What is it and what is it used for? Ravicti - Glycerol Phenylbutyrate?
Ravicti is a medicine used for the long-term treatment of urea cycle disorders in adults and in children aged two months or older, when the disease cannot be managed only with dietary changes. Patients with urea cycle disorders fail to eliminate waste nitrogen from the body due to the lack of some liver enzymes. In the body, waste nitrogen is transformed into ammonia, which is harmful if it accumulates. Ravicti is used in patients with a deficiency of one or more of the following enzymes: carbamoyl phosphate synthetase I, ornithine carbamyltransferase, argininosuccinate synthetase, argininosuccinate lyase, arginase I and ornithine translocase.
Ravicti contains the active ingredient glycerol phenylbutyrate.
Because the number of patients with urea cycle disorders is low, these diseases are considered "rare" and Ravicti was designated an "orphan medicine" (a medicine used in rare diseases) on 10 June 2010
How is Ravicti - Glycerol Phenylbutyrate used?
Ravicti is available as a liquid (1.1 g / ml) to be taken orally or by means of a tube that passes through the nose and reaches the stomach or passes through the belly to the stomach. It can only be obtained with a prescription and must be prescribed by a doctor experienced in treating patients suffering from urea cycle disorders.
Proteins are a source of nitrogen, therefore Ravicti must be used in combination with a special low-protein diet to reduce nitrogen intake and, in some cases, to food supplements (based on the daily protein intake needed to growth and development).
The dose of Ravicti depends on the diet, height and weight of the patient. During treatment, blood tests should be performed regularly to adjust the daily dose. The daily dose of Ravicti must be divided into equal quantities and be given with each meal. For more information, see the summary of product characteristics (also part of the EPAR).
Treatment with Ravicti may be necessary for life, except when the patient receives a successful liver transplant
How does Ravicti - Glycerol Phenylbutyrate work?
The active substance in Ravicti, glycerol phenylbutyrate, is converted to phenylacetate in the body. Phenylacetate combines with the amino acid glutamine present in proteins, which contains nitrogen, to form a substance that can be eliminated from the body by the kidneys. This decreases the levels of nitrogen in the body, reducing the amount of ammonia produced.
What benefit has Ravicti - Glycerol Phenylbutyrate shown during the studies?
A study of 88 adults with urea cycle disorders compared Ravicti with sodium phenylbutyrate (another medicine used to treat urea cycle disorders). The main measure of effectiveness was the change in blood ammonia levels after 4 weeks of treatment. The study revealed that Ravicti is at least as effective as the comparator in controlling blood ammonia: the estimated average ammonia level was around 866 micromoles per liter in patients treated with Ravicti and 977 micromoles per liter in patients treated with sodium phenylbutyrate. Additional data from supportive studies showed analogous effects of Ravicti in children aged 2 months or older.
What is the risk associated with Ravicti - Glycerol Phenylbutyrate?
The most common adverse events of Ravicti (which may affect more than 5 people in 100) are diarrhea, flatulence (passage of gas) headache, decreased appetite, vomiting, tiredness, feeling sick and abnormal skin odor.
Ravicti should not be used for the treatment of acute hyperammonaemia (sudden rise in blood ammonia levels). For the full list of all side effects reported with Ravicti and the limitations, see the package leaflet.
Why has Ravicti - Glycerol Phenylbutyrate been approved?
The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Ravicti's benefits are greater than its risks and recommended that it be approved for use in the EU.
Ravicti has been shown to be effective in reducing the level of ammonia in the blood in patients suffering from urea cycle disorders. Ravicti is a sustained-release medicine, which means that the active ingredient is constantly released during the day. Therefore, even the elimination of waste nitrogen occurs constantly and this produces better control of ammonia levels in the blood throughout the day. For the same reason, Ravicti should not be used to treat acute hyperammonaemia, for which treatments are needed that act more quickly.
Furthermore, as available in liquid formulation, the Committee considered that Ravicti may be more acceptable, especially for children, than other granular medicines to be added to food; the liquid formulation also facilitates its administration by tube in patients who are unable to swallow due to neurological problems.
The undesirable effects of Ravicti were mainly on the intestine and were considered manageable. However, further data on Ravicti's long-term security are expected.
What measures are being taken to ensure the safe and effective use of Ravicti - Glycerol Phenylbutyrate?
A risk management plan has been developed to ensure that Ravicti is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Ravicti, including the appropriate precautions to be followed by healthcare professionals and patients.
Furthermore, the company that markets Ravicti will set up a patient register to get more information on the benefits and long-term safety of the medicine.
Other information on Ravicti - Glycerol Phenylbutyrate
For more information about treatment with Ravicti, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
