Variquel 0.2 mg/ml, solution for injection

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

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

• if you are allergic to terlipressin or any of the other ingredients of this medicine (listed in section 6).

Talk to your doctor or pharmacist before using Variquel.

If you are able, please tell the doctor if you have any of the conditions below:

• a severe infection known as septic shock
• bronchial asthma or other conditions that affect your breathing
• uncontrolled high blood pressure, insufficient blood circulation in the heart vessels (e.g. angina), coronary insufficiency, have previously had a heart attack (myocardial infarction), or you have hardening of the arteries (arteriosclerosis)
• seizure disorder (suffering from fits)
• irregular heart beats (cardiac arrythmias) or a history of QT interval prolongation (disturbance of heart rhythm)
• poor blood circulation to your brain (e.g. you have had a stroke) or to your limbs (peripheral vascular disease)
• impaired kidney function (renal insufficiency)
• disturbances in the level of salt (electrolytes) in your blood
• reduced amount of fluid in your circulation or have already lost a large amount of blood
• are over the age of 70 years
• are pregnant

Variquel is not recommended for use in children and adolescents due to insufficient experience.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without prescriptions.

Please inform your doctor immediately if you take any of the following medicines:

• drugs that have an effect on your heart rate (e.g. beta-blockers, sufentanil or propofol)
• drugs that can trigger irregular beating of the heart (arrhythmia) such as the following:
  • anti-arryhthmic drugs known as Class IA (quinidine, procainamide, disopyramide) and Class III (amiodarone, sotalol, ibutilide, dofetilide)
  • erythromycin (an antibiotic)
  • antihistamines (mainly used to treat allergies but also found in certain cough and cold remedies)
  • tricyclic antidepressants used to treat depression
  • medicines that may alter the level of salt or electrolytes in your blood, particularly diuretics (water tablets used to treat high blood pressure and heart failure)

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

Variquel should only be used during pregnancy if it is vital to treat your condition.

It is not known if Variquel is present in breast milk, therefore the possible effects on your baby are unknown. You should discuss the potential risk to your baby with your doctor.

Ask your doctor or pharmacist for advice before taking any medicine.

No studies on the effects on the ability to drive and use machines have been performed. However, if you feel unwell after receiving the injection, do not drive or operate machinery.

This medicinal product contains less than 1 mmol (23 mg) of sodium per 5 ml, i.e. essentially "sodium-free".

Bleeding of dilated veins (varices) in the food pipe and stomach:

Initially 1-2 mg terlipressin acetate (5-10 ml of Variquel) is given by injection into your vein. Your dose will depend on your body weight.

After the initial injection, your dose may be reduced to 1 mg terlipressin acetate (5 ml of Variquel) every 4 to 6 hours.

The maximum dose you can receive each day is approximately 120 micrograms/kg body weight.

The therapy should be limited to 2-3 days in line with the course of the disease.

Hepatorenal syndrome:

Treatment in adults is usually started with a dose of 1 mg terlipressin acetate (5 ml of Variquel) at 4 to 6-hour intervals.

The dose can be increased to a maximum of 2 mg terlipressin acetate (10 ml of Variquel) every 4 hours if the serum creatinine does not decrease by at least 25% after 3 days of treatment. Treatment is continued until normal kidney function is restored, up to 14 days.

Method and route of administration:

Variquel is injected intravenously (directly into the bloodstream).

If you are over 70 years of age speak with your doctor before you receive Variquel.

Variquel should be used with caution in patients with long standing kidney failure.

No dose adjustment is required in patients with liver failure.

Variquel is not recommended for use in children and adolescents due to insufficient experience.

As this medicine is given by a healthcare professional, then it is unlikely you will be given more than the recommended dose. If you are given too much then you may have a rapid increase in your blood pressure (this will be noticed during the continuous monitoring), especially if you already suffer with high blood pressure. If this happens then you will be given another medicine called an alpha blocker (e.g. clonidine) to control your blood pressure.

If you experience light-headedness, dizziness, or feeling faint, tell your doctor because these could be signs of a low heart rate. This can be treated with another medicine called atropine.

You will be given Variquel in hospital under the supervision of a doctor.

Your doctor will advise when it is time to stop receiving this medicine.

In very rare cases, there may be severe side effects when you are given Variquel.

If you are affected by any of the following side effects, please tell your doctor immediately if you are able to. Your doctor should not give you any more Variquel.

• severe shortness of breath due to an asthma attack
• severe difficulty with or stopping breathing
• severe pain in the chest (angina, heart attack)
• severe and persistent irregular heart beats, including Torsade de Pointes
• dead skin around the injection site (necrosis)
• convulsions (seizure)
• kidney failure.

Common (affects less than 1 in 10 people):

• too little sodium in the blood (hyponatraemia) if not checked regularly
• headache
• very slow heart rate (bradycardia)
• signs of insufficient blood circulation in the heart vessels in the ECG
• insufficient blood circulation in arms, legs and skin
• pale skin
• high or low blood pressure
• abdominal cramps
• nausea
• diarrhoea

Uncommon (affects less than 1 in 100 people)

• rapid heartbeat (tachycardia)
• chest pain
• excess fluid on the lungs
• heart muscle weakness (heart failure)
• reduced blood supply to the intestinal system
• bluish colouration of the skin or lips
• hot flushes
• painful breathing
• vomiting
• inflammation of the lymph vessels – seen as fine red streaks under your skin extending from the affected area to the armpit or groin and by fever, chills, headache, and muscle pain
• dead skin (necrosis) in areas other than at the injection site
• uterine cramps
• decreased blood flow to the uterus

Rare (affects less than 1 in 1000 people):

• shortness of breath

Very rare (affects less than 1 in 10,000 people):

• stroke

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store. By reporting side effects you can help provide more information on the safety of this medicine.

• the active substance is terlipressin acetate. Each vial contains 1 mg terlipressin acetate in 5 ml solution, corresponding to 0.85 mg terlipressin. Each ml contains 0.2 mg terlipressin acetate, corresponding to 0.17 mg terlipressin per ml.
• the other ingredients are: glacial acetic acid, sodium acetate trihydrate and water for injections (see also end of section 2 for further information on sodium).

This medicine is supplied in a clear glass vial containing 5 ml of a clear, colourless solution.

This medicine is available in pack sizes of: 5 x 5ml