1. Name of the medicinal product

Obeticholic acid Tablets 5mg Taj Pharma
Obeticholic acid Tablets 10mg Taj Pharma

  1. Qualitative and quantitative composition

a) Obeticholic acid Tablets 5mg Taj Pharma
Each film-coated tablet contains:
Obeticholic acid 5mg
Excipients: Q.S.

b) Obeticholic acid Tablets 10mg Taj Pharma
Each film-coated tablet contains:
Obeticholic acid 10mg
Excipients: Q.S.

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Film-coated Tablet.

  1. Clinical particulars
  • Therapeutic indications

Obeticholic acid Taj Pharma is indicated for the treatment of primary biliary cholangitis (also known as primary biliary cirrhosis) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA.

  • Posology and method of administration

Posology

Prior to initiation of treatment with Obeticholic acid Taj Pharma the patient’s hepatic status must be known.

The starting dose and dosage titration by PBC patient population is shown in Table 1.

Table 1: Dosage Regimen by PBC Patient Population

Staging/ClassificationNon-Cirrhotic or Child-Pugh Class AChild-Pugh Class B or C or Decompensated Cirrhotic
Starting Dosage5mg once daily5mg once weekly
Dosage TitrationFor patients who have not achieved an adequate reduction in alkaline phosphatase (ALP) and/or total bilirubin after 6 months of treatment and the patient is tolerating Obeticholic acid Taj Pharma, titrate up to 10mg once dailyFor patients who have not achieved an adequate reduction in ALP and/or total bilirubin after 3 months of treatment and the patient is tolerating Obeticholic acid Taj Pharma, titrate up to 5mg twice weekly (at least 3 days apart) and subsequently to 10mg twice weekly (at least 3 days apart) based on response and tolerability
Maximum Dosage10mg once daily10mg twice weekly (at least 3 days apart)

No dose adjustment of concomitant UDCA is required in patients receiving Obeticholic acid Taj Pharma.

Management and dose adjustment for severe pruritus

Management strategies include the addition of bile acid binding resins or antihistamines.

For patients experiencing severe intolerability due to pruritus, one or more of the following should be considered:

For Non-Cirrhotic or Child-Pugh Class A patients:

Reducing the dosage of Obeticholic acid Taj Pharma to:

  • 5mg every other day, for patients intolerant to 5mg once daily
  • 5mg once daily, for patients intolerant to 10mg once daily

Temporarily interrupting Obeticholic acid Taj Pharma dosing for up to 2 weeks followed by restarting at a reduced dosage.

Continue to increase the dosage to 10mg once daily, as tolerated, to achieve optimal response.

For Child-Pugh Class B or C or Decompensated Cirrhotic patients:

  • Reducing the dosage of Obeticholic acid Taj Pharma to:
  • 5mg once weekly, for patients intolerant to 5mg twice weekly
  • 10mg once weekly, for patients intolerant to 10mg twice weekly
  • Temporarily interrupting Obeticholic acid Taj Pharma dosing for up to 2 weeks followed by restarting at a reduced dosage if applicable.
  • Continue to increase the dosage to 10mg twice weekly, as tolerated, to achieve optimal response.

Consider discontinuing treatment with Obeticholic acid Taj Pharma for patients who continue to experience persistent, intolerable pruritus.

Special populations

Patients with hepatic impairment

See table 1 for dose recommendations. Further, see sections 4.4 and 5.2.

Elderly (≥ 65 years)

Limited data exists in elderly patients. No dose adjustment is required for elderly patients (see section 5.2).

Patients with renal impairment

Limited data exists in patients with mild and moderate renal impairment and no data exists in severe renal impairment. No dose adjustment is required for patients with renal impairment (see section 5.2).

Paediatric population

There is no relevant use of Obeticholic acid Taj Pharma in the paediatric population in the treatment of primary biliary cholangitis (PBC).

Method of administration

The tablet should be taken orally with or without food.

For patients taking bile acid binding resins, Obeticholic acid Taj Pharma should be administered at least 4-6 hours before or 4-6 hours after taking a bile acid binding resin, or at as great an interval as possible (see section 4.5).

  • Contraindications
  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
  • Complete biliary obstruction.

