Labetalol S.A.L.F.: detailed information

Package leaflet: Information for the patient

Labetalolo S.A.L.F. 5 mg/ml injection solution/for infusion

labetalol hydrochloride
Equivalent medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you would like more information or advice, consult your doctor, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See Section 4.

Contents of this leaflet:

What Labetalolo S.A.L.F. is and what it is used for
What you need to know before using Labetalolo S.A.L.F.
How to use Labetalolo S.A.L.F.
Possible side effects
How to store Labetalolo S.A.L.F.
Contents of the pack and other information

1. What Labetalolo S.A.L.F. is and what it is used for

Labetalolo S.A.L.F. contains the active substance labetalolo. This medicine is used in the
treatment of severe hypertension (high blood pressure), including severe hypertension in
pregnancy (pregnancy-induced high blood pressure), when rapid control of blood pressure is
required. Labetalolo S.A.L.F. may also be used to control blood pressure during anaesthesia.
Labetalolo belongs to a group of medicines called alpha and beta-blockers. These medicines
lower blood pressure by blocking receptors in the cardiovascular system (circulatory system),
resulting in a reduction of blood pressure in the blood vessels away from the heart.

2. What you need to know before using Labetalolo S.A.L.F.

Do not use Labetalolo S.A.L.F.

if you are allergic to labetalol or to any of the other ingredients of this medicine (listed in section 6)
if you have heart conditions such as heart block or sick sinus syndrome (unless you have a pacemaker), cardiogenic shock, or uncontrolled heart failure
if you have low blood pressure
if you have a very slow heartbeat (severe bradycardia)
if you suffer from a condition known as Prinzmetal's angina
if you suffer from asthma or a similar lung disease (obstructive respiratory diseases)
if you have a particular type of adrenal gland tumour (pheochromocytoma) that has not been adequately treated with appropriate medication (see section "Warnings and Precautions")

Warnings and Precautions
Talk to your doctor or pharmacist before being administered Labetalolo S.A.L.F.:

if you have impaired liver function or liver damage
if you suffer from reduced kidney function
if you have peripheral vascular disease, for example Raynaud’s syndrome, intermittent claudication
if you suffer from diabetes mellitus (type 1 or type 2)
if you suffer from hyperthyroidism (thyrotoxicosis, hyperthyroidism)
if you have previously experienced a severe allergic reaction (anaphylaxis) to any substance
if you suffer from heart failure or other heart conditions (for example: poor left ventricular function, first-degree atrioventricular block)
if you are about to undergo surgery
if you suffer from metabolic acidosis (when the body produces too much acid or when the kidneys do not remove enough acid from the body) and pheochromocytoma
if you suffer from a condition called ischemic heart disease
if you have lung or respiratory system problems
If you develop a slow heart rate (bradycardia) as a result of using Labetalolo S.A.L.F., your doctor may reduce the dose. If you develop skin rashes and/or dry eyes or any type of allergic reaction after using Labetalolo S.A.L.F., inform your doctor, who may decide to reduce or stop treatment.
Surgery
If you are undergoing surgery requiring general anaesthesia, you must inform the surgeon that you are taking Labetalolo S.A.L.F. before the operation, as labetalol may mask the signs of sudden blood loss. Labetalol may affect the pupils during cataract surgery. Inform your ophthalmic surgeon about your current treatment with this medicine before surgery. Do not stop taking labetalol before surgery unless instructed by your surgeon.
Laboratory tests
This medicine may interfere with certain medical examinations/laboratory tests and may cause false results. Make sure that laboratory staff and all your doctors know that you are taking this medicine.

For athletes: using this medicine without therapeutic need constitutes doping
and may lead to a positive anti-doping test.
Children and adolescents
This medicine must not be administered to children and adolescents under 18 years of age.
Other medicines and Labetalolo S.A.L.F.
Inform your doctor if you are taking, have recently taken, or might take any other medicines before being administered Labetalolo S.A.L.F. This is particularly important for the following medicines:

NSAIDs (non-steroidal anti-inflammatory drugs), for example: sulindac or indomethacin, used to treat pain and inflammatory conditions
digoxin (a heart medicine)
adrenaline, which may be used to treat severe anaphylactic (allergic) reactions
medicines for heart disorders (Class I antiarrhythmics, for example disopyramide and quinidine) and (Class II antiarrhythmics, for example amiodarone)
other medicines that lower blood pressure (calcium channel blockers such as verapamil)
general anaesthetics (used in surgery for narcosis)
tricyclic antidepressants, for example: imipramine (used to treat depression)
oral antidiabetics, for example: biguanides (e.g. metformin), sulfonylureas (e.g. glimepiride), meglitinides (e.g. repaglinide), α-glucosidase inhibitors (e.g. acarbose), used to lower blood glucose levels
ergotamine derivatives, for example: ergotamine or dihydroergotamine, used to treat migraine
cholinesterase inhibitors, for example donepezil, galantamine or rivastigmine, used to treat mild cognitive impairment, Alzheimer’s disease and Parkinson’s disease
nitrates, antipsychotics (e.g. phenothiazine derivatives, chlorpromazine) and other antipsychotics, antidepressants
clonidine, used to treat high blood pressure

