Leaflet: information for the user

Trandate 5 mg/ml injectable solution

Labetalol hydrochloride

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you and should not be given to others, even if they have the same symptoms of the disease, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet.

1. What Trandate is and for what it is used

2. What you need to know before starting to use Trandate

3. How to use Trandate

4. Possible side effects

5. Storage of Trandate

6. Contents of the pack and additional information

Trandate belongs to a group of medications known as 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 a hypotensive technique is indicated
• Hypertensive episodes (high blood pressure) following acute myocardial infarction.

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

No use Trandate

- If you are allergic to hydrochloride labetalol or to any other component of Trandate.

- If you have second- and third-degree atrioventricular block (heart 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 airway obstruction.

- In case of hypertension (high blood pressure), after acute myocardial infarction, when there is peripheral vasoconstriction that suggests low cardiac output.

Warnings and precautions

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

No discontinuation of Trandate treatment is necessary 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 allergen (substance that can cause allergic reactions) taking β-blockers (medications 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 medication have not been established in children.

Interaction of Trandate with other medications

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

You should exercise special caution when administering Trandate simultaneously with the following medications:

Class I antiarrhythmic agents or calcium channel blockers of the verapamil type (medications used to suppress or prevent alterations in heart rhythm).

Trandate may potentiate the hypotensive effects of halothane.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before using any medication.

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

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 operating machinery

No effect on the ability to drive or operate machinery has been described due to the use of this medication.

Use in athletes

It is reported to athletes that this medication contains a component that may result in a positive analytical result in doping control as positive.

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

If you estimate that the action of Trandate is too strong or too weak, inform your doctor or pharmacist.

Trandate is indicated for use by intravenous route in hospitalized patients.

Patients should receive the medication always lying on their back or left side.

Avoid lifting the patient before 3 hours as excessive postural hypotension may appear.

Adults

Bolus Injection

If it is essential to rapidly reduce blood pressure, a dose of 50 mg should be administered by intravenous injection for 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 for approximately 6 hours, although it may be prolonged 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 or 5% glucose solution.

Hypertension in Pregnancy

Start the infusion with 20 mg/hour, and 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.

Post-Myocardial Infarction Hypertensive Episodes

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

Hypertension due to Other Causes

Infuse at a rate of approximately 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 response, at the discretion of the doctor.

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

Most patients experience a small decrease in heart rate; severe bradycardia is rare but can be controlled by injecting 1-2 mg of atropine intravenously. Respiratory function should be monitored, especially in patients with known alterations.

Once blood pressure has been adequately reduced by bolus or infusion, maintenance therapy should be replaced with Trandate tablets, 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 done 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, after 5 minutes, a satisfactory hypotension is not achieved, increments of 5-10 mg should be made 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 Trandate injection, blood pressure can be adjusted quickly and easily by altering the concentration of halothane and/or adjusting the tilt of the table. The mean duration of hypotension after 20-25 mg of Trandate is 50 minutes.

Hypotension induced by labetalol is easily reversible by injecting 0.6 mg of atropine intravenously 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 Toxicological Information Service. Phone: 91 562 04 20. It is recommended to bring the packaging and the product leaflet to the healthcare professional.

Deep cardiovascular effects such as excessive postural hypotension (decrease in blood pressure due to sudden changes in position) and, sometimes, bradycardia (decrease in heart rate) are expected. Patients should remain lying down in a supine position with their legs elevated. Gastric lavage or induction of vomiting within the first few hours of ingestion is justified; use a cardiac glycoside (medication to control heart rhythm) and a diuretic (medication to increase fluid elimination) in case of cardiac failure; administer a β2 agonist in aerosol (medication to dilate bronchi) in case of bronchospasm. Give 0.25 to 3 mg of atropine intravenously to alleviate bradycardia. To improve circulation, administer an initial dose of 5 to 10 mcg of noradrenaline intravenously, preferably over isoprenaline, repeating according to response.

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 in glucose or saline should be followed by an intravenous infusion of 5 mg/hour or as needed to maintain cardiac performance.

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

Hemodialysis eliminates less than 1% of labetalol chloride from the circulation.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

Like all medications, Trandate may have adverse effects, although not everyone will experience them.

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

Among rare cases of hypersensitivity, the following have been described: rash, pruritus, angioedema, and dyspnea.

There have also been some cases of nasal congestion.

Rare cases of elevated liver function tests, jaundice (yellow discoloration of the skin, both hepatocellular and cholestatic), hepatitis (inflammation of the liver), and hepatic necrosis (death of liver tissue) have been described. These signs and symptoms are generally reversible upon discontinuation of treatment.

Some cases of bradycardia and cardiac block have been described.

Unknown frequency (cannot be estimated from available data) has been described: nipple pain: intermittent reduction of blood flow to the nipples, which can cause numbness, pallor, and pain in the nipples (Raynaud's phenomenon).

If you consider any of the adverse effects you are experiencing to be severe or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

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

Store in the original packaging to protect it from light.

Do not use Trandate after the expiration date indicated on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medicines at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medicines. By doing so, you will help protect the environment.

Composition of Trandate

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

Appearance of the product and content of the container

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

Other presentations

Trandate 100 mg tablets: Container with 30 tablets.

Trandate 200 mg tablets: Container with 30 tablets.

Holder of the marketing authorization and responsible for manufacturing

Kern Pharma, S.L.

Polígono Ind. Colón II

Venus, 72

08228 Terrassa (Barcelona)

This prospectus was approved in December 2021.

The detailed and updated information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/.

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This information is intended solely for doctors or healthcare professionals:

Trandate is compatible with the following intravenous fluids:

• Glucose 5%
• Sodium chloride 0.18% in glucose 4%
• Potassium chloride 0.3% in glucose 5%
• Lactate sodium compound solution.

Discard unused mixtures after 24 hours of preparation.

Trandate is incompatible with sodium bicarbonate injectable solution 4.2% p/v.