Special warnings and precautions for use

Liver related adverse events

Elevations in alanine amino transferase (ALT) and aspartate aminotransferase (AST) have been observed in patients taking Obeticholic acid Taj Pharma. Clinical signs and symptoms of hepatic decompensation have also been observed. These events have occurred as early as within the first month of treatment. Liver-related adverse events have primarily been observed at doses higher than the maximum recommended dose of 10mg once daily (see section 4.9). In the post marketing setting, serious liver injury and death have been reported with more frequent dosing of Obeticholic acid Taj Pharma than recommended in patients with moderate to severe decreases in liver function.

After initiation of therapy, all patients should be monitored for progression of PBC disease with laboratory and clinical assessment to determine whether dosage adjustment is needed. Patients at an increased risk of hepatic decompensation, including those with laboratory evidence of worsening liver function and /or progression to cirrhosis, should be monitored more closely. Dosing frequency should be reduced for patients who progress to advanced disease (i.e. from Child-Pugh Class A to Child-Pugh Class B or C) (see sections 4.2 and 5.2).

Severe pruritus

Severe pruritus was reported in 23% of patients treated with Obeticholic acid Taj Pharma 10mg arm, 19% of patients in the Obeticholic acid Taj Pharma titration arm, and 7% of patients in the placebo arms. The median time to onset of severe pruritus was 11, 158, and 75 days for patients in the Obeticholic acid Taj Pharma 10mg, Obeticholic acid Taj Pharma titration, and placebo arms, respectively. Management strategies include the addition of bile acid binding resins or antihistamines, dose reduction, reduced dosing frequency, and/or temporary dose interruption (see sections 4.2 and 4.8).

  • Interaction with other medicinal products and other forms of interaction

Medicinal products that are affected by Obeticholic acid Taj Pharma

Warfarin

International normalised ratio (INR) is decreased following co-administration of warfarin and Obeticholic acid Taj Pharma. INR should be monitored and the dose of warfarin adjusted, if needed, to maintain the target INR range when co-administering Obeticholic acid Taj Pharma and warfarin.

Interaction with CYP1A2 substrates with narrow therapeutic index

Obeticholic acid Taj Pharma may increase the exposure to concomitant medicinal products that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended.

Medicinal products that affect Obeticholic acid Taj Pharma

Bile acid binding resins

Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce efficacy of Obeticholic acid Taj Pharma. When concomitant bile acid binding resins are administered, Obeticholic acid Taj Pharma should be taken at least 4-6 hours before or 4-6 hours after taking a bile acid binding resin, or at as great an interval as possible.

  • Fertility, pregnancy and lactation

Pregnancy

There are no data on the use of Obeticholic acid Taj Pharma in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Obeticholic acid Taj Pharma during pregnancy.

Breast-feeding

It is unknown whether Obeticholic acid Taj Pharma is excreted in human milk. Based on animal studies and intended pharmacology, Obeticholic acid Taj Pharma is not expected to interfere with breast-feeding or the growth or development of a breast-fed child. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from Obeticholic acid Taj Pharma therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman (see section 5.3).

Fertility

No fertility data is available in humans. Animal studies do not indicate any direct or indirect effects on fertility or reproduction (see section 5.3).

  • Effects on ability to drive and use machines

Obeticholic acid Taj Pharma has no or negligible influence on the ability to drive and use machines.

  • Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions were pruritus (63%) and fatigue (22%). Adverse reactions leading to discontinuation were 1% in the Obeticholic acid Taj Pharma titration arm and 11% in the Obeticholic acid Taj Pharma 10mg arm. The most common adverse reaction leading to discontinuation was pruritus. The majority of pruritus occurred within the first month of treatment and tended to resolve over time with continued dosing.

Tabulated list of adverse reactions

The adverse reactions reported with Obeticholic acid Taj Pharma in the phase III clinical study are listed in the table below by MedDRA system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).

