Healthcare Professional Information Pack Refer to Package Insert* for further details (*Revlimid® / Pomalyst®)

Contents

1. Introduction ...... 3

2. i-access® Pregnancy Prevention Program ...... 4

2.1. Information for Healthcare Professional ...... 4

i. General advice for all patients ...... 4

ii. Women of Child Bearing Potential (WCBP) ...... 4

iii. Women of non Child Bearing Potential (WNCBP) ...... 6

iv. Men ...... 6

2.2. Information for Patients ...... 6

2.3. i-access® Distribution Control System ...... 7

3. Adverse Events ...... 10

4. Reporting of Adverse Events & Pregnancy ...... 10

5. Celgene Drug Safety Contact Details ...... 10

6. Local Country Contact Details ...... 11

7. Patient Brochure and Package Insert ……………………...... 11 1.0 Introduction

Thalidomide CelgeneTM (Thalidomide) is a powerful human teratogenic substance that causes severe life-threatening birth defects to an unborn child. Revlimid® (Lenalidomide) and Pomalyst® (Pomalidomide) are structurally related to thalidomide and are known as immunomodulatory drug or IMiDs® compound, i.e. compounds that have been designed using the thalidomide structural backbone but with chemical modifications to optimize their immunological and anticancer properties.

As Revlimid® and Pomalyst® are structurally related to thalidomide, teratogenic effects cannot be ruled out when it is taken during pregnancy. An embryo foetal development study in non-human primates indicates that Revlimid® produced malformations in the offspring of female monkeys who received drug during pregnancy; while Pomalyst® was found to be teratogenic in both rats and rabbits when administered during the period of major organogenesis. These are similar to the birth defects observed in humans following exposure to thalidomide during pregnancy.

Revlimid® and Pomalyst® are therefore contraindicated in pregnant Women. Women of Childbearing Potential (WCBP) can take Revlimid® or Pomalyst® if the conditions of the i-access® Pregnancy Prevention Program described in this pack are carried out.

For more information on Revlimid® or Pomalyst®, please see the package insert. i-access® i-access® is a program implemented by Celgene in agreement with health authorities to minimize the risks associated with the use of Celgene IMiDs® (Revlimid® and Pomalyst®), particularly the risk of foetal exposure. i-access® consists of the Pregnancy Prevention Program and furthermore includes general advice for the safe use of Celgene IMiDs®.

For additional copies of this kit or further information about i-access® or Celgene IMiDs® please contact Celgene Risk Management Centre or your local Celgene Representative (refer to contact details on section 6).

Note: Revlimid® and Pomalyst® hereinafter referred to as Celgene IMiDs® or IMiDs®

3 2.0 i-access® Pregnancy Prevention Program

i-access® is a program to minimize the risks associated with the use of Celgene IMiDs® (Revlimid®/ Pomalyst®), particularly the risk of foetal exposure (Pregnancy Prevention Program).

The i-access® Pregnancy Prevention Program has the following mandatory parts:

• Information for healthcare professionals and patients • Distribution control system

2.1 Information for Healthcare Professionals

The i-access® Pregnancy Prevention Program segments IMiDs® patients in different risk categories:

– Women of Childbearing Potential (WCBP) – Women of Non-Childbearing Potential (WNCBP) – Men To minimize the risk of a pregnancy occurring under the treatment of IMiDs®, there are different requirements for each of these risk categories.

i) General Advice for All Patients • Inform of general precautions associated with the use of IMiDs® • Inform patient not to share medication and return unused capsules at the end of treatment • Inform patient not to donate blood whilst taking IMiDs® or for 4 weeks after stopping treatmen t • Inform female patient not to breastfeed during therapy with IMiDs® as it is not known whether IMiDs® is excreted in human milk

ii) Women of Childbearing Potential (WCBP) Counselling

For women of childbearing potential, IMiDs® is contraindicated unless all of the following are met: • She understands the expected teratogenic risk to the unborn child • She understands the need for effective contraception, without interruption, at least 4 weeks before starting treatment, throughout the entire duration of treatment, and at least 4 weeks after the end of treatment • Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective contraception • She should be capable of complying with effective contraceptive measures • She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy • She understands the need to commence the treatment as soon as IMiDs® is dispensed following a negative pregnancy test • She understands the need and accepts to undergo pregnancy testing at least every 4 weeks except in case of confirmed tubal sterilisation • She acknowledges that she understands the hazards and necessary precautions associated with the use of IMiDs®.

