Plasil

Package leaflet: Information for the patient

PLASIL

10 mg tablets
metoclopramide
Read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Plasil is and what it is used for

Plasil is a medicine used to treat vomiting (antiemetic). It contains a drug called "metoclopramide" and belongs to a group of medicines known as "Drugs for gastrointestinal functional disorders – Prokinetics".
It acts on a part of the brain involved in preventing the sensation of nausea or vomiting.

Adult population
Plasil is indicated in adults:

• for the prevention of nausea and vomiting that may occur after chemotherapy;
• for the prevention of nausea and vomiting caused by radiotherapy;
• for the treatment of nausea and vomiting, including nausea and vomiting associated with acute migraine. Metoclopramide may be taken together with oral analgesics (painkillers) during acute migraine to improve their absorption and thereby help the analgesics work more effectively.

Paediatric population
Plasil is indicated in children (aged between 1 and 18 years) when other treatments are not effective or cannot be used, for the prevention of nausea and vomiting that may occur after chemotherapy.

2. What you should know before taking Plasil

Do not take Plasil

• if you are allergic to metoclopramide or to any of the other ingredients of this medicine (listed in section 6);
• if you have bleeding, obstruction, or perforation in the stomach or intestine;
• if you have or may have a rare tumor of the adrenal glands located near the kidneys (pheochromocytoma);
• if you have ever experienced involuntary muscle contractions (tardive dyskinesia) when previously treated with metoclopramide or neuroleptic medicines;
• if you suffer from epilepsy (with increased frequency and intensity of seizures);
• if you have Parkinson's disease;
• if you are taking levodopa (a medicine for Parkinson's disease) or other medicines called dopaminergic agonists (see below "Other medicines and Plasil");
• if you have ever had a blood hemoglobin disorder (methemoglobinemia) or deficiency of a substance called NADH-cytochrome-b5 reductase;
• if you have glaucoma (increased pressure inside the eyeball).

Do not use Plasil in children under 1 year of age (see below "Children and adolescents").
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Plasil:

• if you have conduction disorders of the heart (prolonged QT interval) or any other heart problems (severe bradycardia, cardiac arrest);
• if you have imbalances in blood electrolytes such as potassium, sodium, or magnesium;
• if you are taking other medicines known to affect heart rhythm;
• if you have neurological disorders and are taking other medicines acting on the central nervous system;
• if you have liver or kidney problems (renal insufficiency or severe hepatic insufficiency). In such cases, your doctor may reduce the dose (see section 3).

Your doctor may perform blood tests. If a blood hemoglobin disorder (methemoglobinemia) occurs, treatment must be immediately and permanently discontinued.
Treatment should not exceed 3 months due to the risk of involuntary muscle spasms. If such symptoms occur, you must stop treatment.
You must wait at least 6 hours between each dose of metoclopramide, even if vomiting occurs and the dose is expelled, to avoid overdose.
Use of Plasil may lead to increased levels of a substance called "prolactin". Your doctor will consider this possibility, especially if you have a breast tumor or a benign tumor of the gland called "pituitary" (pituitary adenoma) that causes prolactin production.
Children and adolescents
In children and young adults, uncontrolled movements (extrapyramidal disorders) may occur. The medicine must not be used in children under 1 year of age due to the higher risk of uncontrolled movements (see above "Do not take Plasil").
Other medicines and Plasil
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
This is important because some medicines may affect how Plasil works, or Plasil may affect how other medicines work. These include:

• levodopa or other medicines used to treat Parkinson's disease (dopaminergic agonists) (see above "Do not take Plasil");
• anticholinergics (medicines used to relieve stomach cramps or spasms);
• morphine derivatives (medicines used to treat severe pain);
• medicines that depress the central nervous system (morphine derivatives, anxiolytics, sedative antihistamines, sedative antidepressants, barbiturates, clonidine and related medicines);
• medicines used to treat psychiatric disorders (neuroleptics) and serotonergic medicines;
• digoxin (a medicine used to treat heart failure);
• cyclosporine (a medicine used to treat certain immune system disorders);
• mivacurium and suxamethonium (medicines used to relax muscles);
• fluoxetine and paroxetine (medicines used to treat depression);
• cisplatin: possible increased renal toxicity;
• insulin: your doctor may need to adjust the dose;
• a medicine called apomorphine, as Plasil reduces its effects on the nervous system;
• rifampicin: a medicine used to treat tuberculosis and other infections; if taken simultaneously, it may reduce the amount of metoclopramide in the blood.

