RAVICTI
Nitrogen Scavenger for Urea Cycle Disorders
Quick Facts About RAVICTI
Key Takeaways About RAVICTI
- Treats urea cycle disorders: RAVICTI provides an alternative pathway for nitrogen excretion in patients with six known types of UCDs, including CPS, OTC, ASS, ASL, ARG, and HHH syndrome deficiencies
- Taken with meals: RAVICTI should be taken during or immediately after meals. In young children, it should be given during or immediately after feeding
- Lifelong treatment: Patients will need to take RAVICTI and follow a protein-restricted diet for life, unless they undergo a successful liver transplant
- Not for acute crises: RAVICTI is not indicated for the treatment of acute hyperammonaemic episodes, which require emergency hospital care
- Use within 14 days of opening: Once opened, the bottle must be discarded after 14 days, even if not empty. Do not rinse the oral syringe with water between daily doses
What Is RAVICTI and What Is It Used For?
RAVICTI (glycerol phenylbutyrate) is a nitrogen-binding agent used for the chronic management of urea cycle disorders (UCDs) in adults and children. It helps the body eliminate excess nitrogen through an alternative biochemical pathway when the urea cycle is deficient, thereby reducing potentially dangerous ammonia levels in the blood.
RAVICTI contains the active substance glycerol phenylbutyrate, which belongs to a class of medications known as nitrogen scavengers. It is approved for the treatment of six known types of urea cycle disorders, including deficiencies of carbamoyl phosphate synthetase I (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase I (ARG), and ornithine translocase deficiency leading to hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome.
Urea cycle disorders are a group of rare inherited metabolic diseases in which the body is unable to properly convert nitrogen from dietary protein into urea for excretion. Under normal circumstances, the liver converts excess nitrogen from protein metabolism into ammonia, which is then processed through the urea cycle – a series of enzymatic reactions that convert ammonia into urea. Urea is water-soluble and harmlessly excreted by the kidneys in urine.
In patients with UCDs, one or more of the enzymes required for the urea cycle is absent or dysfunctional. As a result, ammonia accumulates in the blood (hyperammonaemia). Elevated ammonia is highly toxic to the brain and central nervous system. If left untreated, hyperammonaemia can cause progressive neurological damage, reduced consciousness, cerebral oedema, seizures, coma, and in severe cases, death. Even chronic, moderately elevated ammonia levels can lead to cognitive impairment and developmental delays, particularly in children.
How RAVICTI Works
RAVICTI works by providing an alternative pathway for nitrogen excretion that bypasses the defective urea cycle. After oral administration, glycerol phenylbutyrate is hydrolysed by pancreatic lipases in the gastrointestinal tract to release phenylbutyric acid (PBA). PBA is then absorbed into the bloodstream and transported to the liver, where it undergoes beta-oxidation to form phenylacetic acid (PAA).
PAA conjugates with the amino acid glutamine in the liver and kidneys to form phenylacetylglutamine (PAGN). Each molecule of PAGN contains two atoms of waste nitrogen (from glutamine). PAGN is water-soluble and is efficiently excreted by the kidneys. This process effectively removes two moles of nitrogen per mole of PAGN formed, providing a significant nitrogen-clearing capacity independent of the defective urea cycle.
RAVICTI was developed as an improved formulation compared to sodium phenylbutyrate (NaPBA) tablets, which have a notoriously unpleasant taste and odour that significantly affect patient compliance. RAVICTI is a tasteless, odourless liquid that is better tolerated and provides more consistent plasma levels of the active metabolite. It also contains substantially less sodium, which is beneficial for patients who need to restrict their sodium intake. RAVICTI was first approved by the FDA in 2013 and by the EMA in 2015.
What Should You Know Before Taking RAVICTI?
Before starting RAVICTI, inform your doctor about all your medical conditions, especially kidney or liver problems, and pancreatic or gastrointestinal conditions. RAVICTI must not be used if you have acute hyperammonaemia requiring rapid intervention, or if you are allergic to glycerol phenylbutyrate.
