TRANDATE - PACKAGE LEAFLET - DRUGS-HYPERTENSION

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Trandate - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Labetalol

TRANDATE 5 mg / ml solution for injection for intravenous use

Trandate package inserts are available for pack sizes:

TRANDATE 5 mg / ml solution for injection for intravenous use
Trandate Tablets 100mg, Trandate Tablets 200mg,

Indications Why is Trandate used? What is it for?

TRANDATE contains the active substance labetalol, which belongs to a group of medicines called alpha and beta blockers, which relax and dilate blood vessels, lowering blood pressure and reducing the work of the heart.

This medicine is used to treat a sharp increase in blood pressure (severe hypertension), to bring it back to normal in an emergency.

Contraindications When Trandate should not be used

Do not use TRANDATE

if you are allergic to labetalol hydrochloride or any of the other ingredients of this medicine (listed in section 6);
if you have heart beating disturbances (2nd or 3rd degree atrioventricular block), i.e. a block of different degrees of the electrical stimulus transmission between the upper part of the heart (atrium) and the lower part (ventricle);
if you have reduced heart function, despite being treated with digitalis, medicines used to help a poorly functioning heart (heart failure resistant to digitalis treatment);
if you have severely reduced kidney function (severe kidney failure);
if you have higher than normal blood acidity due to diabetes (diabetic acidosis);
if you have a severe heart problem (cardiogenic shock);
if you have a sharp drop in blood pressure (severe and marked hypotension) or have a very slow heartbeat (bradycardia);
if you have very high blood pressure, after having had a heart attack and there are various complications (hypertensive episodes following acute myocardial infarction);

The use of this medicine is contraindicated in children.

Precautions for use What you need to know before taking Trandate

Talk to your doctor or nurse before you are given TRANDATE.

If you suffer from reduced heart function (heart failure), your doctor will start therapy with other medicines used for various heart problems, called digitalis or medicines called diuretics, before starting treatment with this medicine.

This medicine will be given to you with great caution:

if you suffer from liver disease (liver damage); in this case the doctor may decide to decrease the dose. Liver damage (hepatocellular damage) may occur during treatment with TRANDATE. If this happens to you, you will be subjected to some tests to determine whether or not to stop taking this medicine;
if you have or have ever suffered from asthma, as severe breathing problems (bronchospasm) can occur; if this happens, your doctor will decide whether to treat you with other medicines such as selective bronchodilators, i.e. substances that dilate the bronchi allowing you to breathe better, by inhalation or with a drug called atropine (1 mg of atropine intravenously) or to stop the treatment.

For those who practice sports: the use of this medicine without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.

Interactions Which drugs or foods can modify the effect of Trandate

Tell your doctor or nurse if you are using, have recently used or might use any other medicines.

Administration of TRANDATE will be avoided if you are using medicines used to lower blood pressure called calcium channel antagonists such as verapamil, as this combination can lead to severe lowering of blood pressure and heart failure.

This medicine will be given to you with great caution if you are using:

Class I antiarrhythmics (e.g. disopyramide, quinidine) and amiodarone, medicines used for heart rhythm disorders.
Sympathomimetics (adrenaline and noradrenaline), medicines used in case of too low blood pressure or in other diseases
Other antihypertensives, as they can increase the effect of labetalol
Halothane, a medicine used in anesthesia because the simultaneous use of anesthetics with TRANDATE can cause blood pressure to decrease too much. The anesthetist should be informed of the current treatment with Trandate;
Tricyclic antidepressants, medicines used to treat depression;
Cimetidine, a medicine used to treat severe stomach injuries (gastric ulcer).

Please note that using TRANDATE may make you more prone to allergic reactions and at the same time less sensitive to adrenaline, a substance used to treat severe allergic reactions.

The presence of a metabolic of labetalol in the urine may interfere with urine laboratory tests.

