What Is a Urea Cycle Disorder?

If you or your loved one has been diagnosed with a urea cycle disorder (UCD), you may feel overwhelmed at first. The information about UCDs can be hard to understand, and you may be worried. But here you will find useful information to help you better understand UCDs and what you can do to help treat them.

A UCD is a rare genetic condition that a person is born with. In people with UCDs, an enzyme or transporter in the urea cycle is missing or doesn’t work the way it should. Because of this, the body can’t process ammonia properly. Instead of being turned into urea in the liver, ammonia builds up in the body, including in the blood and in the brain. This can be dangerous and cause serious health problems, like coma or brain damage.

How the urea cycle works

We get protein from several sources, including the foods we eat, such as meat, fish, eggs, and cheese. When we eat protein, our bodies break it down into smaller parts. As protein is broken down, a waste product called ammonia is created. The liver helps our bodies change that ammonia into urea, which we get rid of naturally through urine. This process all happens in the urea cycle.

But in people with urea cycle disorders, the liver can’t process ammonia properly. This causes too much ammonia to build up in the body. Ammonia building up in the body can be serious and affect the brain leading to permanent brain damage. When there is too much ammonia in the blood, it’s called hyperammonemia (hi-per-am-oh-NEE-me-uh). Even if you’ve never had a hyperammonemic crisis, it doesn’t mean that high levels of ammonia in your blood aren’t affecting your body. Ammonia levels can go up and down throughout the day and night. You may not feel any symptoms, but you can still have ammonia building up in your body over time. You should be aware that RAVICTI® (glycerol phenylbutyrate) Oral Liquid cannot reverse brain damage and has not been shown to stop it.

There are many places in your body where protein is stored. As protein is broken down, eventually ammonia is produced. The urea cycle's job is to change ammonia into something called urea. Urea then leaves your body through the urine.

Protein from food breaking down in the stomach and small intestine

Stomach Diagram Showing How Protein is Broken Down

Protein from food breaking down in the stomach and small intestine

Urea Cycle Diagram Displaying How Ammonia Changes to Urea in the Liver

Read transcript

Hello, today I want to talk to you about Understanding Urea Cycle Disorders and Your RAVICTI Treatment. First, let's talk about Urea Cycle Disorders. What is a Urea Cycle Disorder?

A urea cycle disorder, or UCD, is a rare inherited condition where toxic levels of waste called ammonia build up in the blood and cause damage throughout the body.

Ammonia is released when the body digests protein from food.

Normally, the liver makes enzymes that break down the ammonia into urea. The body then gets rid of urea through urine.

In people with a UCD, these enzymes don’t work right, so ammonia builds up in the blood.

High levels of ammonia in the blood can make you very sick and cause serious health problems. A low-protein diet and supplements can help keep ammonia levels down, but sometimes this isn’t enough.

Adding RAVICTI can help keep ammonia at a safe level in the blood.

RAVICTI is slowly broken down by a naturally-occurring enzyme found in the digestive tract.

RAVICTI passes through the stomach and starts to slowly break down in the intestine. Once it breaks down, it can start getting to work.

A part of RAVICTI then binds to ammonia molecules to form a RAVICTI/ammonia complex that is excreted in the urine.

When taken correctly, RAVICTI works to keep removing extra ammonia throughout the entire day. RAVICTI may cause side effects. The most common side effects of RAVICTI in adults include: diarrhea, gas, headache, abdomen (stomach) pain, vomiting, tiredness, decreased appetite, indigestion or heartburn.

So how do you take RAVICTI? RAVICTI is a liquid that you take by mouth with a syringe or dosing cup 3 or more times a day with a low-protein diet and in some cases dietary supplements.

It’s important to take RAVICTI exactly as your doctor tells you in order to keep the ammonia in your body at a safe level.

Set reminders so you don’t forget to take your dose...and keep track of when you do take it.

A UCD is a lifelong disease that can cause organ damageand other very serious health problems over time without proper treatment. So even if you’re feeling fine, it’s important to continue taking your Ravicti to help prevent toxic buildup of ammonia in the blood. Talk to your doctor for more information and to help create a routine that works for you.

USE and IMPORTANT SAFETY INFORMATION

What is the most important information I should know about RAVICTI?

RAVICTI may cause serious side effects, including:

Nervous system side effects (Neurotoxicity) Phenylacetate (PAA), a breakdown product of RAVICTI, may cause nervous system side effects. Call your doctor or get medical help right away if you have any of these symptoms while taking RAVICTI:

sleepiness
lightheadedness
change in taste
problems with hearing
confusion
problems with memory
worsening of numbness, tingling, or burning in your hands or feet
headache
feeling very tired (fatigue)
nausea
vomiting

Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with RAVICTI.

