Leaflet: information for the patient

Pre-par 10 mg/ml injectable solution

Ritodrine hydrochloride

Read this leaflet carefully before you start using this 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 or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before starting to use Pre-par

3. How to use Pre-par

4. Possible side effects

5. Storage of Pre-par

6. Contents of the pack and additional information

Pre-par is a medication belonging to the group of parturition inhibitors.

Pre-par contains ritodrine, which presents uterine-relaxing and contraction-inhibiting properties.

Pre-par is used in women who have unexpectedly started labor (preterm labor) between weeks 22 and 37 of gestation, to provide a brief delay in the preterm birth 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 to help improve the baby's health.

No use Pre-par:

• Hypersensitivity to the active ingredient or to any of the excipients of this medication (included in section 6).
• If you are pregnant for less than 22 weeks.
• If you suffer or have a known risk of developing ischemic heart disease (a disease characterized by a reduction in blood supply to the heart, causing symptoms such as chest pain (angina)).
• If you have ever experienced a spontaneous abortion in the first two trimesters of pregnancy.
• If you are pregnant and you or your baby present certain conditions in which prolonging the pregnancy could be dangerous (such as very high blood pressure, uterine infection, bleeding, if the placenta is covering the birth canal or is detached, or if your baby has died in the uterus).
• If you suffer from heart diseases with palpitations (for example, heart valve disease) or long-term lung disease (for example, chronic bronchitis, emphysema) that cause an increase in 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 problems with pregnancy.
• You have broken waters.
• You present any type of infection in the placenta.
• You have a lot of fluid in your lungs that causes difficulty breathing (pulmonary edema).
• You have high blood pressure.
• You have diabetes. In this case, additional blood sugar (glucose) determinations may be necessary when you are administered Pre-par.
• You present an increase in the activity of the thyroid gland (hyperthyroidism).
• You have a history of heart disease (cardiopathy) characterized by difficulty breathing, palpitations, or chest pain (angina of the heart) (if you suffer from heart diseases seeNo 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.

The prolonged administration of this medication by intravenous route is not recommended.

Use of Pre-par with other medications

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication, including those acquired without a prescription. This also includes herbal remedies. Pre-par may affect how some medications work and some medications may have effects on Pre-par.

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

• Medications to treat irregular or rapid heartbeats (such as digoxin).
• Other beta-blockers (such as atenolol or propranolol), including eye drops (such as timolol).
• Xanthines (such as theophylline or aminophylline).
• Glucocorticoids (such as prednisolone).
• Diuretics (such as furosemide).
• Medications for diabetes that reduce blood sugar (glucose) (such as insulin, metformin, and glibenclamide).
• Antidepressants of the monoamine oxidase inhibitor group.

If you are planning surgery with general anesthesia, your doctor, whenever possible, may stop administering Pre-par 6 hours before surgery to avoid possible adverse effects (such as irregular heartbeat or uterine bleeding).

Pregnancy, breastfeeding, and fertility

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

Ritodrine has been shown to cross the placental barrier. Therefore, it is recommended to monitor the newborn for possible side effects of ritodrine.

Driving and operating machines

Not applicable.

Pre-par contains sodium metabisulfitewhich may cause severe allergic reactions and bronchospasm (sudden feeling of suffocation).

This medication contains less than 23 mg (1 mmol) of sodium per ampoule, so it is considered “essentially sodium-free”.

Pre-par can be administered intravenously or intramuscularly.

This medication should never be self-administered. It will be administered by a qualified person after a careful evaluation of the balance between the benefits of Pre-par for your baby and the possible adverse effects the treatment may have on you.

Pre-par will be administered by a doctor or nurse in a facility where it is possible to continuously monitor your health and that of your baby.

In case of need, the following measures will be taken:

• Blood pressure and heart rate. Your doctor may consider reducing the dose or suspending the administration of Pre-par if your heart rate exceeds 120 beats per minute.
• Electrocardiogram (ECG, heart electrical activity).Inform your doctor immediately if you experience chest pain during treatment.If changes occur in the ECG recording and you experience chest pain, your doctor will interrupt the administration of Pre-par.
• Body water and salt balance.Inform your doctor immediately if you experience coughing or shortness of breath during treatment.Your doctor may stop the administration of Pre-par if any sign (e.g. coughing or difficulty breathing) indicates that there is fluid accumulation in your lungs (also known as pulmonary edema).
• Blood sugar level and low pH with lactate accumulation in the blood (also known as lactic acidosis).
• Blood potassium levels (low potassium levels may be associated with an irregular heartbeat risk).