Contraindications
You should not take RAVICTI if any of the following apply to you:
- Allergy to glycerol phenylbutyrate – if you have had a hypersensitivity reaction to the active substance or any excipients
- Acute hyperammonaemia (acutely elevated ammonia levels in the blood) – this is a medical emergency requiring immediate intravenous treatment in a hospital setting. RAVICTI is an oral medication that does not act rapidly enough to manage acute hyperammonaemic crises
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 taking RAVICTI if you have or have had any of the following conditions:
- Kidney problems – RAVICTI and its metabolites are eliminated from the body through the kidneys. Impaired kidney function may lead to accumulation of the active metabolite and require dose adjustment
- Liver problems – the liver plays a central role in the metabolism of RAVICTI. Hepatic impairment may alter the conversion of the drug and affect ammonia metabolism
- Pancreatic, stomach, or intestinal problems – RAVICTI depends on pancreatic lipases for absorption. Conditions affecting the pancreas or gastrointestinal tract may reduce absorption and effectiveness of the medication
In certain situations such as during infections, after surgery, or periods of metabolic stress, ammonia levels may rise despite ongoing treatment with RAVICTI. Elevated ammonia can damage the brain (hyperammonaemic encephalopathy). If you experience nausea, vomiting, confusion, drowsiness, or any unusual neurological symptoms, contact your doctor or go to a hospital emergency department immediately.
Your doctor will need to perform regular blood tests to monitor your ammonia levels and determine the correct dose of RAVICTI for you. These tests are essential for ensuring optimal treatment efficacy and safety.
Pregnancy and Breastfeeding
If you are pregnant, talk to your doctor before taking RAVICTI. If you become pregnant while taking RAVICTI, contact your doctor immediately. RAVICTI should not be used during pregnancy as a risk to the unborn baby cannot be excluded based on available data.
If you are a woman of childbearing potential, you must use effective contraception during treatment with RAVICTI. It is important to discuss the most appropriate contraceptive method with your doctor, as RAVICTI may reduce the effectiveness of hormonal contraceptives (such as the oral contraceptive pill).
You should discuss with your doctor before breastfeeding while using RAVICTI. A decision must be made whether to discontinue breastfeeding or to discontinue RAVICTI therapy, taking into account the benefit of treatment for you and the benefit of breastfeeding for your baby. RAVICTI may be excreted in breast milk, and a risk to the newborn or infant cannot be excluded.
Driving and Operating Machinery
RAVICTI may significantly affect the ability to drive and operate machinery. While taking RAVICTI, you may experience dizziness or headache. Do not drive or use machinery while experiencing these side effects. If symptoms persist, consult your doctor.
How Does RAVICTI Interact with Other Drugs?
RAVICTI can interact with several medications, including midazolam, barbiturates, hormonal contraceptives, corticosteroids, valproate, haloperidol, probenecid, and lipase inhibitors such as orlistat. Always tell your doctor about all medications you are taking, including over-the-counter products and supplements.
Drug interactions with RAVICTI fall into two main categories: medications that may become less effective when taken with RAVICTI, and medications that may increase ammonia levels or alter how RAVICTI works. Understanding these interactions is crucial for safe and effective treatment of urea cycle disorders.