What is RAVICTI?

RAVICTI (glycerol phenylbutyrate) Oral Liquid is a prescription medicine used for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). RAVICTI should be used if the UCD cannot be managed with a low-protein diet and dietary supplements alone. RAVICTI must be used along with a low-protein diet and in some cases dietary supplements.
RAVICTI is not used for the acute treatment of hyperammonemia in people with UCD.
It is not known if RAVICTI is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

Do not take RAVICTI if you are allergic to phenylbutyrate. Call your doctor or go to the nearest hospital emergency room if you have wheezing, shortness of breath, cough, low blood pressure, flushing, nausea or a rash while taking RAVICTI.

Before taking RAVICTI, tell your doctor about all of your medical conditions, including if you:

have liver or kidney problems.
have pancreas or bowel (intestine) problems
are pregnant or plan to become pregnant. It is not known if RAVICTI will harm your unborn baby. If you become pregnant during treatment with RAVICTI, call Horizon at 1‐866‐479‐6742 to report the pregnancy.
are breastfeeding or plan to breastfeed. It is not known if RAVICTI passes into your breast milk. Breastfeeding is not recommended during treatment with RAVICTI. Talk to your doctor about the best way to feed your baby if you take RAVICTI.

What are possible side effects of RAVICTI?
RAVICTI may cause serious side effects, including:

See “What is the most important information I should know about RAVICTI?”

The most common side effects of RAVICTI in adults include:

Have liver or kidney problems.
Have pancreas or bowel (intestine) problems.
Are pregnant or plan to become pregnant. It is not known if RAVICTI will harm your unborn baby.
- Pregnancy Registry: There is a Pregnancy Registry for women who take RAVICTI just before becoming pregnant or who become pregnant during treatment with RAVICTI. The purpose of this registry is to collect information about the health of you and your baby. Talk to your doctor about how you can join the Pregnancy Registry. For more information about this registry, call 1-855-823-2595 or visit www.ucdregistry.com.
Are breastfeeding or plan to breastfeed. It is not known if RAVICTI passes into your breast milk. Breastfeeding is not recommended during treatment with RAVICTI. Talk to your doctor about the best way to feed your baby if you take RAVICTI.

What are possible side effects of RAVICTI?

RAVICTI may cause serious side effects, including:

See “What is the most important information I should know about RAVICTI?”

The most common side effects of RAVICTI in adults include:

diarrhea
gas
headache
abdomen (stomach) pain
vomiting
tiredness
decreased appetite
indigestion or heartburn

The most common side effects of RAVICTI in children 2 years to 17 years of age include:

upper abdomen (stomach) pain
rash
nausea
vomiting
diarrhea
decreased appetite
headache

The most common side effects of RAVICTI in children 2 months to less than 2 years of age include:

low white blood cell count (neutropenia)
vomiting
constipation
diarrhea
fever
reduced food intake
cough
stuffy nose
runny nose
skin rash
small round bumps on the skin

The most common side effects of RAVICTI in children less than 2 months of age include:

vomiting
rash
gastroesophageal reflux
increased levels of liver enzymes in the blood
decreased appetite and reduced food intake
low red blood cell count (anemia)
cough
loss of too much body fluid (dehydration)
too much acid in the blood (acidosis)
high blood platelet count (thrombocytosis)
low blood platelet count (thrombocytopenia)
low blood neutrophil count (type of white blood cell) (neutropenia)
high white blood cell count (lymphocytosis)
diarrhea
gas
constipation
fever
drowsiness (lethargy)
irritability
agitation

These are not all of the possible side effects of RAVICTI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For additional important safety information, see the Medication Guide available at RAVICTI.com and discuss with your doctor.

Symptoms of urea cycle disorders

Having too much ammonia in your blood is called hyperammonemia (hi-per-am-oh-NEE-me-uh). Here are some symptoms that could mean you or your loved one may have a UCD without even knowing it:

Confusion
Headache
Dizziness
Seizures

Vomiting
Feeling more tired than usual
Not being hungry
Avoiding protein

Growth problems
Behavior changes
Coma

Even if you’re not having a hyperammonemic crisis, which happens when the amount of ammonia in the blood is dangerously high, daily elevated ammonia levels can be dangerous and cause long-term damage and permanent health problems. That’s why it’s important to be on the lookout for these subtle signs and symptoms.

Because there are different types of urea cycle disorders, symptoms may happen at different ages and vary from person to person. Many other health conditions have the same symptoms. Only your doctor can make a UCD diagnosis.