Table 2. Frequency of adverse reactions in PBC patients*

System Organ ClassVery commonCommon
Endocrine disordersThyroid function abnormality
Nervous system disordersDizziness
Cardiac disordersPalpitations
Respiratory, thoracic and mediastinal disordersOropharyngeal pain
Gastrointestinal disordersAbdominal pain and discomfortConstipation
Skin and subcutaneous tissue disordersPruritusEczema, Rash
Musculoskeletal and connective tissue disordersArthralgia
General disorders and administration site conditionsFatigueOedema peripheral, Pyrexia

* Adverse reactions are defined as events occurring at a rate of greater than or equal to 5% of patients on Obeticholic acid Taj Pharma treatment arm and at an incidence greater than or equal to 1% higher than in the placebo treatment arm.

Description of selected adverse reactions

Pruritus

Approximately 60% of patients had a history of pruritus upon enrollment in the phase III study. Treatment-emergent pruritus generally started within the first month following the initiation of treatment.

Relative to patients who started on 10mg once daily in the Obeticholic acid Taj Pharma 10mg arm, patients in the Obeticholic acid Taj Pharma titration arm had a lower incidence of pruritus (70% and 56% respectively) and a lower discontinuation rate due to pruritus (10% and 1%, respectively).

The percentages of patients who required interventions (i.e, dosage adjustments, treatment interruptions, or initiation of antihistamines or bile acid binding resins) were 41% in the Obeticholic acid Taj Pharma 10mg arm, 34% in the Obeticholic acid Taj Pharma titration group, and 19% in the placebo group.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

  • Overdose

The highest single dose exposure of Obeticholic acid Taj Pharma in healthy volunteers has been at the 500mg dose. Repeated doses of 250mg have been administered for 12 consecutive days and some subjects experienced pruritus and reversible transaminase liver elevations. In PBC patients who received Obeticholic acid Taj Pharma 25mg once daily (2.5 times the highest recommended dosage) or 50mg once daily (5 times the highest recommended dosage), a dose-dependent increase in the incidence of liver-related adverse reactions (e.g., ascites, primary biliary cholangitis flare, new onset jaundice), and transaminase and bilirubin elevations (up to greater than 3-times upper limit of normal [ULN]) were reported. In the case of overdose, patients should be carefully observed and supportive care administered, as appropriate.

  1. Pharmacological properties
  • Pharmacodynamic properties

Pharmacotherapeutic group: Bile and liver therapy, Bile acid preparations.

Mechanism of action

Obeticholic acid Taj Pharma is a selective and potent agonist for the farnesoid X receptor (FXR), a nuclear receptor expressed at high levels in the liver and intestine. FXR is thought to be a key regulator of bile acid, inflammatory, fibrotic, and metabolic pathways. FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol, as well as, by increasing transport of bile acids out of the hepatocytes. These mechanisms limit the overall size of the circulating bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids.

Pharmacodynamic effects

Clinical efficacy and safety

A phase III, randomised, double-blind, placebo-controlled, parallel-group, 12-month study (POISE) evaluated the safety and efficacy of Obeticholic acid Taj Pharma in 216 patients with PBC who were taking UDCA for at least 12 months (stable dose for ≥ 3 months) or who were unable to tolerate UDCA and did not receive UDCA for ≥3 months. Patients were included in the trial if the alkaline phosphatase (ALP) was greater than or equal to 1.67 times upper limit of normal (ULN) and/or if total bilirubin was greater than 1 x ULN but less 2 x ULN. Patients were randomised (1:1:1) to receive once daily placebo, Obeticholic acid Taj Pharma 10mg, or Obeticholic acid Taj Pharma titration (5mg titrated to 10mg at 6 months dependent on therapeutic response/tolerability). The majority (93%) of patients received treatment in combination with UDCA and a small number of patients (7%) unable to tolerate UDCA received placebo, Obeticholic acid Taj Pharma (10mg) or Obeticholic acid Taj Pharma titration (5mg to 10mg) as monotherapy. ALP and total bilirubin were assessed as categorical variables in the primary composite endpoint, as well as continuous variables over time.

The study population was predominantly female (91%) and white (94%). The mean age was 56 years, with the majority of patients less than 65 years old. Mean baseline ALP values ranged from 316 U/L to 327 U/L. Mean baseline total bilirubin values ranged from 10 μmol/L to 12 μmol/L across treatment arms, with 92% of patients within normal range.

