Isosorbide Mononitrate (Ingenus Pharmaceuticals, LLC): FDA Package Insert, Page... (2024)

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 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 pO₂ . 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 50742-175-01

Bottles of 500 NDC 50742-175-05

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 50742-176-01

Bottles of 500 NDC 50742-176-05

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 50742-177-01

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

Manufactured for:

Ingenus Pharmaceuticals, LLC

Orlando, FL 32811-7193

Made in India

DRUGS/TS/23/2007

Rev.: 09/2023

Ingenus Logo

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

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

ingenus

NDC 50742-175-01

Isosorbide Mononitrate Extended-Release Tablets, USP

30 mg

Rx Only

100 Tablets

30 mg Tablet -100s Count Bottle Label

Package Label — Principal Display Panel – 30 mg, 500 Tablets

ingenus

NDC 50742-175-05

Isosorbide Mononitrate Extended-Release Tablets, USP

30 mg

Rx Only

500 Tablets

30 mg Tablet -500s Count Bottle Label

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

ingenus

NDC 50742-176-01

Isosorbide Mononitrate Extended-Release Tablets, USP

60 mg

Rx Only

100 Tablets

60 mg Tablet -100s Count Bottle Label

Package Label — Principal Display Panel – 60 mg, 500 Tablets

ingenus

NDC 50742-176-05

Isosorbide Mononitrate Extended-Release Tablets, USP

60 mg

Rx Only

500 Tablets

60 mg Tablet -500s Count Bottle Label

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

ingenus

NDC 50742-177-01

Isosorbide Mononitrate Extended-Release Tablets, USP

120 mg

Rx Only

100 Tablets

120 mg Tablet -100s Count Bottle Label

Labeler — Ingenus Pharmaceuticals, LLC (833250017)

Registrant — RICONPHARMA LLC (859035318)

Revised: 10/2023 Ingenus Pharmaceuticals, LLC