Prospecto: information for the patient

Ravicti1,1g/ml oral liquid

glycerol phenylbutyrate

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section4.

1.What isRavictiand how it is used

2.What you need to know before starting to takeRavicti

3.How to takeRavicti

4.Adverse effects

5.Storage ofRavicti

6.Contents of the package and additional information

Ravicticontains the active ingredient «glycine phenylbutyrate», which is used to treat six «urea cycle disorders» (UCDs) known in adults, adolescents, and children. The UCDs include deficiencies of certain liver enzymes, such as carbamoyl phosphate synthetase I (CPS I),ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase I (ARG), and ornithine translocase deficiency‑hyperammonemia-hyperornithinemia‑homocitrullinuria (HHH).

RAVICTI should be combined with a low-protein diet and, in some cases, with a diet supplemented with essential amino acids (arginine, citrulline, non-protein calorie supplements).

About urea cycle disorders

• In urea cycle disorders, the body is unable to eliminate excess nitrogen from the proteins we consume.
• Normally, the body converts excess nitrogen from proteins into a waste compound called «ammonia». The liver then eliminates ammonia from the body through a cycle called the «urea cycle».
• In urea cycle disorders, the body is not able to produce sufficient liver enzymes to eliminate excess nitrogen.
• As a result, ammonia accumulates in the body. If ammonia is not eliminated from the body, it can damage the brain and cause partial loss of knowledge or a coma.
• Urea cycle disorders are rare.

How Ravicti worksRavicti

Ravictihelps the body to eliminate waste nitrogen. This reduces the amount of ammonia in the body.

Do not takeRavicti

• if you are allergic toglycerol phenylbutyrate.
• if you have hyperammonemia (high levels of ammonia in the blood), which requires faster intervention (see the "Warnings and precautions" section.

If you are not sure if you are in any of the above circumstances, consult your doctor or pharmacist before takingRavicti.

Warnings and precautions

Consult your doctor or pharmacist before starting to takeRavicti:

• if you have liver or kidney problems, as RAVICTIis eliminated from the body through these
• if you have pancreas, stomach, or intestine problems, as these organs are responsible for the absorption of RAVICTI in the body.

If you are in any of the above circumstances, consult your doctor or pharmacist before takingRavicti.

In some cases,such as infection or postoperative, the amount of ammonia may increase despite treatment with glycerol phenylbutyrateand may damage the brain (hyperammonemic encephalopathy).

In other cases, the amount of ammonia in the blood increases rapidly. In this case, RAVICTI will not cause the amount of ammonia in the blood to increase to excessively high levels.

High levels of ammonia in the blood cause nausea, vomiting, or a feeling of confusion.

Inform your doctor or go to the hospital immediately if you notice any of these signs.

It will be necessary to perform analytical tests so that your doctor can determine and maintain the correct dose for you.

Other medications and RAVICTI

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Particularly, inform your doctor or pharmacist if you are taking any of the following medications, which may be less effective when used withRAVICTI. If you are taking these medications, it may be necessary to perform periodic blood tests:

• midazolam and barbiturates (used for sedation, sleep problems, or epilepsy)
• contraceptives

Also, inform your doctor if you are taking any of the following medications, as they may increase the amount of ammonia in the body or change the functioning of RAVICTI:

• corticosteroids (used to treat inflamed areas of the body)
• valproic acid (a medication for epilepsy)
• haloperidol (used to treat some mental health problems)
• probencid (to treat high levels of uric acid in the blood, which can cause gout ["hyperuricemia"])
• lipase inhibitors (such as orlistat): used to treat obesity
• lipase in enzyme replacement therapy.

If you are in any of the above circumstances (or are unsure), consult your doctor before takingRavicti.

Pregnancy, contraception, and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before usingRavicti. If you become pregnant during treatment withRavicti, consult your doctor. RAVICTI should not be used during pregnancy, as the risks to the fetus cannot be ruled out.
• If you are a woman who can become pregnant, you must use an effective contraceptive method during treatment withRavicti. Consult your doctor to determine the best contraceptive method for you.
• If you plan to breastfeed while taking RAVICTI, you must talk to your doctor. It must be decided whether to interrupt breastfeeding or interrupt treatment after considering the benefit of breastfeeding for the baby and the benefit of treatment for you, as RAVICTI may pass into breast milk and the risk in newborns/children cannot be ruled out.

