Ocaliva 5mg 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, Farnesoid X receptor (FXR) agonist
Pharmacologic Class
Farnesoid X receptor (FXR) agonist
Pregnancy Category
Not assigned (Risk Summary available)
FDA Approved
May 2016
DEA Schedule
Not Controlled
Overview
What is this medicine?
Ocaliva is a prescription medicine used to treat a chronic liver disease called primary biliary cholangitis (PBC). It works by helping your liver manage bile acids, which can build up and cause damage in PBC. By improving bile flow and reducing bile acid levels, Ocaliva can help slow the progression of liver damage and improve symptoms like itching.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. 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.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe 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. Instead, check with your pharmacist for guidance on the best disposal method or explore local drug take-back programs.
Missing 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 to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. 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.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe 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. Instead, check with your pharmacist for guidance on the best disposal method or explore local drug take-back programs.
Missing 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 to make up for the missed one.
Lifestyle & Tips
- Take Ocaliva exactly as prescribed by your doctor. Do not stop taking it without consulting your doctor.
- Report any new or worsening symptoms, especially severe itching, yellowing of your skin or eyes, dark urine, or swelling in your abdomen or legs.
- If you are taking bile acid sequestrants (like cholestyramine), take Ocaliva at least 4-6 hours before or 4-6 hours after these medications.
- Attend all scheduled doctor appointments and laboratory tests to monitor your liver function and overall health.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 5 mg orally once daily for the first 3 months. If tolerated and adequate response not achieved, 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 tolerated and adequate response, may 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.
Moderate:
No dose adjustment needed.
Severe:
No dose adjustment needed.
Dialysis:
Not studied. Use with caution.
Hepatic Impairment:
Mild:
Child-Pugh Class A: No dose adjustment needed.
Moderate:
Child-Pugh Class B: Initial: 5 mg orally once weekly. If tolerated and adequate response after 3 months, may increase to 5 mg twice weekly (e.g., Monday and Thursday).
Severe:
Child-Pugh Class C: Initial: 5 mg orally once weekly. If tolerated and adequate response after 3 months, may increase to 5 mg twice weekly (e.g., Monday and Thursday). Contraindicated in decompensated cirrhosis (Child-Pugh B or C) or prior decompensation event.
Pharmacology
Mechanism of Action
Obeticholic acid (OCA) is a potent and selective agonist for the farnesoid X receptor (FXR), a nuclear receptor expressed in the liver and intestine. Activation of FXR by OCA suppresses de novo bile acid synthesis by inhibiting cholesterol 7-alpha-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) via increased expression of fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP). This leads to reduced intracellular bile acid pool size, increased bile flow, and reduced hepatocyte exposure to toxic bile acids. It also has anti-inflammatory and anti-fibrotic effects.
Pharmacokinetics
Absorption:
Bioavailability:
Rapidly absorbed (not explicitly quantified as percentage)
Tmax:
1.5 hours (median, range 0.5-4 hours)
FoodEffect:
No clinically significant effect of food on absorption.
Distribution:
Vd:
Approximately 1000 L
ProteinBinding:
>99% (primarily to albumin and alpha1-acid glycoprotein)
CnssPenetration:
Limited
Elimination:
HalfLife:
2.5-5.5 hours (parent drug)
Clearance:
Primarily via fecal excretion
ExcretionRoute:
Fecal (primarily as conjugates and unconjugated OCA)
Unchanged:
<1% (excreted in urine)
Pharmacodynamics
OnsetOfAction:
Not precisely defined for chronic effect, but biochemical markers (e.g., ALP) begin to improve within weeks.
PeakEffect:
Not precisely defined for chronic effect.
DurationOfAction:
Not precisely defined for chronic effect.
Safety & Warnings
BLACK BOX WARNING
Hepatotoxicity: Ocaliva has been associated with liver decompensation and failure in patients with primary biliary cholangitis (PBC) with cirrhosis, including those with Child-Pugh Class B or C hepatic impairment and those with compensated cirrhosis who have evidence of portal hypertension. Ocaliva is contraindicated in patients with PBC with decompensated cirrhosis (Child-Pugh Class B or C), or with a prior decompensation event. Patients with compensated cirrhosis should be monitored for evidence of hepatic decompensation. Discontinue Ocaliva if a patient develops hepatic decompensation.
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 medical attention immediately:
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
+ Trouble tolerating heat or cold
+ Menstrual changes
+ Shakiness
+ 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 problems with daily activities. Contact your doctor immediately if you experience severe itching that interferes with your daily life or does not go away.
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 medical attention immediately:
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
+ Trouble tolerating heat or cold
+ Menstrual changes
+ Shakiness
+ 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 problems with daily activities. Contact your doctor immediately if you experience severe itching that interferes with your daily life or does not go away.
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)
- Unusual tiredness or fatigue
- Dark urine
- Light-colored or clay-colored stools
- Swelling in your abdomen (ascites) or legs/ankles (edema)
- Confusion or difficulty thinking clearly (hepatic encephalopathy)
- Easy bruising or bleeding
- Nausea or vomiting
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 symptoms you experienced.
If you have a bile tract blockage.
* If you are currently taking cyclosporine.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help determine if it is safe to take this medication in conjunction with your other medications and health conditions.
Remember, do not start, stop, or change the dosage of any medication without first consulting your doctor to ensure your safety.
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 symptoms you experienced.
If you have a bile tract blockage.
