Buphenyl 500mg Tablets
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
Agent for urea cycle disorders
Pharmacologic Class
Nitrogen-binding agent; ammonia scavenger
Pregnancy Category
Category C
FDA Approved
Apr 1996
DEA Schedule
Not Controlled
Overview
What is this medicine?
Sodium phenylbutyrate is a medicine used to help your body get rid of extra waste nitrogen, which can build up as a harmful substance called ammonia in people with certain genetic conditions called urea cycle disorders. It helps prevent serious health problems caused by high ammonia levels.
How to Use This Medicine
Taking Your Medication
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. It's recommended to take this medication with meals to help your body absorb it properly.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding the bathroom. Make sure to keep the lid tightly closed when not in use. Keep all medications in a secure, inaccessible place to prevent accidental ingestion by children and pets.
What to Do If You Miss a Dose
If you forget to take a dose, take it as soon as you remember, with a meal. However, if it's almost 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 the missed one.
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. It's recommended to take this medication with meals to help your body absorb it properly.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding the bathroom. Make sure to keep the lid tightly closed when not in use. Keep all medications in a secure, inaccessible place to prevent accidental ingestion by children and pets.
What to Do If You Miss a Dose
If you forget to take a dose, take it as soon as you remember, with a meal. However, if it's almost 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 the missed one.
Lifestyle & Tips
- Adhere strictly to the prescribed low-protein diet as recommended by your doctor or dietitian.
- Take the medication exactly as prescribed, usually divided into multiple doses throughout the day with meals or snacks.
- Do not stop taking the medication without consulting your doctor, even if you feel well.
- Maintain regular follow-up appointments and blood tests 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 ammonia levels. Typically 9.9-13 g/m²/day or 450-600 mg/kg/day, divided into 3-6 doses.
Dose Range:
450 - 600 mg
Condition-Specific Dosing:
maximum_daily_dose:
20 g/day
Pediatric Dosing
Neonatal:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max 20 g/day. Dosing is based on body surface area (BSA) or weight.
Infant:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max 20 g/day. Dosing is based on body surface area (BSA) or weight.
Child:
450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max 20 g/day. Dosing is based on body surface area (BSA) or weight.
Adolescent:
450-600 mg/kg/day or 9.9-13 g/m²/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max 20 g/day. Dosing is based on body surface area (BSA) or weight.
Dose Adjustments
Renal Impairment:
Mild:
Use with caution; monitor sodium, potassium, and phenylacetate/phenylacetylglutamine levels.
Moderate:
Use with caution; monitor sodium, potassium, and phenylacetate/phenylacetylglutamine levels. Dose adjustment may be necessary.
Severe:
Use with caution; monitor sodium, potassium, and phenylacetate/phenylacetylglutamine levels. Dose adjustment likely necessary.
Dialysis:
Considerations: Phenylacetate and its conjugates are renally excreted. Dialysis may remove metabolites. Consult nephrologist.
Hepatic Impairment:
Mild:
Use with caution; monitor ammonia and drug levels. Metabolism may be impaired.
Moderate:
Use with caution; monitor ammonia and drug levels. Dose adjustment may be necessary.
Severe:
Use with caution; monitor ammonia and drug levels. Dose adjustment likely necessary.
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, which is then excreted by the kidneys. This process provides an alternative pathway for nitrogen excretion, reducing elevated ammonia levels in patients with urea cycle disorders.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified as a percentage, but rapidly absorbed.
Tmax:
Phenylbutyrate: ~1 hour; Phenylacetate: ~1-1.3 hours; Phenylacetylglutamine: ~2.5-3 hours
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption.
Distribution:
Vd:
Not available
ProteinBinding:
Not explicitly quantified
CnssPenetration:
Limited for phenylbutyrate; phenylacetate can cross the blood-brain barrier.
Elimination:
HalfLife:
Phenylbutyrate: ~0.8 hours; Phenylacetate: ~0.8-1.1 hours; Phenylacetylglutamine: ~2.4-4.6 hours
Clearance:
Not explicitly quantified
ExcretionRoute:
Renal (as phenylacetylglutamine)
Unchanged:
Minimal
Pharmacodynamics
OnsetOfAction:
Not acutely defined; chronic effect on ammonia reduction.
PeakEffect:
Not acutely defined; chronic effect on ammonia reduction.
DurationOfAction:
Not acutely defined; chronic effect on ammonia reduction.
Safety & Warnings
Side Effects
Serious 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 experience any of the following symptoms, contact your doctor or seek medical attention immediately:
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
+ Abnormal heartbeat
+ Severe stomach pain, upset stomach, or vomiting
+ Feeling extremely sleepy
+ Shortness of breath
+ Feeling very tired or weak
Signs of electrolyte problems, such as:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Balance changes
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe upset stomach or vomiting
Feeling extremely tired or weak
Dizziness or headache
Upset stomach or vomiting
Feeling sleepy
Feeling confused
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 experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Decreased appetite
Bad taste in your mouth
Changes in body odor
Menstrual changes or absence of periods
Reporting Side Effects
This is not an exhaustive list of 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 attention immediately:
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
+ Abnormal heartbeat
+ Severe stomach pain, upset stomach, or vomiting
+ Feeling extremely sleepy
+ Shortness of breath
+ Feeling very tired or weak
Signs of electrolyte problems, such as:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Balance changes
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe upset stomach or vomiting
Feeling extremely tired or weak
Dizziness or headache
Upset stomach or vomiting
Feeling sleepy
Feeling confused
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 experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Decreased appetite
Bad taste in your mouth
Changes in body odor
Menstrual changes or absence of periods
Reporting Side Effects
This is not an exhaustive list of 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
- Frequent vomiting
- Irritability or changes in behavior
- Difficulty with coordination (ataxia)
- Seizures
- Confusion or disorientation
- Unusual headache
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. Describe the symptoms you experienced with the allergy.