Getting a urea cycle disorder diagnosis

Because of the wide range of signs and symptoms, identifying a urea cycle disorder can be difficult. Many other health conditions have similar symptoms as UCDs, so a UCD diagnosis must be made by your doctor.

Your doctor can test your blood for high ammonia levels and certain amino acids
Further testing such as genetic or enzyme tests can help tell which type of UCD you have

A high level of ammonia in your body may mean that you have a UCD but a genetic test is used to confirm it.

Know the risks of high
ammonia levels

What is
Hyperammonemia

Learn about the most
common type of UCD

OTC
Deficiency

Find out who should
get tested for a UCD

Genetics:
The Cause of UCDs

Managing urea cycle disorders with your UCD care team

People with urea cycle disorders usually work with a healthcare team. This may include a dietitian and a metabolic geneticist. It can also include a primary care doctor, nurse practitioners, and social workers who can help you manage your UCD.

Connect with other UCD patients

Read transcript

Voiceover:

USE and IMPORTANT SAFETY INFORMATION

What is the most important information I should know about RAVICTI?

RAVICTI may cause serious side effects, including:

Nervous system side effects (Neurotoxicity) Phenylacetate (PAA), a breakdown product of RAVICTI, may cause nervous system side effects. Call your doctor or get medical help right away if you have any of these symptoms while taking RAVICTI:

sleepiness
lightheadedness
change in taste
problems with hearing
confusion
problems with memory
worsening of numbness, tingling, or burning in your hands or feet
headache
feeling very tired (fatigue)
nausea
vomiting

Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with RAVICTI.

Amy:

Mya was diagnosed at 6 months old. Our first step was low-protein diet. And she was just on that until about a year. At a year, we added some supplements. At 2 years, we had to add a medication, an ammonia scavenger.

The ammonia scavenger she was on could leave a bad taste in the mouth.

It was challenging to just flat out get her to take it.

And I thought there has to be another treatment. I was willing to try something new.

So I went to the Internet, and I searched and I searched, and I found RAVICTI. And I thought, I have to get my child on this.

I did talk to my doctor about starting RAVICTI.

I had found most of the information online, so I pretty much sent him a link and said, "Here's this information." And he responded, "Great. I support you." RAVICTI may not be a fit for everybody. For Mya specifically, it is convenient because it’s tasteless, it’s odorless. Mya really doesn’t mind taking it.

For us, starting RAVICTI was pretty easy.

It was easy for her to take and the routine was the same, cause she still got the RAVICTI at the same time every day that she got the other one. It was just a different medication.

Every family’s experience is different, but for us Mya has been on RAVICTI for almost 6 years and we continue to like the convenience.

USE and IMPORTANT SAFETY INFORMATION

What is the most important information I should know about RAVICTI?

RAVICTI may cause serious side effects, including:

sleepiness
lightheadedness
change in taste
problems with hearing
confusion
problems with memory
worsening of numbness, tingling, or burning in your hands or feet
headache
feeling very tired (fatigue)
nausea
vomiting

Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with RAVICTI.

What is RAVICTI?

RAVICTI (glycerol phenylbutyrate) Oral Liquid is a prescription medicine used for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). RAVICTI should be used if the UCD cannot be managed with a low-protein diet and dietary supplements alone. RAVICTI must be used along with a low-protein diet and in some cases dietary supplements.
RAVICTI is not used for the acute treatment of hyperammonemia in people with UCD.
It is not known if RAVICTI is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

Before taking RAVICTI, tell your doctor about all of your medical conditions, including if you:

have liver or kidney problems.
have pancreas or bowel (intestine) problems
are pregnant or plan to become pregnant. It is not known if RAVICTI will harm your unborn baby. If you become pregnant during treatment with RAVICTI, call Horizon at 1‐866‐479‐6742 to report the pregnancy.
are breastfeeding or plan to breastfeed. It is not known if RAVICTI passes into your breast milk. Breastfeeding is not recommended during treatment with RAVICTI. Talk to your doctor about the best way to feed your baby if you take RAVICTI.

What are possible side effects of RAVICTI?
RAVICTI may cause serious side effects, including:

See “What is the most important information I should know about RAVICTI?”

The most common side effects of RAVICTI in adults include:

Have liver or kidney problems.
Have pancreas or bowel (intestine) problems.
Are pregnant or plan to become pregnant. It is not known if RAVICTI will harm your unborn baby.
- Pregnancy Registry: There is a Pregnancy Registry for women who take RAVICTI just before becoming pregnant or who become pregnant during treatment with RAVICTI. The purpose of this registry is to collect information about the health of you and your baby. Talk to your doctor about how you can join the Pregnancy Registry. For more information about this registry, call 1-855-823-2595 or visit www.ucdregistry.com.
Are breastfeeding or plan to breastfeed. It is not known if RAVICTI passes into your breast milk. Breastfeeding is not recommended during treatment with RAVICTI. Talk to your doctor about the best way to feed your baby if you take RAVICTI.

