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The goal of the Bosentan REMS Program is to mitigate the risk of hepatotoxicity and embryofetal
toxicity associated with bosentan by:
Ensuring prescribers are educated on the following:
the risks of hepatotoxicity and embryo-fetal toxicity
Ensuring prescribers are educated on and adhere to the following:
counseling patients about these risks and the need for monthly monitoring
enrolling patients in the Bosentan REMS Program
monitoring patients at baseline and monthly
Ensuring that pharmacies are educated on the following:
the risks of hepatotoxicity and embryo-fetal toxicity
Ensuring that pharmacies are educated on and adhere to the following:
confirming that the appropriate patient monitoring and counseling has occurred before dispensing bosentan
Ensuring that patients are informed about:
the risks of hepatotoxicity and embryo-fetal toxicity
appropriate baseline and monthly patient monitoring
appropriate contraception
What do participants need to know?
Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.
Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program.
| Prescriber Enrollment Form |
Before treatment initiation
(first dose)
For all patients: Counsel the patient on the risk of hepatotoxicity
associated with bosentan, the signs and symptoms of
hepatotoxicity, to contact the prescriber if the patient has any
signs or symptoms of liver problems, and REMS Program
requirements including the need to complete liver testing using the
Guide for Patients.
| Guide for Patients |
For all patients: Assess the patient’s liver function. Document and
submit to the REMS Program using the Patient Enrollment Form.
| Patient Enrollment Form |
For all females: Assess the patient’s reproductive status using the
definitions in the Prescriber Guide. Document and submit to the
REMS Program using the Patient Enrollment Form.
| Prescriber Guide |
| Patient Enrollment Form |
For pre-pubertal females: Counsel the patient about the risk of
embryo-fetal toxicity and the need to immediately contact the
prescriber when the patient begins to menstruate using the
Guide for Patients.
| Guide for Patients |
For females of reproductive potential: Assess the patient’s
pregnancy status by ordering a pregnancy test and reviewing the
results. Document and submit to the REMS Program using the
Patient Enrollment Form.
| Patient Enrollment Form |
Enroll the patient by completing the Patient Enrollment Form and
submitting it to the REMS Program. Provide a completed copy of
the form to the patient.
| Patient Enrollment Form |
During treatment; monthly
For all patients: Assess the patient’s liver function and counsel the
patient on the risk of hepatotoxicity.
For females of reproductive potential: Counsel the patient on the
risk of embryo-fetal toxicity.
For females of reproductive potential: Assess the patient’s
pregnancy status by ordering a pregnancy test and reviewing the
results.
Enroll in the REMS Program by completing the Patient Enrollment
Form with the prescriber. Enrollment information will be provided
to the REMS Program.
| Patient Enrollment Form |
Receive counseling from the prescriber on the risk of liver
problems, the signs and symptoms of liver problems, the need to
contact the prescriber if you have any signs or symptoms of liver
problems, the need to complete liver testing, the risk of serious
birth defects, the need to use reliable contraception during
treatment and for one month following treatment discontinuation,
the need to complete pregnancy testing, the need to contact the
prescriber if you suspect you are pregnant, and emergency
contraception using the Guide for Patients.
| Guide for Patients |
During treatment;
Get a liver test and a pregnancy test.
Adhere to the safe use condition: Communicate with the REMS
Program or pharmacy to confirm completion of pregnancy testing
and liver testing.
Receive counseling from the prescriber or pharmacy on the risks of
liver problems and serious birth defects associated with bosentan
treatment.
During treatment
and after
treatment
discontinuation for
one month
Adhere to the safe use condition: Use reliable contraception as
described in the Guide for Patients.
| Guide for Patients |
After treatment
discontinuation;
one month
Get a pregnancy test.
At all times
At all times
Inform the prescriber if you have any signs or symptoms of liver
problems as described in the Guide for Patients.
| Guide for Patients |
Inform the prescriber immediately if you suspect you may be
pregnant.
Enroll in the REMS Program by completing the Patient Enrollment
Form with the prescriber. Enrollment information will be provided
to the REMS Program.
| Patient Enrollment Form |
Receive counseling from the prescriber on the risk of liver
problems, the signs and symptoms of liver problems, the need to
contact the prescriber if you have any signs or symptoms of liver
problems, the need to complete liver testing, the risk of serious
birth defects, and the need to contact the prescriber when you
begin to menstruate using the Guide for Patients.
| Guide for Patients |
During treatment;
before each
prescription
Get a liver test.
