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Sodium Phenylbutyrate 500mg Tablets

Manufacturer PAR Active Ingredient Sodium Phenylbutyrate Tablets(SOW dee um fen il BYOO ti rate) Pronunciation SOW-dee-um fen-il-BYOO-ti-rate
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.
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Drug Class
Urea cycle disorder agent
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Pharmacologic Class
Nitrogen-binding agent; Ammonia scavenger
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Pregnancy Category
Category C
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FDA Approved
May 1987
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DEA Schedule
Not Controlled

Overview

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What is this medicine?

Sodium phenylbutyrate is a medication used to help your body get rid of extra ammonia, a harmful substance that can build up in people with certain genetic conditions called urea cycle disorders. It works by helping your body create a different substance that can be easily removed by your kidneys, thus lowering the ammonia levels in your blood.
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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 as directed.

Storing and Disposing of Your Medication

Store your medication at room temperature in a dry location, avoiding the bathroom. Keep the container tightly closed and store all medications in a safe place, out of the reach of children and pets.

Missing 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 resume your regular dosing schedule. Do not take two doses at the same time or take extra doses.
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Lifestyle & Tips

  • Strict adherence to a prescribed low-protein diet is crucial for the effectiveness of this medication. Do not change your diet without consulting your doctor or dietitian.
  • Take the medication exactly as prescribed, usually divided into multiple doses throughout the day, to maintain stable ammonia levels.
  • Do not skip doses. If you miss a dose, take it as soon as you remember, unless it's almost time for your next dose. Do not double dose.
  • Maintain adequate hydration.
  • Avoid excessive protein intake, especially during illness or stress, as this can trigger hyperammonemia.
  • Carry emergency medication (e.g., ammonia scavenger, glucose) as advised by your doctor for hyperammonemic crises.
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Available Forms & Alternatives

Available Strengths:

Dosing & Administration

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Adult Dosing

Standard Dose: Individualized based on protein tolerance and plasma ammonia levels. Typical initial dose: 9.9-13 g/m² body surface area/day or 450-600 mg/kg/day, divided into 3-6 doses. For 500mg tablets, this means many tablets per day.
Dose Range: 450 - 600 mg

Condition-Specific Dosing:

hyperammonemia: Dose may be increased or decreased based on plasma ammonia levels and clinical response. Max dose: 20g/day or 900mg/kg/day (whichever is less).
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Pediatric Dosing

Neonatal: Initial dose: 450-600 mg/kg/day, divided into 3-6 doses. Max dose: 900 mg/kg/day.
Infant: Initial dose: 450-600 mg/kg/day, divided into 3-6 doses. Max dose: 900 mg/kg/day.
Child: Initial dose: 450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max dose: 20g/day or 900mg/kg/day (whichever is less).
Adolescent: Initial dose: 450-600 mg/kg/day or 9.9-13 g/m²/day, divided into 3-6 doses. Max dose: 20g/day or 900mg/kg/day (whichever is less).
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Dose Adjustments

Renal Impairment:

Mild: Use with caution. Monitor for metabolic acidosis and electrolyte imbalances.
Moderate: Use with caution. Monitor for metabolic acidosis and electrolyte imbalances. Dose reduction may be necessary.
Severe: Contraindicated in patients with severe renal impairment due to risk of accumulation of phenylacetate and phenylacetylglutamine, and exacerbation of metabolic acidosis.
Dialysis: Not available (Generally not recommended due to severe renal impairment contraindication).

Hepatic Impairment:

Mild: Use with caution. Monitor for metabolic acidosis and electrolyte imbalances.
Moderate: Use with caution. Monitor for metabolic acidosis and electrolyte imbalances. Dose reduction may be necessary.
Severe: Use with extreme caution. Significant hepatic impairment may impair metabolism of sodium phenylbutyrate to phenylacetate and subsequent conjugation, potentially leading to accumulation and toxicity. Dose reduction is likely necessary, and close monitoring is essential.

Pharmacology

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Mechanism of Action

Sodium phenylbutyrate is a pro-drug that is rapidly metabolized to phenylacetate. Phenylacetate then conjugates with glutamine in the liver and kidneys to form phenylacetylglutamine. Phenylacetylglutamine is then excreted renally. This process provides an alternative pathway for nitrogen excretion, thereby reducing elevated plasma ammonia and glutamine levels in patients with urea cycle disorders (UCDs).
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Pharmacokinetics

Absorption:

Bioavailability: High (well-absorbed orally)
Tmax: Phenylacetate: ~1 hour; Phenylacetylglutamine: ~3-4 hours
FoodEffect: Food may delay absorption but does not significantly affect the extent of absorption.

