Phenylbutyrate

What it is used for

Sodium phenylbutyrate tablets are indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life).

It is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy. It is important that the diagnosis be made early and treatment initiated immediately to improve survival. Any episode of acute hyperammonemia should be treated as a life-threatening emergency.

Sodium phenylbutyrate tablets must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation (see Nutritional Supplementation subsection of the DOSAGE AND ADMINISTRATION section). Previously, neonatal-onset disease was almost universally fatal within the first year of life, even when treated with peritoneal dialysis and essential amino acids or their nitrogen-free analogs.

However, with hemodialysis, use of alternative waste nitrogen excretion pathways (sodium phenylbutyrate, sodium benzoate, and sodium phenylacetate), dietary protein restriction, and, in some cases, essential amino acid supplementation, the survival rate in newborns diagnosed after birth but within the first month of life is almost 80%.

Most deaths have occurred during an episode of acute hyperammonemic encephalopathy. Patients with neonatal-onset disease have a high incidence of mental retardation. Those who had IQ tests administered had an incidence of mental retardation as follows: ornithine transcarbamylase deficiency, 100% (14/14 patients tested); argininosuccinic acid synthetase deficiency, 88% (15/17 patients tested); and carbamylphosphate synthetase deficiency, 57% (4/7 patients tested).

Retardation was severe in the majority of the retarded patients. In patients diagnosed during gestation and treated prior to any episode of hyperammonemic encephalopathy, survival is 100%, but even in these patients, most subsequently demonstrate cognitive impairment or other neurologic deficits. In late-onset deficiency patients, including females heterozygous for ornithine transcarbamylase deficiency, who recover from hyperammonemic encephalopathy and are then treated chronically with sodium phenylbutyrate and dietary protein restriction, the survival rate is 98%.

The two deaths in this group of patients occurred during episodes of hyperammonemic encephalopathy. However, compliance with the therapeutic regimen has not been adequately documented to allow evaluation of the potential for sodium phenylbutyrate tablets and dietary protein restriction to prevent mental deterioration and recurrence of hyperammonemic encephalopathy if carefully adhered to.

The majority of these patients tested (30/46 or 65%) have IQ’s in the average to low average/borderline mentally retarded range. Reversal of preexisting neurologic impairment is not likely to occur with treatment and neurologic deterioration may continue in some patients. Even on therapy, acute hyperammonemic encephalopathy recurred in the majority of patients for whom the drug is indicated.

Sodium phenylbutyrate tablets may be required lifelong unless orthotopic liver transplantation is elected. (See CLINICAL PHARMACOLOGY, Pharmacodynamics subsection for the biochemical effects of sodium phenylbutyrate tablets).

The most important thing to know

Glycerol phenylbutyrate oral liquid may cause serious side effects, including: Nervous system problems (Neurotoxicity). Phenylacetate (PAA), a breakdown product of glycerol phenylbutyrate, may cause nervous system side effects. Call your doctor or get medical help right away if you get any of these symptoms while taking glycerol phenylbutyrate oral liquid: sleepiness worsening of numbness, tingling, or burning in your hands or feet lightheadedness headache change in taste feeling very tired (fatigue) problems with hearing nausea confusion vomiting problems with memory Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with glycerol phenylbutyrate oral liquid.

What is Glycerol phenylbutyrate oral liquid? Glycerol phenylbutyrate oral liquid is a prescription medicine used for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). Glycerol phenylbutyrate oral liquid should be used if the UCD cannot be managed with a low protein diet and dietary supplements alone.

Glycerol phenylbutyrate oral liquid must be used along with a low protein diet and in some cases dietary supplements. Glycerol phenylbutyrate oral liquid is not used for the acute treatment of hyperammonemia in people with UCD. It is not known if glycerol phenylbutyrate oral liquid is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

How to take it

Take glycerol phenylbutyrate oral liquid exactly as your doctor tells you. Your doctor will tell you how much glycerol phenylbutyrate oral liquid to take and when to take it. Your doctor may change your dose if needed. Take glycerol phenylbutyrate oral liquid with food or formula. In an infant who is breastfeeding, give glycerol phenylbutyrate oral liquid just before breastfeeding.

Glycerol phenylbutyrate oral liquid is an oral liquid that is taken by mouth using an oral syringe. Ask your pharmacist for oral syringes and a reclosable bottle cap adapter for each bottle you receive if you do not have them. Use the glycerol phenylbutyrate oral liquid bottle and oral syringe as follows: Use a new reclosable bottle cap adapter with each new glycerol phenylbutyrate oral liquid bottle that is opened.

