Actigall

Name: Actigall

What should I discuss with my healthcare provider before taking Actigall (ursodiol)?

You should not use ursodiol if you are allergic to it, or if you have an obstruction in your liver or gallbladder.

To make sure ursodiol is safe for you, tell your doctor if:

  • you have been coughing up blood; or

  • you have gained weight rapidly, especially in your face and midsection.

FDA pregnancy category B. Ursodiol is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether ursodiol passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

What other drugs will affect Actigall (ursodiol)?

Other drugs may interact with ursodiol, 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.

What do I need to tell my doctor BEFORE I take Actigall?

  • If you have an allergy to ursodiol or any other part of Actigall (ursodiol).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have a biliary tract block.
  • If you have a certain bile duct problem (cholangitis).
  • If you have any of these health problems: Abnormal opening in the biliary and GI (gastrointestinal) tracts, pancreatitis, or swelling of the gallbladder (cholecystitis).

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Actigall with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Actigall Description

Actigall is a bile acid available as 300 mg capsules suitable for oral administration.

Actigall is ursodiol, USP (ursodeoxycholic acid), a naturally occurring bile acid found in small quantities in normal human bile and in the biles of certain other mammals. It is a bitter-tasting, white powder freely soluble in ethanol, methanol, and glacial acetic acid; sparingly soluble in chloroform; slightly soluble in ether; and insoluble in water. The chemical name for ursodiol is 3α,7β-Dihydroxy-5β-cholan-24-oic acid (C24H40O4). Ursodiol, USP has a molecular weight of 392.57. Its structure is shown below:

Inactive Ingredients: Colloidal silicon dioxide, magnesium stearate, and starch (corn). Gelatin capsules contain ferric oxide, gelatin, and titanium dioxide. The capsules are printed with edible ink containing black iron oxide.

Contraindications

  1. Actigall will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment  stones. Hence, patients with such stones are not candidates for Actigall therapy.
  2. Patients with compelling reasons for cholecystectomy including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula are not candidates for Actigall therapy.
  3. Allergy to bile acids.

Adverse Reactions

The nature and frequency of adverse experiences were similar across all groups.

The following tables provide comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level:

 GALLSTONE DISSOLUTION
   Ursodiol  Placebo
 8 - 10 mg/kg/day
(N = 155)
 
(N = 159)
   N  (%)  N  (%)
 Body as a Whole        
    Allergy  8  (5.2)  7  (4.4)
    Chest Pain  5  (3.2)  10  (6.3)
    Fatigue  7  (4.5)  8  (5.0)
    Infection Viral
 30
 (19.4)
 41
 (25.8)
 Digestive System        
    Abdominal Pain  67  (43.2)  70  (44.0)
    Cholecystitis  8  (5.2)  7  (4.4)
    Constipation  15  (9.7)  14  (8.8)
    Diarrhea  42  (27.1)  34  (21.4)
    Dyspepsia  26  (16.8)  18  (11.3)
    Flatulence  12  (7.7)  12  (7.5)
    Gastrointestinal Disorder  6  (3.9)  8  (5.0)
    Nausea  22  (14.2)  27  (17.0)
    Vomiting
 15
 (9.7)
 11
 (6.9)
 Musculoskeletal System        
    Arthralgia  12  (7.7)  24  (15.1)
    Arthritis  9  (5.8)  4  (2.5)
    Back Pain  11  (7.1)  18  (11.3)
    Myalgia
 9
 (5.8)
 9
 (5.7)
 Nervous System        
    Headache  28  (18.1)  34  (21.4)
    Insomnia  3  (1.9)  8  (5.0)
 Respiratory System        
    Bronchitis  10  (6.5)  6  (3.8)
    Coughing  11  (7.1)  7  (4.4)
    Pharyngitis  13  (8.4)  5  (3.1)
    Rhinitis  8  (5.2)  11  (6.9)
    Sinusitis  17  (11.0)  18  (11.3)
    Upper Respiratory        
    Tract Infection
 24
 (15.5)
 21
 (13.2)
 Urogenital System        
    Urinary Tract Infection
 10
 (6.5)
 7
 (4.4)
 
GALLSTONE PREVENTION
   Actigall  Placebo
 600 mg
(N = 322)
 
(N = 325)
 N  (%)  N  (%)
 Body as a Whole        
    Fatigue  25  (7.8)  33  (10.2)
    Infection Viral  29  (9.0)  29  (8.9)
    Influenza-like Symptoms
 21
 (6.5)
 19
 (5.8)
 Digestive System        
    Abdominal Pain  20  (6.2)  39  (12.0)
    Constipation  85  (26.4)  72  (22.2)
    Diarrhea  81  (25.2)  68  (20.9)
    Flatulence  15  (4.7)  24  (7.4)
    Nausea  56  (17.4)  43  (13.2)
    Vomiting
 44  (13.7)  44  (13.5)
 Musculoskeletal System        
    Back Pain  38  (11.8)  21  (6.5)
    Musculoskeletal Pain  19  (5.9)  15  (4.6)
 Nervous System        
    Dizziness  53  (16.5)  42  (12.9)
    Headache  80  (24.8)  78  (24.0)
 Respiratory System        
    Pharyngitis  10  (3.1)  19  (5.8)
    Sinusitis  17  (5.3)  18  (5.5)
    Upper Respiratory        
    Tract Infection
 40
 (12.4)
 35
 (10.8)
 Skin and Appendages        
    Alopecia
 17
 (5.3)
 8
 (2.5)
 Urogenital System        
    Dysmenorrhea
 18
 (5.6)
 19
 (5.8)

Overdosage

Neither accidental nor intentional overdosing with Actigall has been reported. Doses of Actigall in the range of 16 - 20 mg/kg/day have been tolerated for 6 to 37 months without symptoms by 7 patients. The LD50 for ursodiol in rats is over 5000 mg/kg given over 7 to 10 days and over 7500 mg/kg for mice. The most likely manifestation of severe overdose with Actigall would probably be diarrhea, which should be treated symptomatically.