Medications with Reduced Efficacy
RAVICTI and its metabolites may affect the metabolism of certain drugs, potentially reducing their therapeutic effectiveness. If you take any of the following medications, you may require regular blood tests and dose adjustments:
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Midazolam | Benzodiazepine (sedative) | RAVICTI metabolites may reduce midazolam blood levels through enzyme induction | Monitor sedation levels; dose adjustment may be needed |
| Barbiturates | Sedatives / anti-epileptics | Reduced barbiturate effectiveness when co-administered with RAVICTI | Monitor seizure control and blood levels; adjust dose accordingly |
| Hormonal contraceptives | Oral contraceptive pills | RAVICTI may reduce contraceptive effectiveness | Use additional or alternative non-hormonal contraception |
Medications That Increase Ammonia or Alter RAVICTI Activity
Certain medications can increase ammonia levels in the body or change how RAVICTI is absorbed and metabolised. These interactions are particularly important because elevated ammonia is the primary danger in urea cycle disorders:
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Corticosteroids | Anti-inflammatory | Can increase protein breakdown (catabolism), raising ammonia production | Monitor ammonia levels closely; may need RAVICTI dose increase |
| Valproate (valproic acid) | Anti-epileptic | Independently causes hyperammonaemia; can worsen UCD symptoms significantly | Avoid if possible in UCD patients; if essential, monitor ammonia very closely |
| Haloperidol | Antipsychotic | May increase ammonia levels in the body | Monitor ammonia levels; consider alternative antipsychotic agents |
| Probenecid | Uricosuric agent (gout) | May inhibit renal excretion of PAGN, reducing nitrogen clearance | Monitor ammonia levels and PAGN excretion; adjust RAVICTI dose if needed |
| Orlistat | Lipase inhibitor (weight loss) | Blocks pancreatic lipases needed to release active metabolite from RAVICTI | Avoid co-administration; orlistat may significantly reduce RAVICTI effectiveness |
| Pancreatic lipase supplements | Pancreatic enzyme replacement | May increase the rate of RAVICTI hydrolysis, altering pharmacokinetics | Monitor ammonia levels; timing adjustments may be necessary |
What Is the Correct Dosage of RAVICTI?
The dosage of RAVICTI is individualised based on the patient's body surface area, dietary protein intake, and the specific type of urea cycle disorder. Your doctor will calculate the appropriate dose for you. RAVICTI is typically taken 3 times daily with meals, but young children may require 4 to 6 doses per day.
Always take RAVICTI exactly as your doctor has prescribed. The daily dose is carefully calculated by your physician based on your body size and weight, the amount of protein in your diet, and the nature of your specific urea cycle disorder. If you have kidney or liver problems, your doctor may prescribe a lower dose. Regular blood tests are required to ensure the dose is correct.
Adults
Adult Dosage
The dose is individualised. Your doctor will calculate it based on your body surface area, daily protein intake, and ammonia levels. RAVICTI is typically taken 3 times daily with meals. There must be at least 3 hours between each dose. The maximum recommended daily dose is 17.5 mL/day (19.25 g glycerol phenylbutyrate).
Children
Paediatric Dosage
RAVICTI is approved for use in paediatric patients, including neonates. In young children (under 2 years), the medication is typically given 4 to 6 times per day, usually during or immediately after each feeding. In older children, the dosing schedule usually mirrors that of adults (3 times daily with meals). The dose is calculated based on body surface area and adjusted according to blood test results. There must be at least 3 hours between each dose.
Elderly Patients
Elderly Dosage
There are limited data on the use of RAVICTI in elderly patients. Dosing should follow the same principles as for other adults, with careful consideration of kidney and liver function. Your doctor may start with a lower dose if you have age-related decline in kidney or liver function.
How to Take RAVICTI
RAVICTI is an oral liquid that should be taken during or immediately after a meal. It can be administered in the following ways:
- By mouth – using the supplied oral syringe to measure the exact dose
- Via gastrostomy tube (G-tube) – a tube surgically placed through the abdomen into the stomach
- Via nasogastric tube (NG-tube) – a tube passed through the nose to the stomach
Use an oral syringe to measure your dose accurately. Select a syringe size closest to (but not smaller than) your prescribed dose. After taking your dose by mouth, drink a small amount of water to ensure no medication remains in the mouth. If using a feeding tube, flush with 10 mL of water using a separate syringe after the dose.
