Chemical formula: C₃H₅N₃O₉ Molecular mass: 227.087 g/mol PubChem compound: 4510
Glyceryl trinitrate interacts in the following cases:
The non-steroidal anti-inflammatory drugs except acetyl salicylic acid may diminish the therapeutic response of glyceryl trinitrate.
Nitroglycerin can delay the metabolism of morphine-type analgesics.
An enhanced hypotensive effect with sublingual apomorphine may occur as a result of concomitant administration with glyceryl trinitrate.
There is evidence that systemic nitrates may interfere with the anticoagulant effects of heparin. Early and frequent monitoring of anticoagulation is recommended when systemic nitrates and heparin are used in combination.
Treatment with other agents with hypotensive effects (e.g. vasodilators, antihypertensives, diuretics, beta-blockers, calcium channel blockers and neuroleptics, tricyclic antidepressants and sapropterin) may potentiate the hypotensive effect of glyceryl trinitrate.
Ergot alkaloids may oppose the coronary vasodilatation of nitrates. Ergot alkaloids can precipitate angina and glyceryl trinitrate can reduce the first pass hepatic metabolism of dihydroergotamine.
N-acetylcysteine may potentiate the vasodilator effects of glyceryl trinitrate.
During the simultaneous use of dihydroergotamine, glyceryl trinitrate may lead to an increase in the DHE level and thus potentiate its hypertensive action.
For glyceryl trinitrate no clinical data on exposed pregnancies are available.
Animal studies did not indicate harmful effects with respect to pregnancy, embryofoetal development, parturition or postnatal development. However, the relevance of these animal findings to man is unknown. The administration of glyceryl trinitrate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
It is unknown if glyceryl trinitrate or its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue/abstain from breast-feeding or to discontinue/abstain from glyceryl trinitrate therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Animal studies did not indicate harmful effects with respect to fertility. However, the relevance of these animal findings to man is unknown.
As gyceryl trinitrate can cause dizziness, patients should make sure they are not affected before driving or operating machinery. This effect appears to be accentuated by alcohol.
It is recommended that patients wait at least five minutes after using the spray before driving or operating machinery. If the patient feels faint, dizzy or unwell, the patient should wait until they feel better. This can occur in particular at the beginning of the treatment, with an increase of the dosage, when changing the medicinal product or when used in combination with alcohol.
Adverse reactions are listed below in descending order by frequency of occurrence.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very common (≥1/10), Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
Very rare: Methaemoglobinaemia
Very rare: Restlessness
Very common: Headache*
Common: Dizziness, Drowsiness
Uncommon: Syncope
Very rare: Cerebral ischaemia**
Common: Tachycardia
Uncommon: Enhanced angina pectoris symptoms, Bradycardia, Cyanosis, Cardiac disorders
Common: Orthostatic hypotension*
Uncommon: Facial flushing, Circulatory collapse
Uncommon: Nausea, vomiting
Very rare: Impairment of respiration***
Very rare: Exfoliative dermatitis, Drug rash
Common: Asthenia
Not known: Drug tolerance****, Diaphoresis
Common: Blood pressure decreased*
* Particularly upon initiation of therapy and following an increase in dose.
** Glyceryl trinitrate-induced hypotension may cause cerebral ischaemia.
*** During the administration of glyceryl trinitrate, a transient hypoxaemia may occur due to relative redistribution of the blood flow in hypoventilated alveolar regions, which, in patients with coronary heart disease, may lead to ischaemia.
**** The development of tolerance and the occurrence of cross tolerance to other nitro compounds have been described. In order to avoid attenuation or loss of effect, high continuous dosage should be avoided.
Very Common (≥1/10), Common (≥1/100 <1/10), Uncommon (≥1/1000 <1/100), Rare (≥1/10,000 <1/1000), Very Rare (<1/10,00), Frequency not known (cannot be estimated from the available data)
Very Rare: Methaemoglobinaemia
Very Rare: Restlessness
Very Common: Throbbing headache**
Common: Vertigo**, Dizziness, Drowsiness
Uncommon: Syncope
Very Rare: Cerebral ischaemia
Frequency not known: Increased ocular pressure
Common: Tachycardia
Rare: Enhanced angina, Pectoris symptoms, Bradycardia, Cyanosis
Frequency not known: Hypoxaemia, palpitation
Common: Orthostatic hypertension*
Uncommon: Facial flushing, Circulatory collapse
Uncommon: Nausea, Vomiting
Very Rare: Heartburn, Halitosis
Not known: Tongue swelling**, Tongue blistering
Very Rare: Impairment of respiration
Rare: Allergic skin reactions
Very Rare: Exfoliative dermatitis, Drug rash
Common: Asthenia
Uncommon: Localised burning sensation, Tongue blisters
Frequency not known: Weakness
Common: Blood pressure decreased*
* Particularly upon initiation of therapy and following an increase in dose.