Plasil and alcohol
You must not consume alcohol during treatment with metoclopramide, as it increases the sedative effect of Plasil.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Plasil may be used during pregnancy if necessary, but administration should be avoided towards the end of pregnancy, as it may cause movement disorders in the newborn (extrapyramidal syndrome). If you use Plasil, your doctor will monitor your baby through neonatal monitoring.
Your doctor will decide whether or not you should take this medicine.
Breastfeeding
Plasil is not recommended during breastfeeding, as it passes into breast milk in low concentrations and adverse effects in the breastfed infant cannot be ruled out. Therefore, if you are breastfeeding, your doctor will consider discontinuing Plasil.
Driving and using machines
You may feel drowsy, dizzy, or experience uncontrolled spasms, contractions, convulsive movements, or unusual muscle tone causing body distortions after taking Plasil.
These symptoms may affect your vision and may also impair your ability to drive or operate machinery.

3. How to take Plasil

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
All indications (adult patients)
The recommended single dose is 10 mg, repeated up to a maximum of three times daily.
The maximum recommended daily dose is 30 mg or 0.5 mg/kg body weight.
The maximum recommended duration of treatment is 5 days.
For the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) (paediatric patients aged
between 1 and 18 years)
The recommended dose is 0.1 to 0.15 mg/kg body weight, repeated up to 3 times daily administered
orally. The maximum dose in a 24-hour period is 0.5 mg/kg body weight.
Dosing table

Do not take this medicine for more than 5 days for the prevention of delayed nausea and vomiting that may occur after chemotherapy.
Plasil tablets are not suitable for use in children weighing less than 61 kg.
Other pharmaceutical forms/concentrations may be more appropriate for administration.

Method of administration
You must wait at least 6 hours between each dose of metoclopramide, even in case of vomiting and rejection of the dose, to avoid overdose.

Elderly
The dose may need to be reduced based on renal impairment, hepatic impairment, and general health status.

Adults with renal impairment
Talk to your doctor if you have kidney problems. The dose must be reduced in case of moderate or severe renal impairment and in end-stage renal disease.

Adults with hepatic impairment
Discuss with your doctor if you have liver problems. The dose must be reduced in case of severe hepatic impairment.

Children and adolescents
Metoclopramide must not be used in children under 1 year of age (see section 2).

If you take more Plasil than you should
Contact your doctor or pharmacist immediately. You may experience uncontrollable movements (extrapyramidal symptoms), feel drowsy, have disturbances of consciousness, confusion, hallucinations, and cardiac problems. Your doctor may prescribe treatment for these symptoms, if necessary.
In case of accidental ingestion/overdose of Plasil, contact your doctor immediately or go to the nearest hospital.

If you forget to take Plasil
Do not take a double dose to make up for the forgotten dose.
If you have any doubts about the use of this medicine, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop treatment and speak to your doctor, pharmacist, or nurse immediately if you experience any of the following symptoms during treatment with this medicine:

• uncontrollable movements (often affecting the head or neck). These may occur in children or young adults, particularly when high doses are used. These symptoms usually appear at the beginning of treatment and may even occur after a single dose. The movements disappear if appropriately treated.
• High fever, high blood pressure, seizures, sweating, excessive salivation. These may be signs of a disorder called neuroleptic malignant syndrome.
• Itching or skin rashes, swelling of the face, lips, or throat, breathing difficulties. These may be signs of an allergic reaction, which can be severe.

The following side effects may occur with the frequency listed below:
Very common (may affect more than 1 in 10 people)

• feeling sleepy.

Common (may affect up to 1 in 10 people)

• depression
• uncontrollable movements such as tics, tremors, twisting movements (extrapyramidal disorders) or muscle contractions (rigidity)
• Parkinson-like symptoms (stiffness, tremors)
• feeling restless and agitated (akathisia)
• low blood pressure (particularly when administered intravenously)
• diarrhoea
• feeling weak.

Uncommon (may affect up to 1 in 100 people)

• increased levels of a hormone called prolactin, which may cause: milk production in men and women who are not breastfeeding
• irregular menstrual cycle
• hallucinations
• reduced level of consciousness
• slow heart rate (particularly when administered intravenously)
• allergic reaction
• movement disorders (dyskinesia)
• adopting abnormal postures (dystonia)
• visual disturbances and involuntary deviation of the eye.

