Active ingredients: Isosorbide dinitrate
Carvasin 5 mg sublingual tablets
Carvasin 10 mg tablets
Carvasin 40 mg tablets
Indications Why is Carvasin used? What is it for?
Pharmacotherapeutic group
Vasodilator used in heart diseases
Therapeutic indications
Coronary insufficiency, prevention and treatment of angina pectoris. Sublingual Carvasin due to its rapidity of action can be indicated in the treatment of chest angina; for the duration of its action, which is about 2 hours, it is indicated in the prevention of angina attack when one engages in an effort that can provoke the attack (muscle activity, sexual act, large meal).
Carvasin for oral use, of less rapid but more prolonged action, is indicated in the prevention of chest angina attacks and in the treatment of coronary insufficiency.
Use in children
The safety and efficacy of Carvasin in children has not been established.
Geriatric use
Clinical trials of Carvasin did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other clinical experiences have not identified differences in response between young and elderly patients.
In general, the choice of dose for an elderly patient should be cautious, normally starting with the lowest dosage, considering an increased frequency of impaired hepatic, renal, or cardiac function, concomitant disease or other drug therapies.
Contraindications When Carvasin should not be used
Hypersensitivity to the active substance, to other nitrates or to any of the excipients.
Myocardial infarction in the acute phase
Acute circulatory failure (shock, circulatory collapse)
Cardiogenic shock (unless sufficient end-diastolic pressure is maintained by means of appropriate measures)
Severe arterial hypotension (systolic blood pressure <90 mmHg)
Obstructive hypertrophic cardiomyopathy
Constrictive pericarditis
Severe hypovolemia
Cardiac tamponade
Patients with primary pulmonary hypertension
Phosphodiesterase inhibitors (sildenafil, vardenafil and tadalafil) potentiate the hypotensive effects of nitrates and therefore, co-administration with organic nitrates is contraindicated (see interactions section).
Precautions for use What you need to know before taking Carvasin
Particularly careful control of the doctor is necessary in the following cases:
- glaucoma
- marked anemia
- hyperthyroidism
- head trauma
- cerebral hemorrhage
- aortic or mitral stenosis
- subjects with predisposition to orthostatic hypotension
- subjects with intracranial hypertension, although a further increase in blood pressure was observed only after taking intravenous doses of nitroglycerin
- patients with renal insufficiency
For CARVASIN 10 mg tablets and CARVASIN 40 mg tablets formulations the onset of effect is not rapid enough to treat an acute anginal attack.
Carvasin dilating the intracranial vessels, can cause headache in the initial period of therapy which, in sensitive subjects, can be severe and persistent; it can sometimes be prevented by administering lower doses in the first few days of treatment
Temporary hypoxemia may occur during treatment with Carvasin due to relative redistribution of blood flow to hypoventilated alveolar areas. This can lead to myocardial hypoxia, particularly in patients with coronary artery disease
As with other vasodilators, Carvasin can cause paradoxical effects in sensitive patients, these effects can increase ischaemia and also lead to extension of myocardial damage and advanced congestive heart failure.
If cyanosis occurs without intercurrent lung disease, the level of methemoglobin should be measured (methemoglobinemias occur more frequently during treatments with high doses).
Even with low doses of Carvasin, cases of severe hypotensive effects, particularly orthostatic hypotension, can occur. Paradoxical bradycardia and aggravation of angina pectoris may accompany nitrate-induced hypotension. The medicinal product should be used with caution in subjects who may have a reduction in volume induced by diuretic therapy.
In the treatment of congestive heart failure, capillary pulmonary pressure should not fall below 15 mmHg or systolic pressure below the physiological range in normal or hypertensive patients. Systolic blood pressure should be maintained in the range of 90-100 mmHg in patients with pre-existing hypotension (see contraindications). The simultaneous intake of organic nitrates with calcium channel blockers can potentiate the hypotensive effect. A dose adjustment of both types of drugs may be necessary.
Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy (see Contraindications). In clinical trials of patients with angina pectoris, angina induced attacks have been reported as "rebound" of haemodynamic effects soon after nitrate withdrawal. It seems prudent, therefore, gradually discontinue isosorbide dinitrate when therapy is to be terminated, especially in the case of high dose use.