* If you are currently taking cyclosporine.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help determine if it is safe to take this medication in conjunction with your other medications and health conditions.
Remember, do not start, stop, or change the dosage of any medication without first consulting your doctor to ensure your safety.
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 about these tests with your doctor.
This medication may decrease levels of high-density lipoprotein (HDL), also known as "good" cholesterol. If you have concerns about the potential effects on your cholesterol levels, 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. This will help you make an informed decision about your treatment and ensure the best possible outcome for you and your baby.
This medication may decrease levels of high-density lipoprotein (HDL), also known as "good" cholesterol. If you have concerns about the potential effects on your cholesterol levels, 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. This will help you make an informed decision about your treatment and ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
What to Do:
In case of suspected overdose, contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention. Treatment is supportive.
Drug Interactions
Contraindicated Interactions
- None (except in specific hepatic impairment conditions as per Black Box Warning)
Major Interactions
- Bile Acid Sequestrants (e.g., cholestyramine, colestipol, colesevelam): Reduce absorption of obeticholic acid. Administer Ocaliva at least 4-6 hours before or 4-6 hours after bile acid sequestrants.
- Warfarin: May increase INR. Monitor INR and adjust warfarin dose as needed.
- CYP1A2 substrates with narrow therapeutic index (e.g., tizanidine, theophylline): Obeticholic acid may increase exposure to these drugs. Monitor and adjust dose.
Moderate Interactions
- CYP3A4 substrates (e.g., cyclosporine, tacrolimus, statins): Obeticholic acid is a weak inhibitor of CYP3A4. May increase exposure to sensitive CYP3A4 substrates. Monitor and adjust dose.
- P-glycoprotein (P-gp) substrates (e.g., digoxin, dabigatran): Obeticholic acid is a weak inhibitor of P-gp. May increase exposure to P-gp substrates. Monitor and adjust dose.
Minor Interactions
- None specifically identified as minor with clinical significance.
Monitoring
Baseline Monitoring
Liver Function Tests (ALP, AST, ALT, total bilirubin, albumin, INR)
Rationale: To assess baseline liver function and disease severity.
Timing: Prior to initiation of therapy.
Lipid Panel (total cholesterol, HDL, LDL, triglycerides)
Rationale: To assess baseline lipid profile, as dyslipidemia can be associated with PBC and may be affected by treatment.
Timing: Prior to initiation of therapy.
Routine Monitoring
Liver Function Tests (ALP, AST, ALT, total bilirubin)
Frequency: Every 3 months for the first year, then every 6 months or as clinically indicated.
Target: Improvement in ALP and/or total bilirubin towards normal range.
Action Threshold: Significant increases in AST/ALT or bilirubin, or signs of hepatic decompensation, warrant dose reduction or discontinuation.
Lipid Panel
Frequency: Periodically (e.g., every 6-12 months or as clinically indicated).
Target: Maintain within acceptable clinical limits.
Action Threshold: Significant worsening of lipid profile may require management or re-evaluation of therapy.
Pruritus severity
Frequency: Regularly (e.g., at each follow-up visit).
Target: Acceptable level of itching.
Action Threshold: Severe or intolerable pruritus may require dose reduction or symptomatic treatment.
Symptom Monitoring
- Worsening pruritus
- Jaundice (yellowing of skin or eyes)
- Dark urine
- Light-colored stools
- Ascites (abdominal swelling)
- Peripheral edema (swelling in legs/ankles)
- Hepatic encephalopathy (confusion, disorientation, altered mental status)
- Gastrointestinal bleeding (e.g., from varices)
Special Patient Groups
Pregnancy
Based on animal data, obeticholic acid may cause fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal studies.
Second Trimester:
Potential for fetal harm based on animal studies.
Third Trimester:
Potential for fetal harm based on animal studies.
Lactation
It is unknown if obeticholic acid is excreted in human milk. The decision to breastfeed should consider the developmental and health benefits of breastfeeding, the mother's clinical need for Ocaliva, and any potential adverse effects on the breastfed infant from Ocaliva or from the underlying maternal condition.
Infant Risk:
Unknown. Due to high protein binding, large amounts are not expected in milk, but as a bile acid, excretion is possible. Use with caution, especially in newborns/preterm 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 (âĨ65 years) and younger patients. No specific dose adjustment is required based on age alone, but consider overall health status and comorbidities.
Clinical Information
Clinical Pearls
- Pruritus is a very common and often dose-dependent side effect, which can be severe and lead to treatment discontinuation. Management strategies include dose reduction, antihistamines, bile acid sequestrants (taken at separate times), or rifampin.
- Careful dose titration and monitoring are crucial, especially in patients with hepatic impairment, due to the risk of liver decompensation.
- Ocaliva is typically used in combination with ursodeoxycholic acid (UDCA) in patients who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
- Patients with compensated cirrhosis should be closely monitored for signs of hepatic decompensation (e.g., ascites, jaundice, encephalopathy).
- This medication is not a cure for PBC but aims to slow disease progression and improve biochemical markers.
Alternative Therapies
- Ursodeoxycholic acid (UDCA): First-line therapy for PBC.
- Fibrates (e.g., fenofibrate): Sometimes used off-label as add-on therapy for PBC, particularly in patients with incomplete biochemical response to UDCA.
- Liver transplantation: For patients with end-stage liver disease due to PBC.
Cost & Coverage
Average Cost:
$7,000 - $10,000+ per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. Please read it 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 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 details about the overdose, including the substance taken, the amount, and the time it occurred.