Rare (may affect up to 1 in 1,000 people)

• confusion
• seizures (especially in epileptic patients)
• abnormal secretion of milk or milky fluid from the breasts in women who are not breastfeeding or in men (galactorrhoea).

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

• allergic reactions (such as anaphylaxis, angioedema, and urticaria) which can be severe (particularly when administered intravenously). Symptoms may include skin rash, itching, breathing difficulties, shortness of breath, swelling of the face, lips,
  throat or tongue, cold and clammy skin, palpitations, dizziness, weakness and
  fainting. Contact your doctor or another healthcare professional immediately or go
  immediately to the nearest hospital emergency department.

• abnormal levels of blood pigment, which may change skin colour (sulfhaemoglobinaemia)

• abnormal levels of methaemoglobin (a protein similar to haemoglobin) (methaemoglobinaemia)

• abnormal breast development in men (gynaecomastia)

• involuntary muscle contractions (spasms) after prolonged use, particularly in elderly patients (dyskinesia)

• high fever, high blood pressure, seizures, sweating, excessive salivation. These may be symptoms of a disorder called neuroleptic malignant syndrome

• QT interval prolongation on electrocardiogram and torsades de pointes

• cardiac arrest (particularly following injection)

• atrioventricular block and sinus arrest (particularly following injection)

• shock (severe drop in blood pressure) (particularly following injection)

• fainting (particularly when administered intravenously)

• very high blood pressure

• suicidal thoughts (suicidal ideation).

If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
The following reactions, sometimes occurring together, are more frequent when high doses are administered:

• movement problems (extrapyramidal disorders: acute dystonia and dyskinesia, parkinsonism, akathisia), even after a single dose of the medicine, particularly in children and young adults;
• drowsiness;
• reduced level of consciousness;
• confusion;
• hallucinations.

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

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Plasil contains

• The active substance is metoclopramide. One tablet contains 10.5 mg of metoclopramide hydrochloride monohydrate (equivalent to 10 mg of anhydrous substance).
• The other components are: guar gum; methylcellulose; ethylcellulose; hydrated colloidal silica; potato starch; magnesium stearate; pentaerythritol.

Description of the appearance of Plasil and package contents
Plasil is available in tablet form.
It is supplied in packs containing 24 tablets.

Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan, Italy

Manufacturer
SANOFI S.r.l.
S.S. n. 17, km. 22 – 67019 Scoppito (AQ), Italy.

Package leaflet: information for the patient

PLASIL

10 mg/10 ml syrup
metoclopramide
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Plasil is and what it is used for

Plasil is a medicine used to treat vomiting (antiemetic). It contains an active substance called
"metoclopramide" and belongs to a group of medicines known as "Drugs for functional gastrointestinal disorders – Prokinetics".
It acts on a part of the brain to prevent the sensation of nausea or vomiting.

Adult population
Plasil is indicated in adults:

• for the prevention of nausea and vomiting that may occur after chemotherapy
• for the prevention of nausea and vomiting caused by radiotherapy
• for the treatment of nausea and vomiting, including nausea and vomiting associated with acute migraine. Metoclopramide may be taken together with oral analgesics (pain-relieving medicines) during acute migraine to improve their absorption and thereby help the analgesics work more effectively.

Paediatric population
Plasil is indicated in children (aged between 1 and 18 years) when other treatments are not effective or cannot be used, for the prevention of nausea and vomiting that may occur after chemotherapy.

2. What you need to know before taking Plasil

Do not take Plasil

• if you are allergic to metoclopramide or to any of the other ingredients of this medicine (listed in section 6);
• if you have bleeding, obstruction, or perforation in the stomach or intestines;
• if you have or may have a rare tumour of the adrenal glands located near the kidneys (pheochromocytoma);
• if you have ever experienced involuntary muscle contractions (tardive dyskinesia) when previously treated with metoclopramide or neuroleptic medicines;
• if you suffer from epilepsy (with increased frequency and intensity of seizures);
• if you have Parkinson’s disease;
• if you are taking levodopa (a medicine for Parkinson’s disease) or other medicines called dopamine agonists (see below “Other medicines and Plasil”);
• if you have ever had a blood haemoglobin disorder (methaemoglobinaemia) or lack a substance (deficiency) called NADH cytochrome-b5 reductase;
• if you have glaucoma (increased pressure inside the eye).