In patients with functional or organic gastrointestinal hypermotility or malabsorption syndrome, the use of 5 mg or 10 mg Carvasin should be preferred, as with Carvasin 40 mg in some cases the tablet has only partially disintegrated and has been recovered. in the stool.
Use in children
The safety and efficacy of Carvasin in children has not been established.
Geriatric use
Clinical trials of Carvasin did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other clinical experiences have not identified differences in response between young and elderly patients.
In general, the choice of dose for an elderly patient should be cautious, normally starting with the lowest dosage, considering an increased frequency of impaired hepatic, renal, or cardiac function, concomitant disease or other drug therapies.
Interactions Which drugs or foods can modify the effect of Carvasin
Isosorbide dinitrate can act as a physiological antagonist of norepinephrine, acetylcholine and histamine. Nitrates can cause hypotension as a result of peripheral vasodilation. Alcohol may enhance this effect. The concomitant administration of drugs with hypotensive properties (eg beta-blockers, vasodilators, diuretics, calcium channel blockers, ACE inhibitors), neuroleptics and tricyclic antidepressants can potentiate the hypotensive effect.
Co-administration of phosphodiesterase inhibitors (eg sildenafil, vardenafil and tadalafil) used in the treatment of erectile dysfunction potentiates the hypotensive effect of organic nitrates. This can lead to life-threatening cardiovascular complications; therefore in patients receiving Carvasin the use of phosphodiesterase inhibitors (eg sildenafil, vardenafil, tadalafil) is contraindicated (see "Contraindications"). Some reports suggest that concomitant administration of isosorbide dinitrate may increase blood levels of dihydroergotamine and its effect.
Warnings It is important to know that:
Tolerance to the medicinal drug (reduced efficacy) and cross tolerance with other nitrites and nitrates (decreased effect in case of prior therapy with another organic nitrate) may develop.
Prolonged high-dose therapy should be avoided to reduce or eliminate tolerance.
Patients undergoing maintenance therapy with Carvasin should be advised that they should not use medicinal products containing phosphodiesterase inhibitors used for the treatment of erectile dysfunction (e.g. sildenafil, vardenafil, tadalafil). Carvasin therapy should not be interrupted to take products containing phosphodiesterase inhibitors as this may increase the risk of developing an angina pectoris attack.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine
Pregnancy
There are no adequate and well-controlled studies in women during pregnancy. Carvasin can only be used during pregnancy if strictly necessary and under the prescription and continuous supervision of a doctor.
Feeding time
There is data showing that nitrates are excreted in breast milk and can cause methemoglobinemia in newborns. The extent of excretion of isosorbide dinitrate and its metabolites in human milk has not been determined. Therefore, particular caution should be exercised if Carvasin is administered to breastfeeding women
Effects on ability to drive and use machines
Carvasin can impair the ability to react and reduce reflexes when driving vehicles and controlling machines. This effect can be enhanced by the consumption of alcohol.
Important information about some of the ingredients of Carvasin
Carvasin contains lactose: in case of ascertained intolerance to sugars, contact your doctor before taking the medicine.
Carvasin 10 mg contains sucrose: in case of ascertained intolerance to sugars, contact your doctor before taking the medicine.
Dosage and method of use How to use Carvasin: Dosage
The starting dose should not exceed 5 mg due to the occasional occurrence of severe hypotensive effects. Sublingual Carvasin: (tablets dissolve in 20 seconds) let one tablet dissolve under the tongue as a cure and / or prevention of chest angina attack. Sublingual administration can be repeated every 2-3 hours.
Carvasin 10 mg tablets: one tablet 4 times a day, before three meals and at bedtime.
Carvasin 40 mg tablets: one tablet every 12 hours.
The choice of sublingual or oral Carvasin should be made on the basis of the duration of action rather than the degree of response, as this is the major difference observed between these formulations.
To obtain a complete therapeutic effect it is important that the dosage of the sublingual and oral form is individualized in accordance with the needs of the individual patient, with the clinical response and hemodynamic monitoring.
