Pre-Par 10 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Pre-par 10 mg/ml injection solution

Ritodrine hydrochloride

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Pre-par is and what it is used for

Pre-par is a medicine belonging to the group of tocolytic agents (medicines that inhibit labour).

Pre-par contains ritodrine, which has uterine relaxant properties and inhibits uterine contractions.

Pre-par is used in women who have unexpectedly started labour (preterm labour) between weeks 22 and 37 of pregnancy, in order to provide a short delay in the premature delivery of the baby.

You will receive Pre-par for a maximum of 48 hours. This will give your doctor or midwife time to take additional measures that help improve the baby's health.

2. What you need to know before using Pre-par

Do not use Pre-par:

• If you are hypersensitive to the active substance or to any of the excipients of this medicine (listed in section 6).
• If you are pregnant and less than 22 weeks pregnant.
• If you have or are known to be at risk of developing ischemic heart disease (a condition characterized by reduced blood supply to the heart, causing symptoms such as chest pain (angina)).
• If you have ever had a spontaneous miscarriage during the first two trimesters of pregnancy.
• If you are pregnant and you or your baby have certain conditions in which prolonging the pregnancy could be dangerous (such as very high blood pressure, uterine infection, bleeding, placenta covering the birth canal or being detached, or if your baby has died inside the uterus).
• If you have heart disease with palpitations (e.g., heart valve disease) or chronic lung disease (e.g., chronic bronchitis, emphysema) causing increased blood pressure in the lungs (pulmonary hypertension).

Warnings and precautions

Consult your doctor or nurse before starting to use Pre-par if:

• You have had complications during pregnancy.
• Your water has broken.
• You have any type of infection in the placenta.
• You have excess fluid in the lungs causing difficulty breathing (pulmonary edema).
• You have high blood pressure.
• You have diabetes. In this case, additional blood sugar (glucose) monitoring may be required when Pre-par is administered.
• You have overactivity of the thyroid gland (hyperthyroidism).
• You have a history of heart disease (cardiopathy) characterized by difficulty breathing, palpitations, or chest angina (if you have heart diseases, see Do not use Pre-par).
• You are more than 37 weeks pregnant.

Your doctor will monitor your heart and your unborn baby. Additionally, your doctor may perform blood tests to monitor any changes that may occur in your blood.

Prolonged intravenous administration of this medicine is not recommended.

Use of Pre-par with other medicines

Tell your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription. This also includes herbal medicines. Pre-par may affect how some medicines work, and some medicines may have effects on Pre-par.

In particular, inform your doctor or nurse if you are taking:

• Medicines to treat irregular or rapid heartbeat (such as digoxin).
• Other beta-blocking medicines (such as atenolol or propranolol), including eye drops (such as timolol).
• Xanthines (such as theophylline or aminophylline).
• Steroids (such as prednisolone).
• Diuretics (such as furosemide).
• Medicines for diabetes that lower blood sugar (glucose) (such as insulin, metformin, and glibenclamide).
• Antidepressant medicines known as monoamine oxidase inhibitors.

If you are scheduled for surgery under general anesthesia, your doctor may, whenever possible, stop administration of Pre-par 6 hours before surgery to avoid potential adverse effects (e.g., irregular heartbeat or uterine bleeding).

Pregnancy, breastfeeding, and fertility

Pre-par is not recommended during the first 22 weeks of pregnancy.

It has been shown that ritodrine crosses the placental barrier. Therefore, it is advisable to monitor the newborn for possible side effects of ritodrine.

Driving and use of machines

Not applicable.

Pre-par contains sodium metabisulfite, which may cause severe allergic reactions and bronchospasm (sudden sensation of suffocation).

This medicine contains less than 23 mg (1 mmol) of sodium per ampoule and is therefore considered “essentially sodium-free”.

3. How to use Pre-par

Pre-par can be administered intravenously or intramuscularly.

You must never administer this medicine to yourself. It will always be administered by a qualified healthcare professional, following careful assessment of the balance between the benefits of Pre-par for your baby and the potential adverse effects the treatment may have on you.

Pre-par will be administered by a doctor or nurse in a facility where continuous monitoring of your health and that of your baby is possible.

If necessary, the following measures will be taken:

• Blood pressure and heart rate monitoring. Your doctor may consider reducing the dose or stopping administration of Pre-par if your heart rate exceeds 120 beats per minute.
• Electrocardiogram (ECG, electrical activity of your heart). Inform your doctor immediately if you experience chest pain during treatment. If changes in the ECG recording occur along with chest pain, your doctor will discontinue administration of Pre-par.
• Monitoring of fluid and electrolyte balance in your body. Inform your doctor immediately if you experience cough or shortness of breath during treatment. Your doctor may stop administration of Pre-par if any signs (e.g., cough or difficulty breathing) suggest fluid accumulation in your lungs (also known as pulmonary edema).
• Blood glucose (sugar) levels and low body pH with accumulation of lactate in the blood (also known as lactic acidosis).
• Blood potassium levels (low potassium levels may be associated with an increased risk of irregular heartbeat).

The recommended dose is:

• Short-term treatment of uncomplicated preterm labour

• Intravenous infusion (slow administration of a liquid intravenously): The initial dose is 0.05 mg/minute, gradually increased according to response, by increments of 0.05 mg/minute every 10 minutes, until the desired effect is achieved or until adverse effects occur, or until labour progresses despite treatment with the maximum dose of 0.35 mg/minute. Once uterine contractions have decreased, the infusion should be continued for 12–48 hours.