If you are currently taking any of the following medications: divalproex, haloperidol, or valproic acid.
For Children:
* If your child weighs less than 44 pounds (20 kilograms), as this medication is not intended for use in children below this weight threshold.
This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting 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. Describe the symptoms you experienced with the allergy.
If you are currently taking any of the following medications: divalproex, haloperidol, or valproic acid.
For Children:
* If your child weighs less than 44 pounds (20 kilograms), as this medication is not intended for use in children below this weight threshold.
This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
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 this may require a dosage adjustment. 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:
- Metabolic acidosis (symptoms may include rapid breathing, confusion, fatigue)
- Hypokalemia (low potassium, symptoms may include muscle weakness, cramps, irregular heartbeats)
- CNS depression (drowsiness, confusion, coma)
- Nausea
- Vomiting
What to Do:
In case of suspected overdose, seek immediate medical attention. Call your local poison control center (e.g., 1-800-222-1222 in the US) or emergency services. Treatment is supportive and may include correction of metabolic acidosis and electrolyte imbalances, and potentially hemodialysis to remove the drug and its metabolites.
Drug Interactions
Moderate Interactions
- Valproic acid (may increase plasma ammonia levels)
- Haloperidol (may increase plasma ammonia levels)
- Corticosteroids (may increase plasma ammonia levels)
- Probenecid (may inhibit renal excretion of phenylacetylglutamine)
Monitoring
Baseline Monitoring
Plasma ammonia levels
Rationale: To establish baseline and guide initial dosing.
Timing: Prior to initiation of therapy.
Plasma amino acid profile (especially glutamine)
Rationale: To assess metabolic status and guide dietary management.
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 tests (BUN, creatinine)
Rationale: To assess renal function, as metabolites are renally excreted.
Timing: Prior to initiation of therapy.
Electrolytes (sodium, potassium, bicarbonate, chloride)
Rationale: To monitor for potential electrolyte imbalances (e.g., hypokalemia, metabolic acidosis).
Timing: Prior to initiation of therapy.
Complete Blood Count (CBC)
Rationale: To assess general health and rule out other conditions.
Timing: Prior to initiation of therapy.
Routine Monitoring
Plasma ammonia levels
Frequency: Initially frequently (e.g., daily/weekly) until stable, then periodically (e.g., monthly or as clinically indicated).
Target: Within normal limits for age, or as determined by treating physician.
Action Threshold: Elevated levels indicate inadequate control or non-adherence; requires dose adjustment or re-evaluation of diet.
Plasma amino acid profile (especially glutamine)
Frequency: Periodically (e.g., every 3-6 months or as clinically indicated).
Target: Within therapeutic range, or as determined by treating physician.
Action Threshold: Abnormal levels may indicate need for dietary adjustment or dose change.
Electrolytes (sodium, potassium, bicarbonate)
Frequency: Periodically (e.g., every 1-3 months or as clinically indicated).
Target: Within normal limits.
Action Threshold: Abnormalities (e.g., hypokalemia, metabolic acidosis) require intervention.
Growth and development (pediatric patients)
Frequency: Regularly at clinic visits.
Target: Normal growth trajectory for age.
Action Threshold: Growth failure may indicate inadequate metabolic control or nutritional deficiencies.
Symptom Monitoring
- Lethargy
- Vomiting
- Irritability
- Ataxia
- Seizures
- Coma (signs of hyperammonemia)
- Unusual fatigue
- Confusion
- Headache
- Changes in mental status
Special Patient Groups
Pregnancy
Category C. Animal studies have shown adverse effects on the fetus. Sodium phenylbutyrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenic effects based on animal data.
Second Trimester:
Potential for adverse developmental effects.
Third Trimester:
Potential for adverse developmental effects.
Lactation
It is not known whether sodium phenylbutyrate is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, 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:
Potential for unknown adverse effects; caution advised.
Pediatric Use
Sodium phenylbutyrate is indicated for pediatric patients with urea cycle disorders. Dosing is weight or body surface area-based and requires careful monitoring of growth, development, and metabolic parameters.
Geriatric Use
Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Use with caution, generally 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 must be used in conjunction with a restricted protein diet and, in some cases, amino acid supplements (e.g., arginine, citrulline) to manage urea cycle disorders effectively.
- The medication has a salty taste, which can affect palatability, especially for pediatric patients. It can be mixed with food or liquids.
- Regular and frequent monitoring of plasma ammonia, plasma amino acids (especially glutamine), and electrolytes is crucial for optimizing therapy and preventing hyperammonemic crises.
- Patients and caregivers must be educated on the signs and symptoms of hyperammonemia and when to seek urgent medical attention.
- Adherence to both medication and dietary restrictions is paramount for long-term success and prevention of neurological damage.
Alternative Therapies
- Glycerol phenylbutyrate (Ravicti) - another nitrogen-binding agent, often preferred due to less frequent dosing and better palatability.
- Carglumic acid (Carbaglu) - specifically for N-acetylglutamate synthase (NAGS) deficiency, a rare form of UCD.
- Arginine or Citrulline supplementation (depending on the specific UCD defect).
- Dietary protein restriction.
- Dialysis (in acute hyperammonemic crisis).
Cost & Coverage
Average Cost:
Highly variable, typically several thousand USD per 30 tablets (500mg)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance due to orphan drug status).
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 your 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 medication taken, the amount, and the time it occurred.