Isosorbide mononitrate causes vasodilation of blood vessels. It has direct vasodilatory effects on coronary blood vessels and is used in patients with angina or chest pain.
Isosorbide mononitrate Uses:
-
Angina pectoris:
- Used for treatment (immediate-release only) & prevention of coronary artery disease-induced angina pectoris.
Note: Cannot be used to abort an acute anginal attack as its onset of action is not sufficiently rapid. Off Label Use of Isosorbide mononitrate in Adults:
-
- HFrEF (Heart failure with reduced ejection fraction)
Isosorbide mononitrate dose in Adults:
Isosorbide mononitrate dose in the treatment of Angina pectoris: Oral:
Note: Chronic exposure results in tolerance to nitrates and this effect is not overcome by dose escalation. The only way to overcome tolerance is by short periods of nitrate absence from the body. Nitrate-free intervals of 14 or more hours (immediate-release products) or more than 18 hours (sustained-release products) may help minimize tolerance.
-
Immediate release:
- 20 mg twice a day with the 2 doses given 7 hours apart (eg, 9 AM and 4 PM) to decrease tolerance development of tolerance; small-statured patients may begin therapy with 5 mg twice a day and titrate to at least 10 mg twice a day in first 2 to 3 days of therapy.
-
Extended-release:
- Initial: 30 to 60 mg once a day in the morning; after several days, may titrate to 120 mg once a day; rarely, dose as high as 240 mg once a day may be required.
Isosorbide mononitrate dose in the treatment of Heart failure with reduced ejection fraction (off-label):
Note:
- As an additional therapy for persistent NYHA class III or IV heart failure with reduced ejection fraction (HFrEF) when symptoms are not controlled despite optimal medical therapies or in patients with tolerance issues to an ACE inhibitor, angiotensin II receptor blocker (ARB), or angiotensin II-neprilysin inhibitor (ARNI).
- Although ACCF/AHA guidelines have recommended isosorbide dinitrate in combination with hydralazine, some experts, for the sake of reduction of pill burden and improvement of adherence, have substituted isosorbide mononitrate for isosorbide dinitrate.
Oral:
-
Extended-release:
- Initial: 30 to 60 mg once a day with hydralazine 3 or 4 times a day; dose should be titrated every 2 to 4 weeks with a maximum dose: 120 mg once a day.
- Note: Use of the fixed-dose combination of isosorbide dinitrate/hydralazine instead of separate components may also be considered.
Dose in Children:
Not indicated.
Pregnancy Risk Factor B
- Certain adverse events have been observed in animal reproduction studies.
- The use of nitric oxide donors, such as isosorbide for cervical ripening and pre-eclampsia has been evaluated.
Use during breastfeeding:
- It is not known if there is isosorbide mononitrate in breast milk.
- Manufacturer suggests being cautious when giving isosorbide mononitrates to nursing mothers.
Dose in Kidney Disease:
Dosage adjustment is not necessary.
- Hemodialysis: No Supplemental dose is not required. Dose after dialysis.
- Continuous ambulatory peritoneal dialysis: Supplemental dose is not required.
Dose in Liver disease:
Dosage adjustment is not necessary.