Distribution:

Vd: Not extensively studied, but distributes into total body water.
ProteinBinding: Phenylacetate: ~80%
CnssPenetration: Limited (phenylacetate can cross the blood-brain barrier to some extent, but phenylacetylglutamine does not readily).

Elimination:

HalfLife: Phenylacetate: 0.8-1.3 hours; Phenylacetylglutamine: 2.4-4.6 hours
Clearance: Rapid
ExcretionRoute: Renal (as phenylacetylglutamine)
Unchanged: <1%
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Pharmacodynamics

OnsetOfAction: Within hours (reduction in ammonia levels)
PeakEffect: Within days to weeks (stabilization of ammonia levels with chronic therapy)
DurationOfAction: Dependent on continuous dosing to maintain ammonia scavenging.

Safety & Warnings

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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 immediately or seek emergency 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, contact your doctor for advice:

Decreased appetite
 Bad taste in your mouth
Changes in body odor
 Menstrual changes or irregular periods

Reporting Side Effects

This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, 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.
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Seek Immediate Medical Attention If You Experience:

  • Unusual tiredness or lethargy
  • Frequent vomiting
  • Irritability or changes in behavior
  • Poor feeding (in infants)
  • Difficulty walking or coordination problems (ataxia)
  • Seizures
  • Confusion or disorientation
  • Unusual body odor (fishy or musty smell)
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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 symptoms you experienced.
 If you are currently taking any of the following medications: Divalproex, haloperidol, or valproic acid.

For Parents or Guardians of Pediatric Patients:

If your child weighs less than 44 pounds (20 kilograms), as this medication is not intended for use in children below this weight threshold.

Additional Considerations:

 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.
To ensure safe use, verify that it is acceptable to take this medication with all your other medications and health conditions.
 Do not initiate, discontinue, or adjust the dosage of any medication without first consulting your doctor.
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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.
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Overdose Information

Overdose Symptoms:

  • Severe metabolic acidosis
  • Hypokalemia
  • Elevated plasma ammonia levels
  • Central nervous system depression (lethargy, confusion, coma)
  • Unusual body odor (strong fishy/musty smell)

What to Do:

Seek immediate medical attention. Call 911 or your local emergency number. Contact a poison control center (1-800-222-1222). Treatment is supportive and may include discontinuation of the drug, correction of metabolic acidosis and electrolyte imbalances, and measures to reduce ammonia levels (e.g., hemodialysis if severe).

Drug Interactions

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Major Interactions

  • Valproic Acid: May inhibit the metabolism of phenylacetate, leading to increased plasma levels of phenylacetate and decreased levels of phenylacetylglutamine, potentially reducing the efficacy of sodium phenylbutyrate and increasing the risk of toxicity. Avoid concomitant use or monitor closely.
  • Probenecid: May inhibit the renal excretion of phenylacetylglutamine, potentially leading to increased plasma levels of phenylacetylglutamine and phenylacetate. Monitor for toxicity.
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Moderate Interactions

  • Corticosteroids: May increase tissue catabolism, potentially leading to increased ammonia levels. Monitor ammonia levels closely when initiating or discontinuing corticosteroids.
  • Haloperidol: Case reports suggest potential for increased ammonia levels.

Monitoring

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Baseline Monitoring

Plasma Ammonia

Rationale: To establish baseline and guide initial dosing.

Timing: Prior to initiation of therapy.

Plasma Amino Acids (especially glutamine)

Rationale: To assess the severity of the urea cycle disorder and monitor therapeutic efficacy.

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 excretion is renal.

Timing: Prior to initiation of therapy.

Electrolytes (including bicarbonate, chloride)

Rationale: To monitor for metabolic acidosis, a potential side effect.

Timing: Prior to initiation of therapy.

Complete Blood Count (CBC)

Rationale: To monitor for potential hematologic abnormalities.

Timing: Prior to initiation of therapy.

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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 warrant dose adjustment or investigation of compliance/diet.

Plasma Amino Acids (especially glutamine, phenylacetate, phenylacetylglutamine)

Frequency: Periodically (e.g., every 3-6 months) or as clinically indicated.

