Ravicti 1.1 g/ml oral liquid

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Ravicti 1.1 g/ml oral liquid

glycerol phenylbutyrate

Read this entire leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet as 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 give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What RAVICTI is and what it is used for

Ravicti contains the active substance glycerol phenylbutyrate, which is used to treat six known urea cycle disorders (UCDs) in adults, adolescents, and children. UCDs include deficiencies of certain hepatic enzymes, such as carbamoylphosphate synthetase I (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase I (ARG), and hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome due to ornithine translocase deficiency.

RAVICTI should be used in combination with a protein-restricted diet and, in some cases, with dietary supplements such as essential amino acids (arginine, citrulline) and non-protein caloric supplements.

About urea cycle disorders

• In urea cycle disorders, the body is unable to remove nitrogen from the proteins we consume.
• Normally, the body converts excess nitrogen from proteins into a waste compound called ammonia. The liver then removes ammonia from the body through a process known as the urea cycle.
• In urea cycle disorders, the body cannot produce enough of the necessary liver enzymes to eliminate excess nitrogen.
• As a result, ammonia accumulates in the body. If ammonia is not removed, it can damage the brain and lead to partial loss of consciousness or coma.
• Urea cycle disorders are rare.

How RAVICTI works

Ravicti helps the body eliminate waste nitrogen. This reduces the amount of ammonia in the body.

2. What you need to know before starting to take RAVICTI

Do not take RAVICTI

• if you are allergic to glycerol phenylbutyrate.
• if you have hyperammonemia (high levels of ammonia in the blood) requiring more rapid intervention (see section "Warnings and precautions").

If you are unsure whether any of the above apply to you, consult your doctor or pharmacist before taking RAVICTI.

Warnings and precautions

Talk to your doctor or pharmacist before starting RAVICTI:

• if you have liver or kidney problems, as RAVICTI is eliminated from the body through these organs.
• if you have problems with your pancreas, stomach, or intestines, as these organs are responsible for the absorption of RAVICTI into the body.

If any of the above apply to you, consult your doctor or pharmacist before taking RAVICTI.

In some cases, such as during infection or after surgery, ammonia levels may rise despite treatment with glycerol phenylbutyrate, potentially causing brain damage (hyperammonemic encephalopathy).

In other cases, blood ammonia levels may increase rapidly. In such situations, RAVICTI will not prevent blood ammonia levels from rising to dangerously high levels.

Elevated ammonia levels in the blood may cause nausea, vomiting, or confusion.

Contact your doctor or go to hospital immediately if you notice any of these symptoms.

Blood tests will be necessary so your doctor can determine and maintain the correct dose for you.

Other medicines and RAVICTI

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

In particular, inform your doctor or pharmacist if you are taking any of the following medicines, which may be less effective when used together with RAVICTI. If you are taking these medicines, periodic blood tests may be required:

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

Also, inform your doctor if you are taking any of the following medicines, as they may increase ammonia levels in the body or alter the action of RAVICTI:

• corticosteroids (used to treat inflamed areas of the body)
• valproic acid (a medicine for epilepsy)
• haloperidol (used to treat certain mental health conditions)
• probenecid (used 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 pancreatic enzyme replacement therapies.

If any of the above apply to you (or if you are unsure), consult your doctor before taking RAVICTI.

Pregnancy, contraception, and breastfeeding

• If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor before using RAVICTI. If you become pregnant during treatment with RAVICTI, consult your doctor. RAVICTI should not be used during pregnancy, as risks to the fetus cannot be ruled out.
• If you are a woman of childbearing potential, you must use an effective method of contraception during treatment with RAVICTI. Consult your doctor to determine the most suitable contraceptive method for you.
• If you plan to breastfeed while taking RAVICTI, you must discuss this with your doctor. A decision must be made whether to discontinue breastfeeding or discontinue treatment, taking into account the benefit of breastfeeding for the child and the benefit of treatment for you, as RAVICTI may pass into breast milk and risk to newborns/children cannot be excluded.

Driving and using machines

The effect of RAVICTI on the ability to drive and use machines is significant. When taking RAVICTI, you may feel dizzy or have a headache. Do not drive or operate machinery while experiencing these adverse effects.

3. How to take RAVICTI

Follow exactly the instructions given by your doctor for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

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

• 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 require lifelong treatment and dietary management unless you undergo a successful liver transplant.

Dosage

Your doctor will tell you how much Ravicti to take each day.

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

How to take this medicine

Your doctor will tell you how to take oral Ravicti liquid. It can be taken in the following ways:

• by mouth (orally)
• through a tube from the abdomen into the stomach called a "gastrostomy tube"
• through a tube from the nose into the stomach called a "nasogastric tube."

Take RAVICTI orally unless your doctor instructs otherwise.

RAVICTI and meals

Take Ravicti during or immediately after a meal. Young children should receive the medicine during or immediately after feeding.

Measuring the dose

• Use an oral syringe to measure your dose.
• You must have the RAVICTI bottle together with an oral syringe to administer the correct amount of RAVICTI.