Do not use Plasil in children under 1 year of age (see below “Children and adolescents”).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Plasil

• if you have heart conduction disorders (prolonged QT interval) or any other heart problems (severe bradycardia, cardiac arrest);
• if you have imbalances in blood electrolytes such as potassium, sodium, or magnesium;
• if you are taking other medicines known to affect heart rhythm;
• if you have neurological disorders and are taking other medicines acting on the central nervous system;
• if you have liver or kidney problems (renal failure or severe hepatic insufficiency). In these cases, your doctor may reduce the dose (see section 3).

Your doctor may carry out blood tests. If you develop a blood haemoglobin disorder (methaemoglobinaemia), treatment must be immediately and permanently discontinued.
You must wait at least 6 hours between each dose of metoclopramide, even if vomiting or regurgitation of the dose occurs, to avoid overdose.
Treatment should not exceed 3 months due to the risk of involuntary muscle spasms. If such symptoms occur, you must stop treatment.
Use of Plasil may cause an increase in a substance called "prolactin". Your doctor will consider this possibility, especially if you have a breast tumour or a benign tumour of the gland called "pituitary" (pituitary adenoma) that causes prolactin production.
Children and adolescents
In children and young adults, uncontrolled movements (extrapyramidal disorders) may occur. This medicine must not be used in children under 1 year of age due to the higher risk of uncontrolled movements (see above “Do not take Plasil”).
Other medicines and Plasil
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
This is important because some medicines may affect how Plasil works, or Plasil may affect how other medicines work. These include:

• levodopa or other medicines used to treat Parkinson’s disease (dopamine agonists) (see above “Do not take Plasil”);
• anticholinergics (medicines used to relieve stomach cramps or spasms);
• morphine derivatives (medicines used to treat severe pain);
• medicines that depress the central nervous system (morphine derivatives, anxiolytics, sedative H1 antihistamines, sedative antidepressants, barbiturates, clonidine and related medicines);
• medicines used to treat psychiatric disorders (neuroleptics) and serotonergic medicines;
• digoxin (a medicine used to treat heart failure);
• cyclosporine (a medicine used to treat certain immune system disorders);
• mivacurium and suxamethonium (medicines used to relax muscles);
• fluoxetine and paroxetine (medicines used to treat depression);
• cisplatin: due to a possible increase in renal toxicity;
• insulin: your doctor may need to adjust the dose;
• rifampicin: a medicine used to treat tuberculosis and other infections; if taken together, it may reduce the amount of metoclopramide in the blood;
• a medicine called apomorphine, as Plasil reduces its effects on the nervous system.

Plasil and alcohol
You must not consume alcohol during treatment with metoclopramide, as it increases the sedative effect of Plasil.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Plasil may be used during pregnancy if necessary, but administration should be avoided towards the end of pregnancy, as it may cause movement disorders in the newborn (extrapyramidal syndrome). If you take Plasil, your doctor will monitor your baby through neonatal monitoring.
Your doctor will decide whether or not you should take this medicine.
Breastfeeding
Plasil is not recommended during breastfeeding, as it passes into breast milk in low amounts and adverse effects in the breastfed infant cannot be ruled out. Therefore, if you are breastfeeding, your doctor will consider stopping Plasil.
Driving and using machines
You may feel drowsy, dizzy, or experience uncontrolled spasms, contractions, convulsive movements, or unusual muscle tone causing body distortions after taking Plasil.
These symptoms may affect your vision and may also impair your ability to drive or operate machinery.
Plasil contains methyl 4-hydroxybenzoate and propyl 4-hydroxybenzoate which may cause allergic reactions (including delayed-type reactions).
Plasil syrup contains ethanol.
This medicine contains 286.2 mg of alcohol (ethanol) per 30 mg dose of metoclopramide. The amount in each 30 mg dose of this medicine is equivalent to less than 7 ml of beer or 3 ml of wine. The small amount of alcohol in this medicine will not produce significant effects.
Plasil syrup contains propylene glycol
This medicine contains 84.5 mg of propylene glycol per 10 ml syrup dose.
Plasil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 10 ml syrup dose, i.e. essentially “sodium-free”.

