TRANDATE 5 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Trandate 5 mg/ml Solution for Injection

Labetalol Hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet.

Contents of the Package Leaflet:

1. What is Trandate and what is it used for
2. What you need to know before you use Trandate
3. How to use Trandate
4. Possible side effects
5. Storage of Trandate
6. Contents of the pack and other information

1. What is Trandate and what is it used for

Trandate belongs to a group of medicines called alpha- and beta-blockers.

Trandate is indicated for the treatment of:

• Severe hypertension (high blood pressure), including that of pregnancy, when rapid control of blood pressure is essential
• Anesthesia, when hypotensive technique is indicated
• Hypertensive episodes (high blood pressure) after acute myocardial infarction.

Trandate does not have a harmful effect on kidney function and is particularly suitable for use in hypertensive patients with kidney dysfunction.

2. What you need to know before you use Trandate

Do not use Trandate

• If you are allergic to labetalol hydrochloride or any other component of Trandate.
• If you have second- or third-degree atrioventricular block (cardiac block).
• In case of cardiogenic shock (heart failure).
• In case of prolonged and severe hypotension (low blood pressure).
• If you have severe bradycardia (slow heart rate).
• If you have asthma or respiratory tract obstruction.
• In case of hypertension (high blood pressure) after acute myocardial infarction, when there is peripheral vasoconstriction suggesting low cardiac output.

Warnings and precautions

Special care should be taken in patients with limited cardiac reserve (the heart's ability to function above its normal level) and heart failure. These cases should be controlled with a cardiac glycoside (a medicine to control heart rate) and a diuretic (a medicine to increase fluid elimination) before starting therapy with Trandate.

It is not necessary to discontinue treatment with Trandate before anesthesia, although patients should receive atropine intravenously before induction.

Risk of anaphylactic reaction (severe allergic reaction): Patients with a history of severe anaphylactic reaction to any variety of allergens (substances that can cause allergic reactions) who are taking beta-blockers (medicines for the treatment of high blood pressure) may be more sensitive to repeated exposure, either accidental, diagnostic, or therapeutic. These patients may not respond to the usual doses of adrenaline used to treat allergic reactions.

Children and adolescents

The safety and efficacy of this medicine in children have not been established.

Interaction of Trandate with other medicines

Tell your doctor or pharmacist if you are using, or have recently used, any other medicines, including those obtained without a prescription, as it may be necessary to interrupt treatment or adjust the dose of one of them.

Special care should be taken with the simultaneous administration of the following medicines:

Class I antiarrhythmic agents or calcium antagonists of the verapamil type (medicines used to suppress or prevent cardiac rhythm disturbances).

Trandate may potentiate the hypotensive effects of halothane.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before using any medicine.

Cases of pain and Raynaud's phenomenon in the nipples (see section 4) have been reported.

Pregnancy

Trandate should only be used in the first trimester of pregnancy if the potential benefit outweighs the potential risk.

Breastfeeding

Trandate is excreted in breast milk, although no adverse effects have been described in breastfed infants.

Driving and using machines

No effects on the ability to drive or use machines have been described due to the use of this medicine.

Use in athletes

Athletes are informed that this medicine contains a component that may result in a positive doping test.

3. How to use Trandate

Follow the administration instructions for Trandate exactly as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

If you think the action of Trandate is too strong or too weak, tell your doctor or pharmacist.

Trandate is indicated for intravenous use in hospitalized patients.

Patients should receive the drug while always in a supine position (lying on their back) or left lateral position (lying on their left side).

Avoid lifting the patient before 3 hours have passed, as excessive postural hypotension may occur.

Adults

Bolus injection

If it is essential to reduce blood pressure quickly, a dose of 50 mg should be administered intravenously over at least one minute and repeated, if necessary, at 5-minute intervals until a satisfactory response is achieved. The total dose should not exceed 200 mg.

The maximum effect usually occurs within the first 5 minutes and lasts about 6 hours, although it may be prolonged up to 18 hours.

Intravenous infusion

A solution of 1 mg/ml should be used. Dilute, for example, the contents of two ampoules (200 mg) in 200 ml with sodium chloride and glucose injectable solution or 5% glucose.

Hypertension in pregnancy

Start the infusion at 20 mg/hour, then the dose can be doubled every 30 minutes until a satisfactory response is achieved or a dose of 160 mg/hour is reached. Occasionally, higher doses may be needed.

Hypertensive episodes after acute myocardial infarction

Start the infusion at 15 mg/hour and gradually increase up to a maximum of 120 mg/hour, depending on blood pressure control.

Hypertension due to other causes

Infuse at a rate of about 2 mg/min until a satisfactory response is achieved, then stop the infusion. The effective dose is usually 50-200 mg, but higher doses may be needed, especially in patients with pheochromocytoma. The infusion rate can be adjusted according to the response, at the doctor's discretion.

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

In most patients, there is a small decrease in heart rate; severe bradycardia is uncommon but can be controlled by injecting 1-2 mg of atropine intravenously. Respiratory function should be monitored, especially in patients with known alteration.