Driving and using machines

Lthe influence ofRaviction the ability to drive and use machines is important. When taking RAVICTIyou may feel dizzy or have a headache. Do not drive or use machines while experiencing these adverse effects.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

You must follow a special low-protein diet during treatment withRAVICTI.

• This diet will be designed for you by your doctor and dietitian.
• You must follow it carefully.
• You may need to take amino acid supplements.
• You will need to receive treatment and follow a diet for the rest of your life, unless you undergo a successful liver transplant.

Amount to take

Your doctor will tell you how muchRavictiyou should take each day.

• Your daily dose will depend on your size and weight, the amount of protein in your diet, and the general state of the urea cycle disorder.
• Your doctor may give you a lower dose if you have kidney or liver problems.
• You will need periodic blood tests so that your doctor can determine the correct dose for you.
• Your doctor may tell you to takeRavictimore than 3times a day. In young children, it may be 4 to 6 times a day. There should be at least 3hours between each dose.

Administration of this medication

Your doctor will tell you how to takeRavictiliquid orally. It can be taken in the following ways:

• by mouth
• through a tube that goes from the abdomen (stomach) to the stomach called a «gastrostomy tube»
• through a tube that goes from the nose to the stomach called a «nasogastric tube».

Take RAVICTI orally unless your doctor tells you otherwise.

Ravictiand meals

TakeRavictiwith a meal or right after. Young children should receive the medication with a meal or right after.

Dose measurement

• Use an oral syringe to measure your dose.

• Make sure to have the RAVICTI bottle along with an oral syringe to administer the correct amount of RAVICTI

1. Open the RAVICTI bottle by pressing the cap and turning it to the left.
2. 
   Place the tip of the oral syringe into the insertion piece of the syringe integrated into the bottle.

1. Hold the bottle down while keeping the oral syringe inserted.

1. Fill the oral syringeby pulling the plunger back until the syringe is filledwith the amount ofRAVICTIliquid that your doctor has indicated you should take.
   1. Nota: If possible, use the size of the oral syringe in milliliters that is closest to the recommended dose, without being less than this (for example, if the dose is 0.8ml, use an oral syringe of 1ml).

1. Give the oral syringe a tap to remove any air bubbles, making sure you have filled it with the correct amount of liquid.

1. Swallow the liquid from the oral syringe or connect the oral syringe to a gastrostomy tube or nasogastric tube.

1. Important note:Do not add Ravicti to large volumes of liquid or mix it with these, as RAVICTI is denser than most liquids. If you mix RAVICTI with large volumes of liquid, you may not get the full dose.
2. RAVICTI can be added to a small amount of soft food, such as ketchup, medical formulas, apple puree, orcarrot puree.
3. If the volume of the oral syringe is less than the prescribed dose, you will need to repeat these steps to get the full dose. Use an oral syringe for all doses taken each day.
4. After taking the full dose, drink a little water to make sure there is no medication left in your mouth, or rinse the nasogastric or gastrostomy tube with 10ml of water using a new oral syringe. The oral syringe used to rinse the nasogastric or gastrostomy tube should not be used to measure the RAVICTI dose, to avoid contact between the water and the medication.

1. Close the bottle by screwing the cap.

1. Important note:Do not rinse the oral syringe between daily doses, as the addition of water causes RAVICTI degradation. If RAVICTI comes into contact with water, the liquid will appear cloudy. Keep the bottle and oral syringe in a clean and dry place between doses.
2. Discard the oral syringe after the last dose of the day. Do not reuse the oral syringe to measure the RAVICTI dose another day.
3. Unused oral syringes should be kept to use with another bottle.Each bottle should be discarded after 14days.

If you take moreRavictithan you should

If you take more of this medication than you should, consult your doctor.