3. How to take Plasil

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
All indications (adult patients)
The recommended single dose is 10 mg, repeated up to three times daily.
The maximum recommended daily dose is 30 mg or 0.5 mg/kg body weight.
The maximum recommended duration of treatment is 5 days.
For the prevention of delayed chemotherapy-induced nausea and vomiting (children aged between 1
and 18 years)
The recommended dose is 0.1 to 0.15 mg/kg body weight, repeated up to 3 times daily and
taken orally. The maximum dose in a 24-hour period is 0.5 mg/kg body weight.
Dosing table

The dosing syringe for oral administration of the medicine, included in the syrup pack, is graduated in mg and allows the correct amount of metoclopramide to be administered. The correspondence to body weight is detailed in the dosing table. The dose is obtained by pulling the plunger up to the corresponding mark in mg.
The oral syringe must only be used for administering this syrup.
The dosing syringe should be rinsed after each use.
Do not leave the dosing syringe immersed in the bottle.
Treatment must not exceed 5 days when used for prevention of delayed nausea and vomiting that may occur after chemotherapy.
Administration of the medicine at the recommended doses is advised, preferably before meals.

Method of administration
You must wait at least 6 hours between each dose of metoclopramide, even in case of vomiting and rejection of the dose, in order to avoid overdose.

Instructions for use
To open the bottle, press and simultaneously unscrew the cap (1); to close, press the cap and screw it tightly (2).

Elderly patients
The dose may need to be reduced based on renal problems, hepatic problems, and general health status.

Adults with renal problems
Talk to your doctor if you have renal problems. The dose must be reduced in cases of moderate or severe renal impairment and in end-stage renal disease.

Adults with hepatic problems
Discuss with your doctor if you have hepatic problems. The dose must be reduced in cases of severe hepatic impairment.

Children and adolescents
Metoclopramide must not be used in children under 1 year of age (see section 2).

If you take more Plasil than you should
Contact your doctor or pharmacist immediately. You may experience uncontrollable movements (extrapyramidal symptoms), drowsiness, disturbances of consciousness, confusion, hallucinations, and cardiac problems. Your doctor may prescribe treatment for these symptoms, if necessary.
In case of accidental ingestion/overdose of Plasil, contact your doctor immediately or go to the nearest hospital.

If you forget to take Plasil
Do not take a double dose to make up for the missed dose.
If you have any doubts about the use of this medicine, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop treatment and speak to your doctor, pharmacist, or nurse immediately if you experience any of the following symptoms while taking this medicine:

• involuntary movements (often affecting the head or neck). These may occur in children or young adults, particularly when high doses are used. These symptoms usually occur at the beginning of treatment and may even appear after a single dose. The movements disappear if appropriately treated.
• high fever, high blood pressure, seizures, sweating, saliva production. These may be signs of a disorder called neuroleptic malignant syndrome.
• itching or skin rash, swelling of the face, lips, or throat, difficulty breathing. These may be signs of an allergic reaction, which can be severe.

The following side effects may occur with the frequency indicated:
Very common (may affect more than 1 in 10 people)

• feeling of drowsiness.

Common (may affect up to 1 in 10 people)

• depression
• involuntary movements such as tics, tremors, twisting movements (extrapyramidal disorders) or muscle contractions (rigidity)
• Parkinson-like symptoms (stiffness, tremors)
• feeling of restlessness and agitation (akathisia)
• low blood pressure (particularly when administered intravenously)
• diarrhoea
• feeling of weakness.

Uncommon (may affect up to 1 in 100 people)

• increase in a hormone called prolactin, which may cause milk production in men and women who are not breastfeeding
• irregular menstrual cycle
• hallucinations
• reduced level of consciousness
• slow heart rate (particularly when administered intravenously)
• allergy
• movement disorders (dyskinesia)
• adoption of abnormal postures (dystonia)
• visual disturbances and involuntary deviation of the eye.

Rare (may affect up to 1 in 1,000 people)

• confusion
• seizures (especially in epileptic patients)
• abnormal secretion of milk or milky fluid from the breasts in women who are not breastfeeding or in men (galactorrhoea).

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

• allergic reactions (such as anaphylaxis, angioedema and urticaria) which can be severe (particularly when administered intravenously). Symptoms may include skin rash, itching, breathing difficulties, shortness of breath, swelling of the face, lips, throat or tongue, cold and clammy skin, palpitations, dizziness, weakness and fainting. Contact your doctor or another healthcare professional immediately or go immediately to the nearest hospital emergency department.
• abnormal levels of blood pigment, which may change the colour of the skin (sulfhaemoglobinaemia)
• abnormal levels of methaemoglobin (a protein similar to haemoglobin) (methaemoglobinaemia)
• abnormal breast development in men (gynaecomastia)
• involuntary muscle contractions (spasms) after prolonged use, particularly in elderly patients (dyskinesia)
• high fever, high blood pressure, seizures, sweating, saliva production. These may be symptoms of a disorder called neuroleptic malignant syndrome
• QT interval prolongation on electrocardiogram and torsade de pointes
• cardiac arrest (particularly with injection)
• atrioventricular block and sinus arrest (particularly with injection)
• shock (severe drop in blood pressure) (particularly with injection)
• fainting (particularly when administered intravenously)
• very high blood pressure
• suicidal thoughts (suicidal ideation).