The recommended dose is:

• Intravenous infusion (slow administration of a liquid through an intravenous line):The initial dose of 0.05 mg/minutes will be gradually increased according to response, at a rate of 0.05 mg/minutes every 10 minutes, until the desired results are achieved, or until adverse effects occur or the birth continues to progress despite treatment with the maximum dose of 0.35 mg/minutes. Once uterine contractions have decreased, the infusion should be continued for 12-48 hours.

• Intramuscular injection: In the absence of necessary elements for infusion, treatment can be initiated with the intramuscular injection of 1 ml (10 mg). If the obtained effect is insufficient, another 10 mg will be administered after 1 hour, followed by 10-20 mg every 2-6 hours and then every 12-48 hours. Dosing will be increased or decreased according to the patient's response or possible adverse effects.

The goal when using ritodrine in these cases is to gain the necessary time to make a definitive decision on the best way to proceed with the birth.

• Intravenous infusion: The initial dose of 0.05 mg/minutes will be rapidly increased until uterine activity is suppressed. The effective dose generally ranges from 0.15 to 0.35 mg/minutes.

If undesirable uterine motility occurs, the recommended procedure is the same as that applied in the case of premature birth threat.

For the preparation of the infusion, consult the section “Instructions for correct use of Pre-par ampoules”, at the end of this prospectus.

If you use more Pre-par than you should

The symptoms of overdose are: nausea, vomiting, tremors, tachycardia, dyspnea (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. Phone 915 620 420, indicating the medication and the amount used.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

Rare (affect 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 side effects have also been observed with all beta agonist medicines (Pre-par belongs to this group of medicines) when used to delay premature labor.

Very common (affect more than 1 in 10 people)

• Fast heart rate (tachycardia).
• Flushing (redness) of the face.
• Nausea, vomiting.
• Trembling, headache.
• Erythema (redness).

Common (affect less than 1 in 10 people)

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

Uncommon (affect less than 1 in 100 people)

• Pulmonary edema (fluid accumulation in the lungs), which may cause difficulty breathing.

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

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

-Dilation of blood vessels.

• Liver function alteration (increased transaminases), hepatitis.
• Alteration of salivary glands or parotid glands.
• Blood cell alteration (white blood cells), leukopenia, granulocytopenia.

• Very rare (may affect fewer than 1 in 10,000 patients)
• vasculitis (inflammation of blood vessels).
• Epilepsy.
• Anaphylactic shock (severe allergic reaction).
• Increased enzymes (creatine phosphokinase).
• Rhabdomyolysis.

The most frequent adverse reactions of Pre-par are correlated with 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 an appropriate adjustment of the dose. These reactions usually resolve with the suspension 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 that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

Do not store at a temperature above 86°F (30°C).

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

Do not use this medication after the expiration date that appears on the box after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if you observe precipitation or discoloration in the vials.

Composition of Pre-par

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

Aspect of the product and content of the package

Package containing 3 glass ampoules of transparent type I with 5 ml of transparent solution.

Holder of the marketing authorization and responsible for manufacturing

Reig Jofre, S.A.

Gran Capitán, 10 - 08970 Sant Joan Despí (Barcelona)

Date of the last review of this leaflet: August 2017

Other sources of information

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

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This information is intended solely for doctors or healthcare professionals:

Instructions for correct use of Pre-par ampoules

Preparation of the infusion:

Administration with 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 colorless. Administer according to the specified speed in the section “How to use Pre-par”.

Administration without 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 colorless. Administer according to the specified speed in the posology “How to use Pre-par”, considering that 20 drops of the prepared solution are equivalent to 1 ml.

The diluent fluid should normally be 5% dextrose solution because with saline diluents, the probability of pulmonary edema increases. Saline diluents will be reserved for cases where dextrose solution is medically contraindicated, for example, in diabetes mellitus.