_ S. IIE.P.S.
`Systemfor Thalidomide Edacation and Prescribing Safety
`
`INSTRUCTIONS FOR PHYSICIANS
`
`
`PHYSICIAN REGISTRATION
`
`0 All physicians must register in the S. T£.RS. Physician Registry via the Physician Registration Card that is located in
`every S. IERS. folder. Only licensed Medical Doctors or Doctors of Osteopathy may register.
`
`0 Complete, sign, and return the Physician Registration Card. By doing so, you agree to prescribe THALOMID“
`(thalidomide) in accordance with all the terms listed on the card.
`
`0 Wait for confirmation of your registration prior to prescribing Tl-IALOMID"‘ (thalidomide).
`
`. .. S.TE.P.S. PROGRAM MATERIALS
`
`0 All materials that are necessary to comply with S. IE.RS. program requirements are contained in the
`S.T[:'.RS. folder.
`
`0 The contents of ONE FOLDER should be used with ONE PATIENT, and kept with the patient’s medical record.
`
`0 Additional $.IIE.RS. folders can be obtained from your Celgene Immunology Specialist, or by calling
`1-888-4-CELGENE.
`
`S. TE.P.S. FOLDER CONTENTS
`
`The S.'IZE.RS. Folder contains the following information and materials to help ensure that fetal exposure to
`Tl-IALOMID" (thalidomide) does not occur:
`
`0’ Physician Registration Card: All physicians must register.
`0 Thalidomide Victims Association of Canada letter: A cautionary message to the physician and patient from
`thalidomide victims.
`-
`
`0 IrybrmationforMen and Women Taking THALOMID“ (thalidomide): Use this brochure for patient counseling regarding
`the teratogenic risks, as well as other side effects and precautions associated with THALOMID” (thalidomide)
`therapy.A video presentation of this information will be provided to your office upon registration.
`° Your Contraceptive Choices: This brochure is provided to assist in counseling patients on the selection of two
`appropriate contraceptive methods.
`0 Emergency Contraception: Use this brochure to assist patients in the event they have unprotected sexual intercourse
`while taking THALOMID” (thalidomide).
`'
`’
`0 Patient Referral Form: A form that must be used if you choose to have another health care professional provide
`contraceptive counseling for your patient.
`0 Patient Quiz: The quiz is provided to verify patient understanding of risks and requirements of therapy.
`0 Consent Form: This informed consent document must be understood and signed before your patient can
`receive THALOMID“ (thalidomide).
`.
`0 Thalidomide Survey Forms: These mandatory and confidential enrollment and follow-up surveys must be completed
`by the patient and physician. Men must participate, as well as women, because fetal exposure to THAI.0MID”‘ (thalidomide)
`could occur as a result of the presence of the drug in semen or through sharing of the medication. Included are forms
`for patients ages 18 or older. Formsforpatients under 18years ofage are available by calling 1-888-4-CELGENE.
`
`Important Information for Men and Women Taking THALOMID" (thalidomide), the Consent Form, the Patient Quiz
`and the Survey Forms are available in 14 languages and can be obtained through your Celgene Immunology Specialist
`or by calling 1-888-4-CELGENE.
`
`PLEASE REFER TO THE FOLLOWING STEP-BY-STEP GUIDELINESFOR PRESCRIBING
`THALOMID" (thalidomide) TO MALE AND FEMALE PATIENTS.
`'
`
`« P
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`age 1 of 4
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`Case |PRd015-01096
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`CELGENE EXHIBIT 2066
`
`Case IPR2015-01096
`
`CELGENE EXHIBIT 2066
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`Page 1 of 4
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`
`PRESCRIBING THALOMID” (thalidomide) FOR FEMALE PATIENTS
`
`INITIAL VISIT
`
`0 Establish appropriateness of THALOMID“ (thalidomide) therapy versus therapeutic alternatives.
`
`— Tl-IALOMID“ (thalidomide) is indicated for the treatment of cutaneous manifestations of moderate to severe
`erythema nodosum leprosum (ENL). THALOMID" (thalidomide) is not indicated as monotherapy for ENL in
`the presence of moderate to severe neuritis. Tl-IALOMID” (thalidomide) is also indicated as maintenance therapy
`for prevention and suppression of the cutaneous manifestations of ENL recurrence. Efficacy has not been established
`in HIV disease.
`
`0 Provide comprehensive counseling on the risks and benefits of THALOMID" (thalidomide) therapy.
`— Patients must be counseled on the risk of birth defects, other side effects, and important precautions associated
`with THALOMID" (thalidomide) therapy.