If you notice any of the following symptoms, consult a doctor or go to the hospital immediately, as they may be signs of overdose or elevated ammonia:

• drowsiness, fatigue, or dizziness, sometimes confusion
• headache
• changes in taste
• hearing problems
• feeling disoriented
• decreased ability to remember things
• existing neurological disorders may worsen.

If you forgot to takeRavicti

If you forget a dose, take it as soon as you remember. However, in adults, if the next dose is due in less than 2hours, skip the missed dose and take the next one at the usual time.

For children: if the next dose is due in less than 30minutes, skip the missed dose and administer the next one at the usual time.

• Do not take a double dose to make up for missed doses.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

If you interrupt treatment withRavicti

You will need to take this medication and follow a special low-protein diet for the rest of your life. Do not stop taking RAVICTI without consulting your doctor.

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

Inform your doctor or pharmacist if you experience any side effects.

This medicine may cause the following side effects:

Frequent:may affect up to 1 in 10people

• swelling or stomach pain, constipation, diarrhea, heartburn, gas, vomiting, nausea, mouth pain, hiccups
• swelling of the hands or feet, feeling tired
• feeling dizzy, headache, or tremors
• decrease or increase in appetite
• aversion to certain foods
• bleeding between menstrual periods
• acne, abnormal skin odor
• results in tests showing an increase in liver enzymes, imbalances in blood salts, low white blood cell count («lymphocytes»), or low vitaminD levels

Rare:may affect up to 1 in 100people

• dry mouth
• eructation, stomach pain or discomfort, changes in bowel movements, for example, oily appearance, urgent need to defecate, painful defecation, inflammation of the mouth and lips
• feeling hungry
• increased temperature
• headaches
• gallbladder pain
• urinary tract pain
• back pain, joint pain, muscle spasms, pain in the arms or legs, heel spur syndrome
• gastrointestinal viral infection
• tingling sensation, feeling anxious, drowsiness, sleepiness, speech problems, feeling confused, feeling depressed, altered taste
• cessation of menstruation or irregular menstrual periods
• voice changes, nasal bleeding, nasal congestion, or throat inflammation or pain
• hair loss, increased sweating, skin rash with itching
• irregular heartbeats
• decreased thyroid function
• weight loss or gain
• results in tests showing an increase or decrease in potassium levels in the blood
• results in tests showing an increase in triglycerides, low-density lipoproteins, or white blood cells in the blood
• abnormal ECG («electrocardiogram») results
• increased prothrombin time in tests
• results in tests showing a decrease in albumin in the blood

Side effects in children under 2 months:

The following side effects were observed in a clinical study with 16patients under 2months of age:

• diarrhea, constipation, flatulence, gastroesophageal reflux, inadequate feeding
• exanthema
• reduced red blood cell count
• increased platelet count (may cause blood to clot)
• increased liver enzymes
• decreased amino acid concentrations

Side effects in children 2 months to less than 2 years of age:

• diarrhea, constipation
• eczema, nail striations, exanthema

Reporting side effects:

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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 and the bottle label, after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions. Once the bottle is opened,youmustuse this medication within a period of 14days after opening. The bottle must be discarded even if it is not empty.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition ofRavicti

• The active ingredient is glycerol phenylbutyrate.
• Each milliliter of the liquid contains 1.1g of glycerol phenylbutyrate. This corresponds to a density of 1.1g/ml.
• There are no other components.

Appearance of the product andcontents of the packaging

The liquid is contained in a transparent glass bottle of 25ml with a child-resistant plastic cap.

To ensure the correct administration of RAVICTI, oral syringes with CE marking, suitable for the dose and compatible with the syringe insertion piece, can be obtained from the pharmacy. Ask your doctor or pharmacist which type of syringe you need, according to the prescribed dose volume.

Marketing authorization holderand manufacturer

Marketing authorization holder

Immedica Pharma AB

SE-113 63 Stockholm

Sweden

Manufacturer

Unimedic AB

Storjordenvägen 2

SE-864 31 Matfors

Sweden

Last review date of this leaflet: 10/2022

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.