Sodium Phenylbutyrate and Taurursodiol - Pharmacological Aspects, Dosage, Warnings and Precautions

Overview:

Sodium phenylbutyrate and Taurursodiol are used to treat amyotrophic lateral sclerosis (ALS), a disease where the nerves that control muscles slowly die, causing muscles to weaken and shrink. Sodium phenylbutyrate is a histone deacetylase inhibitor, and Taurursodiol is a bile acid. It is not clear how they work together, but they may help protect nerve cells and slow down ALS symptoms. Sodium phenylbutyrate and Taurursodiol help manage ALS but do not cure it. Keep taking it even if the person feels fine, and do not stop without consulting the doctor. Ask the pharmacist or doctor for more information if needed. The Food and Drug Administration (FDA) approved Sodium phenylbutyrate and Taurursodiol on September 29, 2022.

Available Doses and Dosage Forms:

Sodium phenylbutyrate and Taurursodiol oral suspension come in packets of white to yellow powder, each containing three grams of Sodium phenylbutyrate and one gram of Taurursodiol. It is available in two package options:

• A box with seven individual packets.

• A larger package with 56 individual packets is divided into four boxes, each containing 14 packets.

For oral suspension, it is a powder that ranges in color from white to yellow. Each packet contains a single dose of three grams of Sodium phenylbutyrate and one gram of Taurursodiol.

For Patients:

What Is Amyotrophic Lateral Sclerosis?

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a condition that affects the nerve cells controlling muscle movements and breathing. In ALS, these nerve cells slowly break down and die, stopping communication with the muscles. This leads to muscle weakness, twitching, and shrinking. Over time, the brain loses its ability to control voluntary movements like walking, talking, chewing, and breathing. ALS is a progressive disease, which means it gets worse over time.

How Does Sodium Phenylbutyrate and Taurursodiol Work?

Sodium phenylbutyrate and Taurursodiol are used to treat amyotrophic lateral sclerosis (ALS). They help protect nerve cells and slow down the progression of symptoms, but they do not cure the disease.

What Is the Dosage of Sodium Phenylbutyrate and Taurursodiol?

To start with Sodium phenylbutyrate and Taurursodiol oral suspension, take one packet daily for the first three weeks. After that, increase the dose to one packet twice daily as the regular dose.

How Effective Are Sodium Phenylbutyrate and Taurursodiol?

There is no clear evidence of how exactly Sodium phenylbutyrate and Taurursodiol work together, but they might help by preventing nerve cells from breaking down and dying, which can slow down the worsening of ALS symptoms.

What Are the Things to Inform the Doctor Before Taking Sodium Phenylbutyrate and Taurursodiol?

• Before taking Sodium phenylbutyrate and Taurursodiol, inform the doctor and pharmacist if allergic to these drugs, any other medications, or any of the ingredients in the powder. Ask for a list of ingredients if needed.

• Let the physician know about all other medications, vitamins, supplements, and herbal products that the person is taking or planning to take, as the doctor might need to adjust doses or monitor for side effects.

• If the person is using aluminum-based antacids, consult the doctor, as they can affect how well the medication is absorbed.

• Inform the doctor about any previous issues with the pancreas, digestive system, gallbladder, or liver or if had any surgery on the intestines.

• Mention if having heart failure, high blood pressure, or kidney disease, as the medication contains 928 mg (milligram) of sodium, which may require limiting sodium in the diet.

• Inform the doctor about pregnancy, planning to become pregnant, or breastfeeding, and notify them if one becomes pregnant while on the medication.

How Are Sodium Phenylbutyrate and Taurursodiol Administered?

• Sodium phenylbutyrate and Taurursodiol are available as a powder to mix with water and take by mouth or through a feeding tube.

• Typically, it is taken once daily before a snack or meal for three weeks, then twice daily. It is taken at the same times each day, following the prescription exactly.

• Do not change the dose without the doctor's advice.

• Mix one packet with eight ounces of room-temperature water and stir well. Drink it within an hour, and discard any leftover mixture.

• This medication helps manage ALS but does not cure it.

• Keep taking it even if the person feels fine, and do not stop without consulting the doctor. Ask the pharmacist or doctor for more detailed information.

What Are the Side Effects of Sodium Phenylbutyrate and Taurursodiol?

• Risk for patients with disorders affecting bile circulation, pancreas, or intestines.

• Use in patients who are sensitive to consuming high amounts of sodium.