** Headache and dizziness, persisting after relief of angina may be minimised by removing the glyceryl trinitrate tablet before it has completely dissolved. Glyceryl trinitrate-induced hypotension may cause cerebral ischaemia.
Large dose of glyceryl trinitrate may cause vomiting, cyanosis, restlessness, methaemoglobinaemia and impairment of respiration.
During treatment with glyceryl trinitrate, temporary hypoxemia may occur due to a relative redistribution of the blood flow in hypoventilated alveolar areas.
In patients treated with glyceryl trinitrate 4 mg/g rectal ointment, the most common treatment related adverse reaction was dose-related headache which occurred with an incidence of 57%.
Adverse reactions from clinical studies are displayed by system organ class in the table below. Within the system organ class, the adverse reactions are listed by frequency using the following groupings: very common (>1/10), common (>1/100 <1/10), uncommon (>1/1000 <1/100).
Very common: Headache
Common: Dizziness
Common: Nausea
Uncommon: Diarrhoea, anal discomfort, vomiting, rectal bleeding, rectal disorder
Uncommon: Pruritus, anal burning and itching
Uncommon: Tachycardia
Adverse reactions to glyceryl trinitrate are generally dose-related and almost all of these reactions are the result of vasodilator activity. Headache, which may be severe, is the most commonly reported side effect. In the Phase III clinical trials with glyceryl trinitrate 4 mg/g rectal ointment the incidence of mild, moderate and severe headache was 18%, 25% and 20%. Patients with a previous history of migraine or recurrent headache were at a higher risk of developing headache during treatment. Headache may be recurrent with each daily dose, especially at higher doses. Headache can be treated with mild analgesics e.g. paracetamol and is reversible on discontinuation of treatment.
Rare cases of orthostatic hypotension-type events associated with symptoms of vertigo and dizziness were reported in clinical trials. There was no discernible dose-related trend in the incidence of these events.
The orthostatic hypotension-type event was of mild intensity in the majority of these patients, and there were no severe orthostatic hypotension-type events reported during the Phase III clinical studies.
Dizziness and vertigo contributed to the discontinuation of glyceryl trinitrate in a few cases.
Because these reactions are received from spontaneous reporting, the frequency is not known (cannot be estimated from the available data).
Nervous system disorders: Lightheadedness, syncope
Vascular disorders: Hypotension, orthostatic hypotension
Immune system disorders: Hypersensitivity, anaphylactoid reaction
General disorders and administration site conditions: Application site irritation, application site rash, application site pain
Lightheadedness and hypotension (including orthostatic hypotension) in some patients may be severe enough to warrant discontinuation of therapy.
Extremely rarely, ordinary doses of organic nitrates have caused methaemoglobinaemia in normal–seeming patients. Flushing, unstable angina and withdrawal hypertension may also occur.
Adverse reactions are ranked in descending order of frequency, as follows: Very common (=1/10); common (=1/100-<1/10); uncommon (=1/1000-<1/100); rare (=1/10,000-<1/1,000); very rare (<1/10,000), including isolated reports.
Very Common: Headache
Common: Dizziness
Uncommon: Syncope, burning sensation
Rare: Tachycardia, bradycardia (in the presence of syncope)
Uncommon: Hypotension, circulatory collapse
Rare: Flushing
Uncommon: Allergic skin disorders including, eczema, dermatitis, pruritus, urticaria and non-specific rashes.
Common: Nausea, vomiting
Very Rare: Heartburn
Rare: Hypersensitivity reactions and anaphylaxis
Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (The adverse drug reactions have been derived from post-marketing experience with glyceryl trinitrate via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency).
Common: Headache1
Very rare: Dizziness
Not known: Syncope
Rare: Tachycardia2
Not known: Palpitation, fainting
Rare: Orthostatic hypotension, flushing2
Very common: Nausea, vomiting
Uncommon: Dermatitis contact
Not known: Rash generalized
Uncommon: Application site erythema, pruritus, burning, irritation3
Rare: Heart rate increase
1 Like other nitrate preparations, glyceryl trinitrate commonly causes dose-dependent headaches due to cerebral vasodilatation. These often regress after a few days despite the maintenance of therapy. If headaches persist during intermittent therapy, they should be treated with mild analgesics. Unresponsive headaches are an indication for reducing the dosage of glyceryl trinitrate or discontinuing treatment.
2 A slight reflex-induced increase in heart rate can be avoided by resorting, if necessary, to combined treatment with a beta-blocker.
3 Upon removal of the patch, any slight reddening of the skin will usually disappear within a few hours. The application site should be changed regularly to prevent local irritation.
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