`— Utilize the patient education materials provided.
`
`0 Determine if patient has childbearing potential.
`
`’
`
`-— If patient has undergone a hysterectomy, been post-menopausal or had no menses for at least 24 consecutive
`months, or agrees to abstain from sexual intercourse with men, continue with the instructions provided in the
`INITIATING Tl-IALOMID” (thalidomide) THERAPY section below.
`— If patient does not meet the above criteria, provide contraceptive counseling, including counseling on
`emergency contraception.
`- Female patients must thoroughly understand the need for two forms of contraception to be used AT THE
`SAME TIME, beginning 4 weeks before therapy, throughout therapy, and for 4 weeks after stopping
`therapy with Tl-IALOMID" (thalidomide).
`
`.
`
`- Contraceptive methods must include at least one highly efiective method (eg, IUD, hormonal, tubal ligation.
`or partners vasectomy) and one additional effective method (eg, condom, diaphragm, or cervical cap).
`
`o If hormonal or EBB contraception is medically contraindicated, two other effective or highly efiective
`methods must be used.
`'
`
`- Utilize the patient education materials provided.
`—Physicians may refer patients to another health careprofessional for contraceptive counseling using the Patient
`Referral Form.
`
`0 Continue selected birth control options for 4 weeks prior to initiating THALOMID“ (thalidomide).
`
`INITIATING THALOMID” (thalidomide) THERAPY
`
`0 Repeat patient counseling.
`
`0 Perform pregnancy test, even if continuous abstinence is the chosen method of birth control.
`- Test must be performed in the physician’s office or lab and satisfy a sensitivity of at least 50 mlU/mL.
`— Test must be performed on female patients with childbearing potential, with negative results, within
`the 24 hours before beginning Tl-IALOMID" (thalidomide) therapy.
`— Women of childbearing potential must also receive a pregnancy test every week for the first 4 weeks, then
`every 4 weeks thereafter if their menstrual cycles are regular.
`—- If the menstrual cycle is irregular, they must receive a pregnancy test every 2 weeks thereafter.
`-- Pregnancy testing must also be performed if a patient misses her period or if there is any abnormality in
`menstrual bleeding.
`— If pregnancy does occur during treatment, the drug must be immediately discontinued and the physician and
`patient should discuss the implications of the pregnancy. Under these conditions, the patient should be referred
`to an obstetrician/gynecologist experienced in reproductive toxicity.
`
`Page 2 of 4
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`Page 2 of 4
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`

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`. .. '. ....... .................u._.-..............naaus5-.-.3._u
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`
`PRESCRIBING THALOMIDW (thalidomide) FOR FEMALE PATIENTS
`
`
`
`0 Administer the THALOMID“ (thalidomide) Patient Quiz.
`
`—- Gauge patient understanding of the requirements for taking the drug.
`-— If the patient cannot answer all of the questions correctly, review the material that she does not understand.
`-— Re—administer patient quiz. Repeat until the patient satisfactorily understands all risks and correctly answers all
`questions or reconsider the appropriateness of T1-IALOM1D"' (thalidomide) therapy.
`
`0 Complete the informed consent form.
`—— The consent form must be read to the patient in the language of their choice. Each statement must be
`initialed by the patient to indicate understanding, and the fonn must be completed and signed by both
`physician and patient.
`-— The signature of a parent or guardian will also be required if the patient is under 18 years of age. Patients
`under 12 years of age must have a parent or guardian sign on their behalf.
`— Retain “Physician” copy with patient record.
`— Mail “Survey Coordinator” copy (via self-mailing format).
`— Instruct patient to retain "Patient" copy and to present “Pharmacist” copy with prescription to pharmacist.
`
`0 Complete the mandatory and confidential survey enrollment form.
`— Instruct patients to complete the confidential section, seal the survey and return to you.
`. — Complete physician section and return in envelope provided to the Slone Epidemiology Unit of
`Boston University School of Public Health.
`0 Provide prescription.
`— Initial prescriptions cannot be issued by telephone.
`— Prescribe no more than 4 weeks (28 days) of therapy with no automatic refills.
`— It is recommended that female patients initially receive no more than a 1-week supply for each of the first
`4 weeks to coincide with weekly pregnancy testing requirements.
`
`PATIENT MONITORING DURING FIRST 4 WEEKS OF THERAPY
`
`0 Repeat patient counseling.
`
`_
`
`0 Perform pregnancy tests every week for the first 4 weeks of therapy.
`—It is recommended that pregnancy tests be performed within the 24 hours before providing subsequent prescriptions.
`—Pregnancy tests must be performed even if continuous abstinence is the chosen method of birth control.