If you experience any side effect, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse.
The following reactions, sometimes occurring together, occur more frequently when high doses are administered:

• movement problems (extrapyramidal disorders: acute dystonia and dyskinesia, parkinsonism, akathisia), even after a single dose of the medicine, particularly in children and young adults,
• drowsiness,
• reduced level of consciousness,
• confusion,
• hallucinations.

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

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "Exp.". The expiry
date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Plasil contains

• The active substance is metoclopramide. 100 ml of syrup contain metoclopramide monohydrochloride monohydrate 105 mg (equivalent to 100 mg of anhydrous substance).
• The other components are: methyl parahydroxybenzoate, propyl parahydroxybenzoate, sorbic acid, hydroxyethylcellulose, saccharin, propylene glycol, ethanol, mandarin flavour, caramel flavour, vanilla flavour (containing ethanol), sodium hydrate, purified water.

Description of the appearance of Plasil and contents of the pack
Plasil 10 mg/10 ml is presented as a syrup.
The pack contains a 120 ml bottle with an oral dosing syringe.
Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15 - 20143 Milan
Manufacturer
SANOFI S.r.l.
Via Valcanello, 4 - 03012 Anagni (FR) - Italy

Patient information leaflet

Plasil 10 mg/2 ml injectable solution

metoclopramide
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Plasil is and what it is used for

Plasil is a medicine used to treat vomiting (antiemetic). It contains an active substance called "metoclopramide" and belongs to a group of medicines known as "Drugs for gastrointestinal functional disorders – Prokinetics".
It acts on a part of the brain to prevent the sensation of nausea or vomiting.
Plasil is indicated for:
Adult population
Plasil is used in adults:

• for the prevention of nausea and vomiting that may occur after surgical procedures;
• for the prevention of nausea and vomiting caused by radiotherapy;
• for the treatment of nausea and vomiting, including nausea and vomiting associated with acute migraine.

Paediatric population
Plasil is used in children (aged between 1 and 18 years) only when other treatments are ineffective or cannot be used:

• for the prevention of nausea and vomiting that may occur following chemotherapy;
• for the treatment of nausea and vomiting occurring after surgical procedures.

2. What you need to know before taking Plasil

Do not take Plasil

• If you are allergic to metoclopramide or to any of the other ingredients of this medicine (listed in section 6);
• if you have bleeding, obstruction, or perforation in the stomach or intestine;
• if you have or may have a rare tumor of the adrenal glands located near the kidneys (pheochromocytoma);
• if you have ever experienced involuntary muscle contractions (tardive dyskinesia) when treated with metoclopramide or neuroleptic medicines;
• if you suffer from epilepsy (with increased frequency and intensity of seizures);
• if you have Parkinson's disease;
• if you are taking levodopa (a medicine for Parkinson's disease) or other medicines called dopaminergic agonists (see below “Other medicines and Plasil”);
• if you have ever had a blood hemoglobin disorder (methemoglobinemia) or deficiency of a substance called NADH-cytochrome-b5 reductase;
• if you have glaucoma (increased pressure inside the eyeball).

Do not use Plasil in children under 1 year of age (see below “Children and adolescents”).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Plasil

• if you have heart conduction disorders (QT interval prolongation) or any other heart problems (severe bradycardia, cardiac arrest);
• if you have imbalances in blood electrolytes such as potassium, sodium, or magnesium;
• if you are taking other medicines known to affect heart rhythm;
• if you have neurological disorders or are taking other medicines acting on the central nervous system;
• if you have liver or kidney problems (renal failure or severe hepatic insufficiency). In these cases, your doctor may reduce the dose (see section 3).