Warnings It is important to know that:

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Pregnancy

In the first 3 months of pregnancy this medicine will only be given to you if your doctor deems it strictly necessary because it can cause problems for your baby such as:

decrease in blood pressure (hypotension);
very slow heartbeat (bradycardia);
difficulty in breathing (respiratory depression);
low blood sugar (hypoglycemia);
decrease in body temperature (hypothermia);
decreased response to other treatments (supportive care e.g. intravenous solutions and glucose), especially if this medicine has been used for a long time or if the pregnant woman has a disease called pre-eclampsia, characterized by high blood pressure, swelling due to fluid accumulation and the presence of protein in the urine;
intrauterine and neonatal death, following the use of this medicine and the simultaneous existence of other complications (use of other drugs such as vasodilators, drugs that depress respiratory function, pre-eclampsia, intrauterine growth retardation and prematurity);

For these reasons, this medicine will not be given to you for a long time and at the same time as another medicine used for high blood pressure called hydralazine; moreover, we will try not to delay the birth too much.

Feeding time

Labetolol (TRANDATE) is secreted in breast milk, therefore breastfeeding is not recommended.

Driving and using machines

Since labetalol (TRANDATE) can cause dizziness and lethargy, patients should be advised to exercise caution when driving and using machines.

Dosage and method of use How to use Trandate: Dosage

This medicine will always be given to you exactly as your doctor has told you. If in doubt, consult your doctor or nurse.

This medicine will be given to you in a hospital or other specialized center by a doctor or nurse.

This medicine will be given to you by 'injection into a vein or injection into a slow vein (intravenous infusion), lying down and remaining in this position for at least 3 hours after administration of TRANDATE.

The recommended dose to bring down very high blood pressure rapidly is 50 mg which, if necessary, can be given every 5 minutes up to a maximum of 200 mg. In some patients, such as those with a type of cancer called pheochromocytoma, the maximum dose can be as high as 300 mg.

Your doctor will monitor your blood pressure, heart rate (heart rate) and, if necessary, your ability to breathe (respiratory function) for the duration of treatment with TRANDATE.

This medicine will be given to you at different rates, depending on whether it is given to lower blood pressure during pregnancy or after a heart attack.

Overdose What to do if you have taken too much Trandate

This medicine will be given to you by trained personnel, so it is unlikely that an overdose will occur.

However, in the event of an overdose, heart or blood circulation problems such as dizziness on standing up quickly (postural hypotension) or very slow heartbeat (bradycardia) may occur.

The doctor will establish a suitable therapy for the treatment of these symptoms.

If you think you have been given an overdose of TRANDATE, tell your doctor or nurse immediately.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

Side Effects What are the side effects of Trandate

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects may occur:

Frequency not known (the frequency of which cannot be estimated from the available data)

dizziness on standing up quickly (orthostatic hypotension), especially if you get up within 3 hours after taking this medicine;
stuffy nose (congestion) and dryness inside the nose (dryness of the nasal mucosa);
disorders of sexuality in men (failure to ejaculate);
difficulty urinating (acute urinary retention, urination disturbances);
stomach pain (epigastric pain), nausea and vomiting;
dizziness (vertigo), headache (headache), drowsiness (lethargy), very intense dreams (vivid dreams), depression;
fatigue (asthenia);
cramps, tingling of the scalp, muscle disease (toxic myopathy);
fever;
skin irritations (sometimes lichenoid-like rashes, that is, with a lichen-like appearance, with arborescent skin striae);
dry eyes and vision disturbances;
inflammation of the liver (hepatitis), liver malfunction leading to a disease characterized by yellowish discoloration of the skin (jaundice) both hepatocellular, i.e. by damage to liver cells and cholestatic, i.e. by obstruction of the canaliculi where bile passes or by alteration of the tests indicating liver function, severe damage to liver tissue (liver necrosis);
blood cell disorders (blood crasis);
difficulty in breathing due to temporary narrowing of the bronchi (bronchospasm);
very slow heartbeat (bradycardia);
severe heart rhythm problems (heart block, conduction disturbances);
allergic reactions such as swelling of the face especially around the eyes and mouth (angioedema), shortness of breath (dyspnoea), skin irritations (rash, itching);
severe disease of the immune system (lupus erythematosus);
sweating;
appearance of positivity to a diagnostic test called anti-nucleus antibodies.