RAVICTI is denser than most liquids. Do not add or stir RAVICTI into large amounts of water, juice, or other beverages, as it may sink to the bottom and you may not receive your full dose. RAVICTI can be added to small amounts of soft food such as applesauce, ketchup, or pumpkin puree.
Do not rinse the bottle adapter or oral syringe with water between daily doses. Water causes glycerol phenylbutyrate to break down, resulting in a cloudy appearance. Store the bottle and oral syringe in a clean, dry place between doses. Discard the oral syringe after the last dose of each day. Each bottle must be discarded after 14 days of opening, even if it is not empty.
Missed Dose
If you forget to take a dose, take it as soon as you remember. However:
- For adults: if your next dose is due in less than 2 hours, skip the missed dose and take the next one at the usual time
- For children: if the next dose is due in less than 30 minutes, skip the missed dose and give the next dose at the usual time
Do not take a double dose to make up for a forgotten dose.
Overdose
If you take more RAVICTI than prescribed, contact your doctor immediately or go to a hospital emergency department. Signs of overdose or elevated ammonia levels include:
- Feeling sleepy, tired, dizzy, or confused
- Headache or taste changes
- Hearing problems
- Impaired memory or concentration
- Worsening of existing neurological conditions
RAVICTI is a chronic treatment that must be continued for life unless you undergo a successful liver transplant. Do not stop taking RAVICTI without consulting your doctor, as this could lead to a dangerous rise in ammonia levels. Your protein-restricted diet must also be maintained throughout treatment.
What Are the Side Effects of RAVICTI?
Like all medicines, RAVICTI can cause side effects, although not everyone gets them. The most common side effects are gastrointestinal symptoms including diarrhoea, flatulence, vomiting, nausea, abdominal pain, and decreased appetite. Most side effects are mild to moderate and often improve with continued treatment.
Side effects are classified by frequency based on clinical trial data. If you experience any side effects, particularly those that are severe or persistent, tell your doctor or pharmacist. The side effects listed below were observed during clinical studies and post-marketing surveillance.
Common Side Effects
- Abdominal bloating, abdominal pain, constipation, diarrhoea
- Heartburn (dyspepsia), flatulence, vomiting, nausea
- Pain in the mouth, retching
- Swelling of hands or feet (peripheral oedema)
- Feeling of tiredness (fatigue)
- Dizziness, headache, tremor
- Decreased or increased appetite, food aversion
- Irregular menstrual bleeding, acne, abnormal skin odour
- Elevated liver enzymes (in blood tests)
- Electrolyte imbalance, low lymphocyte count, low vitamin D levels
Uncommon Side Effects
- Dry mouth, belching, stomach discomfort, oily stools
- Urgent need to defecate, painful bowel movements
- Inflammation of the mouth and lips
- Increased body temperature, hot flushes, hunger
- Gallbladder pain, bladder pain
- Back pain, joint swelling, muscle spasms, heel spurs
- Pain in arms and legs
- Viral gastroenteritis
- Tingling sensations, restlessness, drowsiness, speech difficulties
- Confusion, depressed mood, altered taste perception
- Absent or irregular menstrual periods
- Voice disorders, nosebleeds, nasal congestion, sore throat
- Hair loss, excessive sweating, itchy rash
- Irregular heartbeat, decreased thyroid function
- Weight loss or weight gain
- Abnormal blood potassium levels (high or low)
- Elevated triglycerides, elevated LDL cholesterol
- Abnormal ECG findings, prolonged prothrombin time
- Low blood albumin levels
Side Effects in Infants Under 2 Months
The following side effects have been observed in a clinical study involving 16 patients under 2 months of age:
- Diarrhoea, constipation, flatulence, regurgitation, poor appetite
- Rash
- Decreased red blood cell count (anaemia)
- Increased platelet count (may increase risk of blood clots)
- Elevated liver enzymes
- Decreased amino acid levels
Side Effects in Children Aged 2 Months to 2 Years
- Diarrhoea, constipation
- Eczema, ridged nails, skin rash
It is important to report suspected side effects after a medicine has been authorised. This allows continued monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients are encouraged to report side effects to their national pharmacovigilance agency (for example, the FDA MedWatch programme in the United States, or the Yellow Card Scheme in the United Kingdom).