• Intramuscular injection: If the necessary equipment for infusion is not available, treatment may be initiated with an intramuscular injection of 1 ml (10 mg). If the effect is insufficient, another 10 mg dose may be given after 1 hour, followed by 10–20 mg every 2–6 hours, and subsequently every 12–48 hours. Dosage should be adjusted upward or downward according to the patient's response or the possible occurrence of adverse effects.

• Acute fetal distress

The aim of using ritodrine in these cases is to gain sufficient time to make a definitive decision on the best mode of delivery.

• Intravenous infusion: Initial dose of 0.05 mg/minute, rapidly increased until uterine activity is suppressed. The effective dose generally ranges between 0.15 and 0.35 mg/minute.

• Prevention of preterm birth following surgical procedures

If undesirable uterine motility occurs, the recommended procedure is the same as that used in cases of threatened preterm labour.

For instructions on preparing the infusion, refer to the section "Instructions for correct use of Pre-par ampoules" at the end of this leaflet.

If you use more Pre-par than you should

Symptoms of overdose include: nausea, vomiting, tremors, tachycardia, and dyspnoea (difficulty breathing). In case of overdose, symptomatic treatment will be initiated.

In case of overdose or accidental ingestion, consult your doctor or pharmacist, or call the Toxicology Information Service at telephone number 915 620 420, stating the name of the medicine and the amount taken.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The possible adverse effects that Pre-par may cause are:

Rare (affects less than 1 in 1,000 people)

• Chest pain (due to heart problems, such as angina). Inform your doctor or nurse immediately if you experience this symptom.

The following adverse effects have also been observed with all beta-agonist type medicines (Pre-par belongs to this group of medicines) when used to delay premature labour.

Very common (affects more than 1 in 10 people)

• Fast heartbeat (tachycardia).
• Flushing (reddening) of the face.
• Nausea, vomiting.
• Tremor, headache.
• Erythema (redness).

Common (affects less than 1 in 10 people)

• Strong heartbeats (palpitations).
• Low blood pressure which may cause dizziness or vertigo.
• Low potassium levels in the blood which may cause muscle weakness, thirst, or “pins and needles”.
• Sweating, skin rash.
• Nervousness, agitation, restlessness, emotional lability, anxiety.
• Fever, general malaise.

Uncommon (affects less than 1 in 100 people)

• Fluid accumulation in the lungs (pulmonary edema), which may cause difficulty breathing.

Rare (affects less than 1 in 1,000 people)

• Unusual or irregular heartbeats.

• High levels of sugar (glucose) and/or lactic acid in the blood.

• Blood vessel dilation.

• Liver function disturbance (increased transaminases), hepatitis.

• Salivary gland or parotid gland disturbance.

• Blood cell abnormalities (white blood cells), decreased white blood cells (leucopenia), decreased neutrophils (agranulocytosis).

• Very rare (may affect less than 1 in 10,000 patients)

• Inflammation of blood vessels (vasculitis).

• Epilepsy.

• Anaphylactic shock (severe allergic reaction).

• Increased enzyme levels (creatine phosphokinase).

• Rhabdomyolysis.

The most frequent adverse reactions of Pre-par are related to the pharmacological activity of beta-agonists and can be limited or avoided by close monitoring of blood circulation parameters such as blood pressure and heart rate, and appropriate dose adjustment. These reactions usually resolve upon discontinuation of treatment.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Pre-par

Do not store above 30°C.

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

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date is the last day of the month indicated.

Do not use this medicine if you observe precipitation or discoloration in the ampoules.

6. Contents of the pack and other information

Composition of Pre-par

• The active substance is ritodrine hydrochloride. Each ml of solution contains 10 mg of ritodrine hydrochloride.
• The other components (excipients) are: acetic acid, sodium hydroxide, sodium metabisulfite (E-223), sodium chloride, water for injections.

Appearance of the product and contents of the pack

Pack containing 3 clear glass ampoules of type I, each containing 5 ml of clear solution.

Marketing Authorization Holder and Manufacturer

Laboratorio Reig Jofre, S.A.
Gran Capitán, 10 - 08970 Sant Joan Despí (Barcelona)

Date of the most recent revision of this summary: August 2017

Other sources of information

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended exclusively for physicians or healthcare professionals:

Instructions for the correct use of Pre-par ampoules

Preparation of the infusion:

Administration using an infusion pump: Dilute 150 mg of ritodrine (3 ampoules) in 50 ml of 5% dextrose. The resulting concentration is 3 mg/ml and the solution is colourless. Administer according to the rate specified in section "How to use Pre-par".

Administration without an infusion pump: Dilute 150 mg (3 ampoules) in 500 ml of 5% dextrose. The resulting concentration is 0.3 mg/ml and the solution is colourless. Administer according to the rate specified in the dosage section "How to use Pre-par", considering that 20 drops of the prepared solution are equivalent to 1 ml.

The diluent should normally be 5% dextrose solution, since saline diluents increase the risk of pulmonary edema. Saline diluents should be reserved for cases in which dextrose solution is medically contraindicated, for example, in patients with diabetes mellitus.