Carvasin therapy should begin with the lowest effective dose and then adjusted as needed based on left ventricular efficiency. The starting dose depends on the assessment of the severity of the heart failure.
Overdose What to do if you have taken too much Carvasin
In case of ingestion / intake of an excessive dose of Carvasin notify your doctor immediately or go to the nearest hospital
Symptoms:
- Blood pressure drop
- Pallor
- Sweating
- Weak heartbeat
- Tachycardia
- Postural vertigo
- Headache
- Asthenia
- Vertigo
- Nausea
- He retched
- Diarrhea
- Drowsiness
- Flushes
Methaemoglobinaemia has been reported in patients receiving other organic nitrates. During the biotransformation of isosorbide dinitrate nitrite ions are released which can cause methemoglobinemia and cyanosis resulting in tachypnea, anxiety, loss of consciousness and cardiac arrest. It cannot be excluded that an overdose of isosorbide dinitrate may cause this adverse reaction.
With very high dosages the intracranial pressure can be increased. This can involve cerebral symptoms.
IF YOU HAVE ANY DOUBTS ABOUT THE USE OF CARVASIN, ASK YOUR DOCTOR OR PHARMACIST
Side Effects What are the side effects of Carvasin
Like all medicines, Carvasin can cause side effects, although not everybody gets them.
Most adverse reactions are attributable to pharmacodynamic activity and are dose dependent. Headache may occur at the start of treatment, which usually disappears with continued therapy. Hypotension and / or light-headedness on standing may be observed commonly (1-10% of patients) at initiation of therapy or with dose escalation. These symptoms may be associated with dizziness, drowsiness, reflex tachycardia and a sense of weakness and generally disappear during continued therapy.
The frequency of undesirable effects is defined using the following convention: very common (≥1 / 10), common (≥1 / 100,
Nervous system disorders
Very common: headache
Common: dizziness (including postural dizziness), somnolence
Cardiac pathologies
Common: tachycardia (reflex)
Uncommon: worsening of angina pectoris
Vascular pathologies
Common: orthostatic hypotension
Uncommon: circulatory collapse (sometimes accompanied by bradyarrhythmia and syncope)
Not known: hypotension
Gastrointestinal disorders
Common: nausea.
Uncommon: vomiting, diarrhea
Very rare: heartburn. Musculoskeletal and connective tissue disorders
Very rare: myalgia
Skin and subcutaneous tissue disorders
Uncommon: allergic skin reactions (e.g. rash), redness
Not known: exfoliative dermatitis
General disorders and administration site conditions:
Common: asthenia
Not known: development of tolerance and cross-tolerance to other nitrates Temporary hypoxemia may occur during treatment with Carvasin due to relative redistribution of blood flow to hypoventilated alveolar areas. This can lead to myocardial hypoxia, particularly in patients with coronary artery disease.
Severe hypotensive responses have been reported with organic nitrates, including nausea, vomiting, asthenia, agitation, paleness, excessive sweating and collapse. Alcohol can intensify this effect. Measures that facilitate venous return (eg Trendeleburg position, deep breathing and movements of the extremities) usually resolve the syndrome.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine. "
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.
Do not use this medicine if you notice visible signs of deterioration.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What CARVASIN contains
CARVASIN 5 mg sublingual tablets - Each sublingual tablet contains:
Active ingredient: Isosorbide dinitrate 5 mg.Excipients: lactose, starch, erythrosine (E127), cellulose powder, magnesium stearate.
CARVASIN 10 mg tablets - Each tablet contains:
Active ingredient: Isosorbide dinitrate 10 mg. Excipients: lactose, mannitol, starch, sucrose, magnesium stearate.
CARVASIN 40 mg tablets - Each tablet contains:
Active ingredient: Isosorbide dinitrate 40 mg. Excipients: lactose, aluminum tristearate, magnesium stearate, talc, methylcellulose, sodium silico aluminate, polacrilin potassium.
Description of what CARVASIN looks like and contents of the pack
CARVASIN 5 mg sublingual tablets: 50 sublingual tablets
CARVASIN 10 mg tablets: 50 tablets
CARVASIN 40 mg tablets: 50 tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CARVASIN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
CARVASIN 5 mg sublingual tablets
Each sublingual tablet contains:
Active ingredient: Isosorbide dinitrate 5 mg.
