Isosorbide Mononitrate (Page 4 of 4)

OVERDOSAGE

Hemodynamic Effects

The ill effects of isosorbide mononitrate overdose are generally the result 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 doses of 2000 mg/kg and 3000 mg/kg, respectively.

No data are available to suggest physiological maneuvers (eg, maneuvers to change the pH of the urine) that might accelerate elimination of isosorbide mononitrate. In particular, dialysis is known to be ineffective in removing isosorbide mononitrate from the body.

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 b 5 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 manifest 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 to 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 to 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.

Not with standing 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 pO 2 . 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 to 2 mg/kg intravenously.

DOSAGE AND ADMINISTRATION

The recommended starting dose of Isosorbide Mononitrate Extended-Release Tablets, USP is 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily. After several days, the dosage may be increased to 120 mg (given as a single 120 mg tablet or as two 60 mg tablets) once daily. Rarely, 240 mg may be required. The daily dose of Isosorbide Mononitrate Extended-Release Tablets, USP should be taken in the morning on arising. Isosorbide Mononitrate Extended-Release Tablets, USP should not be chewed or crushed and should be swallowed together with a half-glassful of fluid.

HOW SUPPLIED

Isosorbide Mononitrate Extended-Release Tablets USP, 30 mg are white to off-white, uncoated, oval shaped tablets debossed with ‘ING 175’ one side and scored on the other side. They are supplied as follows:

Bottles of 100 NDC 51407-208-01

Bottles of 500 NDC 51407-208-05

Isosorbide Mononitrate Extended-Release Tablets USP, 60 mg are white to off-white, uncoated, capsule shaped tablets debossed with ‘ING 176’ one side and scored on the other side. They are supplied as follows:

Bottles of 100 NDC 51407-209-01

Bottles of 500 NDC 51407-209-05

Isosorbide Mononitrate Extended-Release Tablets USP, 120 mg are white to off-white, uncoated, oval shaped tablets debossed with ‘ING 177’ one side and plain on the other side. They are supplied as follows:

Bottles of 100 NDC 51407-210-01

Store at 20 o -30 o C (68 o -86 o F) [See USP Controlled Room Temperature].

Manufactured for:

Ingenus Pharmaceuticals, LLC

Orlando, FL 32839-6408

Made in India

Rev.: 03/2020

Ingenus Logo

Marketed/Packaged by:

GSMS, Inc.

Camarillo, CA USA 93012

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Package Label — Principal Display Panel – 30 mg, 100 Tablets

NDC 51407-208-01

Isosorbide Mononitrate Extended-Release Tablets, USP

30 mg

Rx Only

100 Tablets

//medlibrary.org/lib/images-rx/isosorbide-mononitrate-24/51407-208-01lb-300x223.jpg
(click image for full-size original)

Package Label — Principal Display Panel – 60 mg, 100 Tablets

NDC 51407-209-01

Isosorbide Mononitrate Extended-Release Tablets, USP

60 mg

Rx Only

100 Tablets

//medlibrary.org/lib/images-rx/isosorbide-mononitrate-24/51407-209-01lb-300x223.jpg
(click image for full-size original)

Package Label — Principal Display Panel – 120 mg, 100 Tablets

NDC 51407-210-01

Isosorbide Mononitrate Extended-Release Tablets, USP

120 mg

Rx Only

100 Tablets

//medlibrary.org/lib/images-rx/isosorbide-mononitrate-24/51407-210-01lb-300x223.jpg
(click image for full-size original)
ISOSORBIDE MONONITRATE isosorbide mononitrate tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51407-208(NDC:50742-175)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ISOSORBIDE MONONITRATE (ISOSORBIDE MONONITRATE) ISOSORBIDE MONONITRATE 30 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE
HYDROXYPROPYL CELLULOSE (TYPE M)
HYPROMELLOSE 2208 (100000 MPA.S)
SILICON DIOXIDE
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
Product Characteristics
Color white (white to off-white) Score 2 pieces
Shape OVAL Size 9mm
Flavor Imprint Code ING175
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:51407-208-01 100 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC None
2 NDC:51407-208-05 500 TABLET, EXTENDED RELEASE in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA210918 11/05/2018
ISOSORBIDE MONONITRATE isosorbide mononitrate tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51407-209(NDC:50742-176)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ISOSORBIDE MONONITRATE (ISOSORBIDE MONONITRATE) ISOSORBIDE MONONITRATE 60 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE
HYDROXYPROPYL CELLULOSE (TYPE M)
HYPROMELLOSE 2208 (100000 MPA.S)
SILICON DIOXIDE
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
Product Characteristics
Color white (white to off-white) Score 2 pieces
Shape CAPSULE Size 14mm
Flavor Imprint Code ING176
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:51407-209-01 100 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC None
2 NDC:51407-209-05 500 TABLET, EXTENDED RELEASE in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA210918 11/05/2018
ISOSORBIDE MONONITRATE isosorbide mononitrate tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51407-210(NDC:50742-177)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ISOSORBIDE MONONITRATE (ISOSORBIDE MONONITRATE) ISOSORBIDE MONONITRATE 120 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE
HYDROXYPROPYL CELLULOSE (TYPE M)
HYPROMELLOSE 2208 (100000 MPA.S)
SILICON DIOXIDE
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
Product Characteristics
Color white (white to off-white) Score no score
Shape OVAL Size 16mm
Flavor Imprint Code ING177
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:51407-210-01 100 TABLET, EXTENDED RELEASE in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA210918 11/05/2018
Labeler — Golden State Medical Supply, Inc. (603184490)
Establishment
Name Address ID/FEI Operations
Golden State Medical Supply, Inc. 603184490 relabel (51407-208), repack (51407-208), relabel (51407-209), repack (51407-209), relabel (51407-210), repack (51407-210)

Revised: 12/2021 Golden State Medical Supply, Inc.

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