Ocaliva 10mg Tablets
WARNING: Serious liver problems have happened with this drug. If you have ever had liver problems, talk with your doctor. This drug may not be right for people with some types of liver cirrhosis. Worsening of liver problems has happened in these people. Sometimes, this has led to a liver transplant or been deadly. Call your doctor right away if you have signs of liver problems like dark urine; feeling tired or weak; decreased appetite; upset stomach, stomach pain, or swelling in stomach area; light-colored stools; throwing up; yellow skin or eyes; black, tarry, or bloody stools; coughing up blood; throwing up blood or throw up that looks like coffee grounds; or mental or mood changes like confusion, feeling very sleepy, mood swings, or change in behavior. Call your doctor right away if you have any of these effects and they are severe or do not go away: diarrhea, fever, chills, weight loss, feeling lightheaded, or passing urine less often. @ COMMON USES: It is used to treat primary biliary cholangitis (PBC).
Drug Class
Bile acid derivative
Pharmacologic Class
Farnesoid X receptor (FXR) agonist
Pregnancy Category
Not available
FDA Approved
May 2016
DEA Schedule
Not Controlled
Overview
What is this medicine?
Ocaliva (obeticholic acid) is a medication used to treat a liver disease called primary biliary cholangitis (PBC). It works by helping your liver manage bile acids, which can build up and damage the liver in PBC. It's often used when another medicine, ursodeoxycholic acid (UDCA), doesn't work well enough or can't be tolerated.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. However, it's essential to avoid taking colesevelam, colestipol, or cholestyramine within 4 hours before or 4 hours after taking this medication, as it may interfere with its effectiveness.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry place, away from the bathroom. Keep all medications in a secure location, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so by your pharmacist. Instead, check with your pharmacist for guidance on the best disposal method or inquire about drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses, as this may increase the risk of side effects.
To ensure you get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. However, it's essential to avoid taking colesevelam, colestipol, or cholestyramine within 4 hours before or 4 hours after taking this medication, as it may interfere with its effectiveness.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry place, away from the bathroom. Keep all medications in a secure location, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so by your pharmacist. Instead, check with your pharmacist for guidance on the best disposal method or inquire about drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses, as this may increase the risk of side effects.
Lifestyle & Tips
- Take Ocaliva exactly as prescribed by your doctor.
- If you are taking bile acid sequestrants (like cholestyramine), take Ocaliva at least 4-6 hours before or 4-6 hours after them.
- Report any new or worsening symptoms, especially severe itching, yellowing of skin/eyes, or swelling in your abdomen/legs.
- Avoid alcohol as it can worsen liver disease.
- Maintain a healthy diet as recommended by your doctor.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 5 mg orally once daily for the first 3 months. If adequate reduction in alkaline phosphatase and tolerability, increase to 10 mg orally once daily.
Dose Range:
5 - 10 mg
Condition-Specific Dosing:
Primary Biliary Cholangitis (PBC):
Initial: 5 mg orally once daily. After 3 months, if adequate response and tolerated, increase to 10 mg orally once daily. Maximum: 10 mg once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed (CrCl 50-80 mL/min)
Moderate:
No dose adjustment needed (CrCl 30-49 mL/min)
Severe:
No dose adjustment needed (CrCl <30 mL/min)
Dialysis:
No dose adjustment needed
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A)
Moderate:
Initial: 5 mg orally twice weekly. If adequate response and tolerated after 3 months, consider increasing to 10 mg orally twice weekly (Child-Pugh B)
Severe:
Initial: 5 mg orally once weekly. If adequate response and tolerated after 3 months, consider increasing to 10 mg orally once weekly (Child-Pugh C)
Pharmacology
Mechanism of Action
Obeticholic acid is a potent and selective agonist for the farnesoid X receptor (FXR), a nuclear receptor expressed in the liver and intestine. FXR activation suppresses bile acid synthesis by downregulating cholesterol 7-alpha-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) through increased expression of fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP). It also increases bile acid excretion by upregulating bile acid transporters (e.g., BSEP, MRP2) and reducing uptake (e.g., NTCP). This leads to a reduction in the intracellular accumulation of bile acids, which are toxic to hepatocytes in cholestatic conditions like PBC.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (highly variable due to first-pass metabolism)
Tmax:
Approximately 1.5 hours (range 0.5 to 4 hours)
FoodEffect:
No clinically significant effect of food on absorption
Distribution:
Vd:
Not available
ProteinBinding:
Greater than 99% (primarily to albumin and alpha1-acid glycoprotein)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 2.5 to 4.8 hours (for unconjugated obeticholic acid); longer for active conjugates
Clearance:
Not available
ExcretionRoute:
Primarily fecal (approximately 87% as obeticholic acid and its conjugates)
Unchanged:
Less than 1% in urine
Pharmacodynamics
OnsetOfAction:
Not precisely defined for chronic effect on liver biochemistry, but biochemical changes (e.g., alkaline phosphatase reduction) are observed within weeks to months.