Excipients: lactose
CARVASIN 10 mg tablets
Each tablet contains:
Active ingredient: Isosorbide dinitrate 10 mg.
Excipients: lactose, sucrose
CARVASIN 40 mg tablets
Each tablet contains:
Active ingredient: Isosorbide dinitrate 40 mg.
Excipients: lactose
For the list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Sublingual tablets
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Coronary insufficiency, prevention and treatment of angina pectoris. Due to its rapidity of action, sublingual Carvasin can be indicated in the treatment of chest angina; for the duration of its action, about 2 hours, it is indicated in the prevention of "angina attack when one engages in an effort that can provoke the attack (muscle activity, sexual act, large meal).
Carvasin for oral use, of less rapid but more prolonged action, is indicated in the prevention of chest angina attacks and in the treatment of coronary insufficiency.
04.2 Posology and method of administration
The starting dose should not exceed 5 mg due to the occasional occurrence of severe hypotensive effects.
Sublingual Carvasin: (tablets dissolve in 20 seconds) let one tablet dissolve under the tongue as a cure and / or prevention of chest angina attack. Sublingual administration can be repeated every 2-3 hours.
Carvasin 10 mg tablets: one tablet 4 times a day, before three meals and at bedtime.
Carvasin 40 mg tablets: one tablet every 12 hours.
The choice of sublingual or oral Carvasin should be made on the basis of the duration of action rather than the degree of response, as this is the major difference observed between these formulations.
To obtain a complete therapeutic effect it is important that the dosage of the sublingual and oral form is individualized in accordance with the needs of the individual patient, with the clinical response and hemodynamic monitoring.
Carvasin therapy should begin with the lowest effective dose and then adjusted as needed based on left ventricular efficiency. The starting dose depends on the assessment of the severity of the heart failure.
Pediatric populations
The safety and efficacy of Carvasin in children has not been established.
Geriatric use
Clinical trials of Carvasin did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other clinical experiences have not identified differences in response between young and elderly patients.
In general, the choice of dose for an elderly patient should be cautious, usually starting with the lowest dosage, considering an increased frequency of impaired hepatic, renal, or cardiac function, concomitant disease or other drug therapies.
04.3 Contraindications
Hypersensitivity to the active substance, to other nitrates or to any of the excipients.
Myocardial infarction in the acute phase
Acute circulatory failure (shock, circulatory collapse)
Cariogenic shock (unless sufficient end-diastolic pressure is maintained by means of appropriate measures)
Severe arterial hypotension (systolic pressure
Obstructive hypertrophic cardiomyopathy
Constrictive pericarditis
Severe hypovolemia
Cardiac tamponade
Patients with primary pulmonary hypertension
Phosphodiesterase inhibitors (sildenafil, vardenafil, tadalafil) potentiate the hypotensive effects of nitrates and, therefore, co-administration with organic nitrates is contraindicated (see section 4.5).
04.4 Special warnings and appropriate precautions for use
WARNINGS
Carvasind should be used with caution and under medical supervision in the following conditions:
- glaucoma
- marked anemia
- hyperthyroidism
- head trauma
- cerebral hemorrhage
- aortic or mitral stenosis
- subjects with predisposition to orthostatic hypotension
- subjects with intracranial hypertension, although a further increase in blood pressure was observed only after taking intravenous doses of nitroglycerin
- patients with renal insufficiency
For CARVASIN 10 mg tablets and CARVASIN 40 mg tablets formulations the onset of effect is not rapid enough to treat an acute anginal attack.
Carvasin dilating the intracranial vessels, can cause headache in the initial period of therapy which, in sensitive subjects, can be severe and persistent; Sometimes it can be prevented by administering lower doses in the first days of treatment (for example, half a 10 mg tablet four times a day) or it can be treated by combining an analgesic.
Temporary hypoxemia may occur during treatment with Carvasin due to relative redistribution of blood flow to hypoventilated alveolar areas. This can lead to myocardial hypoxia, particularly in patients with coronary artery disease (see section 4.8).