Adhere to the safe use condition: Communicate with the REMS
Program or pharmacy to confirm completion of liver testing.
Receive counseling from the prescriber or pharmacy on the risks of
liver problems and serious birth defects associated with bosentan
treatment.
At all times
If over the age of 8: Be monitored for a change in reproductive
status.
Inform the prescriber if you have any signs or symptoms of liver
problems as described in the Guide for Patients.
| Guide for Patients |
Inform the prescriber if there is a change in reproductive status.
Post-menopausal females or females with other medical reasons for
permanent, irreversible infertility who are prescribed bosentan:
Enroll in the REMS Program by completing the Patient Enrollment
Form with the prescriber. Enrollment information will be provided
to the REMS Program.
| Patient Enrollment Form |
Receive counseling from the prescriber on the risk of liver
problems, the signs and symptoms of liver problems, the need to
contact the prescriber if you have any signs or symptoms of liver
problems, and the need to complete liver testing using the Guide
for Patients.
| Guide for Patients |
During treatment;
before each
prescription
Get a liver test.
Adhere to the safe use condition: Communicate with the REMS
Program or pharmacy to confirm completion of liver testing.
Receive counseling from the prescriber or pharmacy on the risk of
liver problems associated with bosentan treatment.
At all times
Inform the prescriber if you have any signs or symptoms of liver
problems as described in the Guide for Patients.
| Guide for Patients |
Inform the prescriber if there is a change in reproductive status.
Enroll in the REMS Program by completing the Patient Enrollment
Form with the prescriber. Enrollment information will be provided to
the REMS Program.
| Patient Enrollment Form |
Receive counseling from the prescriber on the risk of liver
problems, the signs and symptoms of liver problems, the need to
contact the prescriber if you have any signs or symptoms of liver
problems, and the need to complete liver testing using the Guide
for Patients.
| Guide for Patients |
During treatment;
before each
prescription
Get a liver test.
Adhere to the safe use condition: Communicate with the REMS
Program or pharmacy to confirm completion of liver testing.
Receive counseling from the prescriber or pharmacy on the risk of
liver problems associated with bosentan treatment.
At all times
Inform the prescriber if you have any signs or symptoms of liver
problems as described in the Guide for Patients.
| Guide for Patients |
Outpatient pharmacies that dispense bosentan must:
To become
certified to
dispense
Designate an authorized representative to carry out the
certification process and oversee implementation and compliance
with the REMS Program on behalf of the pharmacy.
Have the authorized representative review the
Pharmacy Guide.
| Pharmacy Guide |
Have the authorized representative enroll in the REMS
Program by completing the Outpatient Pharmacy
Enrollment Form or Chain Pharmacy Headquarters
Enrollment Form and submitting it to the REMS Program
| Chain Pharmacy Headquarters Enrollment |
| Outpatient Enrollment Form |
Train all relevant staff involved in dispensing bosentan on
the REMS Program requirements using the Pharmacy Guide.
| Pharmacy Guide |
Before dispensing
For all patients: Obtain authorization to dispense each
prescription by contacting the REMS Program to verify the
patient is enrolled, the prescriber is certified, the pharmacy
is certified, if counseling is complete, liver testing is
complete, the reproductive status has not changed for
female patients, and the pregnancy test is completed for
females of reproductive potential or the prescriber
authorizes the refill.
For patients without documented testing: Communicate with
the patient or prescriber to confirm testing. Document and
submit the confirmation of testing using the REMS Program
website or Contact Center.
For all patients without documented counseling on
hepatotoxicity: Counsel the patient on the risk of
hepatotoxicity. Document and submit the confirmation of
counseling using the REMS Program website or Contact
Center.
For females of reproductive potential and pre-pubertal females
without documented counseling on embryo-fetal toxicity: Counsel
the patient on the risk of embryo-fetal toxicity. Document and
submit the confirmation of counseling using the REMS Program
website or Contact Center.
Dispense no more than a 30 days’ supply.
To maintain
certification to
dispense
Have the new authorized representative certify in the REMS
Program by completing the Outpatient Pharmacy Enrollment Form
or Chain Pharmacy Headquarters Enrollment Form if the
authorized representative changes.
| Chain Pharmacy Headquarters Enrollment |
| Outpatient Enrollment Form |
At all times
Report adverse events suggestive of hepatotoxicity to the REMS
Report pregnancies to the REMS Program.