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. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. 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 package after "EXP". The expiry date refers to the last day of that month.

Store at a temperature not exceeding 25 ° C.

The doctor and nurse know how to store the medicine.

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.

Other information

What Trandate 5 mg / ml solution for injection for intravenous use contains

The active ingredient is labetalol hydrochloride. Each vial contains 100 mg of labetalol hydrochloride.
The other component is water for injections.

Description of the appearance of TRANDATE and contents of the package

Carton containing 1 vial of 20 ml.

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.

Further information on Trandate can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

TRANDATE VIALS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

One vial contains:

Active ingredient: Labetalol hydrochloride 100 mg.

Excipients: Water p.p.i. q.s. to 20 ml.

03.0 PHARMACEUTICAL FORM

Vials.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

TRANDATE vials are indicated when rapid normalization of blood pressure values is required in patients with severe hypertension.

04.2 Posology and method of administration

Adults

The TRANDATE vials are reserved for intravenous use in hospitalized patients.

The plasma levels reached after intravenous administration of TRANDATE in severe hypertension are substantially higher than those obtained after oral administration of the drug and allow to obtain that more intense blocking effect on alpha-adrenergic receptors which is necessary to control the hypertensive state. more serious. However, the drug should be injected while keeping patients in the supine position at all times.

Intravenous injection

If it is necessary to reduce blood pressure rapidly, as, for example, in hypertensive encephalopathy, a dose of 50 mg of TRANDATE should be administered intravenously over not less than one minute. If necessary, doses of 50 mg may be given. repeated at intervals of 5 minutes until a satisfactory response is obtained. The total dose should not exceed 200 mg. Generally the maximum effect occurs within 5 minutes after injection of a single dose and the duration of action is usually of about 6 hours although it can also last for 18 hours.

Intravenous infusion

An alternative method of administration is the intravenous infusion of a solution obtained by diluting the contents of two ampoules (200 mg) in 200 ml of sodium chloride or dextrose for parenteral use. The infusion solution thus obtained contains 1 mg / ml of TRANDATE.

It should be administered using a pediatric infusion device fitted with a 50 ml graduated burette to facilitate accurate dosing.

The infusion rate of TRANDATE should be approximately 2 mg (2 ml of infusion solution) per minute, until a sufficient response is obtained; the infusion must then be stopped.

The useful dose usually lies in a range between 50 and 200 mg, in relation to the severity of the hypertensive state. In the majority of patients, it is not necessary to administer doses greater than 200 mg, however doses up to 300 mg may be required, especially in patients with pheochromocytoma. The rate of infusion should be modified in relation to the response obtained at the discretion of the treating physician. Blood pressure should be kept under control throughout the infusion period.

Hypertension in pregnancy: the infusion rate should be initially 20 mg / hour and then doubled every 30 minutes until a satisfactory response is obtained or 160 mg / hour is reached. If necessary, higher doses can be administered.

Hypertensive episodes following myocardial infarction: the infusion rate should be initially 15 mg / hour and then gradually increased, in relation to blood pressure control, up to a maximum of 120 mg / hour.

It is advisable to monitor blood pressure and heart rate after injection and during the infusion.

In most patients, there is a small decrease in heart rate; Excessive bradycardia is unusual, however it can be controlled by injecting 1-2 mg of atropine intravenously.

The respiratory function will be kept under observation especially in patients with pre-existing alterations of the same.

The TRANDATE vials should be administered while keeping the patient in a supine position. Returning the patient to an upright position should be avoided before three hours following the intravenous administration of TRANDATE, as heightened postural hypotension may occur.

When the blood pressure values are adequately reduced, maintenance therapy with TRANDATE tablets is started starting from a dosage of 200 mg twice a day.

TRANDATE ampoules have been administered to patients with hypertension resistant to other antihypertensive drugs, including beta-blockers, without undesirable effects.

Children

Find no indication.

04.3 Contraindications

Second or third degree atrioventricular block, heart failure resistant to digitalis treatment, severe renal failure, diabetic acidosis.

