Sodium Phenylbutyrate Powder
It is used to treat urea cycle problems.This drug is not for use to treat sudden high ammonia levels. Be sure you know the signs of high ammonia levels. Sudden high ammonia levels need emergency medical care and can be deadly. Talk with the doctor.
Drug Class
Urea Cycle Disorder Agent
Pharmacologic Class
Nitrogen-scavenging agent; Ammonia detoxicant
Pregnancy Category
Category C
FDA Approved
May 1996
DEA Schedule
Not Controlled
Overview
What is this medicine?
Sodium phenylbutyrate is a medicine used to help the body get rid of extra nitrogen, which can build up in people with certain genetic conditions called urea cycle disorders. This helps prevent harmful levels of ammonia in the blood, which can cause serious health problems.
How to Use This Medicine
Taking Your Medication Correctly
To use this medication safely and effectively, follow your doctor's instructions and read all the information provided. Take your medication with meals to help your body absorb it properly. Before using, shake the container well. If you are using the powder form, mix it with a liquid or soft food, and use only the scoop provided to measure the correct dose. If you mix the powder with food, take the dose immediately and do not store it for later use. However, if you mix it with water, you can store it at room temperature or in the refrigerator for up to 1 week.
If you have a feeding tube, you can still use this medication. Follow the instructions provided by your healthcare provider, and be sure to flush the feeding tube after administering the dose.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry place, away from the bathroom. Keep the lid tightly closed, and store all medications in a secure location out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember, with a meal. However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for a missed dose.
To use this medication safely and effectively, follow your doctor's instructions and read all the information provided. Take your medication with meals to help your body absorb it properly. Before using, shake the container well. If you are using the powder form, mix it with a liquid or soft food, and use only the scoop provided to measure the correct dose. If you mix the powder with food, take the dose immediately and do not store it for later use. However, if you mix it with water, you can store it at room temperature or in the refrigerator for up to 1 week.
If you have a feeding tube, you can still use this medication. Follow the instructions provided by your healthcare provider, and be sure to flush the feeding tube after administering the dose.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry place, away from the bathroom. Keep the lid tightly closed, and store all medications in a secure location out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember, with a meal. However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for a missed dose.
Lifestyle & Tips
- Adhere strictly to prescribed dietary protein restrictions.
- Mix the powder with food or liquid (e.g., formula, milk, applesauce) immediately before use.
- Do not store mixed doses.
- Maintain adequate hydration.
- Report any signs of illness (e.g., vomiting, lethargy) immediately, as these can indicate rising ammonia levels.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Maximum 20 g/day.
Dose Range:
450 - 600 mg
Condition-Specific Dosing:
Urea Cycle Disorders:
Initial dose based on body surface area or weight, adjusted to maintain plasma ammonia and glutamine levels within acceptable ranges.
Pediatric Dosing
Neonatal:
450-600 mg/kg/day, divided into 3-6 doses. Dosage should be individualized based on clinical response and plasma ammonia levels.
Infant:
450-600 mg/kg/day, divided into 3-6 doses. Dosage should be individualized based on clinical response and plasma ammonia levels.
Child:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Maximum 20 g/day. Dosage should be individualized based on clinical response and plasma ammonia levels.
Adolescent:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Maximum 20 g/day. Dosage should be individualized based on clinical response and plasma ammonia levels.
Dose Adjustments
Renal Impairment:
Mild:
Use with caution; monitor sodium and potassium levels.
Moderate:
Use with caution; monitor sodium and potassium levels. Consider dose reduction.
Severe:
Not recommended due to potential for accumulation of phenylacetate and its metabolites, and sodium load.
Dialysis:
Not available
Hepatic Impairment:
Mild:
Use with caution; monitor for signs of toxicity.
Moderate:
Use with caution; monitor for signs of toxicity. Consider dose reduction.
Severe:
Not recommended due to impaired metabolism of phenylbutyrate to phenylacetate and subsequent conjugation.
Pharmacology
Mechanism of Action
Sodium phenylbutyrate is a prodrug that is rapidly metabolized to phenylacetate. Phenylacetate conjugates with glutamine in the liver and kidneys to form phenylacetylglutamine. Phenylacetylglutamine is then excreted by the kidneys, providing an alternative pathway for nitrogen waste excretion, thereby reducing elevated plasma ammonia and glutamine levels in patients with urea cycle disorders.
Pharmacokinetics
Absorption:
Bioavailability:
Not precisely quantified, but well absorbed orally.
Tmax:
Approximately 1 hour (for phenylacetate, the active metabolite).
FoodEffect:
Food does not significantly affect absorption.
Distribution:
Vd:
Not well-defined.
