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The goal of the Macitentan-Containing Products REMS is to mitigate the risk of embryo-fetal toxicity associated with
macitentan-containing products by:
Ensuring prescribers are educated on the following:
the risks of 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 Macitentan-Containg Products REMS
monitoring patients at baseline and monthly
Ensuring that pharmacies are educated on the following:
the risks of 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 macitentan-containing products
Ensuring that patients are informed about:
the risks of 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 Macitentan-Containing Products REMS.
| Prescriber Enrollment and Agreement Form |
Before treatment
initiation (first
dose)
For all females: Assess the patient's reproductive status using the definitions
in the Prescriber and Pharmacy Guide. Document and submit the results to
the Macitentan-Containing Products REMS using the Patient Enrollment
Form.
| Prescriber and Pharmacy Guide |
| Patient Enrollment Form |
For all females: Counsel the patient that the drug is only available through a
restricted distribution program.
For females of reproductive potential: Assess the patient’s pregnancy status
by ordering and reviewing her pregnancy test result.
For females of reproductive potential: Counsel the patient on the risk of
embryo-fetal toxicity, the need to use reliable contraception during treatment
and for one month following treatment discontinuation, and emergency
contraception using the Guide for Female Patients.
| Guide for Female Patients |
For pre-pubertal females: Counsel the patient on the risk of embryo-fetal
toxicity and to immediately contact her prescriber if she begins to menstruate
using the Guide for Female Patients.
| Guide for Female Patients |
Enroll all female patients by completing and submitting the Patient
Enrollment Form and submitting it to the Macitentan-Containing Products
REMS.
| Patient Enrollment Form |
During
treatment;
before each
prescription
For females of reproductive potential: Counsel the patient if she is not
complying with required testing, if she is not using appropriate contraception,
and to contact her prescriber if she misses a menstrual period or suspects that
she is pregnant.
For females of reproductive potential: Assess the patient's pregnancy status
by ordering and reviewing her pregnancy test result.
During
Treatment; at
least annually
For pre-pubertal females at least age 8 years or older: Document reproductive
potential status and submit to the Macitentan-Containing Products REMS using
the Change in Reproductive Potential Status and Pre-pubertal Annual
Verification Form.
| Change in Reproductive Potential Status and Pre-pubertal Annual Verification Form |
After treatment
discontinuation,
one month
For females of reproductive potential: Assess the patient's pregnancy status
by ordering and reviewing her pregnancy test result.
At all times
For pre-pubertal females: Assess the patient’s reproductive status.
Report pregnancies to the REMS Coordinating Center.
Enroll in the REMS by completing the Patient Enrollment Form with the
prescriber. Enrollment information will be provided to the Macitentan-
Containing Products REMS.
| Patient Enrollment Form |
Receive counseling from the prescriber on the risk of embryo-fetal toxicity, the
need to use reliable contraception, and emergency contraception using the
Guide for Female Patients.
| Guide for Female Patients |
Adhere to the safe use condition: Communicate with the pharmacy to confirm
completion of pregnancy testing.
During treatment;
before each
dispensing
Receive counseling from the pharmacy on the risk of embryo-fetal toxicity, the
need for reliable contraception during treatment and for one month after
stopping treatment, to get monthly pregnancy tests, and to immediately
contact her prescriber if she misses a menstrual period or suspects she is
pregnant.
Get a pregnancy test.
Adhere to the safe use condition: Communicate with the pharmacy to confirm
completion of pregnancy testing.
During treatment
and after treatment
discontinuation for
one month
Adhere to the safe use condition: Use reliable contraception as described in
the Guide for Female Patients.
| Guide for Female Patients |
Agree to be contacted by the REMS Coordinating Center if you become
pregnant.
After treatment
discontinuation;
one month
Get a pregnancy test.
At all times
Inform the prescriber immediately if you miss a menstrual period or suspect a
pregnancy.
Pre-pubertal females who are prescribed macitentan-containing products:
Enroll in the Macitentan-Containing Products REMS by completing the Patient
Enrollment Form with the prescriber. Enrollment information will be provided
to the Macitentan-Containing Products REMS.
| Patient Enrollment Form |
Receive counseling from the prescriber on the risk of embryo-fetal toxicity and
to contact your prescriber if you begin to menstruate using the Guide for
Female Patients.
| Guide for Female Patients |
At all times
If over the age of 8: Be monitored for a change in reproductive status.
Inform the prescriber if there is a change in reproductive status.
Post-menopausal females or females with other medical reason for permanent,
irreversible infertility who are prescribed macitentan-containing products:
Enroll in the Macitentan-Containing Products REMS by completing the Patient
Enrollment Form with the prescriber. Enrollment information will be provided
to the Macitentan-Containing Products REMS.
| Patient Enrollment Form |
At all times
Inform the prescriber if there is a change in your reproductive status.
Outpatient Pharmacies that dispense macitentan-containing products must:
To become certified
to dispense
Designate an authorized representative to carry out the certification process
and oversee implementation and compliance with the Macitentan-Containing
Products REMS on behalf of the outpatient pharmacy.
