Cholbam

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Cholic acid works best if you take it with food.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Do not crush or chew a cholic acid capsule.

To make swallowing easier, you may open the cholic acid capsule and sprinkle the medicine into a spoonful of soft food. If you are giving cholic acid to a young child, mix the medicine with a small amount of baby formula or breast milk. Stir the mixture for 30 seconds and use it right away. Do not save the mixture for later use.

Cholic acid comes in different capsule sizes. Your dose may require that you take only 1 capsule per day or up to 8 capsules per day. Cholic acid doses are based on weight and you may need to use two different capsule sizes to make up your entire dose. Follow your doctor's dosing instructions very carefully.

The recommended dose of cholic acid increases with every few pounds gained as you grow from infancy to adulthood. Tell your doctor if you have any changes in weight.

While using cholic acid, you may need frequent blood tests.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Before taking Cholbam, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Cholbam or to any of its ingredients
• have liver problems
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

There are no well-controlled studies that have been done in pregnant women or animals. Cholbam should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

There is a pregnancy surveillance program that monitors pregnancy outcomes in women exposed to Cholbam during pregnancy and women who become pregnant during Cholbam treatment are encouraged to enroll. Contact your healthcare provider for more information.

When you take your cholic acid dose, avoid taking other medicines by mouth at the same time. Since cholic acid aids in digestion, it can affect how well your body absorbs any other medicines you need to take. Take cholic acid at least 1 hour before or 4 to 6 hours after you take:

• cholestyramine;

• colesevelam;

• colestipol; or

• an antacid that contains aluminum--Acid Gone, Di-Gel, Gaviscon, Gelusil, Maalox, Mylagen, Mylanta, Rulox, and others.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• blood in your stools, changes in your bowel habits (such as diarrhea or constipation);

• pain or burning when you urinate; or

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• heartburn, acid reflux;

• nausea, diarrhea, stomach pain;

• general ill feeling;

• jaundice;

• skin sores; or

• numbness, tingling, or burning pain in your hands or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may interact with cholic acid, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Bile Acid Synthesis Disorders

Management of bile acid synthesis disorders due to single enzyme defects (designated an orphan drug by FDA for this use).1 2 5

Safety and efficacy for management of extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects not established.1

Peroxisomal Disorders

Adjunctive management of peroxisomal disorders (e.g., Zellweger spectrum disorders) in patients experiencing symptoms of liver disease, steatorrhea, or complications resulting from decreased absorption of fat-soluble vitamins (designated an orphan drug by FDA for this use).1 2 5 10

Safety and efficacy for management of extrahepatic manifestations of peroxisomal disorders not established.1

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Exacerbation of Hepatic Impairment

Exacerbation of hepatic impairment (e.g., elevations in AST, ALT, and bilirubin concentrations, worsening cholestasis on liver biopsy), sometimes necessitating liver transplant, reported in patients with and without baseline evidence of hepatic impairment (e.g., cholestasis) during treatment with cholic acid.1 Exacerbation of hepatic impairment due to cholic acid cannot be ruled out.1

Monitor liver function; discontinue treatment in patients who develop worsening of liver function.1 Discontinue treatment for clinical or laboratory indicators of worsening liver function or cholestasis.1

Specific Populations

No studies assessing risks of cholic acid in pregnant women or animals.1 In 2 out of 15 patients receiving cholic acid for a median of 12 years, 4 normal pregnancies resulted in the birth of 4 healthy infants.4 Limited data may not adequately predict presence or absence of risk during pregnancy.1

Encourage patients to enroll in COCOA Pregnancy registry (Cholbam: Child and Mother's Health) at 844-202-6262 to monitor pregnancy outcomes in women exposed to cholic acid.1

Endogenous cholic acid distributed into human milk; no data available in nursing women or lactating animals to determine distribution of exogenously administered cholic acid in milk.1 Effects of drug on nursing infants or human milk production unknown.1

Consider benefits of breast-feeding and importance of drug to the woman; also consider potential adverse effects on the breast-fed child from the drug or underlying maternal condition.1

Safety and efficacy not established in infants <3 weeks of age.1

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

If liver function does not improve within 3 months of therapy initiation or if persistent worsening of clinical or laboratory parameters of liver function or cholestasis occurs at any time, discontinue therapy.1