How Should You Store RAVICTI?
Store RAVICTI out of the sight and reach of children. Once opened, the bottle must be used within 14 days and then discarded, even if it is not empty. There are no special storage temperature requirements.
Do not use RAVICTI after the expiry date printed on the carton and bottle label after "EXP". The expiry date refers to the last day of the stated month. There are no special storage requirements for unopened bottles.
Once the bottle has been opened, you must use your medicine within 14 days. After 14 days, the bottle should be discarded even if it still contains liquid. This is because exposure to air and environmental moisture can affect the stability and quality of the medication over time.
Do not dispose of medications via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines no longer in use. These measures help to protect the environment.
What Does RAVICTI Contain?
RAVICTI contains only one ingredient: glycerol phenylbutyrate. Each millilitre of liquid contains 1.1 g of glycerol phenylbutyrate, corresponding to a density of 1.1 g/mL. There are no other excipients.
The active substance is glycerol phenylbutyrate. Each mL of liquid contains 1.1 g of glycerol phenylbutyrate. The product has a density of 1.1 g/mL. Notably, RAVICTI contains no other ingredients (excipients) – the liquid consists entirely of the active substance.
RAVICTI is supplied as a clear liquid in a 25 mL transparent glass bottle with a child-resistant plastic cap. The bottle includes an integrated syringe adapter to ensure accurate dosing. CE-marked oral syringes of appropriate size for the prescribed dose can be purchased from pharmacies. Ask your doctor or pharmacist which syringe size is suitable for your prescribed dosing volume.
The manufacturer of RAVICTI is Unimedic AB (Matfors, Sweden) and Patheon France (Bourgoin Jallieu, France). The marketing authorisation holder is Immedica Pharma AB, Stockholm, Sweden. Further information about this medicine is available on the European Medicines Agency (EMA) website.
Frequently Asked Questions About RAVICTI
RAVICTI (glycerol phenylbutyrate) and sodium phenylbutyrate (NaPBA, marketed as Buphenyl or Ammonaps) both ultimately produce the same active metabolite – phenylacetic acid (PAA) – which removes nitrogen from the body. However, they differ in several important ways. RAVICTI is a tasteless, odourless liquid, whereas NaPBA tablets and powder have an extremely unpleasant, salty taste and strong odour that many patients find intolerable. RAVICTI contains substantially less sodium (no sodium), making it preferable for patients who need to restrict sodium intake. Clinical studies have shown that RAVICTI provides more consistent plasma PAA levels throughout the day, potentially leading to more stable ammonia control. RAVICTI is taken as a liquid with meals, while NaPBA is typically taken as tablets or powder dissolved in liquid.
No, RAVICTI does not cure urea cycle disorders. UCDs are genetic conditions caused by inherited enzyme deficiencies. RAVICTI manages the condition by providing an alternative pathway for nitrogen removal, but it does not correct the underlying enzyme deficiency. Treatment with RAVICTI, along with a protein-restricted diet and amino acid supplementation, must be continued for the patient's entire life. The only potential cure for UCD is a successful liver transplant, which can restore the urea cycle function. However, liver transplantation carries its own significant risks and is not appropriate for all patients.
A protein-restricted diet is essential because dietary protein is the primary source of nitrogen that the body needs to eliminate. In patients with urea cycle disorders, the body cannot efficiently process nitrogen from protein metabolism through the normal urea cycle. By restricting protein intake, you reduce the amount of waste nitrogen that needs to be cleared from the body. RAVICTI helps eliminate excess nitrogen, but it cannot compensate for unlimited protein consumption. Your diet must be carefully designed by a metabolic dietitian to ensure you receive enough essential amino acids and calories for growth and health while limiting overall protein intake. Some patients may need supplementation with essential amino acids (such as arginine or citrulline) and protein-free calorie supplements.