As with other vasodilators, Carvasin can cause paradoxical effects in sensitive patients, these effects can increase ischemia and also lead to extension of myocardial damage and advanced congestive heart failure.
If cyanosis occurs without intercurrent lung disease, the level of methemoglobin should be measured (methemoglobinemias occur more frequently during treatments with high doses).
Patients undergoing maintenance therapy with Carvasin should be advised that they should not use medicinal products containing phosphodiesterase inhibitors used for the treatment of erectile dysfunction (e.g. sildenafil, vardenafil, tadalafil). Carvasin therapy should not be interrupted to take products containing phosphodiesterase inhibitors as this may increase the risk of an angina pectoris attack (see sections 4.3 and 4.5).
Adequate supportive care has not been studied, but it is reasonable to treat this event in the same way as a nitrate overdose (see section 4.8).
PRECAUTIONS FOR USE
Drug tolerance (decreased efficacy) and cross tolerance with other nitro derivatives (decreased effect in case of prior therapy with another organic nitrate) may develop. Prolonged high-dose therapy should be avoided to reduce or eliminate tolerance.
Even with low doses of Carvasin, cases of severe hypotensive effects, particularly orthostatic hypotension, can occur. Paradoxical bradycardia and aggravation of angina pectoris may accompany nitrate-induced hypotension. The medicinal product should be used with caution in subjects who may have a reduction in volume induced by diuretic therapy.
In the treatment of congestive heart failure, capillary pulmonary pressure should not fall below 15 mmHg or systolic pressure below the physiological range in normal or hypertensive patients. Systolic blood pressure should be maintained in the range of 90-100 mmHg in patients with pre-existing hypotension (see section 4.3).
The simultaneous intake of organic nitrates with calcium channel blockers can potentiate the hypotensive effect. A dose adjustment of both types of drugs may be necessary.
Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy (see section 4.3).
In clinical trials in patients with angina pectoris attacks of angina provoked as "rebound" of haemodynamic effects soon after nitrate withdrawal have been reported. It seems prudent, therefore, to gradually discontinue isosorbide dinitrate when therapy is to be terminated, especially in the case of high dose use.
The concomitant consumption of alcohol can increase the hypotensive effects of nitrates and reduce reflexes, for example when driving or controlling machinery that requires special attention.
Use in children
The safety and efficacy of Carvasin in children has not been established.
In patients suffering from functional or organic gastrointestinal hypermotility or malabsorption syndrome, the use of 5 mg or 10 mg Carvasin should be preferred, as with the 40 mg tablets in some cases the tablet has partially disintegrated and has been recovered. in the stool.
This medicine contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
CARVASIN 10 mg tablets also contains sucrose is therefore not suitable for subjects with hereditary fructose intolerance, glucose / galactose malabsorption syndrome or sucrase-isomaltase deficiency.
04.5 Interactions with other medicinal products and other forms of interaction
Isosorbide dinitrate can act as a physiological antagonist of norepinephrine, acetylcholine and histamine. Nitrates can cause hypotension as a result of peripheral vasodilation. Alcohol can enhance this effect.
The simultaneous administration of drugs with hypotensive properties (eg beta-blockers, vasodilators, diuretics, calcium channel blockers, ACE inhibitors), neuroleptics and tricyclic antidepressants can enhance the hypotensive effect
Co-administration of phosphodiesterase inhibitors (eg sildenafil, vardenafil and tadalafil) used in the treatment of erectile dysfunction potentiates the hypotensive effect of organic nitrates. This can lead to life-threatening cardiovascular complications; therefore in patients under therapy with Carvasinl "use of phosphodiesterase inhibitors (eg sildenafil, vardenafil, tadalafil) is contraindicated. (see paragraph 4.3)
Some reports suggest that concomitant administration of isosorbide dinitrate may increase blood levels of dihydroergotamine and its effect.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate and well-controlled studies in women during pregnancy. Carvasin can only be used during pregnancy if strictly necessary and under the prescription and continuous supervision of a doctor.
Feeding time
There is data showing that nitrates are excreted in breast milk and can cause methemoglobinemia in newborns. The extent of excretion of isosorbide dinitrate and its metabolites in human milk has not been determined. Therefore, particular caution should be exercised if Carvasin is administered to breastfeeding women
Embryotoxicity, mutagenesis and fertility disorders see section 5.3.