Common Side Effects of Isosorbide mononitrate:
-
Central nervous system:
- Headache
- Dizziness
Less Common Side Effects of Isosorbide mononitrate:
-
Cardiovascular:
- Abnormal Heart Sounds
- Atrial Arrhythmia
- Atrial Fibrillation
- Bradycardia
- Bundle Branch Block
- Cardiac Arrhythmia
- Cardiac Failure
- Chest Pain
- ECG Abnormality
- Edema
- Exacerbation Of Angina Pectoris
- Extrasystoles
- Flushing
- Heart Murmur
- Hypertension
- Hypotension
- Intermittent Claudication
- Myocardial Infarction
- Palpitations
- Tachycardia
- Varicose Veins
- Ventricular Tachycardia
- Cardiovascular Toxicity
-
Central Nervous System:
- Anxiety
- Confusion
- Depression
- Drowsiness
- Fatigue
- Hypoesthesia
- Insomnia
- Lack Of Concentration
- Malaise
- Migraine
- Myasthenia
- Nervousness
- Neuritis
- Nightmares
- Paresis
- Paresthesia
- Rigors
- Vertigo
- Pain
- Emotional Lability
-
Dermatologic:
- Abnormal Hair Texture
- Acne Vulgaris
- Diaphoresis
- Leg Ulcer
- Pruritus
- Skin Rash
-
Endocrine & Metabolic:
- Decreased Libido
- Hot Flash
- Hyperuricemia
- Hypokalemia
-
Gastrointestinal:
- Abdominal Pain
- Constipation
- Diarrhea
- Dyspepsia
- Flatulence
- Gastric Ulcer
- Gastric Ulcer With Hemorrhage
- Gastritis
- Glossitis
- Hemorrhoids
- Loose Stools
- Melena
- Nausea
- Vomiting
- Xerostomia
-
Genitourinary:
- Atrophic Vaginitis
- Impotence
- Mastalgia
- Urinary Tract Infection
-
Hematologic & Oncologic:
- Hypochromic Anemia
- Nonthrombocytopenic Purpura
- Thrombocytopenia
-
Hepatic:
- Increased Serum Alanine Aminotransferase
- Increased Serum Aspartate Aminotransferase
-
Hypersensitivity:
- Hypersensitivity Reaction
-
Infection:
- Bacterial Infection
- Candidiasis
- Viral Infection
-
Neuromuscular & Skeletal:
- Arthralgia
- Asthenia
- Back Pain
- Musculoskeletal Pain
- Myalgia
- Myositis
- Shoulder Stiffness
- Tendon Disease
- Torticollis
- Tremor
-
Ophthalmic:
- Blepharoptosis
- Conjunctivitis
- Photophobia
- Visual Disturbance
-
Otic:
- Otalgia
- Perforated Tympanic Membrane
- Tinnitus
-
Renal:
- Nephrolithiasis
- Polyuria
-
Respiratory:
- Bronchitis
- Bronchospasm
- Cough
- Dyspnea
- Flu-Like Symptoms
- Increased Bronchial Secretions
- Nasal Congestion
- Pharyngitis
- Pneumonia
- Pulmonary Infiltrates
- Rales
- Rhinitis
- Sinusitis
- Upper Respiratory Infection
- Increased Cough
-
Miscellaneous:
- Fever
- Nodule
Contraindications to Isosorbide mononitrate:
- Hypersensitivity (To isosorbide mononitrate and any other component of the formulation).
- Use concurrently with phosphodiesterase inhibitors such as tadalafil (sildenafil), vardenafil or avanafil).
- Concurrent use of riociguat
Canadian labeling: Additional contraindications not in US labeling
- Shock and collapsing states (acute circulation failure associated with severe hypotension).
- Orthostatic hypotension
- Any obstruction that causes myocardial dysfunction (eg, constrictive or mitral stenosis, aortic or mitral blockage)
- Elevated intracranial pressure
- Severe anemia.
Warnings and precautions
-
CNS depression:
- It is possible to develop CNS depression from its use, which can cause impairment of physical or mental capabilities.
- Patients should be aware of tasks that require mental alertness, such as driving or operating machinery.
-
Hypotension/bradycardia:
- This can lead to severe hypotension, paradoxical bradycardia, and worsening angina pectoris.
- It can also lead to orthostatic hypotension, which can be made worse by ethanol.
- Be cautious in hypotension and volume depletion. Extreme caution is advised for inferior wall MI and right ventricular infarctions.
- Even small amounts can lead to severe hypotension, especially if you are upright.
-
The intracranial pressure rose:
- An increase in intracranial pressure could be caused or exacerbated by the use nitrates.
- This may then be linked to worse outcomes for patients with neurologic injuries (eg, intracranial bleeding, traumatic brain injury).
-
Cardiovascular disease
- There are no studies available so it is not recommended for patients with acute myocardial injury (MI) or heart disease (has not been researched).
- Use caution when there is volume depletion or moderate hypotension
- You should exercise extreme caution when dealing with inferior wall MI or suspected right ventricular Infarctions.
- Canadian labeling prohibits the use of this medication in acute circulatory failure, marked hypotension, postural hypertension, and myocardial dysfunction due to obstruction (eg in the presence aortic, mitral, or constrictive pericarditis).
-
Hypertrophic cardiomyopathy, (HCM)
- Patients with HCM and outflow tract obstruction should avoid nitrates.
- They can reduce preload, exacerbate obstruction, hypotension, syncope, and/or worsening heart failure.