Other Requirements

  • Store Actigall at room temperature.
  • Keep this and all medications out of the reach of children.

For the Consumer

Applies to ursodiol: oral capsule, oral tablet

Along with its needed effects, ursodiol (the active ingredient contained in Actigall) 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 while taking ursodiol:

More common
  • Bladder pain
  • bloody or cloudy urine
  • difficult, burning, or painful urination
  • dizziness
  • fast heartbeat
  • frequent urge to urinate
  • indigestion
  • lower back or side pain
  • severe nausea
  • skin rash or itching over the entire body
  • stomach pain
  • vomiting
  • weakness
Less common
  • Black, tarry stools
  • chest pain
  • chills or fever
  • cough
  • pinpoint red spots on the skin
  • severe or continuing stomach pain
  • sore throat or swollen glands
  • sores, ulcers, or white spots on the lips or in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Incidence not known
  • Clay-colored stools
  • dark urine
  • difficulty with swallowing
  • headache
  • hives or welts
  • hoarseness
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • nausea
  • redness of the skin
  • slow or irregular breathing
  • tightness in the chest
  • unpleasant breath odor
  • yellow eyes or skin

Some side effects of ursodiol 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:

More common
  • Back pain
  • body aches or pain
  • congestion
  • constipation
  • general feeling of discomfort or illness
  • heartburn
  • loss of voice
  • muscle aches
  • muscle or bone pain
  • pain, swelling, or redness in the joints
  • runny nose
  • sweating
  • trouble sleeping
Less common
  • Diarrhea
Rare
  • Worsening psoriasis
Incidence not known
  • Acid or sour stomach
  • belching bloating or swelling of face, arms, hands, lower legs, or feet
  • difficulty with moving
  • rapid weight gain
  • stomach discomfort or upset
  • tingling of the hands or feet
  • unusual weight gain or loss

Ursodiol Levels and Effects while Breastfeeding

Summary of Use during Lactation

Because of the low levels of ursodiol (ursodeoxycholic acid) in breastmilk, amounts ingested by the infant are small and are not expected to cause any adverse effects in breastfed infants. No special precautions are required.

Drug Levels

Maternal Levels. A woman received oral ursodiol 750 mg daily throughout pregnancy for primary biliary cirrhosis. She continued ursodiol postpartum and ursodiol was undetectable in her breastmilk by HPLC assay. Details of milk collection and assay limits were not reported.[1]

Seven mothers with intrahepatic cholestasis of pregnancy were given oral ursodiol 14 mg/kg daily beginning an average of 14 days prior to delivery and continuing postpartum. Colostrum samples taken in the first 72 hours postpartum contained an average of 118 mcg/L. The mothers treated with ursodiol had levels of bile acids in colostrum that were much less elevated than 9 untreated control women with cholestasis of pregnancy.[2]

A woman with primary biliary cirrhosis developed severe pruritus and elevated serum bile acids 3 weeks postpartum. Ursodiol was started at a dose of 500 mg (7.5 mg/kg) daily increased to 1500 mg (25 mg/kg) daily over the next 8 weeks. Total bile acids in breastmilk increased from 0.5 micromol/L to 1 micromol/L after 8 weeks of therapy; after 16 weeks, total bile acids in milk were 0.6 micromol/L. Urodiol milk levels were undetectable before drug initiation, 63 mcg/L at an ursodiol dose of 500 mg daily after 2 weeks, 118 mcg/L with a dose of 1 gram daily after 4 weeks, 79 mcg/L with a dose of 1.5 grams daily after 11 weeks, and 196 mcg/L with a dose of 1.5 grams daily after 19 weeks.[3]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

One breastfed (extent not stated) infant developed normally over the first 6 months of life during maternal ursodiol therapy of 750 to 1000 mg daily.[1]

Seven women who were taking ursodiol 14 mg/kg daily near term and postpartum. They reported no adverse reactions in their breastfed infants during the early postpartum period.[2]

A mother receiving oral ursodiol 250 mg 3 times daily for primary biliary cirrhosis reportedly breastfed her infant normally, although the extent and duration of breastfeeding was not stated.[4]

A woman with primary biliary cirrhosis developed severe pruritus and elevated serum bile acids 3 weeks postpartum. Ursodiol was started at a dose of 500 mg (7.5 mg/kg) daily, increasing to 1500 mg (25 mg/kg) daily over the next 8 weeks. Psychomotor development of her breastfed (extent not stated) infant was normal, and no apparent side effects were observed in the infant.[3]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1. Rudi J, Schonig T, Stremmel W. [Therapy with ursodeoxycholic acid in primary biliary cirrhosis in pregnancy]. Zentralbl Gastroenterol. 1996;34:188-91. PMID: 8650973

2. Brites D, Rodrigues CMP. Elevated levels of bile acids in colostrum of patients with cholestasis of pregnancy are decreased following ursodeoxycholic acid therapy. J Hepatol. 1998;29:743-51. PMID: 9833912

3. Vitek L, Zelenkova M, Bruha R. Safe use of ursodeoxycholic acid in a breast-feeding patient with primary biliary cirrhosis. Dig Liver Dis. 2010;42:911-2. PMID: 20619755

4. Goh SK, Gull SE, Alexander GJ. Pregnancy in primary biliary cirrhosis complicated by portal hypertension: report of a case and review of the literature. BJOG. 2001;108:760-2. PMID: 11467706

(web3)