SPB11 (Oral)

Sodium phenylbutyrate is used along with a proper diet to help treat urea cycle disorders, including carbamylphosphate synthetase deficiency (CPS), ornithine transcarbamylase deficiency (OTC), or argininosuccinate synthetase (AS).

Ammonia is produced when the body breaks down protein. If the body cannot remove the ammonia, it can build up and cause serious unwanted effects. This medicine helps to lower high levels of ammonia in the blood.

This medicine is available only with your doctor's prescription.

It is very important for your doctor to check your progress at regular visits to ensure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

This medicine may cause problems with the nervous system. Contact your doctor right away if you experience confusion, headache, lightheadedness, nausea, sleepiness, tiredness, or vomiting.

In case of emergency—There may be times when you need emergency help for a problem caused by your urea cycle disorders. You should be prepared for these emergencies. It is a good idea to wear a Medic Alert tag at all times. Also, keep an ID card in your wallet or purse that states you have this disease and lists all of your medicines.

Do not take other medicines unless your doctor has discussed them with you. This includes prescription or over-the-counter (OTC) medicines, as well as herbal or vitamin supplements.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the benefits it will provide. This is a decision you and your doctor will make together. For this medicine, consider the following:

Allergies

Inform your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also, let your healthcare professional know if you have any other allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies done so far have not shown any specific problems in children that would limit the use of Olpruva™ in children weighing 20 kilograms (kg) or more and with a body surface area (BSA) of 1.2 square meters (m). Safety and effectiveness have been established. It is not recommended to use this medicine to treat acute hyperammonemia in children, in children weighing less than 20 kg, or in children weighing 20 kg or more with a BSA of less than 1.2 m.

Studies done so far have not shown any specific problems in children that would limit the use of Pheburane® in children. Safety and effectiveness have been established. It is not recommended to use this medicine to treat acute hyperammonemia in children.

Due to the toxicity of Buphenyl®, it is not recommended for use in children weighing less than 20 kilograms (44 pounds).

Geriatric

Studies done so far have not shown any specific problems in elderly patients that would limit the use of Pheburane® and Olpruva™ in older adults. However, older patients are more likely to have age-related liver, kidney, or heart issues, which may require caution and an adjustment in the dose for patients taking this medicine.

No information is available on how age affects the effects of Buphenyl® in elderly patients.

Breast Feeding

There are no adequate studies in women to determine the risk to infants when using this medication while breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Some medicines should not be used together at all, while in other cases, two different medicines may be used together even if an interaction might happen. In these situations, your doctor may need to change the dose or take other precautions. When taking this medicine, it is very important that your healthcare professional knows if you are taking any of the medicines listed below. The following interactions have been chosen based on their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be necessary in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you take one or both of the medicines.

• Probenecid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or certain types of food, as interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions. Talk to your healthcare professional about using your medicine with food, alcohol, or tobacco.

Other Medical Problems

Other medical problems may affect the use of this medicine. Be sure to tell your doctor if you have any other medical issues, especially:

• Diabetes or
• Edema (swelling due to excess fluid in the body) or
• Fructose intolerance, history of or
• Glucose-galactose malabsorption, history of or
• Heart disease or
• Heart failure or
• Severe kidney disease or
• Sucrase-isomaltase insufficiency, history of—Use with caution. May worsen these conditions.

• Kidney disease or
• Liver disease—Use with caution. The effects may be stronger due to slower removal of the medicine from the body.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Change in the frequency of breathing
• Lack of or irregular menstruation
• Lower back, side, or stomach pain
• Mood or mental changes
• Muscle pain or twitching
• Nausea or vomiting
• Nervousness or restlessness
• Swelling of the feet or lower legs
• Unpleasant taste
• Unusual tiredness or weakness

Less common

• Absent, missed, or irregular menstrual periods
• Black, tarry stools
• Bleeding gums
• Bloating
• Blood in the urine or stools
• Bone pain
• Burning, tingling, numbness or pain in the hands, arms, feet, or legs
• Chest pain or tightness
• Chills
• Constipation
• Cough
• Darkened urine
• Discouragement
• Dizziness
• Fainting
• Fast heartbeat
• Feeling sad or empty
• Fever
• Headache
• Indigestion
• Irritability
• Joint pain, stiffness, or swelling
• Large, flat, blue or purplish patches in the skin
• Loss of appetite
• Loss of interest or pleasure
• Mood changes
• Muscle pain, cramps, or twitching
• Numbness or tingling in hands, feet, or lips
• Pains in stomach, side, or abdomen, possibly radiating to the back
• Painful or difficult urination
• Pinpoint red spots on the skin
• Rectal bleeding
• Seizures
• Sensation of pins and needles
• Severe or continuing stomach pain
• Sore throat
• Sores, ulcers, or white spots on the lips or in the mouth
• Stabbing pain
• Stopping of menstrual bleeding
• Swelling of the feet or lower legs
• Swollen or painful glands
• Trouble breathing
• Trouble concentrating
• Trouble sleeping
• Uneven heartbeat
• Unusual bleeding or bruising
• Yellow eyes or skin

