Isorsorbide Mononitrate Extended-release (Page 3 of 3)

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 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 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 2-4 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 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, 1-2 mg/kg intravenously.

DOSAGE AND ADMINISTRATION

The recommended starting dose of isosorbide mononitrate extended-release tablets 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 two 60 mg tablets) once daily. Rarely, 240 mg may be required. The daily dose of isosorbide mononitrate extended-release tablets should be taken in the morning on arising. Isosorbide mononitrate extended-release tablets should not be chewed or crushed and should be swallowed together with a half-glassful of fluid.

HOW SUPPLIED:

30 mg — Each white, oval, bisected, film coated tablet imprinted with Image from Drug Label Content 713 contains 30 mg of isosorbide mononitrate. Tablets are supplied in bottles of 100 (NDC 0228-2713-11) and 500 (NDC 0228-2713-50).

60 mg — Each beige, oval, bisected, film coated tablet imprinted with Image from Drug Label Content 711 contains 60 mg of isosorbide mononitrate. Tablets are supplied in bottles of 100 (NDC 0228-2711-11) and 500 (NDC 0228-2711-50).

Dispense in a tight, light-resistant container as defined in the USP.

Store at controlled room temperature 15° to 30°C (59° to 86°F).

Rx only

Manufactured by:

PUREPAC PHARMACEUTICAL CO.

Elizabeth, NJ 07207 USA

40-8820

Rev — May 1999

ISORSORBIDE MONONITRATE EXTENDED-RELEASE
isorsorbide mononitrate tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0228-2713
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
carnauba wax
colloidal silicon dioxide
hydroxypropl methylcellulose
lactose monohydrate
magnesium stearate
maltodextrin
polyethylene glycol
stearic acid
titanium dioxide
triacetin
Product Characteristics
Color WHITE Score 2 pieces
Shape OVAL Size 13mm
Flavor Imprint Code 713
Contains
Coating true Symbol true
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0228-2713-11 100 TABLET, COATED (100 TABLET) in 1 BOTTLE None
2 NDC:0228-2713-50 500 TABLET, COATED (500 TABLET) in 1 BOTTLE None
ISORSORBIDE MONONITRATE EXTENDED-RELEASE
isorsorbide mononitrate tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0228-2711
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
carnauba wax
colloidal silicon dioxide
hydroxypropl methylcellulose
lactose monohydrate
magnesium stearate
maltodextrin
polyethylene glycol
stearic acid
titanium dioxide
triacetin
synthetic red iron oxide
synthetic yellow iron oxide
Product Characteristics
Color WHITE (beige) Score 2 pieces
Shape OVAL Size 13mm
Flavor Imprint Code 711
Contains
Coating true Symbol true
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0228-2711-11 100 TABLET, COATED (100 TABLET) in 1 BOTTLE None
2 NDC:0228-2711-50 500 TABLET, COATED (500 TABLET) in 1 BOTTLE None
Labeler — Actavis Elizabeth LLC

Revised: 03/2007 Actavis Elizabeth LLC

Page 3 of 3 1 2 3

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.