Isosorbide Mononitrate

Registered South African indications:

• Angina pectoris

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Constrictive pericarditis
• Constrictive cardiomyopathy
• Aortic/Mitral valve stenosis
• Cardiac tamponade
• Severe anaemia
• Hypertrophic obstructive cardiomyopathy
• Low filling pressure
• Severe cerebrovascular insufficiency
• Severe hypotension (systolic blood pressure <90 mmHg)
• Raised intracranial pressure
  - Head trauma
  - Cerebral haemorrhage
• Angle closure glaucoma
• Acute myocardial infarction with low filling pressures
• Acute circulatory failure (shock, vascular collapse)
• Severe hypovolaemia
• Coadministration with phosphodiesterase type 5 inhibitors (e.g. sildenafil, tadalafil, vardenafil)
• Coadministration with soluble guanylate cyclase stimulator, riociguat

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Severe hepatic impairment
• Elderly
• Relief of acute anginal attacks
• Hypothyroidism
• Hypothermia
• Impaired left ventricular function (left ventricular failure)
• Orthostatic dysfunction
• Malnutrition
• Labile circulation
• Abrupt withdrawal
• Decreased gastrointestinal transit time
• Hypoxaemia
• Hypoxaemia and ventilation/ perfusion imbalance due to lung disease or ischaemic heart failure
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• Fructose intolerance (certain formulations)
• Sucrase-isomaltase insufficiency (certain formulations)

Forms avail. in SA and covered in this monograph: tab, slow release tab (SR tab)

Prophylaxis of angina pectoris

• Oral (tab): 20mg, 8-12hrly; Max: 120mg/24hrs 

Dosage regime should be designed according to the clinical response of the patient

Tablets should be taken after meals, unchewed with water

In patients taking one tablet twice daily the second dose should be taken 8hrs after the first dosage. If the dose is one tablet three times daily, take one every 6hrs and ensure 12hrs treatment-free interval every 24hrs

Taper dose gradually to discontinue use

• Oral (SR tab): 50-120mg, dly in the morning; Max: 120mg/24hrs 

Tablets should be taken after meals, unchewed with water

The lowest effective dose should be used

Taper dose gradually to discontinue use

Not established for use in children

Pregnancy

• Caution; no evidence of risk in studies
• No data have been reported which would indicate the possibility of adverse effects resulting from the use of isosorbide mononitrate in pregnancy. Safety in pregnancy, however, has not been established. Isosorbide mononitrate should only be used in pregnancy if the possible benefits outweigh the possible hazards

Breastfeeding

• Caution
• It is not known whether nitrates are excreted in human milk and therefore caution should be exercised when administered to breastfeeding women

Fertility

• There is no data available on the effect of isosorbide mononitrate on fertility in humans

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Special care may be needed in those with increased susceptibility to hypotension or marked hepatic or renal insufficiency
  Initiate at the lower end of the dosage range

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Fainting
• Somnolence
• Asthenia

Cardiovascular Disorders

• Tachycardia
• Aggravated angina pectoris
• Orthostatic hypotension
• Circulatory collapse
  - Bradyarrhythmias
  - Syncope
• Hypotension
  - Nausea and vomiting
  - Restlessness
  - Pallor and excessive perspiration
• Temporary hypoxaemia

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Heartburn

Musculoskeletal Disorders

• Myalgia

Skin and Subcutaneous Tissue Disorders

• Allergic skin reactions
• Flushing
• Dermatitis exfoliative
• Rash
• Pruritis

Immune, Blood and Lymphatic System Disorders

• Angioedema

• Phosphodiesterase type 5 inhibitors
• Sildenafil
• Tadalafil
• Vardenafil
• Riociguat
• Beta-blockers
• Calcium channel blockers
• Vasodilators
• Glyceryl trinitrate
• Isosorbide dinitrate
• Isosorbide 5-mononitrate
• Angiotensin-converting enzyme inhibitors
• Alprostadil
• Aldesleukin
• Angiotensin II receptor antagonists
• Neuroleptics
• Tricyclic antidepressants
• Dihydroergotamine
• Sapropterine

Other interactions

• Alcohol

None specific. Some cases may require

• Blood pressure
• Heart rate

An acute angina attack

• In the event of an acute angina attack, a sublingual treatment such as a glyceryl trinitrate spray or tablet should be used instead of isosorbide mononitrate. The onset of action of isosorbide mononitrate is not sufficiently rapid to be useful to treat an acute anginal attack

Isosorbide mononitrate, an organic nitrate, acts as a donor of nitric oxide (NO). NO causes a relaxation of vascular smooth muscle via the stimulation of guanylyl cyclase and the subsequent increase of intracellular cyclic guanosine monophosphate (cGMP) concentration. A cGMP-dependent protein kinase is thus stimulated, with resultant alteration of the phosphorylation of various proteins in the smooth muscle cell. This eventually leads to the dephosphorylation of the light chain of myosin and the lowering of smooth muscle tone, resulting in vasodilation.

It produces decreased left and right ventricular end-diastolic pressures to a greater extent than the decrease in systemic arterial pressure, thereby reducing after load and especially the preload of the heart. Isosorbide mononitrate influences the oxygen supply to ischaemic myocardium by causing the redistribution of blood flow along collateral channels and from epicardial to endocardial regions by selective dilation of large epicardial vessels. It reduces the requirements of the myocardium for oxygen by increasing venous capacitance, causing a pooling of blood in peripheral veins, thereby reducing ventricular volume and heart wall distension.

Tablet 20mg

• Elantan (GSK) originator
• Ismo 20 (Pharmaco) originator

Capsule sr 50mg

• Elantan LA (AHN Pharma) originator

Tablet sr 60mg 

• Imdur (AstraZeneca) originator
• Monicor SR (Pharma Dynamics)