Cardiogenic shock and other conditions associated with severe and prolonged hypotension, marked bradycardia.

The use of Trandate vials is contraindicated to control hypertensive episodes following acute myocardial infarction, when peripheral vasoconstriction suggests low cardiac output.

Known individual hypersensitivity to the drug.

04.4 Special warnings and appropriate precautions for use

In case of heart failure, patients should undergo appropriate treatment with digitalis and diuretics before starting therapy.

Use with caution in patients with hepatic impairment who may have higher than normal plasma concentrations of labetalol due to impaired metabolism. Consequently, such patients may require lower than usual doses of TRANDATE.

Beta-blockers, even cardioselective ones, should not be used in patients with asthma or a history of bronchostruction, unless alternative treatment is not possible. In these cases, the risk of inducing bronchospasm must be carefully considered and adequate precautions taken.

The possible occurrence of bronchospasm can be controlled by resorting to selective inhaled bronchodilators (possibly at higher doses than usual in asthma). Should further treatment be required, it is recommended to administer 1 mg of atropine intravenously. If bronchospasm is not resolved, treatment must be stopped.

There have been rare reports of severe, usually reversible, hepatocellular damage associated with short- and long-term labetalol therapy.

Appropriate laboratory tests should be performed when the first symptoms of liver dysfunction appear.

If the results indicate the presence of liver damage or in the presence of jaundice, labetalol should be discontinued and no longer re-administered.

04.5 Interactions with other medicinal products and other forms of interaction

Attention should be paid to the simultaneous use of labetalol and Class I antiarrhythmics and the association with calcium antagonists of the verapamil type should be avoided.

Patients undergoing treatment with beta-blockers may be more reactive (with greater risk of anaphylactic reactions) to both accidental and diagnostic or therapeutic exposures of various allergens. Such patients may be less sensitive to the usual doses of adrenaline used for the treatment of allergic reactions.

The effect of the halotome on blood pressure values can be enhanced by the Trandate.

04.6 Pregnancy and breastfeeding

Although no teratogenic effects have been demonstrated in animals, TRANDATE should only be used during the first trimester of pregnancy if the foreseeable benefits outweigh the potential risks.

Since TRANDATE crosses the placental barrier, the possible consequences for the fetus and the neonate deriving from alpha and beta-adrenergic blockade must be kept in mind.

Perinatal and neonatal distress (bradycardia, hypotension, respiratory depression, hypoglycemia, hypothermia) has been reported rarely. In some cases, these symptoms appeared within a day or two of birth.

Response to supportive care (eg intravenous solutions and glucose) is generally rapid, but in severe pre-eclampsia and particularly after prolonged treatment with intravenous labetalol, recovery may be slower. This may be related to decreased hepatic metabolism in premature babies.

Cases of intrauterine and neonatal death have been reported, but other drugs (eg, vasodilators, drugs that depress respiratory function), the effects of pre-eclampsia, intrauterine growth retardation, and prematurity have been implicated. These clinical data advise against excessively prolonging the use of high doses of labetalol, delaying childbirth, as well as concomitant administration of hydralazine.

Our experience to date, however, has shown that this has had very rare response.

Labetalol is secreted in breast milk, but no side effects have been seen in naturally breastfed babies.

04.7 Effects on ability to drive and use machines

The product does not affect the driving ability and the use of machines.

04.8 Undesirable effects

TRANDATE is generally well tolerated. Accentuated postural hypotension may occur if patients are allowed to stand upright within 3 hours following the injection of TRANDATE.

In a limited number of patients, congestion or dryness of the nasal mucosa, intense dreams, ejaculation failure, acute urinary retention, gastrointestinal disturbances (nausea and vomiting) have been reported. Dizziness, headache, lethargy, asthenia, cramps and tingling of the scalp, usually transient, which tend to disappear after a few weeks, and very rarely drug fever have also been observed. In a very limited number of patients, and not always correlated to the treatment with labetalol, the following have been reported: cutaneous eruptions sometimes of the lichenoid type and dry eyes with irritation and visual disturbances; in the majority of cases these disturbances disappeared with the interruption of treatment.