1. Open the RAVICTI bottle by pressing down on the cap and turning it to the left.
2. Insert the tip of the oral syringe into the syringe adapter built into the bottle.

1. Turn the bottle upside down while keeping the oral syringe inserted.

1. Draw the RAVICTI liquid into the oral syringe by pulling back the plunger until the syringe contains the amount prescribed by your doctor.
   1. Note: If possible, use an oral syringe with a milliliter capacity closest to, but not smaller than, the prescribed dose (e.g., if the dose is 0.8 ml, use a 1 ml oral syringe).

1. Tap the oral syringe gently to remove air bubbles, ensuring the correct amount of liquid is drawn up.

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

1. Important note: Do not add Ravicti to large volumes of liquid or mix it with liquids, as RAVICTI is heavier than most liquids. Mixing RAVICTI with large volumes of liquid may result in an incomplete dose.
2. RAVICTI may be mixed with a small amount of soft food, such as ketchup, medical formulas, applesauce, or pumpkin puree.
3. If the oral syringe capacity is smaller than the prescribed dose, repeat these steps to obtain the full dose. Use an oral syringe for all doses taken each day.
4. After taking the full dose, drink a small amount of water to ensure no medicine remains in the mouth, or flush the nasogastric or gastrostomy tube with 10 ml of water using a new oral syringe. The syringe used to flush the tube must not be used to measure RAVICTI, to avoid contact between water and the medicine.

1. Close the bottle by screwing the cap back on.

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

If you take more RAVICTI than you should

If you take more of this medicine than prescribed, contact your doctor.

If you experience any of the following symptoms, seek medical advice or go to a hospital immediately, as they may be signs of overdose or elevated ammonia levels:

• drowsiness, fatigue, or dizziness, sometimes confusion
• headache
• changes in taste sensation
• hearing problems
• disorientation
• reduced ability to remember things
• worsening of existing neurological disorders.

If you forget to take RAVICTI

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

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

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

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

If you stop taking RAVICTI

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

4. Possible adverse effects

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

If you experience any adverse effect, inform your doctor or pharmacist.

This medicine may cause the following adverse effects:

Frequent: may affect up to 1 in 10 people

• stomach swelling or pain, constipation, diarrhea, heartburn, gas, vomiting, feeling like vomiting (nausea), mouth pain, retching
• swelling of the hands or feet, feeling tired
• dizziness, headache, or tremors
• decreased or increased appetite
• aversion to certain foods
• bleeding between menstrual periods
• acne, abnormal body odour
• blood test results showing increased liver enzymes, imbalances in blood salts, low number of white blood cells («lymphocytes»), or low vitamin D levels.

Uncommon: may affect up to 1 in 100 people

• dry mouth
• burping, stomach pain or discomfort, changes in stools (e.g. oily appearance), urgent need to defecate, painful defecation, inflammation of the mouth and lips
• feeling of hunger
• increased body temperature
• hot flushes
• gallbladder pain
• bladder pain
• back pain, joint pain, muscle spasms, pain in arms or legs, heel spur syndrome
• viral gastrointestinal infection
• tingling sensation, feeling very restless, drowsiness, sleepiness, speech problems, confusion, feeling depressed, taste disturbances
• cessation of menstruation or irregular menstrual periods
• voice changes, nosebleeds, nasal congestion, or throat inflammation or pain
• hair loss, increased sweating, itchy skin rash
• irregular heartbeat
• decreased thyroid function
• weight loss or weight gain
• blood test results showing increased or decreased blood potassium levels
• blood test results showing increased triglyceride levels, low-density lipoproteins, or white blood cells in the blood
• abnormal ECG («electrocardiogram») results
• prolonged prothrombin time in blood tests
• blood test results showing decreased blood albumin levels

Adverse effects in children under 2 months of age

The following adverse effects have been observed in a clinical study involving 16 patients under 2 months of age:

• diarrhea, constipation, flatulence, stomach contents reflux, inadequate feeding
• rash
• reduced number of red blood cells
• increased number of platelets (may cause blood to clot)
• increased liver enzymes
• decreased amino acid concentrations

Adverse effects in children from 2 months to under 2 years of age

• diarrhea, constipation
• eczema, nail streaks, rash

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. RAVICTI Storage

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

Do not use this medicine after the expiry date stated on the carton and on the label of the bottle, after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions. After opening the bottle, this medicine should be used within 14 days of opening. The bottle should be discarded even if it is not empty.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Package contents and other information

Composition of Ravicti

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

Appearance of the product and contents of the container

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

To ensure correct administration of RAVICTI, CE-marked oral syringes of appropriate size for the prescribed dose and compatible with the syringe adapter may be obtained from the pharmacy. Ask your doctor or pharmacist which type of syringe you need, depending on the prescribed dose volume.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Immedica Pharma AB
SE-113 63 Stockholm
Sweden

Manufacturer

Unimedic AB
Storjordenvägen 2
SE-864 31 Matfors
Sweden

Date of the most recent review of this leaflet: 10/2022

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also provided.