Treatment with Obeticholic acid Taj Pharma 10mg or Obeticholic acid Taj Pharma titration (5mg to 10mg) resulted in clinically and statistically significant increases (p < 0.0001) relative to placebo in the number of patients achieving the primary composite endpoint at all study time points (see Table 3). Responses occurred as early as 2 weeks and were dose dependent (Obeticholic acid Taj Pharma 5mg compared with 10mg at 6 months, p=0.0358).

Table 3. Percentage of PBC patients achieving the primary composite endpointat month 6 and month 12 with or without UDCAb

Obeticholic acid Taj Pharma

10mgc

(N = 73)

Obeticholic acid Taj Pharma

Titrationc

(N = 70)

Placebo

(N=73)

Month 6
Responders, n (%)

Corresponding 95% CI

37 (51)

39%, 62%

24 (34)

23%, 45%

5 (7)

1%, 13%

p-valued<0.0001<0.0001NA
Month 12
Responders, n (%)

Corresponding 95% CI

35 (48)

36%, 60%

32 (46)

34%, 58%

7 (10)

4%, 19%

p-valued<0.0001<0.0001NA
Components of primary endpointe
ALP less than 1.67-times ULN, n (%)40 (55)33 (47)12 (16)
Decrease in ALP of at least 15%, n (%)57 (78)54 (77)21 (29)
Total bilirubin less than or equal to 1-times ULNf, n (%)60 (82)62 (89)57 (78)

Percentage of subjects achieving a response, defined as an ALP less than 1.67-times the ULN, total bilirubin within the normal range, and an ALP decrease of at least 15%. Missing values were considered a non-response. The Fisher’s exact test was used to calculate the 95% Confidence Intervals (Cis).

b In the trial there were 16 patients (7%) who were intolerant and did not receive concomitant UDCA: 6 patients (8%) in the Obeticholic acid Taj Pharma 10mg arm, 5 patients (7%) in the Obeticholic acid Taj Pharma titration arm, and 5 patients (7%) in the placebo arm.

c Patients were randomized (1:1:1) to receive Obeticholic acid Taj Pharma 10mg once daily for the entire 12 months of the trial, or Obeticholic acid Taj Pharma titration (5mg once daily for the initial 6 months, with the option to increase to 10mg once daily for the last 6 months, if the patient was tolerating Obeticholic acid Taj Pharma but had ALP 1.67-times the ULN or greater, and/or total bilirubin above the ULN, or less than 15% ALP reduction) or placebo.

dObeticholic acid Taj Pharma titration and Obeticholic acid Taj Pharma 10mg versus placebo. P-values are obtained using the Cochran-Mantel-Haenszel General Association test stratified by intolerance to UDCA and pretreatment ALP greater than 3-times ULN and/or AST greater than 2-times ULN and/or total bilirubin greater than ULN.

e Response rates were calculated based on the observed case analysis (i.e., [n=observed responder]/[N=Intention to Treat (ITT) population]); percentage of patients with Month 12 values are 86%, 91% and 96% for the Obeticholic acid Taj Pharma 10mg, Obeticholic acid Taj Pharma titration and placebo arms, respectively.

f The mean baseline total bilirubin value was 0.65mg/dL, and was within the normal range (i.e., less than or equal to the ULN) in 92% of the enrolled patients.

Mean reduction in ALP

Mean reductions in ALP were observed as early as Week 2 and were maintained through Month 12 for patients who were maintained on the same dosage throughout 12 months. For patients in the Obeticholic acid Taj Pharma titration arm whose Obeticholic acid Taj Pharma dosage was increased from 5mg once daily to 10mg once daily, additional reductions in ALP were observed at Month 12 in the majority of patients.

Mean reduction in gamma-glutamyl transferase (GGT)

The mean (95% CI) reduction in GGT was 178 (137, 219) U/L in the Obeticholic acid Taj Pharma 10mg arm, 138 (102, 174) U/L in the Obeticholic acid Taj Pharma titration arm, and 8 (-48, 32) U/L in the placebo arm.