Dietary Considerations:

Unless the doctor instructs to change the diet while taking Sodium phenylbutyrate and Taurursodiol

Missed Dose:

If a person misses a dose, they should take it as soon as they remember. If it is close to the time for the next dose, skip the missed one and stick to the usual schedule. Do not take extra medicine to make up for the missed dose.

Overdose:

Inform the doctor or call an emergency if someone collapses, has a seizure, has difficulty breathing, or cannot wake up due to an overdose.

Storage:

Store between 68 to 77 degrees Fahrenheit (20 to 25 degrees Celsius) in a dry place. Avoid temperatures outside 59 to 86 degrees Fahrenheit (15 to 30 degrees Celsius). Follow specific instructions for storing Sodium phenylbutyrate and Taurursodiol once it is mixed into a suspension.

For Doctors:

Indication:

Sodium phenylbutyrate and Taurursodiol are used to treat amyotrophic lateral sclerosis (ALS) in adults.

Dose and Dosing Considerations:

The dosage of Sodium phenylbutyrate and Taurursodiol will vary among patients. Adhere to the physician's instructions or the directions on the prescription label. The following information provides the typical dosages of this medication. If the prescribed dose differs, do not adjust it unless instructed by the physician. The quantity of medication taken depends on its potency. Additionally, the frequency of doses, the interval between doses, and the duration of treatment depend on the specific medical condition being treated.

For Oral Dosage Forms (Powder for Suspension):

For Amyotrophic Lateral Sclerosis (ALS):

• Adults: Initially, one packet daily for three weeks. After three weeks, the physician may increase the dosage to one packet twice daily. Each packet contains three grams (g) of Sodium phenylbutyrate and one gram of Taurursodiol.

• Children: Use and dosage must be determined by the physician.

What Are the Pharmacological Aspects of Sodium Phenylbutyrate and Taurursodiol?

• Pharmacodynamics: At the highest recommended dose, Sodium phenylbutyrate and Taurursodiol do not significantly prolong the QT interval, which is a measure of heart electrical activity.

• Mechanism of Action: The mechanism of Action of Sodium phenylbutyrate and Taurursodiol is difficult to explain since its therapeutic effects in patients with amyotrophic lateral sclerosis are unknown.

• Pharmacokinetics: After taking Sodium phenylbutyrate and Taurursodiol orally in an empty stomach, Sodium phenylbutyrate reaches its highest concentration in the bloodstream in about 30 minutes, while Taurursodiol takes around 4.5 hours. Eating a high-fat meal slows down the absorption of Sodium phenylbutyrate significantly and reduces its overall exposure, whereas Taurursodiol is less affected by food intake. Both medications primarily bind to proteins in the blood. The exact metabolic pathways and elimination routes of these drugs in humans are not fully understood. Most of the Sodium phenylbutyrate is excreted in urine within 24 hours in a modified form, while Taurursodiol's major breakdown products are ursodiol and glyco-ursodiol. There is limited information on how age, gender, and ethnicity affect the medication's distribution in the body. The impact of kidney or liver problems on Sodium phenylbutyrate and Taurursodiol's effectiveness has not been extensively studied.

Toxicity:

• Carcinogenesis: Studies to see if Sodium phenylbutyrate and Taurursodiol cause cancer have not been done.

• Mutagenesis: Tests showed that the combination of Sodium phenylbutyrate and Taurursodiol did not cause mutations in bacteria or mammalian cells, nor did it cause genetic damage in mice.

• Impairment of Fertility: Giving the combination of Sodium phenylbutyrate and Taurursodiol to rats before and during mating did not affect their ability to have offspring, even at doses much higher than those recommended for humans.

Clinical Studies:

The safety of Sodium phenylbutyrate and Taurursodiol was studied in a trial involving 137 adults with ALS, where patients were randomly assigned to receive Sodium phenylbutyrate and Taurursodiol or a placebo for 24 weeks. During the study, six percent of those on Sodium phenylbutyrate and Taurursodiol and four percent on placebo passed away, primarily due to ALS progression. The most common side effects with Sodium phenylbutyrate and Taurursodiol, reported by at least 15 percent of patients and five percent more than with placebo, included diarrhea, abdominal pain, nausea, and upper respiratory infections. These gastrointestinal-related side effects were most frequent during the first three weeks of treatment.

Warnings and Precautions:

• Risk in Patients with Digestive System Disorders: Sodium phenylbutyrate and Taurursodiol, a type of bile acid. If a person has conditions that affect how bile acids work in the body, like pancreas or intestinal issues, they might experience worse diarrhea. It is important to be monitored by the healthcare provider if this happens. These conditions can also affect how the body absorbs Sodium phenylbutyrate and Taurursodiol’s components.

