in patients receiving other organic nitrates, and it probably could also occur as a side effect of isosorbide mononitrate. Certainly nitrate ions liberated during metabolism of isosorbide mononitrate can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moiety of isosorbide mononitrate is quantitatively applied to oxidation of hemoglobin, about 2 mg/kg of isosorbide mononitrate should be required before any of these patients manifests clinically significant (≥10%) methemoglobinemia. In patients with normal reductase function, significant production of methemoglobin should require even larger doses of isosorbide mononitrate. In one study in which 36 patients received 2-4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 7.8-11.1 mg of isosorbide mononitrate per hour), the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.

Notwithstanding these observations, there are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusually susceptible.

Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial p02. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.

When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1-2 mg/kg intravenously.

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