4 Pregnancy Testing To confirm the absence of a pregnancy, WCBP must have medically supervised negative pregnancy tests with a minimum sensitivity of 25 mIU/mL before starting, during and after treatment with IMiDs®.

• Prior to starting treatment: A medically supervised pregnancy test should be performed during consultation, when lenalidomide/pomalidomide is prescribed, or in the 3 days prior to the visit to the prescriber once the patient had been using effective contraception for at least 4 weeks. The test should ensure the patient is not pregnant when she starts treatment with IMiDs®.

• During treatment and end of treatment: A medically supervised pregnancy test should be repeated at least every 4 weeks, including at least 4 weeks after the end of treatment, except in the case of confirmed tubal sterilisation. These pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber.

Contraception Women of childbearing potential must use two effective methods of contraception for at least weeks before therapy, during therapy, and until at least 4 weeks after ceasing IMiDs ® therapy and even in case of dose interruption unless the patient commits to absolute and continuous abstinence confirmed on a monthly basis. If not established on effective contraception, the patient must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated.

The following can be considered to be examples of suitable methods of contraception: • Implant • Levonorgestrel-releasing intrauterine system (IUS) • Medroxyprogesterone acetate depot • Tubal sterilisation • Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses • Ovulation inhibitory progesterone-only pills (i.e. desogestrel)

Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking IMiDs® either in combination therapy or as monotherapy, combined oral contraceptive pills are not recommended (refer to package insert for further details).

Your patient should be advised that if a pregnancy does occur (or suspected) whilst she is receiving IMiDs®, she must stop treatment and inform her Physician immediately.

In the event of pregnancy (confirmed or suspected) whilst on treatment with IMiDs® ® • Stop treatment with IMiDs immediately (For WCBP patient) • Refer the patient (or partner of a male patient) to a physician specialized or experienced in teratology for evaluation and advice • Notify Celgene immediately by contacting the Celgene Pte Ltd Regional Drug Safety Department or your local country representative (contact details in section 5.0) and completing the Pregnancy Capture Form (included in this kit). Celgene will follow-up on the progress of all pregnancies occurring under Celgene IMiDs® treatment • Report the event to the National Health Authority as per applicable local guidelines

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iii) Women of Non-Childbearing Potential (WNCBP) Women meeting at least one of the following criteria are considered to be of non-childbearing potential. They do not need to undergo pregnancy testing nor receive contraceptive advice.

• Age 50 years and naturally amenorrhoeic for 1 year* • Premature ovarian failure confirmed by a specialist gynaecologist • Previous bilateral salpingo-oophorectomy, or hysterectomy • XY genotype, Turner syndrome, uterine agenesis. *amenorrhoea following cancer therapy or during breastfeeding does not rule out childbearing potential. Treating physicians are advised to refer their patient for a gynaecological opinion if there is any uncertainty whether a woman meets the criteria of non-childbearing potential.

iv) Men Traces of IMiDs® have been found in semen, therefore: • Male patients should use condoms throughout the duration of treatment, during dose interruption and for 4 weeks after cessation of treatment if engaged in sexual activity with a pregnant woman or a woman of childbearing potential not using effective contraception (even if the man has had a vasectomy)

• Male patients must not donate semen or sperm during therapy (including during dose interruptions) and for 4 weeks following the discontinuation of IMiDs® (Revlimid®/ Pomalyst®).

Male patients should be instructed that if their partner becomes pregnant whilst they take IMiDs® or shortly after the patient stopped IMiDs® treatment, they should inform their doctor immediately.