Monotherapy

Fifty-one PBC patients with baseline ALP 1.67-times ULN or greater and/or total bilirubin greater than ULN were evaluated for a biochemical response to Obeticholic acid Taj Pharma as monotherapy (24 patients received Obeticholic acid Taj Pharma 10mg once daily and 27 patients received placebo) in a pooled analysis of data from the phase III randomised, double-blind, placebo-controlled 12 month study (POISE) and from a randomised, double-blind, placebo-controlled, 3- month study. At month 3, 9 (38%) Obeticholic acid Taj Pharma-treated patients achieved a response to the composite endpoint, compared to 1 (4%) placebo-treated patient. The mean (95% CI) reduction in ALP in Obeticholic acid Taj Pharma-treated patients was 246 (165, 327) U/L compared to an increase of 17 (-7, 42) U/L in the placebo-treated patients.

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with Obeticholic acid Taj Pharma in all subsets of the paediatric population in PBC (see section 4.2 for information on paediatric use).

This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This means that further evidence on this medicinal product is awaited. The European Medicines Agency will review any new information which may become available at least every year and this SmPC will be updated as necessary.

  • Pharmacokinetic properties

Absorption

Obeticholic acid Taj Pharma is absorbed with peak plasma concentrations (Cmax) occurring at a median time (tmax) of approximately 2 hours. Co-administration with food does not alter the extent of absorption of Obeticholic acid Taj Pharma.

Distribution

Human plasma protein binding of Obeticholic acid Taj Pharma and its conjugates is greater than 99%. The volume of distribution of Obeticholic acid Taj Pharma is 618 L. The volume of distributions of glyco- and tauro-Obeticholic acid Taj Pharma has not been determined.

Biotransformation

Obeticholic acid Taj Pharma is conjugated with glycine or taurine in the liver and secreted into bile. These glycine and taurine conjugates of Obeticholic acid Taj Pharma are absorbed in the small intestine leading to enterohepatic recirculation. The conjugates can be deconjugated in the ileum and colon by intestinal microbiota, leading to the conversion to Obeticholic acid Taj Pharma that can be reabsorbed or excreted in faeces, the principal route of elimination.

After daily administration of Obeticholic acid Taj Pharma, there was accumulation of the glycine and taurine conjugates of Obeticholic acid Taj Pharma which have in vitro pharmacological activities similar to the parent drug. The metabolite-to -parent ratios of the glycine and taurine conjugates of Obeticholic acid Taj Pharma were 13.8 and 12.3, respectively, after daily administration. An additional third Obeticholic acid Taj Pharma metabolite, 3-glucuronide is formed but is considered to have minimal pharmacologic activity.

Elimination

After administration of radiolabeled Obeticholic acid Taj Pharma, greater than 87% is excreted in faeces. Urinary excretion is less than 3%.

Dose/Time proportionality

Following multiple-dose administration of 5, 10, and 25mg once daily for 14 days, systemic exposures of Obeticholic acid Taj Pharma increase dose proportionally. Exposures of glyco- and tauro-Obeticholic acid Taj Pharma, and total Obeticholic acid Taj Pharma increase more than proportionally with dose.

Special populations

Elderly

There are limited pharmacokinetic data in elderly patients (≥ 65 years). Population pharmacokinetic analysis, developed using data from patients up to 65 years old, indicated that age is not expected to significantly influence Obeticholic acid Taj Pharma clearance from the circulation.

Paediatric population

No pharmacokinetic studies were performed with Obeticholic acid Taj Pharma in patients less than 18 years of age.

Gender

Population pharmacokinetic analysis indicated that gender does not influence Obeticholic acid Taj Pharma pharmacokinetics.

Race

Population pharmacokinetic analysis indicated that race is not expected to influence Obeticholic acid Taj Pharma pharmacokinetics.

Renal impairment

Obeticholic acid Taj Pharma has minimal renal elimination with less than 3% of the dose recovered in urine. Based on population pharmacokinetic analysis, renal function did not have a meaningful effect on the pharmacokinetics of Obeticholic acid Taj Pharma.