What are possible side effects of RAVICTI?

RAVICTI may cause serious side effects, including:

See “What is the most important information I should know about RAVICTI?”

The most common side effects of RAVICTI in adults include:

diarrhea
gas
headache
abdomen (stomach) pain
vomiting
tiredness
decreased appetite
indigestion or heartburn

The most common side effects of RAVICTI in children 2 years to 17 years of age include:

upper abdomen (stomach) pain
rash
nausea
vomiting
diarrhea
decreased appetite
headache

The most common side effects of RAVICTI in children 2 months to less than 2 years of age include:

low white blood cell count (neutropenia)
vomiting
constipation
diarrhea
fever
reduced food intake
cough
stuffy nose
runny nose
skin rash
small round bumps on the skin

The most common side effects of RAVICTI in children less than 2 months of age include:

vomiting
rash
gastroesophageal reflux
increased levels of liver enzymes in the blood
decreased appetite and reduced food intake
low red blood cell count (anemia)
cough
loss of too much body fluid (dehydration)
too much acid in the blood (acidosis)
high blood platelet count (thrombocytosis)
low blood platelet count (thrombocytopenia)
low blood neutrophil count (type of white blood cell) (neutropenia)
high white blood cell count (lymphocytosis)
diarrhea
gas
constipation
fever
drowsiness (lethargy)
irritability
agitation

These are not all of the possible side effects of RAVICTI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For additional important safety information, see the Medication Guide available at RAVICTI.com and discuss with your doctor.

You don't have to feel alone because you’re living with a urea cycle disorder (UCD). You can share your experiences with other UCD patients and caregivers who know what you're going through because they live with UCDs every day, too. Watch all of the UCD Patient Videos for the stories of other UCD patients and caregivers.

About RAVICTI.

The #1 prescribed ammonia-controlling treatment for UCD*.

A liquid medicine that can be taken by mouth that's FDA-approved to treat most types of UCDs for newborns, babies, children, and adults. See approved uses below.

Learn more

Real Patients. Real Stories.

"As the mother of a child
with a rare disease, you
have to find your own
voice, and use it."
–Amy | Caregiver

Talk to someone who’s been there

*According to data sourced from IQVIA and Horizon, between 6/01/2018 to 5/31/2019. Based on the total number of unique patients who had at least one dispense for RAVICTI in the United States.

USE and IMPORTANT SAFETY INFORMATION

What is the most important safety information I should know about RAVICTI? RAVICTI may cause serious side effects, including: Nervous system side effects (Neurotoxicity) Phenylacetate (PAA), a breakdown product of RAVICTI, may cause nervous system side effects.

USE and IMPORTANT SAFETY INFORMATION

What is the most important safety information I should know about RAVICTI?
RAVICTI may cause serious side effects, including:
Nervous system side effects (Neurotoxicity) Phenylacetate (PAA), a breakdown product of RAVICTI, may cause nervous system side effects. Call your doctor or get medical help right away if you have any of these symptoms while taking RAVICTI:

sleepiness
lightheadedness
change in taste
problems with hearing
confusion
problems with memory

worsening of numbness, tingling, or burning in your hands or feet
headache
feeling very tired (fatigue)
nausea
vomiting

Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with RAVICTI.

What is RAVICTI?

RAVICTI (glycerol phenylbutyrate) Oral Liquid is a prescription medicine used for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). RAVICTI should be used if the UCD cannot be managed with a low-protein diet and dietary supplements alone. RAVICTI must be used along with a low-protein diet and in some cases dietary supplements.
RAVICTI is not used for the acute treatment of hyperammonemia in people with UCD.
It is not known if RAVICTI is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

Before taking RAVICTI, tell your doctor about all of your medical conditions, including if you:

have liver or kidney problems
have pancreas or bowel (intestine) problems.
are pregnant or plan to become pregnant. It is not known if RAVICTI will harm your unborn baby. If you become pregnant during treatment with RAVICTI, call Horizon at 1‐866‐479‐6742 to report the pregnancy.
are breastfeeding or plan to breastfeed. It is not known if RAVICTI passes into your breast milk. Breastfeeding is not recommended during treatment with RAVICTI. Talk to your doctor about the best way to feed your baby if you take RAVICTI.

What are possible side effects of RAVICTI?