2.2 Information for Patients The prescribing physician will need to provide individual i-access® counselling for patients before they receive IMiDs® (Revlimid®/ Pomalyst®) to ensure that the associated risks of IMiDs®, particularly the risks of foetal exposure, are understood. Patient counselling must include the i-access® Pregnancy Prevention Program requirements as described in section 2.1. All patients are required to receive an i-access® Patient Brochure explaining the safe use of IMiDs® and a copy of product package insert.

Counselling checklists for the i-access® Pregnancy Prevention Program that summarize the important information for each category of patient group (men, WCBP, WNCBP) are included in the Quick Guide that can be found in this resource kit.

In additional, patient counselling should include general information (for example safety advice and side effects) about Celgene IMiDs® therapy as described in the product package insert.

6 2.3 i-access® Distribution Control System The i-access® program has been designed in agreement with health authorities to minimize the risk of any unborn child being exposed to Celgene IMiDs®. It is a requirement of the program that sufficient documentation of the i-access® execution is provided. This section will describe the steps of the distribution control system in detail.

Hospital/ Clinic a) * Signed Prescriber Registration Form (FORM 1), or register online b) * Signed Pharmacy/Dispensing Clinic Registration form (FORM 2 or FORM 3), or register online c) * Signed patient agreement form (FORM 4). Fax/Email to Celgene 3. or register patient onli ne Dispense d) Signed Prescription Authorization form (FORM 5), or submit 4. Patients prescription online " e) Complete pregnancy test information on section D of FORM 5, or " $&"" submit online (for WCBP only) " 1. Submit online 2. 3. #Fax/Email (during office hour) # (24/7) online or 1. Fax/Email email i) * UPIN number (upon patient registration) (24/7) ii) Authorization of prescription

2. Registration & Authorization (during office hour) Celgene Risk " Management Program i-access® database (RMP) Team

Figure 1: Overview of i-access® program

Note: * one time process ® i-access online Paper based # if fulfil i-access® requirements

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Step 1: Registration before prescribing or dispensing Celgene IMiDs® All healthcare professionals involved in prescribing or dispensing of Celgene IMiDs® must register with i-access® to confirm that they have read and understood the information provided in this pack. Dispensing of IMiDs® will only be allowed by pharmacies or clinics registered with i-access®. Celgene supplies IMiDs® to pharmacies or clinics registered with i-access®.

® ® IMiDs prescribing physicians register with i-access by Before Prescribing faxing/emailing the completed Prescriber Registration Form Fax/Email Prescriber Registration (FORM 1) to Celgene (or register at i-access ® online) Form (FORM 1) to Celgene; or register at i-access® online

IMiDs® dispensing pharmacies (chief pharmacist or the appointed deputy) register with i-access® by faxing/emailing Before Dispensing the Pharmacy Registration Form (FORM 2) to Celgene (or Fax/Email Pharmacy/Dispensing register online). Clinic Registration Form (FORM 2

IMiDs® (physician) register by faxing/emailing or 3) to Celgene; or register at dispensing clinics i-access® online the Dispensing Clinic Registration Form (FORM 3) to Celgene (or register online).

Provide to patients Step 2: Provide i-access® patient counselling and patient material - Individual counselling - Patient brochure and package ® ® ® Before initiating IMiDs ( Revlimid or Pomalyst ), individual patient insert counselling according to the i-access® risk categories described in section 2.1 must be provided by the physician. Patient materials (i-access® patient brochure and relevant IMiDs® package insert), will need to be given to each patient. Patient Registration Complete i-access® online “Patient Agreement” page Or ® Step 3: Register patient before starting IMiDs treatment Fax/Email Patient Agreement Form- Part 1 (FORM 4a) to Celgene After receiving individual counselling and patient’s material, all patients must complete and sign a Patient Agreement Form (FORM 4) confirming their understanding of the risks associated with foetal exposure of Celgene IMiDs® and their agreement to comply with the applicable i-access® requirements of . To register patients: a) Complete the i-access® online Patient Agreement Page; or b) Fax/Email the completed and signed Patient Agreement Form-Part 1 (FORM 4a) to Celgene. The signed Part 2 (FORM 4b) of the Patient Agreement Form will be kept at the hospital/clinic.