Have the authorized representative review the Prescribing Information and the
Prescriber and Pharmacy Guide.
| Prescriber and Pharmacy Guide |
Have the authorized representative enroll in the Macitentan-Containing
Products REMS by completing the Outpatient Pharmacy Enrollment Form
and submitting it to the Macitentan-Containing Products REMS.
| Outpatient Pharmacy Enrollment Form |
Train all relevant staff involved in dispensing on the Macitentan-Containing
Products REMS requirements, procedures, and REMS materials.
Before dispensing
Obtain authorization to dispense each prescription by contacting the
Macitentan-Containing Products REMS to verify female patients are enrolled,
the reproductive status has not changed, the prescriber is certified, and
pregnancy test is completed for females of reproductive potential or the
prescriber authorizes the refill.
For females of reproductive potential: Counsel the patient on the risk of
embryo-fetal toxicity, the need to use reliable contraception during treatment
and for one month after stopping treatment, to get monthly pregnancy tests,
and to inform the prescriber immediately if she misses a menstrual period or
suspects she is pregnant.
For females of reproductive potential: Dispense no more than a 30-days'
supply.
To maintain
certification to
dispense
Have a new authorized representative enroll in the Macitentan-Containing
Products REMS by completing the Outpatient Pharmacy Enrollment Form if the
authorized representative changes.
At all times
Report pregnancies to the REMS Coordinating Center.
Not distribute, transfer, loan, or sell macitentan-containing products, except to
certified dispensers.
For all females: Maintain and submit records of daily product dispensing data.
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 macitentan-containing products must:
To become certified to dispense
Designate an authorized representative to carry out the certification process
and oversee implementation and compliance with the Macitentan-Containing
Products REMS on behalf of the pharmacy.
Have the authorized representative review the Prescribing Information and the
Prescriber and Pharmacy Guide.
| Prescriber and Pharmacy Guide |
Have the authorized representative enroll in the Macitentan-Containing
Products REMS by completing the Inpatient Pharmacy Enrollment Form
and submitting it to the Macitentan-Containing Products REMS.
| Inpatient Pharmacy Enrollment Form |
Train all relevant staff involved in dispensing macitentan-containing
products on the Macitentan-Containing Products REMS requirements,
procedures, and REMS materials.
Establish processes and procedures to verify the female patient is enrolled in
the Macitentan-Containing Products REMS or will be enrolled prior to
discharge, her reproductive status, and the female patient is under the
supervision and care of a certified prescriber.
For females of reproductive potential: establish processes and procedures to
verify pregnancy testing is complete, and that the patient is counseled on the
risk of embryo-fetal toxicity, the need to use reliable contraception, to get
monthly pregnancy tests, and to inform the prescriber of a pregnancy
immediately.
Before dispensing
Verify the female patient is under the supervision and care of a certified
prescriber, and that she is enrolled or will be enrolled in the Macitentan-
Containing Products REMS prior to discharge through the processes and
procedures established as a requirement of the Macitentan-Containing
Products REMS.
For females of reproductive potential: Verify the pregnancy testing is
complete, and that the patient is counseled on the risk of embryo-fetal
toxicity, the need to use reliable contraception, to get monthly pregnancy
tests, and to inform the prescriber of a pregnancy immediately through the
processes and procedures established as a requirement of the Macitentan-
Containing Products REMS.
To maintain
certification to
dispense
Have a new authorized representative enroll in the Macitentan-Containing
Products REMS by completing the Inpatient Pharmacy Enrollment Form if
the authorized representative changes.
| Inpatient Pharmacy Enrollment Form |
At discharge
Dispense no more than a 15-days’ supply.
At all times
Report pregnancies to the REMS Coordinating Center.
Not distribute, transfer, loan, or sell macitentan-containing products, except to
certified dispensers.
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 macitentan-containing products must:
To be able to distribute
Establish processes and procedures to ensure that the drug is distributed only
to certified pharmacies and registered wholesalers-distributors.
Train all relevant staff involved in distribution on the Macitentan-Containing
Products REMS requirements.
At all times
Distribute only to certified pharmacies and registered wholesalers-distributors.
Maintain and submit records of monthly drug distribution for all macitentancontaining
products shipments.
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.
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 Macitentan-Containing Products 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
03/22/2024
Modified to:
Add Opsynvi (macitentan and tadalafil) product information
Change the name of the REMS to Macitentan-Containing Products REMS
Allow for greater than 30-days’ supply when initiating Opsynvi in patients who are treatment naïve or those transitioning from endothelium receptor antagonist (ERA) monotherapy
Add information on “Office Contacts” and their role in assisting prescribers with the REMS
Clarify the certification requirements of the outpatient pharmacy
02/01/2023
Modified to:
Streamline the REMS by removing redundancies and unnecessary features
including the Patient Enrollment Form – For VA Use Only, Patient Pre-Enrollment
functionality, Patient Portal, and patient’s ability to initiate Prescriber Transfer.
Change the outpatient pharmacy certification and REMS Dispensing
Authorization (RDA) processes to ensure REMS requirements are met prior to
dispensing.
Update the Prescriber and Pharmacy Guide to include additional instructions
for pharmacies to provide reasons for dispensing a greater than 30 days’ for a
female of reproductive potential and to provide reasons for treatment interruption.
Update the REMS assessment timetable.
Update the REMS website URL and website functionality to remove duplicate
screens and to align with updated processes.
04/06/2021
Approval of the Shared System 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.