Hepatic impairment

Obeticholic acid Taj Pharma is metabolised in the liver and intestines. The systemic exposure of Obeticholic acid Taj Pharma, its active conjugates, and endogenous bile acids is increased in patients with moderate and severe hepatic impairment (Child-Pugh Class B and C, respectively) when compared to healthy controls. Therefore, a modified dose regimen for patients with moderate or severe hepatic impairment is required to achieve plasma exposure levels similar to patients with no hepatic impairment (see section 4.2).

The impact of mild hepatic impairment (Child-Pugh Class A) on the pharmacokinetics of Obeticholic acid Taj Pharma was negligible, therefore, no dose adjustment is necessary for patients with mild hepatic impairment.

In subjects with mild, moderate and severe hepatic impairment (Child-Pugh Class A, B, and C, respectively), mean AUC of total Obeticholic acid Taj Pharma, the sum of Obeticholic acid Taj Pharma and its two active conjugates, increased by 1.13-, 4- and 17-fold, respectively, compared to subjects with normal hepatic function following single-dose administration of 10mg Obeticholic acid Taj Pharma.

  • Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to fertility, reproduction and development.

Oral administration of Obeticholic acid Taj Pharma above the NOAEL to mice, rats, and dogs in pivotal, repeat dose toxicity studies resulted primarily in effects on the hepatobiliary system. These included increased liver weights, alterations in serum chemistry parameters (ALT, AST, LDH, ALP, GGT, and/or bilirubin), and macroscopic/microscopic alterations. All changes were reversible with discontinued dosing, and are consistent with and predict the dose-limiting toxicity in humans (systemic exposure at NOAEL was up to 24-fold higher than that seen at the maximum recommended human dose). In a pre- and post-natal toxicity study in rats, the tauro-conjugate of Obeticholic acid Taj Pharma was found in pups nursing from dams dosed with Obeticholic acid Taj Pharma

  1. Pharmaceutical particulars
  • List of excipients

Tablet core

Microcrystalline cellulose

Sodium starch glycolate (Type A)

Magnesium stearate

Tablet coating

Poly(vinyl alcohol), partially hydrolysed

Titanium dioxide

Macrogol 3350

Talc

Iron oxide yellow

  • Incompatibilities

Not applicable.

  • Shelf life

3 years

  • Special precautions for storage

This medicinal product does not require any special storage conditions.

  • Nature and contents of container

High-density polyethylene (HDPE) bottles with a child resistant polypropylene closure and an aluminium foil induction seal.

Pack size: 5, 10, 15, 30, 60, 90, 100, 120, 240, 360 and 500 film-coated tablets.

Not all pack sizes may be marketed.

  • Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Obeticholic acid Tablets 5mg Taj Pharma
(Film-coated)

Package leaflet: Information for the patient

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

  1. What Obeticholic acid Taj Pharma is and what it is used for
  2. What you need to know before you take Obeticholic acid Taj Pharma
  3. How to take Obeticholic acid Taj Pharma
  4. Possible side effects
  5. How to store Obeticholic acid Taj Pharma
  6. Contents of the pack and other information

1. What Obeticholic acid Taj Pharma is and what it is used for

Obeticholic acid Taj Pharma contains the active substance Obeticholic acid Taj Pharma (farnesoid X-receptor agonist) which helps to improve how your liver works by reducing the production and build up of bile in the liver and also reducing inflammation.

This medicine is used to treat adult patients with a type of liver disease known as primary biliary cholangitis (also known as primary biliary cirrhosis), either by itself or together with another medicine, ursodeoxycholic acid.

  1. What you need to know before you take Obeticholic acid Taj Pharma

Do not take Obeticholic acid Taj Pharma:

  • if you are allergic to Obeticholic acid Taj Pharma or any of the other ingredients of this medicine (listed in section 6).
  • if you have a complete blockage of the biliary tract (liver, gall bladder and bile ducts).

Warnings and precautions

Talk to your doctor or pharmacist before taking Obeticholic acid Taj Pharma.

If you experience itching that is difficult to tolerate, talk to your doctor.

Your doctor will do blood tests to monitor the health of your liver when you start treatment and regularly from there on.

Children and adolescents

This medicine is not for use in children or adolescents.

