Buphenyl 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
Ammonia Scavenger; Nitrogen-Binding Agent
Pregnancy Category
Category C
FDA Approved
Apr 1996
DEA Schedule
Not Controlled
Overview
What is this medicine?
Buphenyl is a medicine used to help people with certain genetic conditions (called urea cycle disorders) remove harmful ammonia from their body. It works by helping the body get rid of extra nitrogen, which can build up and become toxic. It's usually taken as a powder mixed with food or liquid.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, 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're using the powder form, mix it with a liquid or soft food, and use only the scoop that comes with the powder 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. For individuals with feeding tubes, follow the instructions provided by your healthcare provider and flush the feeding tube after administering the medication.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry place, avoiding storage in a bathroom. Ensure the lid is tightly closed when not in use. Store all medications in a safe location, out of the reach of children and pets, to prevent accidental ingestion.
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's close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take two doses at the same time or take extra doses, as this can increase the risk of side effects.
To use this medication correctly, 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're using the powder form, mix it with a liquid or soft food, and use only the scoop that comes with the powder 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. For individuals with feeding tubes, follow the instructions provided by your healthcare provider and flush the feeding tube after administering the medication.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry place, avoiding storage in a bathroom. Ensure the lid is tightly closed when not in use. Store all medications in a safe location, out of the reach of children and pets, to prevent accidental ingestion.
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's close to the time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take two doses at the same time or take extra doses, as this can increase the risk of side effects.
Lifestyle & Tips
- Strict adherence to a low-protein diet as prescribed by your doctor or dietitian is crucial for the effectiveness of this medication.
- Do not stop taking this medication without consulting your doctor, even if you feel well.
- Ensure adequate hydration.
- Follow all dietary and fluid restrictions as advised by your healthcare team.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Highly individualized based on protein tolerance and plasma ammonia levels. Total daily dose typically 9.9-13 g/m² or 450-600 mg/kg, divided into 3-6 doses. Max 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 normal or acceptable ranges. Administer with meals or snacks.
Pediatric Dosing
Neonatal:
Not established (use with extreme caution, often managed with other agents initially).
Infant:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Dosing is highly individualized and adjusted based on clinical response and laboratory parameters.
Child:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Dosing is highly individualized and adjusted based on clinical response and laboratory parameters.
Adolescent:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max 20 g/day. Dosing is highly individualized and adjusted based on clinical response and laboratory parameters.
Dose Adjustments
Renal Impairment:
Mild:
Adjustment needed (monitor closely, as phenylacetylglutamine is renally excreted).
Moderate:
Adjustment needed (monitor closely, as phenylacetylglutamine is renally excreted).
Severe:
Adjustment needed (monitor closely, as phenylacetylglutamine is renally excreted).
Dialysis:
Considerations (specific recommendations not well-established, monitor closely for accumulation of metabolites).
Hepatic Impairment:
Mild:
Adjustment (monitor closely, as metabolism occurs in the liver).
Moderate:
Adjustment (monitor closely, as metabolism occurs in the liver).
Severe:
Adjustment (monitor closely, as metabolism occurs in the liver).
Pharmacology
Mechanism of Action
Sodium phenylbutyrate is a prodrug that is rapidly metabolized to phenylacetate. Phenylacetate is then conjugated with glutamine in the liver and kidneys to form phenylacetylglutamine (PAG). PAG is a nitrogen-containing compound that is excreted by the kidneys. This process provides an alternative pathway for nitrogen excretion, thereby reducing elevated plasma ammonia and glutamine levels in patients with urea cycle disorders.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (rapidly absorbed and metabolized)
Tmax:
1 hour (for phenylacetate)
FoodEffect:
Administer with meals or snacks to minimize gastrointestinal irritation and improve palatability.
Distribution:
Vd:
Not available
ProteinBinding:
Not available
CnssPenetration:
Limited (phenylacetate can cross the blood-brain barrier, but its therapeutic effect is primarily peripheral)
Elimination:
HalfLife:
0.8 hours (for phenylacetate)
Clearance:
Not available
ExcretionRoute:
Renal (as phenylacetylglutamine)
Unchanged:
Not available
Pharmacodynamics
OnsetOfAction:
Days to weeks (to achieve stable ammonia control)
PeakEffect:
Not available (chronic therapy)
DurationOfAction:
Not applicable (requires continuous dosing)
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
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 do not experience any side effects or only have mild ones. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Decreased appetite
Bad taste in your mouth
Changes in body odor
Menstrual changes or irregular periods
Reporting Side Effects
This is not an exhaustive list of all possible side effects. If you have questions or concerns about side effects, contact 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 experience any of the following symptoms, contact your doctor or seek medical help right away:
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 do not experience any side effects or only have mild ones. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Decreased appetite
Bad taste in your mouth
Changes in body odor
Menstrual changes or irregular periods
Reporting Side Effects
This is not an exhaustive list of all possible side effects. If you have questions or concerns about side effects, contact 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
- Irritability or changes in behavior
- Vomiting or poor feeding (especially in infants)
- Confusion or disorientation
- Slurred speech
- Unsteady gait (ataxia)
- Seizures
- Loss of consciousness (these are signs of high ammonia levels and require immediate medical attention)
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, 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 drugs, and it is crucial to discuss all your medications with your doctor.
All your current medications, 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 existing health problems, as they may affect the safety and efficacy of this medication.
Remember, before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm it is safe to do so. This precaution will help prevent potential interactions and ensure your treatment plan is optimized for your specific needs.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, 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 drugs, and it is crucial to discuss all your medications with your doctor.