Open the glycerol phenylbutyrate bottle and twist on the new reclosable bottle cap adapter. Use a new dry oral syringe to remove each prescribed dose of glycerol phenylbutyrate oral liquid. Throw away (discard) the oral syringe after each dose. Tightly close the tethered tab on the reclosable bottle cap adapter after each use.

Do not rinse the reclosable bottle cap adapter. If water or moisture enters the glycerol phenylbutyrate oral liquid bottle, the contents will become cloudy in appearance. If the contents appear cloudy at any time, do not use the remaining glycerol phenylbutyrate oral liquid and return the bottle to your pharmacy to throw it away.

Throw away the bottle and any unused glycerol phenylbutyrate oral liquid 28 days after opening. If you have a nasogastric or gastrostomy tube in place and can swallow, you should take glycerol phenylbutyrate oral liquid by mouth. Stay on the diet that your doctor gives you. If you take too much glycerol phenylbutyrate oral liquid, call your doctor or your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away.

For people who cannot swallow and who have a nasogastric or gastrostomy tube in place, glycerol phenylbutyrate oral liquid should be given as follows: Use a new dry oral syringe to withdraw each prescribed dose of glycerol phenylbutyrate oral liquid from the bottle. Place the tip of the syringe into the nasogastric or gastrostomy tube and push the plunger of the syringe to give glycerol phenylbutyrate oral liquid into the tube.

Use a separate syringe to flush the nasogastric or gastrostomy tube. Add 10 mL of water or formula to the syringe and push the plunger of the syringe to flush any remaining medicine from the nasogastric or gastrostomy tube into the stomach. If needed, flush the nasogastric or gastrostomy tube again with 10 mL of water or formula to clear the nasogastric or gastrostomy tube.

Side effects, and when to stop

Glycerol phenylbutyrate oral liquid may cause serious side effects, including: The most common side effects of glycerol phenylbutyrate oral liquid in adults include: diarrhea vomiting gas tiredness headache decreased appetite abdomen (stomach) pain indigestion or heartburn The most common side effects of glycerol phenylbutyrate oral liquid in children 2 years to 17 years of age include: upper abdomen (stomach) pain diarrhea rash decreased appetite nausea headache vomiting The most common side effects of glycerol phenylbutyrate oral liquid in children 2 months to less than 2 years of age include: low white blood cell count (neutropenia) cough vomiting stuffy nose constipation runny nose diarrhea skin rash fever small round bumps on the skin reduced food intake The most common side effects of glycerol phenylbutyrate oral liquid in children less than 2 months of age include: vomiting low blood neutrophil count (type of white blood cell) (neutropenia) rash high blood white blood cell count (lymphocytosis) gastroesophageal reflux diarrhea increased levels of liver enzymes in the blood gas decreased appetite and reduced food intake constipation low red blood cell count (anemia) fever cough drowsiness (lethargy) loss of too much body fluid (dehydration) irritability too much acid in the blood (acidosis) agitation high blood platelet count (thrombocytosis) low blood platelet count (thrombocytopenia) These are not all of the possible side effects of glycerol phenylbutyrate oral liquid.

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

Who should not take it

Do not take glycerol phenylbutyrate oral liquid if you are allergic to phenylbutyrate. Call your doctor or go to the nearest hospital emergency room if you have wheezing, shortness of breath, cough, low blood pressure, flushing, nausea or a rash while taking glycerol phenylbutyrate oral liquid. Before taking glycerol phenylbutyrate, tell your doctor about all of your medical conditions, including if you: have liver or kidney problems have pancreas or bowel (intestine) problems are pregnant or plan to become pregnant.

It is not known if glycerol phenylbutyrate oral liquid will harm your unborn baby. If you become pregnant during treatment with glycerol phenylbutyrate oral liquid, call Aurobindo Pharma USA, Inc. at 1-866-850-2876 to report the pregnancy. are breastfeeding or plan to breastfeed. It is not known if glycerol phenylbutyrate passes into your breast milk.

Breastfeeding is not recommended during treatment with glycerol phenylbutyrate oral liquid. Talk to your doctor about the best way to feed your baby if you take glycerol phenylbutyrate oral liquid. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, dietary and herbal supplements.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

Storing it

Store glycerol phenylbutyrate oral liquid between 68ºF to 77ºF (20°C to 25°C). Keep glycerol phenylbutyrate oral liquid and all medicines out of the reach of children.