Other medicines and Obeticholic acid Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor if you are taking so-called bile acid binding resins (cholestyramine, colestipol, colesevelam) used to lower blood cholesterol levels as they may lessen the effect of Obeticholic acid Taj Pharma. If you take any of these medicines, take Obeticholic acid Taj Pharma at least 4-6 hours before or 4-6 hours after taking bile acid binding resin, giving as much time as possible.

The levels of some medicines such as theophylline (a medicine to help breathing) or tizanidine (a medicine to relieve the stiffness and restriction of muscles) may be increased and need to be monitored by your doctor while taking Obeticholic acid Taj Pharma. Your doctor may need to monitor how well your blood clots when taking medicines such as warfarin (a medicine to help your blood flow) with Obeticholic acid Taj Pharma.

Pregnancy and breast-feeding

There is little information about the effects of Obeticholic acid Taj Pharma in pregnancy. As a precautionary measure, you should not take Obeticholic acid Taj Pharma if you are pregnant.

It is not known if this medicine passes into human milk. Your doctor will determine whether you should discontinue breast-feeding or discontinue/abstain from Obeticholic acid Taj Pharma therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for you.

Driving and using machines

This medicine has no or negligible influence on your ability to drive or use machines.

  1. How to take Obeticholic acid Taj Pharma

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is one 5mg film-coated tablet once daily by mouth.

Your doctor may adjust your dose depending on your liver function or if you experience itching that is difficult to tolerate.

Depending on your body’s response after 6 months your doctor may increase your dose to 10mg once daily. Your doctor will discuss any change of dose with you.

You can take Obeticholic acid Taj Pharma with or without food. If you take bile acid binding resins, take this medicine at least 4-6 hours before or at least 4-6 hours after the bile acid binding resin (see section “Other medicines and Obeticholic acid Taj Pharma”).

If you take more Obeticholic acid Taj Pharma than you should

If you accidentally take too many tablets, you may experience liver related side effects such as yellowing of the skin. Contact a doctor or go to a hospital for advice immediately.

If you forget to take Obeticholic acid Taj Pharma

Skip the missed dose and take your next dose when you would normally take it. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Obeticholic acid Taj Pharma

You should continue to take Obeticholic acid Taj Pharma for as long as your doctor tells you to. Do not stop taking the medicine without talking to your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or pharmacist if you experience itching of the skin (pruritus) or if the itch gets worse while on this medicine. In general itching of the skin is a very common side effect that begins within the first month following the start of treatment with Obeticholic acid Taj Pharma and usually becomes less severe over time.

Very common side effects (may affect more than 1 in 10 people):

  • stomach pain
  • feeling tired

Common side effects (may affect up to 1 in 10 people):

  • thyroid hormone irregularity
  • dizziness
  • fast or irregular heart beat (palpitations)
  • pain in the mouth and throat
  • constipation
  • dry skin, redness of the skin (eczema)
  • rash
  • pain in your joints
  • swelling in the hands and feet
  • fever

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Obeticholic acid Taj Pharma

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and bottle after “EXP”.

The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Obeticholic acid Taj Pharma contains

The active substance is Obeticholic acid Taj Pharma.

Obeticholic acid Taj Pharma 5mg film-coated tablets: Each film-coated tablet contains 5mg of Obeticholic acid Taj Pharma.

Obeticholic acid Taj Pharma 10mg film-coated tablets: Each film-coated tablet contains 10mg of Obeticholic acid Taj Pharma.

The other ingredients are:

  • Tablet core: Microcrystalline cellulose, sodium starch glycolate (Type A), magnesium stearate.
  • Film-coat: Polyvinyl alcohol, part hydrolysed, titanium dioxide, macrogol 3350, talc, iron oxide yellow.

What Obeticholic acid Taj Pharma looks like and contents of the pack

  • Obeticholic acid Taj Pharma 5mg is a yellow, round film-coated tablet.
  • Obeticholic acid Taj Pharma 10mg is a yellow, triangular film-coated tablet.

Packaging Type:

High-density polyethylene (HDPE) bottles with a child resistant polypropylene closure and an aluminium foil induction seal.

Pack size:

5, 10, 15, 30, 60, 90, 100, 120, 240, 360 and 500 film-coated tablets.

Not all pack sizes may be marketed.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com