All your current medications, 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 existing health problems, as they may affect the safety and efficacy of this medication.
Remember, before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm it is safe to do so. This precaution will help prevent potential interactions and ensure your treatment plan is optimized for your specific needs.
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 dietary 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, it is crucial to discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
- Somnolence
- Fatigue
- Headache
- Nausea
- Vomiting
- Abdominal discomfort
- Metabolic acidosis
- Hypernatremia (due to sodium content)
What to Do:
In case of suspected overdose, seek immediate medical attention or call a poison control center (e.g., 1-800-222-1222). Management is supportive and may include discontinuation of the drug, correction of metabolic acidosis and hypernatremia, and potentially hemodialysis in severe cases.
Drug Interactions
Moderate Interactions
- Valproic acid
- Corticosteroids
- Probenecid
Monitoring
Baseline Monitoring
Plasma ammonia levels
Rationale: To establish baseline and guide initial dosing.
Timing: Prior to initiation of therapy.
Plasma glutamine levels
Rationale: To assess the effectiveness of nitrogen scavenging.
Timing: Prior to initiation of therapy.
Plasma essential amino acids
Rationale: To monitor for nutritional deficiencies.
Timing: Prior to initiation of therapy.
Electrolytes (especially bicarbonate)
Rationale: To monitor for metabolic acidosis, a potential side effect.
Timing: Prior to initiation of therapy.
Liver function tests (ALT, AST, bilirubin)
Rationale: To assess baseline hepatic function.
Timing: Prior to initiation of therapy.
Renal function tests (BUN, creatinine)
Rationale: To assess baseline renal function, as metabolites are renally excreted.
Timing: Prior to initiation of therapy.
Routine Monitoring
Plasma ammonia levels
Frequency: Weekly initially, then monthly or as clinically indicated.
Target: Within normal or acceptable range for age.
Action Threshold: Persistent elevation above target range requires dose adjustment or re-evaluation of therapy.
Plasma glutamine levels
Frequency: Monthly or as clinically indicated.
Target: Within normal or acceptable range.
Action Threshold: Persistent elevation indicates inadequate nitrogen scavenging.
Electrolytes (especially bicarbonate)
Frequency: Monthly or as clinically indicated.
Target: Normal range.
Action Threshold: Development of metabolic acidosis requires intervention.
Growth parameters (weight, height, head circumference in infants)
Frequency: Regularly (e.g., quarterly or at each clinic visit) in pediatric patients.
Target: Appropriate for age and sex.
Action Threshold: Growth faltering may indicate inadequate metabolic control or nutritional deficiency.
Liver and renal function tests
Frequency: Every 6-12 months or as clinically indicated.
Target: Normal range.
Action Threshold: Significant abnormalities require investigation and potential dose adjustment.
Symptom Monitoring
- Lethargy
- Irritability
- Vomiting
- Poor feeding
- Ataxia
- Seizures
- Coma (signs of hyperammonemia)
- Unusual fatigue
- Shortness of breath (signs of metabolic acidosis)
Special Patient Groups
Pregnancy
Category C. Use during pregnancy 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. Close monitoring of ammonia levels is essential.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity not fully established; animal studies show some adverse effects at high doses.
Second Trimester:
Risk of maternal hyperammonemia may increase; close monitoring and dose adjustment may be necessary.
Third Trimester:
Risk of maternal hyperammonemia may increase; close monitoring and dose adjustment may be necessary.
Lactation
It is not known whether sodium phenylbutyrate or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Risk unknown; potential for accumulation of metabolites or adverse effects on infant metabolism.
Pediatric Use
Sodium phenylbutyrate is primarily used in pediatric patients with urea cycle disorders. Dosing is weight or body surface area-based and highly individualized. Close monitoring of growth, development, and nutritional status is crucial.
Geriatric Use
Clinical studies of Buphenyl 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.
Clinical Information
Clinical Pearls
- Sodium phenylbutyrate is a cornerstone therapy for urea cycle disorders, but strict dietary protein restriction is equally critical for effective management.
- The powder form can be mixed with food (e.g., applesauce, pudding) or liquid (e.g., water, formula) to improve palatability. Do not mix with acidic liquids.
- Dosing is highly individualized and requires frequent monitoring of plasma ammonia, glutamine, and amino acid levels.
- Patients and caregivers must be educated on the signs and symptoms of hyperammonemia and the importance of immediate medical attention if they occur.
- Due to its sodium content, monitor for hypernatremia, especially in infants or patients with renal impairment.
- Consider the use of glycerol phenylbutyrate (Ravicti) as an alternative, which may offer different pharmacokinetic properties and dosing convenience for some patients.
Alternative Therapies
- Glycerol phenylbutyrate (Ravicti)
- Arginine (for Argininosuccinic Aciduria and Citrullinemia)
- Citrulline (for OTC Deficiency and Carbamyl Phosphate Synthetase Deficiency)
- Carglumic acid (Carbaglu - for N-acetylglutamate synthase deficiency)
- Dietary protein restriction
- Ammonia scavenger medications (e.g., sodium benzoate, sodium phenylacetate)
Cost & Coverage
Average Cost:
Very high (e.g., thousands of dollars per month) per 250g bottle
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization and often part of a limited distribution network)
General Drug Facts
If your symptoms or health condition do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may have additional patient information leaflets, so it is a good idea to consult with your pharmacist for more information. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the overdose, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.