PeakEffect:
Maximal reduction in alkaline phosphatase typically observed within 3-6 months.
DurationOfAction:
Sustained with continued dosing.
Safety & Warnings
BLACK BOX WARNING
Hepatic Decompensation and Failure in Patients with Cirrhosis: Ocaliva has been associated with hepatic decompensation and failure in patients with cirrhosis, including those with compensated cirrhosis. These adverse reactions have resulted in some cases in liver transplant and death. Ocaliva is contraindicated in patients with complete biliary obstruction. In patients with PBC and cirrhosis, monitor for signs and symptoms of hepatic decompensation. If decompensation occurs, discontinue Ocaliva. In patients with PBC and moderate or severe hepatic impairment (Child-Pugh B or C), reduce the dosing frequency of Ocaliva.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of thyroid problems, including:
+ Weight changes
+ Feeling nervous, excitable, restless, or weak
+ Hair thinning
+ Depression
+ Eye or neck swelling
+ Difficulty focusing
+ Sensitivity to heat or cold
+ Menstrual changes
+ Shakiness
+ Excessive sweating
Swelling in the arms or legs
Fast or abnormal heartbeat
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Feeling dizzy, tired, or weak
Stomach pain
Joint pain
Mouth or throat pain or irritation
Constipation
Skin dryness, irritation, redness, crusting, or drainage (eczema)
* Itching (common with this medication); severe itching can lead to pain, sleep disturbances, and difficulties with daily activities. Contact your doctor immediately if you experience severe itching that interferes with your daily life or does not subside.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of thyroid problems, including:
+ Weight changes
+ Feeling nervous, excitable, restless, or weak
+ Hair thinning
+ Depression
+ Eye or neck swelling
+ Difficulty focusing
+ Sensitivity to heat or cold
+ Menstrual changes
+ Shakiness
+ Excessive sweating
Swelling in the arms or legs
Fast or abnormal heartbeat
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Feeling dizzy, tired, or weak
Stomach pain
Joint pain
Mouth or throat pain or irritation
Constipation
Skin dryness, irritation, redness, crusting, or drainage (eczema)
* Itching (common with this medication); severe itching can lead to pain, sleep disturbances, and difficulties with daily activities. Contact your doctor immediately if you experience severe itching that interferes with your daily life or does not subside.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe or worsening itching (pruritus)
- Yellowing of your skin or the whites of your eyes (jaundice)
- Swelling in your abdomen or legs (ascites, edema)
- Confusion, disorientation, or changes in mental status (hepatic encephalopathy)
- Dark urine or pale stools
- Unusual bleeding or bruising
- New or worsening fatigue
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have a blockage in your bile tract.
If you are currently taking cyclosporine.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and supplements with your doctor. This includes:
All prescription and over-the-counter (OTC) medications
Natural products
Vitamins
Your doctor and pharmacist need to be aware of all your medications and health problems to ensure it is safe for you to take this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have a blockage in your bile tract.
If you are currently taking cyclosporine.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and supplements with your doctor. This includes:
All prescription and over-the-counter (OTC) medications
Natural products
Vitamins
Your doctor and pharmacist need to be aware of all your medications and health problems to ensure it is safe for you to take this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Discuss any concerns or questions you have with your doctor.
This medication may decrease levels of high-density lipoprotein (HDL), also known as "good" cholesterol. If you have concerns about this potential effect, consult with your doctor.
To minimize the risk of side effects, your doctor may prescribe additional medications to be taken in conjunction with this drug.
If you are pregnant, planning to become pregnant, or are breastfeeding, it is crucial to discuss the potential benefits and risks of this medication with your doctor, as they will need to weigh the advantages and disadvantages for both you and your baby.
This medication may decrease levels of high-density lipoprotein (HDL), also known as "good" cholesterol. If you have concerns about this potential effect, consult with your doctor.
To minimize the risk of side effects, your doctor may prescribe additional medications to be taken in conjunction with this drug.