Isosorbide mononitrate: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Alcohol (Ethyl) |
May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). |
|
Aprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Moderate) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
Dapoxetine |
May enhance the orthostatic hypotensive effect of Vasodilators (Organic Nitrates). |
|
Dapsone (Topical) |
May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Duvelisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosnetupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Local Anesthetics |
Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. |
|
Molsidomine |
May enhance the hypotensive effect of Vasodilators (Organic Nitrates). |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Nitric Oxide |
May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Prilocaine |
Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. |
|
Rilmenidine |
Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Rilmenidine. |
|
Rosiglitazone |
Vasodilators (Organic Nitrates) may enhance the adverse/toxic effect of Rosiglitazone. Specifically, a greater risk of ischemia and other adverse effects has been associated with this combination in some pooled analyses. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Sodium Nitrite |
Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Risk Factor D (Consider therapy modification) |
|
|
CYP3A4 Inducers (Strong) |
May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
CYP3A4 Inhibitors (Strong) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
MiFEPRIStone |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
Risk Factor X (Avoid combination) |
|
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Phosphodiesterase 5 Inhibitors |
May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). |
|
Riociguat |
Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Riociguat. |
Monitor:
- Bp
- Pulse rate
How to administer Isosorbide mononitrate?
- Should not be administered around the clock.
- Schedule immediate-release tablet twice a day with doses 7 hours apart (9 AM and 4 PM); extended-release tablet should be administered once a day with a half-glassful of fluid in the morning upon rising.
- Do not chew or crush extended-release tablets should not be chewed or crushed; may be divided in half.
- The extended-release tablets that are scored may be split due to insoluble matrix embedding.
Mechanism of action of Isosorbide mononitrate:
- Nitroglycerin, and other nitrates can create free radical nitric oxygen.
- Nitric oxide activates smooth muscle's guanylate cyclease, which causes an increase in guanosine 5' monophosphate (cGMP).
- This leads to the dephosphorylation and relaxation of myosin light chain light chains.
- It causes vasodilation of both the veins and arteries, with predominant effects on veins.
- It causes a decrease in cardiac oxygen demand (left ventricular preload) and may also cause a slight reduction in afterload.
The onset of action:
- 30 - 45 mins
Duration:
- Immediate release: ≥6 hours
- Extended-release: ≥12 - 24 hours
Absorption: Absorption is rapid and complete Distribution:
- V : nearly 0.6 L/kg
Protein binding:
- Less than 5% drug is protein-bound
Metabolism:
- Mostly in liver
Bioavailability:
- Almost 100%
Half-life elimination:
- 5 - 6 hours
Time to peak
- plasma: 30 - 60 mins
Excretion:
- Predominantly excreted inurine (2% as unchanged drug)
- feces (1%)
International Brand Names of Isosorbide mononitrate:
- APO-ISMN
- Imdur
- ISMN
- PMS-ISMN
- PRO-ISMN-60
- AngiFix
- Angifree SR
- Angirest
- Angisor
- Angistad
- Angitrate
- ApoISMN
- Cardismo
- Cardisorb
- Cardoxx
- Cincordil
- Conpin
- Corangin
- Corangin SR
- Coronur
- Coronur Retard
- Coxine
- Coxine SR
- Danlixin
- Duride
- Effox
- Elan
- Elantan
- Elantan LA
- Elantan Long
- Elonton SR
- Imdex
- Imdex CR
- Imdur
- Imdur 60
- Imdur Durules
- Imtrate
- Ismexin
- ISMN
- ISMN AL
- ISMN Genericon
- ISMN Pharmavit
- Ismo
- ISMO
- Ismo 20
- Ismo-20
- Ismodin
- Ismox
- Isobid
- Isocard
- Isolan
- Isomel
- Isomon
- Isomonat
- Isomonit
- Isomonit Retard
- Isonate
- Isopen-20
- Isorat
- Isosorbide
- Isospan SR
- Isotril ER
- MNI
- Monicor
- Monis
- Monis-XR
- Monit
- Monit 20
- Mono Corax
- Mono Corax Retard
- Mono Mack
- Mono-Mack
- Mono-Sanorania
- Monobide
- Monocinque
- Monocinque Retard
- Monoclair
- Monocord 40
- Monocord 50 SR
- Monodur Durules
- Monoket
- Monoket OD
- Monoket Retard
- Monolong
- Mononit
- Monopront
- Monorem
- Monosan
- Monosorb
- Monosorbitrate
- Monosordil
- Monotab
- Monotrate
- Monotrate OD
- Montra
- Nitramin
- Olicard
- Pentacard
- Rangin
- Solotrate
- Solotrate SR
- Sorbimon
- Sorbinate SR
- Sormon
- Trangina XL
- Unicard
- Uniket
- Vasotrate
- Vasotrate-60 OD
- Vasotrate-OD
- Vasotrol
- Xismox XL
Isosorbide mononitrate Brand Names in Pakistan:
|
Isosorbide mononitrate 10 mg in Pakistan |
|
| Isotrate | Mass Pharma PVT LTD |
|
Isosorbide mononitrate 20 mg in Pakistan |
|
| CORLET | BRYON PHARMACEUTICALS (PVT) LTD. |
| ELANTAN | ATCO LABORATORIES LIMITED |
| FLO | WILSONS PHARMACEUTICALS |
| ISMO 20 | ROCHE PAKISTAN LTD. |
| ISODIL | ROTEX MEDICA PAKISTAN (PVT) LTD |
| ISOMON | PHARMATEC PAKISTAN (PVT) LTD. |
| ISOTAB | EFROZE CHEMICAL INDUSTRIES (PVT) LTD. |
| ISOTIME-20 | SCOTMANN PHARMACEUTICALS |
| ISOTRATE | MASS PHARMA (PRIVATE) LIMITED |
| MONIS | MAPLE PHARMACEUTICALS (PVT) LTD |
| MONIS | MAPLE PHARMACEUTICALS (PVT) LTD |
| MONO CARD | VALOR PHARMACEUTICALS |
| MONOSORBID | BROOKES PHARMACEUTICAL LABORATORIES (PAK.) LTD. |
| SEQUENCE | WERRICK PHARMACEUTICALS |
| SORBIMON | ZAFA PHARMACEUTICAL LABORATORIES (PVT) LTD. |
| SORBIMON | ZAFA PHARMACEUTICAL LABORATORIES (PVT) LTD. |
| UNITRATE | BENSON PHARAMCEUTICALS. |
| VASOCORD | STERN PHARMA |
| VASOCORD | STERN PHARMA |
|
Isosorbide mononitrate 40 mg in Pakistan |
|
| CORLET | BRYON PHARMACEUTICALS (PVT) LTD. |
| ELANTAN | ATCO LABORATORIES LIMITED |
| ISOTAB | EFROZE CHEMICAL INDUSTRIES (PVT) LTD. |
| ISOTRATE | MASS PHARMA (PRIVATE) LIMITED |
| ISOTRATE | MASS PHARMA (PRIVATE) LIMITED |
| MONIS | MAPLE PHARMACEUTICALS (PVT) LTD |
| MONIS | MAPLE PHARMACEUTICALS (PVT) LTD |
| MONOTAB | EPLA LABORATORIES (PVT) LTD. |
| VASOCORD | STERN PHARMA |
|
Isosorbide mononitrate 60 mg in Pakistan |
|
| IMDUR | BARRETT HODGSON PAKISTAN (PVT) LTD. |
| ISOTAB-XR | EFROZE CHEMICAL INDUSTRIES (PVT) LTD. |
| MONIS-XR | MAPLE PHARMACEUTICALS (PVT) LTD |
| MONOSOR XL | UNIMARK PHARMACEUTICALS |
| SEQUENCE | WERRICK PHARMACEUTICALS |
|
Isosorbide mononitrate SR Tablets 60 mg in Pakistan |
|
| MONOSORBID | BROOKES PHARMACEUTICAL LABORATORIES (PAK.) LTD. |
| VASOCORD | STERN PHARMA |
|
Isosorbide mononitrate 50 mg Capsules in Pakistan |
|
| ELANTAN LONG | ATCO LABORATORIES LIMITED |
|
Isosorbide mononitrate 20 mg and 40 mg Capsules in Pakistan |
|
| Savdil | Pharmevo PVT LTD |
|
Isosorbide mononitrate 60 mg Capsules in Pakistan |
|
| Isotime-60 | Scotman Pharma |
| Savdil | Pharmevo PVT LTD |
 Injection.webp)