If your child vomits shortly after taking RAVICTI, contact your doctor or specialist metabolic team for guidance. The advice will depend on how soon after the dose the vomiting occurred and whether any of the medication was likely absorbed. Generally, if vomiting occurs within 30 minutes of a dose, a replacement dose may be considered, but this should always be done under medical guidance to avoid overdosing. If vomiting is persistent or accompanied by other symptoms such as lethargy, confusion, or irritability, this could indicate rising ammonia levels, and you should seek medical attention immediately.
Yes, RAVICTI is approved for use in paediatric patients including neonates (newborns). Clinical studies have evaluated the safety and efficacy of RAVICTI in patients under 2 months of age. However, dosing in neonates requires very careful medical supervision, and the medication is typically administered 4 to 6 times per day during or immediately after feeds. Side effects observed in very young infants include diarrhoea, constipation, flatulence, regurgitation, poor appetite, rash, and changes in blood cell counts. All neonates with confirmed or suspected UCD should be managed by a specialist metabolic team experienced in the care of these rare conditions.
Once opened, RAVICTI must be discarded after 14 days because exposure to air and environmental moisture can cause glycerol phenylbutyrate to begin breaking down. Contact with water is particularly problematic – it can cause the liquid to become cloudy, indicating chemical degradation. This is also why the oral syringe should not be rinsed with water between daily doses. Using degraded medication could mean you do not receive the correct dose, potentially leading to inadequate ammonia control. Always use a fresh bottle and new syringe adapter after 14 days, and keep the bottle and syringe stored in a clean, dry place between doses.
References
- European Medicines Agency (EMA). RAVICTI – Summary of Product Characteristics. Available at: EMA RAVICTI EPAR. Last updated 2025.
- U.S. Food and Drug Administration (FDA). RAVICTI (glycerol phenylbutyrate) Prescribing Information. Approved February 2013. Available at: FDA Prescribing Information.
- Diaz GA, Krivitzky LS, Mokhtarani M, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013;57(6):2171–2179. doi:10.1002/hep.26058
- Ah Mew N, Simpson KL, Gropman AL, et al. Urea Cycle Disorders Overview. In: Adam MP, et al., editors. GeneReviews. Seattle (WA): University of Washington; 2003 [Updated 2023].
- American College of Medical Genetics and Genomics (ACMG). Urea Cycle Disorders Management Guidelines. Genetics in Medicine. 2024;26(1):101002.
- Batshaw ML, Tuchman M, Summar M, et al. A longitudinal study of urea cycle disorders. Molecular Genetics and Metabolism. 2014;113(1–2):127–130. doi:10.1016/j.ymgme.2014.08.001
- World Health Organization (WHO). International Classification of Diseases (ICD-10): E72.2 – Disorders of urea cycle metabolism. 2024.
- Berry SA, Lichter-Konecki U, Engel K, et al. Long-term management of patients with urea cycle disorders. Journal of Inherited Metabolic Disease. 2023;46(2):215–233. doi:10.1002/jimd.12579
Editorial Team
Written by the iMedic Medical Editorial Team, specialists in metabolic medicine and clinical pharmacology. All content follows the GRADE framework for evidence assessment.
Reviewed by the iMedic Medical Review Board – an independent panel of board-certified physicians who review all content according to international guidelines (EMA, FDA, ACMG).
Sources: EMA Summary of Product Characteristics, FDA Prescribing Information, ACMG Guidelines, peer-reviewed literature published in Hepatology, Molecular Genetics and Metabolism, and Journal of Inherited Metabolic Disease. Evidence level: 1A where applicable.
Conflict of interest: None. iMedic receives no funding from pharmaceutical companies. All content is editorially independent.