Once blood pressure has been adequately reduced with bolus or infusion, maintenance therapy with Trandate tablets should be substituted, starting with a dose of 100 mg twice a day.

Trandate has been administered to patients with uncontrolled hypertension who were already receiving other antihypertensive agents, including beta-blockers, without adverse effects.

Hypotensive anesthesia

Induction should be performed with standard agents, e.g., sodium thiopental, and anesthesia should be maintained with nitrous oxide and oxygen with or without halothane. The recommended initial dose of Trandate is 10-20 mg intravenously, depending on the patient's age and condition. Patients for whom halothane is contraindicated generally require a higher initial dose of Trandate (25-30 mg).

If satisfactory hypotension is not achieved after 5 minutes, increments of 5-10 mg should be administered until the desired level of blood pressure is reached.

Halothane and labetalol act synergistically. Therefore, the concentration of halothane should not exceed 1-1.5%, as a significant decrease in blood pressure may occur.

After injection of Trandate, blood pressure can be adjusted quickly and easily by altering the concentration of halothane and/or adjusting the tilt of the table. The average duration of hypotension after 20-25 mg of Trandate is 50 minutes.

The hypotension induced by labetalol is easily reversible by administering 0.6 mg of atropine and discontinuing halothane.

If you use more Trandate than you should

In case of overdose or accidental injection, consult your doctor or pharmacist immediately, or the Toxicology Information Service. Phone: 91 562 04 20. It is recommended to take the package and leaflet of the medicine to the healthcare professional.

Deep cardiovascular effects such as excessive postural hypotension and, sometimes, bradycardia are expected. Patients should remain lying down in a supine position with their legs raised. Gastric lavage or induction of vomiting is justified within the first hours of ingestion; use a cardiac glycoside and a diuretic in case of heart failure; in case of bronchospasm, administer a beta-2 agonist inhaler (medicines to dilate the bronchi). Doses of 0.25 to 3 mg of atropine should be administered intravenously to relieve bradycardia. To improve circulation, an initial dose of 5 to 10 mcg of noradrenaline should be administered intravenously, preferably to isoprenaline, repeated as needed.

Alternatively, noradrenaline can be infused at a rate of 5 mcg per minute until a satisfactory response is achieved.

In severe overdose, glucagon should be administered intravenously, preferably. An initial dose of 5 to 10 mg should be administered in glucose or saline, followed by an intravenous infusion of 5 mg/hour or as needed to maintain cardiac performance.

Oliguric renal failure has been described after massive oral overdose of labetalol. In one case, the use of dopamine to increase blood pressure may have worsened renal failure.

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

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

4. Possible side effects

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

Trandate is generally well tolerated. Postural hypotension may occur if patients are allowed to stand up before 3 hours have passed after administration.

Rare cases of hypersensitivity have been described, including: rash, pruritus, angioedema, and dyspnea.

There have also been some cases of nasal congestion.

Rare cases of elevated liver function tests, jaundice (yellowing of the skin, both hepatocellular and cholestatic), and hepatitis (inflammation of the liver) and liver necrosis (death of liver tissue) have been reported. These signs and symptoms are usually reversible when treatment is discontinued.

Some cases of bradycardia and cardiac block have been described.

Frequency not known (cannot be estimated from the available data): pain in the nipples has been described, a decrease in blood flow to the nipples, which can cause numbness, paleness, and pain in the nipples (Raynaud's phenomenon).

If you think any of the side effects you are experiencing are serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

5. Storage of Trandate

Keep this medicine out of the sight and reach of children.

Store in the original package to protect from light.

Do not use Trandate after the expiry date stated on the package after EXP. The expiry date is the last day of the month stated.

Medicines should not be disposed of via wastewater or household waste. Return any unused medicine to a pharmacy for proper disposal. This will help protect the environment.

6. Contents of the pack and other information

Composition of Trandate

• The active ingredient is labetalol hydrochloride. Each 20 ml ampoule contains 100 mg of labetalol hydrochloride.
• The other ingredients (excipients) are: sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Appearance of the product and pack contents

Pack of 5 glass ampoules of 20 ml with 100 mg of labetalol hydrochloride.

Other presentations

Trandate 100 mg tablets: Pack of 30 tablets.

Trandate 200 mg tablets: Pack of 30 tablets.

Marketing authorization holder and manufacturer

Kern Pharma, S.L.

Polígono Ind. Colón II

Venus, 72

08228 Terrassa (Barcelona)

This leaflet was approved in December 2021.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/.

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This information is intended only for healthcare professionals:

Trandate is compatible with the following intravenous fluids:

• 5% glucose
• 0.18% sodium chloride in 4% glucose
• 0.3% potassium chloride in 5% glucose
• Compound sodium lactate solution.

Unused mixtures should be discarded after 24 hours of preparation.

Trandate is incompatible with 4.2% sodium bicarbonate injectable solution.