Your doctor may perform blood tests. If you develop a blood hemoglobin disorder (methemoglobinemia), treatment must be immediately and permanently discontinued.
Treatment should not exceed 3 months due to the risk of involuntary muscle spasms. If such symptoms occur, you must stop treatment.
Use of Plasil may cause an increase in a substance called "prolactin." Your doctor will consider this possibility, especially if you have a breast tumor or a benign tumor of the gland called "pituitary" (pituitary adenoma) that causes prolactin production.
Children and adolescents
In children and young adults, uncontrolled movements (extrapyramidal disorders) may occur. The medicine must not be used in children under 1 year of age due to the higher risk of uncontrolled movements (see above “Do not take Plasil”).
Other medicines and Plasil
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
This is important because some medicines may affect how Plasil works, or Plasil may affect how other medicines work. These include:

• levodopa or other medicines used to treat Parkinson's disease (dopaminergic agonists) (see above “Do not take Plasil”)
• anticholinergics (medicines used to relieve stomach cramps or spasms)
• morphine derivatives (medicines used to treat severe pain)
• medicines that depress the central nervous system (morphine derivatives, anxiolytics, sedating H1-antihistamines, sedative antidepressants, barbiturates, clonidine, and related medicines)
• medicines used to treat psychiatric disorders (neuroleptics) and serotonergic medicines
• digoxin (a medicine used to treat heart failure)
• cyclosporine (a medicine used to treat certain immune system disorders)
• mivacurium and suxamethonium (medicines used to relax muscles)
• fluoxetine and paroxetine (medicines used to treat depression)
• cisplatin: due to a possible increase in renal toxicity
• insulin: your doctor may adjust the dose
• a medicine called apomorphine, as Plasil reduces its effects on the nervous system
• rifampicin: a medicine used to treat tuberculosis and other infections; when taken concurrently, it may reduce metoclopramide blood levels.

Plasil and alcohol
You must not consume alcohol during treatment with metoclopramide, as it increases the sedative effect of Plasil.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Plasil may be used during pregnancy if necessary, but administration should be avoided towards the end of pregnancy, as it may cause movement disorders in the newborn (extrapyramidal syndrome). If you take Plasil, your doctor will monitor your baby through neonatal surveillance.
Your doctor will decide whether or not you should take this medicine.
Breastfeeding
Plasil is not recommended during breastfeeding, as it passes into breast milk in low amounts and adverse effects in the breastfed infant cannot be ruled out. Therefore, if you are breastfeeding, your doctor will consider discontinuing Plasil.
Driving and using machines
You may feel drowsy, dizzy, or experience uncontrolled spasms, contractions, convulsive movements, or unusual muscle tone causing body distortions after taking Plasil.
These symptoms may affect your vision and impair your ability to drive or operate machinery.
Plasil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 2 ml vial, i.e., essentially 'sodium-free'.

3. How to take Plasil

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
This medicine is normally administered by a doctor or nurse. It will be given as a slow injection into a vein (intravenously) or as an injection into a muscle (intramuscularly).
The ampoule can be opened without a file.
Intravenous doses must be administered unfractionated and slowly (slow bolus), over at least 3 minutes.
The recommended dose is:
All indications (adult patients)
For the treatment of nausea and vomiting, including nausea and vomiting associated with acute migraine, and for the prevention of nausea and vomiting caused by radiotherapy: the recommended single dose is 10 mg, repeated up to 3 times daily.
The maximum recommended dose is 30 mg or 0.5 mg/kg body weight.
For the prevention of nausea and vomiting that may occur after surgery: a single dose of 10 mg is recommended.
The duration of injectable treatment should be as short as possible, switching as soon as possible to oral or rectal administration.
All indications (paediatric patients aged between 1 and 18 years)
The recommended dose is 0.1 to 0.15 mg/kg body weight, repeated up to 3 times daily and administered by slow intravenous injection.
The maximum dose in a 24-hour period is 0.5 mg/kg body weight.
Dosing table

Treatment should not exceed 48 hours in the case of treatment of nausea and vomiting following surgical procedures.
Treatment should not exceed 5 days for prevention of delayed nausea and vomiting that may occur after chemotherapy.
It is recommended to administer the drug at the indicated doses.

Method of administration

Elderly
The dose may need to be reduced based on renal impairment, hepatic impairment, and general health status.

Adults with renal impairment
Speak with your doctor if you have renal problems. The dose should be reduced in cases of moderate or severe renal impairment or end-stage renal disease.

Adults with hepatic impairment
Discuss with your doctor if you have hepatic problems. The dose should be reduced in cases of severe hepatic impairment.

Children and adolescents
Metoclopramide must not be used in children under 1 year of age (see section 2).