ProteinBinding:
Phenylacetate is approximately 80% bound to plasma proteins.
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 0.8 hours (for phenylacetate).
Clearance:
Primarily renal excretion of phenylacetylglutamine.
ExcretionRoute:
Renal (as phenylacetylglutamine)
Unchanged:
Negligible
Pharmacodynamics
OnsetOfAction:
Within hours (reduction in ammonia levels).
PeakEffect:
Not precisely defined, but sustained effect with regular dosing.
DurationOfAction:
Dependent on dosing frequency and continued administration.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of acidosis (too much acid in the blood), such as:
+ Confusion
+ Fast breathing
+ Fast heartbeat
+ Irregular heartbeat
+ Severe stomach pain, nausea, or vomiting
+ Excessive sleepiness
+ Shortness of breath
+ Feeling extremely tired or weak
Signs of electrolyte problems, such as:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Balance problems
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe nausea or vomiting
Feeling extremely tired or weak
Dizziness or headache
Nausea or vomiting
Excessive sleepiness
Confusion
Changes in hearing
Memory problems or loss
Abnormal burning, numbness, or tingling sensations
Swelling
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor for advice:
Decreased appetite
Bad taste in the mouth
Changes in body odor
Menstrual changes or irregular periods
This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of acidosis (too much acid in the blood), such as:
+ Confusion
+ Fast breathing
+ Fast heartbeat
+ Irregular heartbeat
+ Severe stomach pain, nausea, or vomiting
+ Excessive sleepiness
+ Shortness of breath
+ Feeling extremely tired or weak
Signs of electrolyte problems, such as:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Balance problems
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe nausea or vomiting
Feeling extremely tired or weak
Dizziness or headache
Nausea or vomiting
Excessive sleepiness
Confusion
Changes in hearing
Memory problems or loss
Abnormal burning, numbness, or tingling sensations
Swelling
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor for advice:
Decreased appetite
Bad taste in the mouth
Changes in body odor
Menstrual changes or irregular periods
This is not an exhaustive list of possible side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Unusual tiredness or lethargy
- Frequent vomiting
- Irritability or changes in behavior
- Poor feeding (in infants/children)
- Confusion or disorientation
- Slurred speech
- Unusual body odor (fishy or musty, due to phenylacetate accumulation)
- Swelling (edema) in hands, feet, or ankles
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are currently taking any of the following medications: divalproex, haloperidol, or valproic acid. Please note that this is not an exhaustive list of interacting medications.
All medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This information will help your doctor and pharmacist assess potential interactions and ensure safe treatment.
Any health problems you have, as they may affect the safety and efficacy of this medication.
Remember, it is crucial to consult with your doctor before starting, stopping, or changing the dose of any medication to ensure your safety and avoid potential interactions. Always verify with your doctor that it is safe to take this medication with your existing medications and health conditions.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are currently taking any of the following medications: divalproex, haloperidol, or valproic acid. Please note that this is not an exhaustive list of interacting medications.
All medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This information will help your doctor and pharmacist assess potential interactions and ensure safe treatment.
Any health problems you have, as they may affect the safety and efficacy of this medication.
Remember, it is crucial to consult with your doctor before starting, stopping, or changing the dose of any medication to ensure your safety and avoid potential interactions. Always verify with your doctor that it is safe to take this medication with your existing medications and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Adhere to the diet plan recommended by your doctor to ensure safe and effective treatment. Consider wearing a medical alert identification to alert others of your condition in case of an emergency. If you are following a low-sodium or sodium-free diet, consult with your doctor, as some formulations of this medication may contain sodium. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition and adjust treatment as needed. If you are administering this medication to a child, be sure to discuss any changes in the child's weight with your doctor, as the dosage may need to be adjusted accordingly. Additionally, if you are pregnant, planning to become pregnant, or breastfeeding, consult with your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Somnolence
- Fatigue
- Headache
- Nausea
- Vomiting
- Confusion
- Metabolic acidosis
- Hypernatremia
- Hypokalemia
What to Do:
Seek immediate medical attention. Call 911 or Poison Control (1-800-222-1222). Treatment is supportive, including discontinuation of the drug, correction of electrolyte imbalances, and potentially hemodialysis in severe cases.
Drug Interactions
Major Interactions
- Valproic acid (may inhibit phenylacetylglutamine formation, increasing ammonia levels)
- Haloperidol (may increase ammonia levels)
Moderate Interactions
- Probenecid (may inhibit renal excretion of phenylacetylglutamine)
- Corticosteroids (may increase protein catabolism, potentially increasing ammonia levels)
Monitoring
Baseline Monitoring
Plasma Ammonia
Rationale: To establish baseline and guide initial dosing.