Rare

• Dryness of the mouth
• Fast, slow, or irregular heartbeat
• Increased thirst
• Swelling of the face
• Unusual weight gain
• Weak pulse

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Body odor
• Burning feeling in the chest or stomach
• Decreased appetite
• Increased weight
• Skin rash
• Stomach pain or upset

Incidence not known

• Change in taste
• Loss of taste

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

In the U.S.

• Buphenyl
• Olpruva
• Pheburane
• SPB11

Available Dosage Forms:

• Packet
• Powder
• Tablet
• Pellet

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Histone Deacetylase Inhibitor

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects. Also, do not stop using this medicine without checking first with your doctor.

This medicine comes with a patient information leaflet. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

For patients taking the powder form of this medicine:

• Sodium phenylbutyrate should be mixed with water or any food (solid or liquid). If the medicine is mixed with food, it should be taken right away. However, if it is mixed with water, the solution can be stored for up to one week at room temperature or in the refrigerator.
• Shake the mixed solution lightly before each use. Measure the dose with the level teaspoon or tablespoon that comes together with the package of this medicine.

Take this medicine with food.

To use the Olpruva™ oral liquid:

• Pour the entire contents of the Mix-Aid packet into 4 ounces of water in a cup and stir with spoon for 30 seconds to make the water thicker.
• Add the Olpruva™ in the mixture and stir for 15 seconds. Take the mixture within 5 minutes to prevent the coating from dissolving.
• Pour another 4 ounces of water in the cup to make sure you get full dose.
• Throw away the mixture if you have not taken it within 30 minutes of mixing.
• Do not give this medicine through a feeding tube.

To use the Pheburane® oral pellets:

• Measure the medicine with a marked measuring spoon.
• You may swallow the oral pellets with a drink (eg, water, fruit juices, protein-free infant formulas) or you may sprinkle the pellets with apple sauce or carrot puree. Take the mixture right away.
• Do not chew the pellets directly or mix with liquids.

It is important that you follow any special instructions from your doctor, such as following a low-protein diet. Also, your doctor may recommend that you take amino acid supplements. If you have any questions about this, check with your doctor.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For the treatment of urea cycle disorders: For oral dosage form (pellets): Adults and children weighing 20 kilograms (kg) or more—Dose is based on body size and must be determined by your doctor. The dose is usually 9.9 to 13 grams (g) per square meter (m[2]) per day divided into 3 to 6 doses. However, the dose is usually not more than 20 g per day. Children weighing less than 20 kg—Dose is based on weight and must be determined by your doctor. The dose is usually 450 to 600 milligrams per kilogram (mg/kg) of body weight per day divided into 3 to 6 doses. However, the dose is usually not more than 20 g per day. For oral dosage form (powder for solution): Adults, teenagers, and children weighing 20 kilograms (kg) (44 pounds) or more—The dose is based on body size and must be determined by your doctor. It is usually given 4 to 6 times a day. However, the dose is usually not more than 20 grams a day. Children weighing up to 20 kg (44 pounds)—The dose is based on body weight and must be determined by your doctor. The usual dose is 450 to 600 milligrams (mg) per kilogram (kg) (205 to 273 mg per pound) of body weight per day. The dose is divided in equal amounts and given 3 to 6 times a day. However, the dose is usually not more than 20 grams a day. For oral dosage form (suspension): Adults and children weighing 20 kilograms (kg) or more—The dose is based on body size and must be determined by your doctor. The usual dose is 9.9 to 13 grams (g) per square meter (m[2]) per day divided into 3 to 6 doses. However, the dose is usually not more than 20 g per day. Children weighing less than 20 kg—Use of the suspension is not recommended. For oral dosage form (tablets): Adults, teenagers, and children weighing 20 kg (44 pounds) or more—The dose is based on body size and must be determined by your doctor. It is usually given 3 times a day. However, the dose is usually not more than 20 grams (40 tablets) a day. Children weighing up to 20 kg (44 pounds)—Use of the tablets is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Pheburane® oral pellets: If you have less than 3 hours before your next scheduled dose, skip the missed dose and go back to your regular dosing schedule.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Throw away unused Pheburane® oral pellets 45 days after opening the bottle.