• Use in Patients Sensitive to Sodium Intake: Sodium phenylbutyrate and Taurursodiol have a lot of salt. Each daily dose of one packet contains 464 mg of sodium, and the maintenance dose of two packets daily contains 928 mg. If a person is sensitive to salt intake due to conditions like heart failure, high blood pressure, or kidney problems, they should be cautious about how much sodium is taken from Sodium phenylbutyrate and Taurursodiol. The healthcare provider can help to monitor this.

What Are the Drug Interactions Between Sodium Phenylbutyrate and Taurursodiol?

Potential Interactions:

• Bile Acid Sequestering Agents: Drugs like Cholestyramine that lower cholesterol by binding bile acids could affect how Sodium phenylbutyrate and Taurursodiol are absorbed. It is best to use alternative cholesterol medications instead of these agents.

• Inhibitors of Bile Acid Transporters: Medications that block bile acid transporters in the liver, like Cyclosporine, might lead to bile salt buildup. Avoid strong inhibitors of these transporters with Sodium phenylbutyrate and Taurursodiol, or monitor liver function closely if they must be used together.

• Aluminum-based Antacids: Antacids containing aluminum can interfere with how Taurursodiol is absorbed. It is recommended to use other types of antacids that do not contain aluminum.

• Probenecid: This medication can affect how Sodium phenylbutyrate is excreted by the kidneys. Avoid using Probenecid with Sodium phenylbutyrate and Taurursodiol.

• HDAC Inhibitors: Sodium phenylbutyrate and Taurursodiol, where phenylbutyrate inhibits histone deacetylases. Avoid using other medications that also inhibit HDACs with Sodium phenylbutyrate and Taurursodiol.

• Inhibitors of OATP1B3: Sodium phenylbutyrate and Taurursodiol are processed by a transporter called OATP1B3. Drugs that inhibit this transporter could affect how Sodium phenylbutyrate and Taurursodiol work. Avoid using these inhibitors with Sodium phenylbutyrate and Taurursodiol.

Sodium Phenylbutyrate and Taurursodiol's Effects on Other Drugs:

• OAT1 Substrates: If Sodium phenylbutyrate and Taurursodiol are used with drugs that are substrates of OAT1, their levels in the blood may increase. Avoid using these drugs as even small changes in their blood levels could cause serious problems.

• P-glycoprotein (P-gP) and Breast Cancer Resistance Protein (BCRP) Substrates: Sodium phenylbutyrate and Taurursodiol can inhibit P-gP and BCRP, which are proteins that transport drugs out of cells. Using Sodium phenylbutyrate and Taurursodiol with drugs that rely on these proteins could increase their levels in the blood, potentially causing harm. Avoid using these drugs together unless necessary.

• CYP Enzyme Substrates: Sodium phenylbutyrate and Taurursodiol affect certain enzymes in the liver (CYP2C8, CYP1A2, CYP2B6, and CYP3A4) that process other medications. Using Sodium phenylbutyrate and Taurursodiol with drugs that these enzymes metabolize could change their levels in the blood. Avoid using these drugs together if small changes in their blood levels could lead to serious issues.

Specific Considerations:

• Pregnancy: There are no studies on the use of Sodium phenylbutyrate and Taurursodio in pregnant women to determine its effects on pregnancy outcomes. Animal studies with Sodium phenylbutyrate and Taurursodiol showed increased mortality in offspring, but these doses were higher than those used clinically.

• Lactation: It is unknown if Sodium phenylbutyrate or Taurursodiol passes into human breast milk or its effects on breastfed infants. Consider the benefits of breastfeeding, the need for Sodium phenylbutyrate and Taurursodiol, and the potential risks to the infant.

• Pediatric Use: Sodium phenylbutyrate and Taurursodiol have not been studied in children, so their safety and effectiveness in pediatric patients are not established.

• Geriatric Use: In a study with ALS patients, about 28 percent were 65 or older. There were no notable differences in how Sodium phenylbutyrate and Taurursodiol worked or its safety compared to younger patients, but older individuals might be more sensitive to its effects.

• Renal Impairment: Patients with mild kidney impairment do not need dosage adjustments. However, Sodium phenylbutyrate and Taurursodiol should be avoided in patients with moderate or severe kidney impairment due to potential risks.

• Hepatic Impairment: Patients with mild liver impairment do not need dosage adjustments. Avoid Sodium phenylbutyrate and Taurursodiol in patients with moderate or severe liver impairment due to potential risks.