A unique patient identification number (UPIN) will be sent to you after successful patient registration. For i-access® online: the UPIN will be shown on your i-access® online homepage and a copy emailed to your nominated email address. For paper submission: UPIN will be faxed/emailed to your nominated fax number/email address

8 Once the UPIN is received, ensure that you record this UPIN on the patient’s agreement form (FORM 4a), and on all prescriptions. Step 4: Prescribing IMiDs® (Revlimid® or Pomalyst®) • For male patients and WNCBP, it is possible to prescribe per Prescription ® ® Submit Prescription prescription up to 12 weeks supply of Revlimid or Pomalyst information via i-access® online or • For WCBP, only 4 weeks supply of Revlimid®/ Pomalyst® Complete “Prescription per prescription is possible. Authorization Form” (FORM 5) and fax/email to Celgene Each IMiDs® prescription will need to be submitted to Celgene. Submission can be done by completing the i-access® online WCBP only ® Submit *pregnancy test result to “prescription” page; or by faxing/emailing the completed i-access Celgene via i-access® online Prescription Authorization Form (FORM 5, included in this kit) to Celgene. or Complete section D of “Prescription Authorization Form” If the patient is a Woman of Childbearing Potential (WCBP), *pregnancy (FORM 5) test results would need to be submitted to Celgene for each prescription. You can submit the test result either through i-access® online; or by completing section D of the Prescription Authorization Form (FORM 5) and fax/email to Celgene.

* A medically supervised pregnancy test should be done on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber.

IMiDs® cannot be dispensed to the patient before the Prescription Authorization Form has been submitted to and authorized by Celgene.

Step 5: Prescription fulfillment Fulfilment Celgene will release authorization to the dispensing pharmacy or For online submission: ® dispensing clinic if all information submitted meet the i-access authorization status will be program requirement. seen on the webpage. or For i-access® online: the authorization status will be shown on your For paper submission: Celgene i-access® online webpage. For paper based submission (only during will release the Authorization Form to the hospital/clinic office hours: Monday-Friday 9:00am - 5.30pm) the confirmation will be sent to the pharmacy or the preferred number/email after receiving the completed Prescription Authorization Form (FORM 5)

Revlimid®/ Pomalyst® can only be dispensed to the patient after receiving the authorization from Celgene. Dispensing to WCBP should occur within 7 days of the prescription, which is the maximum validity of the prescription.

9 3.0 Adverse Events

For the list of adverse events that may be associated with IMiDs® use please consult the relevant IMiDs® Package Insert.

4.0 Reporting of Adverse Events & Pregnancy The safe use of Celgene IMiDs® is of paramount importance. As part of the ongoing safety monitoring, Celgene wishes to be informed of all adverse events that have occurred during the use of Revlimid® or Pomalyst®.

The Adverse Event reporting form and Pregnancy Capture form are included in this kit. For reporting an adverse event or pregnancy please use the appropriate form provided in this kit and send a copy to Celgene Pte Ltd Singapore/Drug Safety or to your Local Country Representative. Adverse events should also be reported to the national health authority as per applicable guidelines/ legislation.

5.0 Celgene Drug Safety Contact Details Drug Safety ASEAN 80 Marine Parade Road #20­01/09 Parkway Parade Singapore 449269

Tel. direct: +65 6572 5122 Tel. office switch: +65 6572 5100 Fax: +65 6256 0917 Email: [email protected]

10 6.0 Local Country Contact Details

Celgene Risk Management Centre Tel: +65 6572 5292 Email: [email protected] www.celgene.com

7.0 Patient Brochure and Package Insert A copy of i-access® *Patient Brochure and product *package insert would need to be given to patient prior to registration.

*The prescriber would need to provide the i-access® patient brochure and relevant (Revlimid® or Pomalyst®) package insert to the patient based on the treatment that patient is receiving.

11 Celgene Risk Management Centre Singapore (Head office) tel: +65 6572 5292 Email: [email protected] www.celgene.com

This document has been approved by the Health Sciences Authority of Singapore (HSA) as of 27-07-2020.