Timing: Prior to initiation of therapy.
Plasma Amino Acids (especially glutamine, phenylalanine)
Rationale: To assess metabolic control and guide dietary protein restriction.
Timing: Prior to initiation of therapy.
Liver Function Tests (ALT, AST, bilirubin)
Rationale: To assess hepatic function, as metabolism occurs in the liver.
Timing: Prior to initiation of therapy.
Renal Function (BUN, creatinine)
Rationale: To assess renal function, as metabolites are renally excreted.
Timing: Prior to initiation of therapy.
Electrolytes (Sodium, Potassium, Chloride, Bicarbonate)
Rationale: Sodium phenylbutyrate contains a significant sodium load, which can affect electrolyte balance.
Timing: Prior to initiation of therapy.
Routine Monitoring
Plasma Ammonia
Frequency: Weekly initially, then monthly or as clinically indicated.
Target: Within normal limits for age (e.g., <50 µmol/L for adults).
Action Threshold: Elevated levels require dose adjustment, dietary review, or acute intervention.
Plasma Amino Acids (glutamine, phenylalanine)
Frequency: Monthly or every 3-6 months, or as clinically indicated.
Target: Glutamine within target range (e.g., 500-1000 µmol/L); Phenylalanine within target range.
Action Threshold: Abnormal levels indicate need for dose or dietary protein adjustment.
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Every 3-6 months or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant elevations may require investigation or dose adjustment.
Renal Function (BUN, creatinine)
Frequency: Every 3-6 months or as clinically indicated.
Target: Within normal limits.
Action Threshold: Significant abnormalities may require dose adjustment or investigation.
Electrolytes (Sodium, Potassium, Chloride, Bicarbonate)
Frequency: Monthly initially, then every 3-6 months or as clinically indicated.
Target: Within normal limits.
Action Threshold: Abnormalities (e.g., hypernatremia, hypokalemia, metabolic acidosis/alkalosis) require intervention.
Growth and Development (in pediatric patients)
Frequency: Regularly at clinic visits.
Target: Normal growth velocity and developmental milestones.
Action Threshold: Growth failure or developmental delay requires comprehensive evaluation.
Symptom Monitoring
- Lethargy
- Vomiting
- Irritability
- Poor feeding
- Ataxia
- Seizures
- Coma (signs of hyperammonemia)
- Edema (due to sodium load)
- Signs of metabolic acidosis/alkalosis
Special Patient Groups
Pregnancy
Category C. Use only if the potential benefit justifies the potential risk to the fetus. Urea cycle disorders can worsen during pregnancy, posing risks to both mother and fetus.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity not fully established in humans; animal studies show some risk.
Second Trimester:
Risk of maternal hyperammonemia and potential fetal exposure.
Third Trimester:
Risk of maternal hyperammonemia and potential fetal exposure.
Lactation
It is not known whether sodium phenylbutyrate or its metabolites are excreted in human milk. Caution should be exercised when administered to a nursing woman. The decision to breastfeed should consider the importance of the drug to the mother and the potential risks to the infant.
Infant Risk:
Unknown
Pediatric Use
Sodium phenylbutyrate is indicated for pediatric patients of all ages with urea cycle disorders. Dosing is weight or body surface area-based and requires careful titration and monitoring of ammonia and amino acid levels. Palatability can be a challenge in this population.
Geriatric Use
Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Monitor for electrolyte imbalances due to sodium load.
Clinical Information
Clinical Pearls
- Sodium phenylbutyrate has a high sodium content (approximately 115 mg sodium per gram of drug), which must be considered in patients with heart failure, renal impairment, or hypertension.
- The powder form can be mixed with food or liquid (e.g., formula, milk, applesauce) to improve palatability, but should be administered immediately after mixing.
- Strict adherence to dietary protein restriction is crucial for effective management of urea cycle disorders in conjunction with sodium phenylbutyrate.
- Patients and caregivers should be educated on the signs and symptoms of hyperammonemia and instructed to seek immediate medical attention if they occur.
- Regular monitoring of plasma ammonia, amino acids, and electrolytes is essential to optimize therapy and prevent complications.
Alternative Therapies
- Glycerol phenylbutyrate (Ravicti)
- Arginine (for argininosuccinic aciduria, citrullinemia)
- Citrulline (for OTC deficiency, carbamyl phosphate synthetase deficiency)
- Carglumic acid (for N-acetylglutamate synthase deficiency)
- Dietary protein restriction
- Dialysis (for acute hyperammonemic crises)
Cost & Coverage
Average Cost:
High (e.g., thousands of dollars per month) per month
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.