Do not distribute, transfer, loan, or sell bosentan, except to
Maintain records of dispensing.
Maintain records of training.
Maintain records that all processes and procedures are in place and
are being followed.
Comply with audits carried out by the manufacturers or a third
party acting on behalf of the manufacturers to ensure that all
processes and procedures are in place and are being followed.
Inpatient pharmacies that dispense bosentan must:
To become
certified to
dispense
Designate an authorized representative to carry out the
certification process and oversee implementation and compliance
with the REMS Program on behalf of the pharmacy.
Have the authorized representative review the Pharmacy Guide.
| Pharmacy Guide |
Have the authorized representative enroll in the REMS Program by
completing the Inpatient Pharmacy Enrollment Form and
submitting it to the REMS Program.
| Inpatient Pharmacy Enrollment |
Train all relevant staff involved in dispensing bosentan on the
REMS Program requirements using the Pharmacy Guide.
| Pharmacy Guide |
Establish processes and procedures to verify the patient is enrolled
or will be enrolled prior to discharge, the patient is under the care
of a certified prescriber, counseling is complete, and liver testing is
complete.
For females of reproductive potential: Establish processes and
Before dispensing
For all patients: Verify the patient is enrolled or will be prior to
discharge, the patient is under the care of a certified prescriber,
the pharmacy is certified, counseling on the risk of hepatotoxicity is
complete, and that liver testing is complete.
For females of reproductive potential: Verify that pregnancy testing
is complete and counseling on embryo-fetal toxicity is complete.
At discharge
Dispense no more than a 15 days’ supply.
To maintain
Have the new authorized representative certify in the REMS
Program by completing the Inpatient Pharmacy Enrollment Form if
the authorized representative changes.
| Inpatient Pharmacy Enrollment |
At all times
Report adverse events suggestive of hepatotoxicity to the REMS
Program.
Report pregnancies to the REMS Program.
Do not distribute, transfer, loan, or sell bosentan, except to
certified dispensers.
Maintain records of training.
Maintain records that all processes and procedures are in place and
are being followed.
Comply with audits carried out by the manufacturers or a third
party acting on behalf of the manufacturers to ensure that all
processes and procedures are in place and are being followed.
Wholesalers-distributors that distribute bosentan must:
To be able to
distribute
Establish processes and procedures to ensure that bosentan is
distributed only to certified pharmacies.
Train all relevant staff involved in distribution on the REMS
Program requirements.
At all times
Distribute only to certified pharmacies.
Maintain records of drug distribution.
Maintain records that all processes and procedures are in place and
are being followed.
Comply with audits carried out by the manufacturers or a third
What materials are included in the REMS?
The REMS includes a REMS Document.
In addition, the REMS includes the following materials intended for patients and healthcare providers. For a specific Medication Guide of a product in the Bosentan REMS, see the DailyMed link on the Products tab.
REMS assessment plan unavailable for posting at this time.
What updates have been made to the REMS?
Date
Summary of change
04/29/2022
Modified to:
Changes to the outpatient pharmacy operations to verify safe use conditions for the
REMS Pre-Dispense Authorization (PDA).
Addition of the Prescriber Designee role on the REMS website to allow prescribers
to delegate certain administrative activities.
Changes to the REMS website to allow certified pharmacies to enter testing and
counseling information through the REMS website and allow pharmacists requesting a PDA to confirm counsling information.
Changes to the pre-recorded messages in the Interactive Voice Response (IVR)
system to align with the proposed modifications and new workflow.
Conversion of the REMS Document to the new, standardized format.
05/20/2019
Revised to make an editorial change.
04/26/2019
Modified to establish a Single Shared System REMS for the elements to assure safe use and the implementation system required for the reference listed drug (RLD) Tracleer and ANDAs referencing Tracleer, called the Bosentan REMS Program. This modification also removes the Medication Guide as an element of the REMS.
Disclaimer: This webpage provides general information about REMS programs
to various REMS participants (e.g., patients, pharmacies, and healthcare providers).
The summary information provided herein is not comprehensive and may not include
all of the information relevant to REMS participants. This webpage does not
constitute a replacement, modification, or revision of the approved REMS document,
including any appended REMS materials. Refer to the approved REMS document
for complete information on the REMS requirements for each approved application.