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, ask your doctor for advice before using Labetalolo S.A.L.F. The fetus may be affected, but Labetalolo S.A.L.F. may be used during pregnancy when rapid blood pressure control is required.
Labetalolo S.A.L.F. is excreted in breast milk in small amounts. If you are breastfeeding, consult your doctor before using Labetalolo S.A.L.F.
Cases of nipple pain and Raynaud’s phenomenon of the nipple have been reported (see section 4).
Driving and using machines
Not applicable.
Labetalolo S.A.L.F. contains monohydrate glucose
1 ml contains 49.5 mg of monohydrate glucose. This should be taken into consideration by patients with diabetes mellitus.

3. How to use Labetalolo S.A.L.F.

Labetalolo S.A.L.F. must always be used as directed by your doctor. Labetalolo S.A.L.F. is administered intravenously in hospitalized patients and must be given by healthcare personnel.
It is important that you remain lying down during the injection. You will be asked to remain lying down for three hours after treatment with Labetalolo S.A.L.F., as the medicine may cause dizziness (due to low blood pressure) if you move to an upright position sooner.
Labetalolo S.A.L.F. can be administered either as an intravenous bolus injection (where the medicine is injected directly into a vein) or as a continuous intravenous infusion (where the medicine is delivered into a vein over a longer period of time). Your doctor will decide the method of administration of Labetalolo S.A.L.F. and will determine the dose of Labetalolo S.A.L.F. to be administered.
If you use more Labetalolo S.A.L.F. than you should
Symptoms of labetalol (Labetalolo S.A.L.F.) overdose include severe dizziness when moving to an upright position (sitting or standing) and, occasionally, slow heart rate felt as reduced heartbeat (bradycardia).
If you think you have been given too much of the medicine, inform your doctor or nurse immediately.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Common: occurs in less than 1 out of 10 people

congestive heart failure
dizziness caused by low blood pressure when standing up too quickly from a sitting position, or moving rapidly from a lying to a sitting position (postural hypotension). This may occur within three hours after injection of Labetalolo S.A.L.F. and is usually temporary, occurring during the first weeks of treatment
nasal congestion (stuffy nose), typically a temporary effect occurring during the first weeks of treatment
increased liver function tests. This effect is usually reversible after discontinuation of the medicine
erectile dysfunction (impotence)
allergic reactions (hypersensitivity), which may also include skin rashes (of varying severity), itching, shortness of breath, and very rarely fever or rapid swelling of the skin.

Uncommon: occurs in less than 1 out of 100 people

constriction of the lower airways (bronchospasm)

Rare: occurs in less than 1 out of 1,000 people

slow heart rate felt as slow beats (bradycardia)

Very rare: occurs in less than 1 out of 10,000 people

interruption of the electrical impulses controlling the heartbeat (cardiac arrest)
worsening of symptoms of Raynaud's syndrome (cold fingers due to impaired blood circulation)
inflammation of the liver (hepatitis), which is usually reversible after stopping treatment with Labetalolo S.A.L.F.
hepatocellular jaundice (skin and whites of the eyes turn yellow), cholestatic jaundice (symptoms include fatigue and nausea, followed by itching, dark urine and jaundice, and may include a skin rash or fever), and hepatic necrosis (liver tissue damage). These symptoms are generally reversible after discontinuation of treatment with Labetalolo S.A.L.F.

Not known (frequency cannot be estimated from the available data)

nipple pain
intermittent decrease in blood flow to the nipples, which may cause numbness, paleness, and tenderness (Raynaud's phenomenon)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at the website
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.

5. How to store Labetalolo S.A.L.F.

Keep out of the sight and reach of children.
This medicinal product does not require any special storage conditions.
Do not use this medicinal product after the expiry date stated on the vial and packaging after EXP.
The expiry date refers to the last day of that month.
Do not use this medicinal product if signs of deterioration are observed.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C, 30°C and 40°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2 - 8 °C.
Do not dispose of any medicinal product via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Labetalolo S.A.L.F. contains

The active substance is labetalol hydrochloride. One ml of solution contains 5 mg of labetalol hydrochloride.
The other ingredients are monohydrate glucose, disodium edetate, and water for injections; sodium hydroxide and hydrochloric acid (for pH adjustment).