If you take more Plasil than you should
Contact your doctor or pharmacist immediately. You may experience uncontrollable movements (extrapyramidal symptoms), drowsiness, disturbances in consciousness, confusion, hallucinations, and cardiac problems. Your doctor may prescribe treatment for these symptoms, if necessary.
In case of accidental ingestion/overdose of Plasil, contact your doctor immediately or go to the nearest hospital.

If you forget to take Plasil
Do not take a double dose to make up for the missed dose.

If you have any doubts about the use of this medicine, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop treatment and speak immediately with your doctor, pharmacist, or nurse if you experience any of the following symptoms during treatment with this medicine:

• Uncontrollable movements (often affecting the head or neck). These may occur in children or young adults, particularly when high doses are used. These symptoms usually appear at the beginning of treatment and may even occur after a single dose. The movements disappear if appropriately treated.
• High fever, high blood pressure, seizures, sweating, excessive saliva production. These may be signs of a disorder called neuroleptic malignant syndrome.
• Itching or skin rashes, swelling of the face, lips, or throat, difficulty breathing. These may be signs of an allergic reaction, which can be severe.

The following side effects may occur with the frequency indicated below:
Very common (may affect more than 1 in 10 people)

• Feeling of drowsiness.

Common (may affect up to 1 in 10 people)

• Depression
• Uncontrollable movements such as tics, tremors, twisting movements (extrapyramidal disorders) or muscle contractions (rigidity)
• Parkinsonism-like symptoms (rigidity, tremors)
• Feeling of restlessness and agitation (akathisia)
• Low blood pressure (particularly with intravenous administration)
• Diarrhea
• Feeling of weakness.

Uncommon (may affect up to 1 in 100 people)

• Increase in a hormone called prolactin, which may cause: milk production in men and women who are not breastfeeding
• Irregular menstrual cycle
• Hallucinations
• Reduced level of consciousness
• Slow heart rate (particularly with intravenous administration)
• Allergic reaction
• Movement disorders (dyskinesia)
• Adoption of abnormal postures (dystonia)
• Visual disturbances and involuntary deviation of the eye.

Rare (may affect up to 1 in 1,000 people)

• Confusional state
• Seizures (especially in epileptic patients)
• Abnormal secretion of milk or milky fluid from the breasts in women who are not breastfeeding or in men (galactorrhea).

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

• Allergic reactions (such as anaphylaxis, angioedema, and urticaria) which may be severe (particularly with intravenous administration). Symptoms may include skin rash, itching, difficulty breathing, shortness of breath, swelling of the face, lips, throat, or tongue, cold and clammy skin, palpitations, dizziness, weakness, and fainting. Contact your doctor or other healthcare professional immediately or go immediately to the nearest hospital emergency department.
• Abnormal levels of blood pigment, which may change the skin color (sulfhemoglobinemia)
• Abnormal levels of methemoglobin, a blood protein similar to hemoglobin (methemoglobinemia)
• Abnormal breast development in men (gynecomastia)
• Involuntary muscle contractions (spasms) after prolonged use, particularly in elderly patients (dyskinesia)
• High fever, high blood pressure, seizures, sweating, excessive saliva production. These may be symptoms of a disorder called neuroleptic malignant syndrome
• QT interval prolongation on electrocardiogram and torsades de pointes
• Cardiac arrest (particularly with injection)
• Atrioventricular block and sinus arrest (particularly with injection)
• Shock (severe drop in blood pressure) (particularly with injection)
• Fainting (particularly with intravenous administration)
• Very high blood pressure
• Suicidal thoughts (suicidal ideation).

If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
The following reactions, sometimes occurring together, are more frequent when high doses are administered:

• Movement problems (extrapyramidal disorders: acute dystonia and dyskinesia, parkinsonism, akathisia), even after a single dose of the medicine, particularly in children and young adults,
• Drowsiness,
• Reduced level of consciousness,
• Confusion,
• Hallucinations.

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

This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Plasil contains

• The active substance is: metoclopramide hydrochloride. Each vial contains 10.5 mg of metoclopramide hydrochloride (equivalent to 10 mg of anhydrous substance).
• The other components are: sodium chloride; water for injections.

Description of the appearance of Plasil and pack contents
Plasil is a 10 mg/2 ml injectable solution.
It is available in packs of 5 vials of 2 ml each.

Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo, 15 - 20143 Milan, Italy

Manufacturer
SANOFI S.r.l.
Via Valcanello, 4 - 03012 Anagni (FR) - Italy