Isosorbide dinitrate is a nitrate that dilates (widens) blood vessels, making it easier for blood to flow through them and easier for the heart to pump.
Isosorbide dinitrate is used to treat or prevent attacks of chest pain (angina).
Only the sublingual tablet should be used to treat an angina attack that has already begun.
Isosorbide dinitrate regular and extended-release tablets are used to prevent angina attacks but will not treat an angina attack.
Isoket (Isosorbide Dinitrate) is a direct vasodilator primarily affecting the veins (venodilator). It reduces cardiac preload and is used in the treatment and prevention of angina.
Isosorbide dinitrate Uses:
Prevention of Angina pectoris:
Used to prevent angina pectoris secondary to coronary artery disease.
Note: It has a slower onset of action making it inappropriate to abort an acute anginal episode.
Off Label Use of Isosorbide dinitrate in Adults:
Achalasia
HFrEF
Isoket (Isosorbide Dinitrate) Dose in the treatment of Achalasia (off-label): Sublingual:
Immediate release:
5 mg administered 10 to 15 minutes pre meal.
Note: Clinical response is short acting and complete relief of symptoms does not occur with its use; risks should be considered before use.
Isoket (Isosorbide Dinitrate) Dose in the prevention of Angina pectoris:
Note:
It has a slower onset of action making it inappropriate to abort an acute anginal episode. Chronic exposure results in tolerance to nitrates and this effect are 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.
Oral:
Immediate-release:
Initial: 5 to 20 mg 2 to 3 times a day; Maintenance: 10 to 40 mg 2 to 3 times a day or 5 to 80 mg 2 to 3 times a day.
Sustained-release:
40 to 160 mg/day has been used in clinical trials (it is recommended to have more than 18 hours of the nitrate-free interval; however, a clinically efficacious dosage interval has not been clearly established) or 40 mg 1 to 2 times a day.
The maximum dose: 160 mg/day (Dilatrate-SR only).
Sublingual [Canadian product]:
5 to 10 mg every 2 to 4 hours for prophylaxis of acute anginal attack; supplementation with 5 to 10 mg may be done prior to activities that may provoke an anginal episode.
Isoket (Isosorbide Dinitrate) Dose in the 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).
Oral:
Immediate-release:
Initial: 20 to 30 mg 3 or 4 times a day in combination with hydralazine 3 or 4 times a day; dose should be titrated every 2 to 4 weeks;
The maximum dose: 120 mg/day in divided doses.
Some experts start with 20 mg thrice daily in combination with hydralazine thrice daily; evaluation should be done every 2 to 4 weeks and the dose should be gradually titrated as tolerated to a target dose of 40 mg thrice a day in combination with hydralazine thrice a day.
Note: Use of the fixed-dose combination of isosorbide dinitrate/hydralazine instead of separate components may also be considered.
Use in Children:
The safety and efficacy of the drug in children have not been established.
Pregnancy Risk Category: C
Certain animal reproduction studies have shown negative effects.
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 any isosorbide dinitrate in breast milk.
Manufacturer suggests being cautious when giving isosorbide dinitrates to nursing mothers.
Dose in Kidney Disease:
No dosage adjustments are provided in the manufacturer’s labeling.
Hemodialysis: Requires supplemental dose.
Peritoneal dialysis: Supplemental dose is not required.
Dose in Liver disease:
No dosage adjustments are provided in the manufacturer’s labeling.
Side effects of Isoket (Isosorbide Dinitrate):
Cardiovascular:
Hypotension
Rebound hypertension
Syncope
Unstable angina pectoris
Central nervous system:
Headache
Contraindications to Isoket (Isosorbide Dinitrate):
Hypersensitivity (To isosorbide diitrate or any other component of the formulation).
Use concurrently with phosphodiesterase inhibitors such as vardenafil or sildenafil (tadalafil), vardenafil or avanafil
Concurrent use of riociguat
Canadian labeling: Additional contraindications not in US labeling
Cardiogenic shock
Cardiogenic shock: Risk of developing
Warnings and precautions
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 aggravated with the use of Nitrates. This may then be linked to worse outcomes for patients suffering from neurologic injury (eg intracranial hemorhage, trauma brain injury).
Cardiovascular disease
It is not recommended for patients suffering from acute MI or HF.
Hypertrophic cardiomyopathy, (HCM)
Patients with HCM and outflow tract obstruction should not use.
Nitrates can reduce preload, which can lead to exacerbation or worsening heart failure.
Monitoring parameters:
Bp
Pulse rate
How to administer Isoket (Isosorbide Dinitrate)?
Should not be administered around the clock; nitrate-free interval ≥14 hours should be allowed (immediate-release products) and >18 hours (sustained-release products).
Sublingual tablets or sustained-release formulations should not be chewed or crushed.
Immediate-release products:
Consider administering at 8 AM and 1 PM, for a twice-daily dosing regime.
Consider 8 AM, 1 PM, and 6 PM, for a thrice-daily dosing regime.
Sustained-release products:
Consider once a day in the morning or twice a day dosing at 8 AM and between 1 PM and 2 PM.
Mechanism of action of Isoket (Isosorbide Dinitrate):
Free radical nitric dioxide is formed when nitrates and isosorbide dinitrate are combined.Nitric oxide activates guanylate cyclease in smooth muscle, which leads to guanosine 5′ monophosphate (cGMP), and dephosphorylation myosin light chain.
Although it has a vasodilator action on both the arteries and peripheral veins, its primary effect is on the veins.It reduces cardiac oxygen demand by decreasing preload (left-ventricular end-diastolic tension); it may also cause a slight reduction in afterload.Also, the collateral flow to ischemic areas is improved by dilation of coronary arteries.
The onset of action:
S/L tablet: Almost 2 to 5 mins
P/O tablet and capsule (includes extended-release formulations): Almost 1 hour
Duration:
S/L tablet: 1 – 2 hours
P/O tablet and capsule (includes extended-release formulations): Up to 8 hours
Metabolism:
Mabolised extensively in the liver to conjugated active metabolites isosorbide 5-mononitrate and 2-mononitrate