RAVICTI may cause serious side effects, including:

See "What is the most important information I should know about RAVICTI?"

The most common side effects of RAVICTI in adults include:

diarrhea
gas
headache
abdomen (stomach) pain

vomiting
tiredness
decreased appetite
indigestion or heartburn

The most common side effects of RAVICTI in children 2 years to 17 years of age include:

upper abdomen (stomach) pain
rash
nausea
vomiting

diarrhea
decreased appetite
headache

The most common side effects of RAVICTI in children 2 months to less than 2 years of age include:

low white blood cell count (neutropenia)
vomiting
constipation
diarrhea
fever

reduced food intake
cough
stuffy nose
runny nose
skin rash
small round bumps on the skin

The most common side effects of RAVICTI in children less than 2 months of age include:

vomiting
rash
gastroesophageal reflux
increased levels of liver enzymes in the blood
decreased appetite and reduced food intake
low red blood cell count (anemia)
cough
loss of too much body fluid (dehydration)
too much acid in the blood (acidosis)
high blood platelet count (thrombocytosis)

low blood platelet count (thrombocytopenia)
low blood neutrophil count (type of
white blood
cell) (neutropenia)
high white blood cell count (lymphocytosis)
diarrhea
gas
constipation
fever
drowsiness (lethargy)
irritability
agitation

These are not all of the possible side effects of RAVICTI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For additional Important Safety Information, click here for the Medication Guide and discuss with your doctor.

USE and IMPORTANT SAFETY INFORMATION

What is the most important safety information I should know about RAVICTI? RAVICTI may cause serious side effects, including: Nervous system side effects (Neurotoxicity) Phenylacetate (PAA), a breakdown product of RAVICTI, may cause nervous system side effects.

USE and IMPORTANT SAFETY INFORMATION

sleepiness
lightheadedness
change in taste
problems with hearing
confusion
problems with memory

worsening of numbness, tingling, or burning in your hands or feet
headache
feeling very tired (fatigue)
nausea
vomiting

Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with RAVICTI.

What is RAVICTI?

RAVICTI (glycerol phenylbutyrate) Oral Liquid is a prescription medicine used for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). RAVICTI should be used if the UCD cannot be managed with a low-protein diet and dietary supplements alone. RAVICTI must be used along with a low-protein diet and in some cases dietary supplements.
RAVICTI is not used for the acute treatment of hyperammonemia in people with UCD.
It is not known if RAVICTI is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

Before taking RAVICTI, tell your doctor about all of your medical conditions, including if you:

have liver or kidney problems
have pancreas or bowel (intestine) problems.
are pregnant or plan to become pregnant. It is not known if RAVICTI will harm your unborn baby. If you become pregnant during treatment with RAVICTI, call Horizon at 1‐866‐479‐6742 to report the pregnancy.
are breastfeeding or plan to breastfeed. It is not known if RAVICTI passes into your breast milk. Breastfeeding is not recommended during treatment with RAVICTI. Talk to your doctor about the best way to feed your baby if you take RAVICTI.

What are possible side effects of RAVICTI?

RAVICTI may cause serious side effects, including:

See "What is the most important information I should know about RAVICTI?"

The most common side effects of RAVICTI in adults include:

diarrhea
gas
headache
abdomen (stomach) pain

vomiting
tiredness
decreased appetite
indigestion or heartburn

The most common side effects of RAVICTI in children 2 years to 17 years of age include:

upper abdomen (stomach) pain
rash
nausea
vomiting

diarrhea
decreased appetite
headache

The most common side effects of RAVICTI in children 2 months to less than 2 years of age include:

low white blood cell count (neutropenia)
vomiting
constipation
diarrhea
fever

reduced food intake
cough
stuffy nose
runny nose
skin rash
small round bumps on the skin

The most common side effects of RAVICTI in children less than 2 months of age include:

vomiting
rash
gastroesophageal reflux
increased levels of liver enzymes in the blood
decreased appetite and reduced food intake
low red blood cell count (anemia)
cough
loss of too much body fluid (dehydration)
too much acid in the blood (acidosis)
high blood platelet count (thrombocytosis)

low blood platelet count (thrombocytopenia)
low blood neutrophil count (type of
white blood
cell) (neutropenia)
high white blood cell count (lymphocytosis)
diarrhea
gas
constipation
fever
drowsiness (lethargy)
irritability
agitation

These are not all of the possible side effects of RAVICTI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For additional Important Safety Information, click here for the Medication Guide and discuss with your doctor.

*According to data sourced from IQVIA and Horizon, between 6/01/2018 to 5/31/2019. Based on the total number of unique patients who had at least one dispense for RAVICTI in the United States.