Can isosorbide dinitrate be crushed?

Comment by InpharmD Researcher

Evidence from medication-safety and drug-information resources indicates that isosorbide dinitrate should not be crushed when administered as a sublingual or extended-/modified-release formulation. Sublingual tablets are designed to dissolve under the tongue for proper mucosal absorption and should not be crushed, chewed, or swallowed. Extended- or modified-release formulations must be swallowed whole to prevent rapid, uncontrolled drug release and adverse effects. In addition, guidance from the Handbook of Drug Administration via Enteral Feeding Tubes reports that crushing certain immediate-release isosorbide dinitrate tablet formulations is not recommended based on manufacturer communication, and alternative routes of administration should be considered when appropriate. Therefore, while recommendations may vary by formulation, consistent guidance across drug-information and medication-safety resources supports avoiding crushing isosorbide dinitrate tablets, particularly sublingual and modified-release products, and consulting formulation-specific guidance before altering any dosage form.

A targeted literature search was conducted using PubMed, institutional pharmacy references, and authoritative drug-information resources (e.g., Mayo Clinic, NHS, MedlinePlus) with search terms including “isosorbide dinitrate” AND “crush,” “sublingual,” “extended-release,” “modified-release,” and “enteral feeding tube.”

Background

According to the 2015 Handbook of Drug Administration via Enteral Feeding Tubes, guidance for isosorbide dinitrate indicates that crushing certain tablet formulations is not recommended. Specifically, for isosorbide dinitrate tablets (Actavis), the recommendation against crushing is based on personal communication with the manufacturer, and the use of an alternative route of administration is advised. Modified-release formulations (e.g., Isoket Retard) are described as unsuitable for administration via enteral feeding tubes, despite the ability to halve the tablets. Overall, the Handbook notes that crushing certain isosorbide dinitrate tablet formulations is not recommended and highlights alternative formulations or routes when appropriate. [1]

According to the Mayo Clinic, sublingual isosorbide dinitrate tablets should not be chewed, crushed, or swallowed because they are intended to dissolve under the tongue and be absorbed through the lining of the mouth. Additionally, extended-release tablets or capsules should be swallowed whole and should not be split, crushed, or chewed, as they release medicine gradually to provide their effect over several hours. [2]

According to a 2025 institutional pharmacy reference list, crushing certain medications may be considered unsafe due to special pharmaceutical formulations. The document states that sublingual or buccal tablets where dissolution and absorption must occur in the oral mucosa or cavity should not be crushed. In the list of sublingual-use medications that should not be crushed, isosorbide dinitrate (Isordil SL) is specifically included. The guidance further notes that modified-release formulations should not be crushed because they may cause an increased risk of adverse effects or potentially deliver a toxic dose of the active ingredient. Based on this information, isosorbide dinitrate should not be crushed when administered as a sublingual or extended/modified-release formulation. [3]

According to 2024 guidance from the National Health Service (NHS), isosorbide mononitrate and isosorbide dinitrate tablets or capsules should be swallowed whole with a drink of water and should not be chewed or crushed. The NHS states that slow-release tablets and capsules release the medicine gradually into the body, and altering them by chewing or crushing is not recommended. Based on this guidance, isosorbide dinitrate should not be crushed. [4]

According to MedlinePlus, isosorbide comes as a tablet, an extended-release tablet, and an extended-release capsule to take by mouth. The guidance states that extended-release tablets or capsules should be swallowed whole and should not be crushed, chewed, or divided. Patients are instructed to take isosorbide exactly as directed and not to alter the dosage form, as extended-release formulations are designed for long-acting drug delivery. [5]

A 2017 descriptive, observational study evaluated medications that should not be crushed or split, based on pharmaceutical formulation characteristics and safety considerations, to reduce medication errors associated with dosage form modification. The authors compiled an extensive list of oral medications that should not be altered, drawing from indexed literature and drug information resources. Within this list, sublingual isosorbide dinitrate tablets and prolonged release isosorbide dinitrate capsules were specifically identified as medications that should not be split or crushed. The article explains that crushing sublingual formulations disrupts their intended absorption pathway, potentially reducing efficacy and altering pharmacokinetics. Additionally, the authors emphasize that crushing modified-release formulations can result in uncontrolled drug release and increased adverse effects. This suggests that isosorbide dinitrate should not be crushed due to the risk of impaired therapeutic effect and medication-related harm. [6]

References: [1] White R, Bradnam V. Handbook of Drug Administration via Enteral Feeding Tubes. 3rd ed. London, UK: Pharmaceutical Press; 2015.
[2] Mayo Clinic. Isosorbide dinitrate (oral route, sublingual route). Mayo Clinic Drugs and Supplements. Updated September 1, 2025. Accessed January 4, 2026.
[3] Makati Medical Center, Department of Pharmacy Services, Pharmacy Information, Training and Development. Oral dosage forms that should not be crushed. Revision 31. December 16, 2025. Accessed January 5, 2026.
[4] How and when to take isosorbide mononitrate and isosorbide dinitrate. National Health Service (NHS). Updated August 27, 2024. Accessed January 5, 2026.
[5] Isosorbide dinitrate. MedlinePlus. U.S. National Library of Medicine. Updated January 1, 2025. Accessed January 5, 2026.
[6] Gracia-Vásquez SL, González-Barranco P, Camacho-Mora IA, González-Santiago O, Vázquez-Rodríguez SA. Medications that should not be crushed. Medicina Universitaria. 2017;19(75):50-63.