There have been rare reports of hepatitis, jaundice (both hepatocellular and cholestatic) and elevated liver function tests and liver necrosis.

These signs and symptoms are usually reversible on discontinuation of therapy.

The use of beta-blocking drugs causes in rare cases blood crase disorders, bronchospasm, bradycardia and heart block.

04.9 Overdose

In case of overdose of labetalol hydrochloride, intense cardiovascular effects should be expected, for example marked hypotension sensitive to postural changes and, in some cases, bradycardia.

Patients should be placed in a supine position if necessary with their legs raised to improve cerebral circulation. Cardioactive glycosides and diuretics should be administered to deal with heart failure and a selective inhaled bronchodilator against bronchospasm.

To cope with bradycardia, atropine should be administered at a dose of 0.25-3 mg intravenously.

To promote the recovery of cardiocirculatory function, it would be preferable to use intravenous noradrenaline instead of isoprenaline. The recommended initial dose of noradrenaline is 5-10 mcg iv to be repeated, if necessary, based on the response. Alternatively, noradrenaline it can be given by infusion at a rate of 5 mcg per minute until a satisfactory response is achieved.

In the case of severe overdosage, intravenous glucagon is preferred: an initial bolus of 5-10 mg in physiological solution or with dextrose, possibly followed by an infusion at 5 mg / hour. In some cases electrostimulation may be necessary. Renal failure with oliguria has been reported following massive overdose of oral labetalol; in one case the worsening of renal failure was attributed to dopamine administered for the treatment of hypotension.

Hemodialysis removes less than 1% of labetalol hydrochloride from the circulation.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Trandate is an antihypertensive drug that works by simultaneously inhibiting both alpha and beta receptors.

These properties emerge from the set of results collected from experimental tests on animals, both in vivo and in vitro and on humans. The specificity of the blocking action of the product is demonstrated by the fact that the drug is able to dose antagonize - dependent on the effects produced by sympathetic stimulation (cardiac accelerating nerve or splanchnic nerve) and exogenous administration of noradrenaline and isoprenaline (i.e. alpha and beta-receptor agonists, respectively) while it does not influence or influence the response in a variable way to non-adrenergic drugs such as angiotensin and nicotine. The blocking of arteriolar alpha-adrenoceptors leads to the reduction of peripheral vascular resistance. The beta-blocking activity protects the heart from the reflex sympathetic action, normally induced by peripheral vasodilation. L " together of these two actions allows the reduction of blood pressure in the hypertensive subject. Trandate has no CNS activity. Therefore, those sedative effects often found with other hypotensive therapies with central activity should be excluded.

05.2 Pharmacokinetic properties

The pharmacokinetics of labetalol hydrochloride have been studied in animals (rats, dogs) and humans. Animal pharmacokinetics after oral administration showed a time to peak of 2-3 hours in the rat and 2-4 hours in the dog. In humans, the blood peak after administration of oral labetalol hydrochloride is reached within 1-2 hours. hours. With doses of 100, 200, 400 mg, this peak was, on average, equal to 2, 5-8 and 16 mcg / 100 ml. The half-life was found to be 4-5 hours. The serum protein binding was 50%. After intravenous administration of 1 mg / kg, labetalol hydrochloride was rapidly eliminated from the blood in humans with a half-life of approximately 4 hours.Radiochemical analysis of urine shows that over 60% of the radioactivity of the orally administered dose is eliminated in the urine; the remaining radioactive dose is eliminated in the faeces. Labetalol hydrochloride is extensively metabolised; only 5% is excreted unchanged , while the main metabolites are a glucuronide and a hydroxy derivative.

05.3 Preclinical safety data

Long-term studies, with oral administration of labetalol hydrochloride for 18 months in mice and for 2 years in rats, showed no evidence of carcinogenesis.

Studies with labetalol hydrochloride, using lethal dominant assays in rats and mice and subjecting microorganisms to modified Ames tests, did not show mutagenesis. The LD50 in mice is 600 mg / kg and in rats it is greater than 2 g / kg. The DL50 e.v. in these species it ranges from 50 to 60 mg / kg.