04.7 Effects on ability to drive and use machines
Carvasin can impair the ability to react and reduce reflexes when driving vehicles and controlling machines. This effect can be enhanced by the consumption of alcohol.
04.8 Undesirable effects
Most adverse reactions are attributable to pharmacodynamic activity and are dose dependent. Headache may occur at the start of treatment, which usually disappears with continued therapy. Hypotension and / or light-headedness on standing can be observed commonly (1-10% of patients) at initiation of therapy or with increased dose. These symptoms may be associated with dizziness, drowsiness, reflex tachycardia and a sense of weakness and generally disappear during continued therapy.
The frequency of undesirable effects is defined using the following convention: very common (≥1 / 10), common (≥1 / 100,
Nervous system disorders
Very common: headache
Common: dizziness (including postural dizziness), somnolence
Cardiac pathologies
Common: tachycardia (reflex)
Uncommon: worsening of angina pectoris
Vascular pathologies
Common: orthostatic hypotension
Uncommon: circulatory collapse (sometimes accompanied by bradyarrhythmia and syncope)
Not known: hypotension
Gastrointestinal disorders
Common: nausea.
Uncommon: vomiting, diarrhea
Very rare: heartburn
Musculoskeletal and connective tissue disorders
Very rare: myalgia
Skin and subcutaneous tissue disorders
Uncommon: allergic skin reactions (e.g. rash), redness
Not known: exfoliative dermatitis
General disorders and administration site conditions:
Common: asthenia
Not known: development of tolerance and cross tolerance to other nitrates
Temporary hypoxemia may occur during treatment with Carvasin due to relative redistribution of blood flow to hypoventilated alveolar areas. This can lead to myocardial hypoxia, particularly in patients with coronary artery disease.
Severe hypotensive responses have been reported with organic nitrates, including nausea, vomiting, asthenia, agitation, paleness, excessive sweating and collapse. Alcohol can intensify this effect.
Measures that facilitate venous return (eg Trendeleburg position, deep breathing and movements of the extremities) usually resolve the syndrome.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili".
04.9 Overdose
Symptoms:
- Blood pressure drop ≤ 90 mmHg
- Pallor
- Sweating
- Weak heartbeat
- Tachycardia
- Postural vertigo
- Headache
- Asthenia
- Vertigo
- Nausea
- He retched
- Diarrhea
- Somnolence
- Hot flashes
- Methaemoglobinaemia has been reported in patients receiving other organic nitrates. During the biotransformation of isosorbide mononitrate nitrite ions are released which can cause methemoglobinemia and cyanosis resulting in tachypnea, anxiety, loss of consciousness and cardiac arrest. It cannot be excluded that an overdose of isosorbide dinitrate may cause this adverse reaction.
- With very high dosages the intracranial pressure can be increased. This can involve cerebral symptoms.
Ordinary procedure:
- Stop taking the drug
- Ordinary procedures in case of nitro-derived hypotension
• The patient should be placed in a horizontal position with the head lowered and the legs raised
• Administration of oxygen
• Increased plasma volume (intravenous fluids)
• Specific anti-shock treatments (hospitalization of the patient in intensive care)
Special procedure:
- Try to increase blood pressure if it is very low
- Vasopressor agents should only be used in those patients who do not respond to adequate fluid replacement
- Treatment of methemoglobinemia: starting from a level of 0.8 g / 100 ml of methemoglobinemia, the treatment will consist of an intravenous administration of 1% methylene blue (1-2 mg / kg). In less severe cases, the dose of 50 mg / kg should be administered orally and treatment in a specialized center is recommended.
In case of signs of respiratory and circulatory arrest, start resuscitation procedures immediately.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vasodilators used in cardiac diseases
ATC code: C01DA08
Carvasin (Isosorbide dinitrate) is a vasodilator which has proven to be effective in coronary insufficiency and chest angina by increasing the resistance of the heart to exertion due to the better blood flow induced in the coronary bed and thus reducing the frequency and severity of anginal attacks. .