Monitor laboratory parameters of liver function; consider restarting the drug at lower dosage when parameters return to baseline.1

Common Adverse Effects

Diarrhea,1 reflux esophagitis,1 malaise,1 jaundice,1 skin lesion,1 nausea,1 abdominal pain,1 intestinal polyp,1 urinary tract infection,1 peripheral neuropathy.1

• Cholic acid is a primary bile acid synthesized from cholesterol in the liver.1 3 4 Endogenous primary bile acids (i.e., cholic acid, chenodeoxycholic acid) improve bile flow and provide physiologic feedback inhibition of bile acid synthesis.1 5

• Cholic acid and its conjugates are endogenous ligands of the nuclear farnesoid X receptor (FXR), which regulates enzymes and transporters involved in bile acid synthesis and enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions.1 4 Activation of the FXR through binding of cholic acid results in upregulation of transcription of genes coding for hepatic conjugation enzymes, resulting in increased metabolic conjugation of bile acids and bile acid-dependent bile flow.5

• Activated FXR also results in downregulation of cholesterol 7α-hydroxylase encoded by the CYP7A1 gene, potentially resulting in reduction in de novo synthesis of primary bile acids; clinical importance of such downregulation is not fully known.5

Cholic acid is a bile acid used to treat patients with bile acid synthesis disorders caused by single enzyme defects. This medicine is also used to help treat patients with peroxisomal disorders (including Zellweger spectrum disorders) who have symptoms of liver disease, steatorrhea, or have difficulty in absorbing fat soluble vitamins.

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

This section provides information on the proper use of a number of products that contain cholic acid. It may not be specific to Cholbam. Please read with care.

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.

Swallow the capsule whole. Do not crush, break, or chew it. Take this medicine with food.

If you cannot swallow the capsules, you may open it and mix the contents of the capsule with 1 to 2 tablespoons of infant formula or expressed breast milk, or soft foods (eg, mashed potatoes or apple puree). This mixture must be swallowed immediately.

If you are also taking cholestyramine, colesevelam, colestipol, or aluminum-containing antacids, take cholic acid at least 1 hour before or 4 to 6 hours after these medicines.

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 oral dosage form (capsules):
  • For bile acid synthesis disorders and peroxisomal disorders (including Zellweger spectrum disorders):
    • Adults and children 3 weeks of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 10 to 15 milligrams (mg) per kilogram (kg) of body weight once a day, or divided in two doses.
    • Children younger than 3 weeks of age—Use and dose must be determined by your doctor.

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.

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.

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:

• Abdominal or stomach pain
• chills
• clay-colored stools
• dark urine
• diarrhea
• dizziness
• fever
• general feeling of tiredness or weakness
• headache
• itching or rash
• light-colored stools
• loss of appetite
• nausea
• stomach pain, continuing
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting
• vomiting of blood
• yellow eyes or skin

• Bladder pain
• bloody or cloudy urine
• clay-colored stools
• dark urine
• difficult, burning, or painful urination
• frequent urge to urinate
• lower back or side pain
• unpleasant breath odor

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:

• Burning, numbness, tingling, or painful sensations
• chest pain
• difficulty with swallowing
• general feeling of discomfort or illness
• heartburn
• pain or burning in the throat
• skin lesions
• sores, ulcers, or white spots on the lips or tongue or inside the mouth
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

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.

. Effects of other drugs on Cholbam

Drug interactions with Cholbam mainly relate to agents capable of interrupting the enterohepatic circulation of bile acids.

Inhibitors of Bile Acid Transporters

Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended.

Bile Acid Binding Resins

Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of Cholbam. Take Cholbam at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin [see Dosage and Administration (2.3)].

Aluminum-Based Antacids

Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of Cholbam. Take Cholbam at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid [see Dosage and Administration (2.3)].

NDC 45043-002-02
90 capsules

Cholbam™
(cholic acid) capsules

250 mg

Rx Only

Manufactured for:
Manchester Pharmaceuticals, Inc.,
San Diego, CA 92130

Manufactured by:
Patheon France SA
38300 Bourgoin-Jallieu, France

For product information please call 844-246-5226.