If you are pregnant, planning to become pregnant, or are breastfeeding, it is crucial to discuss the potential benefits and risks of this medication with your doctor, as they will need to weigh the advantages and disadvantages for both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe pruritus
- Significant elevations in liver enzymes (AST, ALT)
- Potentially signs of hepatic decompensation
What to Do:
There is no specific antidote. Management should be supportive and symptomatic. Contact a poison control center immediately (e.g., 1-800-222-1222) or seek emergency medical attention.
Drug Interactions
Major Interactions
- Bile acid sequestrants (e.g., cholestyramine, colestipol, colesevelam): May reduce obeticholic acid absorption. Administer obeticholic acid at least 4-6 hours before or 4-6 hours after bile acid sequestrants.
- Warfarin: Increased INR reported in some patients. Monitor INR closely upon initiation or dose adjustment of obeticholic acid.
Moderate Interactions
- CYP1A2 substrates with narrow therapeutic index (e.g., tizanidine, theophylline): Obeticholic acid may increase exposure of these drugs. Monitor and adjust dose as needed.
- CYP3A4 substrates (e.g., midazolam, cyclosporine, tacrolimus, sirolimus): Obeticholic acid may decrease exposure of these drugs. Monitor and adjust dose as needed.
- P-glycoprotein (P-gp) substrates (e.g., digoxin, dabigatran): Obeticholic acid may decrease exposure of these drugs. Monitor and adjust dose as needed.
Monitoring
Baseline Monitoring
Liver function tests (Alkaline Phosphatase, AST, ALT, Total Bilirubin, Albumin, INR)
Rationale: To establish baseline liver function and assess disease severity in PBC.
Timing: Prior to initiation of therapy
Routine Monitoring
Liver function tests (Alkaline Phosphatase, AST, ALT, Total Bilirubin, Albumin, INR)
Frequency: Every 3 months for the first year, then every 6 months or as clinically indicated.
Target: Reduction in alkaline phosphatase towards normal or by at least 15% from baseline. Maintain normal bilirubin.
Action Threshold: Discontinue or reduce dose if signs of hepatic decompensation (e.g., jaundice, ascites, encephalopathy) or significant increase in LFTs occur. Consider dose reduction if pruritus is intolerable.
Pruritus assessment
Frequency: Regularly, especially during dose titration.
Target: Tolerable level of pruritus.
Action Threshold: If severe or intolerable, consider dose reduction or temporary interruption.
Symptom Monitoring
- Worsening pruritus
- Jaundice (yellowing of skin or eyes)
- Ascites (abdominal swelling)
- Hepatic encephalopathy (confusion, disorientation)
- Gastrointestinal discomfort (nausea, diarrhea, constipation)
- Fatigue
Special Patient Groups
Pregnancy
Limited data on use in pregnant women. Animal studies show adverse effects on embryo-fetal development at doses higher than human therapeutic doses. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential risk based on animal data, but human data are insufficient.
Second Trimester:
Potential risk based on animal data, but human data are insufficient.
Third Trimester:
Potential risk based on animal data, but human data are insufficient.
Lactation
It is not known if obeticholic acid or its metabolites are excreted in human milk. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Ocaliva and any potential adverse effects on the breastfed infant from Ocaliva or from the underlying maternal condition. A risk to the infant cannot be excluded.
Infant Risk:
L3 (Moderate risk - no human data, animal data suggest potential for excretion into milk, or drug is known to be excreted into human milk but with low levels and no adverse effects reported in infants)
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Not indicated for use in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients (≥65 years) and younger patients. No dose adjustment is required based on age alone.
Clinical Information
Clinical Pearls
- Ocaliva is a second-line therapy for PBC, typically used in combination with ursodeoxycholic acid (UDCA) in patients with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
- Pruritus is a very common side effect, especially during dose titration. It can be managed with antipruritic agents (e.g., cholestyramine, antihistamines) or by reducing the dose of Ocaliva.
- Close monitoring of liver function tests is crucial, particularly in patients with cirrhosis, due to the risk of hepatic decompensation.
- Patients with moderate to severe hepatic impairment (Child-Pugh B or C) require significant dose reduction and careful monitoring.
- Educate patients on the signs and symptoms of worsening liver disease and the importance of reporting them immediately.
Alternative Therapies
- Ursodeoxycholic acid (UDCA) - first-line therapy for PBC
- Fibrates (e.g., bezafibrate) - sometimes used off-label for PBC, especially with cholestatic pruritus or hyperlipidemia, but not FDA approved for PBC.
- Liver transplant - for end-stage liver disease due to PBC.
Cost & Coverage
Average Cost:
$7,000 - $8,000 per 30 tablets (10mg)
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, don't hesitate to consult with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, don't hesitate to consult with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.