`0 If pregnancy test is negative, provide prescription for a 1-week supply of THAIOMID” (thalidomide).
`
`SUBSEQUENT PATIENT VISITS (after the first 4-week period)
`
`0 Repeat patient counseling.
`
`' Perform pregnancy test every 4 weeks if patient’s menstrual cycles are regular, every 2 weeks if cycles
`are irregular.
`—It is recommended that pregnancy tests be perfonned within the 24 hours before providing subsequent prescriptions.
`—Pregnancy tests must be performed even if continuous abstinence is the chosen method of birth control.
`
`0 If pregnancy test is negative, provide prescription for no more than a 4-week (28-day) supply of
`THALOMID“ (thalidomide) therapy.
`
`0 Complete the follow-up survey form.
`— Forms are included in the S.TIE.BS. folder.
`—— Female patients must complete the fonn every month.
`
`0 Provide a prescription for no more than a 4-week (28-day) supply of Tl-IALOMID therapy. Telephone
`prescriptions are permitted except for initial prescription.
`.
`‘
`
`“
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`Page 3 of 4
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`3
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`Page 3 of 4
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`

`
`
`
`PRESCRIBING THALOMIDTM (thalidomide) FOR MALE PATIENTS
`
`INITIAL VISIT
`
`
`
`0 Establish appropriateness of THALOMID” (thalidomide) therapy versus therapeutic alternatives.
`— THALOMID” (thalidomide) is indicated for the treatment of cutaneous manifestations of moderate to severe
`erythema nodosum leprosum (ENL). THALOMID“ (thalidomide) is not indicated as monotherapy for ENL in
`the presence of moderate to severe neuritis. Ti-lAI.0MID"‘ (thalidomide) is also indicated as maintenance thera-
`py for prevention and suppression of the cutaneous manifestations of ENL recurrence. Eflicacy has not been
`‘
`established in HIV disease.
`
`-
`
`4
`
`_
`.
`"
`
`.
`
`_
`
`'
`
`»
`0 Provide comprehensive counseling on the risks and benefits of Tl-IA.LOMID"‘ (thalidomide) therapy.
`-— Patients must be counseled on the risk ofbirth defects, other side effects, and important precautions associated
`with THALOMID“ (thalidomide) therapy.
`'
`— Utilize the patient education materials provided.
`
`'
`
`0 Provide contraceptive counseling, including counseling on emergency contraception.
`—Men_must be instructed to use a latex condom gm time they have sexual intercourse with a woman.
`—Utiliz_e patient education materials provided.
`
`0 Administer the THALOMID“ (thalidomide) Patient Quiz.
`
`'
`
`——Gauge patient understanding of the requirements for taking the drug.
`—If the patient cannot answer all of the questions correctly,’ review the material that he does not understand.
`—Re-administer patient quiz. Repeat until the patient satisfactorily understands all risks and correctly answers all
`questions or reconsider the appropriateness of Tl-iAI.OMID"' (thalidomide) therapy.
`
`' Complete the informed consent form.
`—The consent form should be read to the patient in the language of their choice. Bach statement must be initialed by
`the patient to indicate understanding, and the fonn must be completed and signed by both physician and patient.
`—The signature of a parent or guardian will also be required if the patient is under 18 years of age. Patients under
`12 years of age must have a parent or guardian sign on their behalf.
`—Retain “Physician”copy with patient record.
`—Mail “Survey Coordinator” copy (via self-mailing format).
`-—-Instruct patient to retain "Patient" copy and to present “Pharmacist” copy with prescription to pharmacist.
`
`~---
`
`- 0 Complete the mandatory and confidential survey enrollment form.
`--Instruct patients to complete the confidential section. seal the survey and return to you.
`' —Complete physician section and return in envelope provided to the Slone Epidemiology Unit of
`Boston University School of Public Health.
`
`0 Provide prescription.
`
`~—lnitial prescriptions can not be issued by telephone.
`—Prescribe no more than 4 weeks (28 days) of therapy with no automatic refills.
`
`SU BSEQUENT PATIENT VISITS
`
`0 Repeat patient counseling.
`
`
`
`0 Complete the follow-up survey form. '
`—Forms are included in the 5.125.128. folder.
`—Male patients must complete the form at each visit or at least once every 3 months.
`
`0 Provide a prescription for no more than a 4-week (28-day) supply of THALOMID“ (thalidomide) therapy.
`Telephone prescriptions are permitted.
`.
`.
`-
`.,
`-
`
`-
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`Page 4 of 4
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`4
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`Page 4 of 4