Description of the appearance of Labetalolo S.A.L.F. and contents of the pack
A clear, colourless solution in a transparent glass vial. Each pack contains 5 vials of 20 ml. Each vial contains 100 mg of labetalol hydrochloride (5 mg/ml).
Marketing Authorisation Holder and Manufacturer
S.A.L.F. S.p.A. Laboratorio Farmacologico Via Marconi, 2
24069 Cenate Sotto (BG) - Italy
Tel. +39 035 940097
INFORMATION FOR HEALTHCARE PROFESSIONALS
The following information is intended for healthcare professionals only:
Administration:
Labetalolo S.A.L.F. is administered intravenously in hospitalised patients and must be given by healthcare personnel. The medicine should be administered with patients lying in the supine position or in the left lateral position. Patients should not be returned to the upright position within three hours after intravenous administration of labetalol, as marked postural hypotension may occur. Blood pressure and heart rate should be monitored after injection and during infusion. In most patients, there is a slight decrease in heart rate; severe bradycardia is uncommon, but if it occurs, it can be treated by intravenous injection of 1–2 mg of atropine. Respiratory function should be closely monitored, especially in patients with pre-existing respiratory impairment. Injectable labetalol vials can be administered either as an intravenous bolus injection or by intravenous infusion. Injectable labetalol has been administered to patients with uncontrolled hypertension who were already receiving other antihypertensive agents, including beta-blockers, without adverse effects.
Oral administration for maintenance treatment:
Once blood pressure has been adequately reduced by bolus injection or infusion, maintenance therapy with labetalol tablets should be initiated at an initial dosage of 100 mg twice daily.
Dosage: Labetalolo S.A.L.F.:

Adults:

Indication	Dose
Severe hypertension	Bolus injection: If it is essential to reduce blood pressure rapidly, a dose of 50 mg should be administered intravenously (over no less than one minute), and repeated at 5-minute intervals if necessary, until a satisfactory response is obtained. The total dose must not exceed 200 mg. The maximum effect usually occurs within 5 minutes, and the duration of action is typically about 6 hours, although it may last up to 18 hours.
Severe hypertension	Intravenous infusion: A solution of 1 mg/ml of labetalol should be used, i.e., the contents of two 20 ml vials (200 mg) diluted to 200 ml with intravenous solutions indicated in the 'Compatibility' section. The infusion rate should normally be about 160 mg/h, but may be adjusted according to the patient's response at the physician's discretion. The effective dose usually ranges between 50 and 200 mg, but the infusion should be continued until a satisfactory response is achieved. Higher doses may be required to achieve a satisfactory response, especially in patients with pheochromocytoma. In cases of severe hypertension during pregnancy, a slower infusion rate should be used, gradually increasing the rate. The infusion should initially start at 20 mg/h, then doubled every 30 minutes until a satisfactory response is achieved or until a rate of 160 mg/h is reached.
Achievement of controlled hypotension during anesthesia	To achieve controlled hypotension during anesthesia, the recommended initial dose of injectable labetalol is 10 to 20 mg intravenously, depending on the patient's age and condition. If a satisfactory level of hypotension is not achieved within 5 minutes, increments of 5 to 10 mg may be administered until the desired blood pressure level is reached. The average duration of hypotension achieved with a dose of 20 to 25 mg of labetalol is 50 minutes.
Hypertension due to other causes	The infusion rate should be 120–160 mg/h until a satisfactory response is achieved; the infusion should then be discontinued. The effective dose usually ranges between 50 and 200 mg, but higher doses may be required, especially in patients with pheochromocytoma.

Paediatric population: The safety and efficacy of labetalol have not been established in paediatric patients aged 0 to 18 years. No data are available.
Compatibility: Labetalol must be diluted only with compatible intravenous infusion solutions under aseptic conditions. Injectable labetalol is compatible with the following intravenous infusion solutions:
5% Dextrose BP
0.18% Sodium Chloride and 4% Dextrose BP
0.3% Potassium Chloride and 5% Dextrose BP
Sodium Lactate Compound BP (Ringer's Lactate)
Sodium Chloride 0.9%

Incompatibility:
Injectable labetalol has been found to be incompatible with Sodium Bicarbonate Injection BP 4.2%
Weight/Volume.
Overdose:
Symptoms and signs:
Pronounced cardiovascular effects can be expected, for example marked hypotension sensitive
to postural changes and, in some cases, bradycardia. Renal failure with oliguria has been reported
following massive oral overdose of labetalol. In one case, the use of dopamine to increase blood pressure may have worsened renal failure.
Treatment:
Patients should be placed in the supine position with legs elevated. Parenteral therapy with adrenergic/anticholinergic agents should be administered to improve circulation.
Haemodialysis removes less than 1% of labetalol hydrochloride from the circulation.