The exact mechanism of action of nitrates in mitigating angina pectoris is not fully understood. It seems that the relief of anginal symptoms is due to the reduction of myocardial oxygen demand, for example through the reduction of cardiac post and pre-load with the dilation of peripheral venous capacitance vessels and to a lesser extent of resistance arterial vessels Nitrates can cause a redistribution of coronary blood flow to ischemic areas by selectively dilating large coronary vessels or collateral vessels that can develop secondary to myocardial ischaemia.
After therapeutic doses of the drug, systemic blood pressure is usually reduced, heart rate remains unchanged or undergoes a slight compensatory increase. In the absence of heart failure, cardiac output temporarily increases and then decreases. Pulmonary vascular resistance and pulmonary pressure are reduced.
The antianginal effect of sublingual carvasin usually occurs within 2-5 minutes after administration and lasts for 1-2 hours. The hemodynamic effect of oral tablets is observed in 20-60 minutes and lasts for 4-6 hours.
05.2 Pharmacokinetic properties
Isosorbide dinitrate has a solubility comparable to that of nitroglycerin and far superior to that of pentaerythritoletranitrate.
Administered sublingually, it is rapidly absorbed and takes effect within 5 minutes. The vasodilating activity persists for about 2 hours.
The nitrate isosorbide is also well absorbed orally. Its effects in this case are slower to manifest (30 minutes).
In vivo and in vitro studies establish that the hepatic inactivation rate of isosorbide dinitrate is much slower than that of nitroglycerin.
Isosorbide dinitrate is metabolized in the liver, with the formation of two metabolites, 2-mononitrate and 5-mononitrate, both, and particularly the first, pharmacologically active.
05.3 Preclinical safety data
The LD50 in the rat (oral route) is about 1100 mg / kg. Animal experiments would indicate that 500 times the usual therapeutic dose should be required to produce toxic effects on humans. Chronic toxicity studies in rats and dogs (oral route) have not shown toxic phenomena at the doses used. In humans, some studies have demonstrated that the drug administered at high doses (120/360 mg / day) for periods of 3-10 months does not produce methemoglobinemia or other haematological or biochemical alterations.
Carcinogenesis, Mutagenesis, Fertility disorders
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of this drug. A bi-generational reproduction study conducted in rats treated with isosorbide dehydrate at a dose of 25 or 100 mg / kg / day revealed no effects on fertility or gestation or any growth pathology on either the parental generation or the offspring of the treated rats. with dehydrated isosorbide compared with rats fed a controlled basal diet.
Isosorbide dehydrate resulted in increased embryotoxicity in rabbits at oral doses of 35 and 150 times the maximum recommended human daily dose. There are no adequate controlled studies in pregnant women.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
CARVASIN 5 mg sublingual tablets: lactose, starch, erythrosine (E127), cellulose powder, magnesium stearate.
CARVASIN 10 mg tablets: lactose, mannitol, starch, sucrose, magnesium stearate.
CARVASIN 40 mg tablets: lactose, aluminum tristearate, magnesium stearate, talc, methylcellulose, sodium silicoaluminate, potassium polacrilin.
06.2 Incompatibility
There are no known incompatibilities.
06.3 Period of validity
CARVASIN 5 mg sublingual tablets: 5 years
CARVASIN 10 mg tablets: 3 years
CARVASIN 40 mg tablets: 3 years
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions
06.5 Nature of the immediate packaging and contents of the package
CARVASIN 5 mg sublingual tablets: 50 tablets
CARVASIN 10 mg tablets: 50 tablets
CARVASIN 40 mg tablets: 50 tablets
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
TEOFARMA S.r.l. - Via F.lli Cervi, 8 - Salimbene Valley (PV).
08.0 MARKETING AUTHORIZATION NUMBER
Carvasin 5 mg sublingual tablets: AIC n. 018269050.
Carvasin 10 mg tablets: AIC n. 018269011.
Carvasin 40 mg tablets: AIC n. 018269035.
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Carvasin 5 mg sublingual tablets: 1975 / June 2010
Carvasin 10 mg tablets: 1960 / June 2010
Carvasin 40 mg tablets: 1975 / June 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of 22 January 2014.