Target: Glutamine: Reduced towards normal; Phenylacetate/Phenylacetylglutamine: Within therapeutic range (e.g., phenylacetate <500 µg/mL).

Action Threshold: Abnormal levels indicate need for dose adjustment or re-evaluation of therapy.

Liver Function Tests (ALT, AST)

Frequency: Every 3-6 months or as clinically indicated.

Target: Within normal limits.

Action Threshold: Significant elevations may require dose adjustment or investigation.

Renal Function Tests (BUN, creatinine)

Frequency: Every 3-6 months or as clinically indicated.

Target: Within normal limits.

Action Threshold: Significant elevations may require dose adjustment or investigation.

Electrolytes (including bicarbonate, chloride)

Frequency: Monthly initially, then every 3-6 months or as clinically indicated.

Target: Within normal limits.

Action Threshold: Metabolic acidosis (low bicarbonate) requires intervention.

Complete Blood Count (CBC)

Frequency: Every 3-6 months or as clinically indicated.

Target: Within normal limits.

Action Threshold: Significant abnormalities may require investigation.

Growth and Development (pediatric patients)

Frequency: Regularly at clinic visits.

Target: Normal growth velocity for age.

Action Threshold: Growth failure may indicate inadequate metabolic control or nutritional issues.

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Symptom Monitoring

  • Lethargy
  • Vomiting
  • Irritability
  • Poor feeding
  • Ataxia
  • Seizures
  • Coma (signs of hyperammonemia)
  • Unusual body odor (due to phenylacetate accumulation)

Special Patient Groups

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Pregnancy

Category C. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. Animal studies have shown adverse effects (e.g., skeletal abnormalities, decreased fetal weight) at doses higher than human therapeutic doses. Untreated hyperammonemia in the mother can also be harmful to the fetus.

Trimester-Specific Risks:

First Trimester: Potential for teratogenicity based on animal data, though human data are limited.
Second Trimester: Risk of maternal metabolic acidosis which can affect fetal well-being.
Third Trimester: Risk of maternal metabolic acidosis and potential for fetal exposure near term.
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Lactation

It is not known whether sodium phenylbutyrate or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of 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. Monitor breastfed infants for signs of metabolic acidosis or other adverse effects.

Infant Risk: Risk unknown, but potential for metabolic acidosis or other adverse effects. L3 (Moderately Safe) is a reasonable classification given the lack of data and potential for serious effects.
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Pediatric Use

Sodium phenylbutyrate is indicated for pediatric patients of all ages with urea cycle disorders. Dosing is weight-based or body surface area-based. Close monitoring of ammonia levels, growth, and development is essential.

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Geriatric Use

Clinical studies of sodium phenylbutyrate 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. Elderly patients may be more susceptible to metabolic acidosis.

Clinical Information

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Clinical Pearls

  • Sodium phenylbutyrate is a cornerstone therapy for chronic management of urea cycle disorders, but it must always be used in conjunction with a strict, individualized low-protein diet.
  • The unpleasant taste and odor of the powder formulation can be a significant barrier to compliance; tablets may improve adherence for some patients.
  • Monitor for signs of metabolic acidosis (e.g., lethargy, hyperventilation, vomiting) and electrolyte imbalances, especially hypokalemia and hyperchloremia.
  • Regular monitoring of plasma ammonia, glutamine, and phenylacetate/phenylacetylglutamine levels is critical to ensure therapeutic efficacy and avoid toxicity.
  • Patients should be educated on the symptoms of hyperammonemia and instructed to seek immediate medical attention if they occur.
  • During intercurrent illnesses, stress, or surgery, patients are at increased risk of hyperammonemia and may require adjustments to their diet or medication, or even intravenous ammonia scavengers.
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Alternative Therapies

  • Sodium Phenylacetate and Sodium Benzoate (Ammonul, Ravicti - different formulations/combinations of ammonia scavengers)
  • Carglumic Acid (Carbaglu - for specific UCDs like NAGS deficiency)
  • Arginine/Citrulline supplementation (depending on the specific UCD defect)
  • Dietary protein restriction
  • Dialysis (for acute hyperammonemic crises)
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Cost & Coverage

Average Cost: Varies widely, typically several thousand dollars per 30 tablets
Generic Available: Yes
Insurance Coverage: Specialty Tier (requires prior authorization)
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General Drug Facts

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't 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 seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.