위의 보고와 관련된 부작용 때문에 FDA와 회사측과 협력을 통해 Isotretinoin 처방함에 있어서 Pregnancy Prevention Program 을 구성을 하게 되고 그 구성요소는 다음과 같다.
Information brochure for patients
Product monograph for patients and physicians
Qualification checklist for placing women of childbearing potential on isotretinoin and concurrent birth control
Verbal information for patients
Consent-to-treatment form
Line drawing representing common birth defects associated with isotretinoin use in pregnancy
Restrictions on prescribing the drug unless the patient has severe, disfiguring acne unresponsive to standard therapies or severe intractable psoriasis, keratosis follicularis, ichthyosis dermatoses or palmoplantar pustulosis
Determination that the patient is reliable in executing instructions
Negative serum pregnancy test 2 weeks before initiation of therapy
Verbal and written warnings to avoid pregnancy during isotretinoin therapy and for 2 months after cessation of therapy
Two negative pregnancy test results before first prescription
Pregnancy tests repeated monthly during therapy
Accutane Qualification Sticker affixed to the prescription form to confirm the prescriber's authorization to prescribe isotretinoin and the patient's eligibility to receive it
Maximum 30-day supply
No automatic refills
[Pregnancy tests]
Screening test : negative results from 2 urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial prescription
Confirmation test : second pregnancy test during the first 5 days of the menstrual period immediately preceding the beginning of therapy
Patients with amenorrhea: second test should be done at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of contraception).
Each month of therapy, the patient must have a negative result from a urine or serum pregnancy test.
A pregnancy test must be repeated each month prior to the female patient receiving each prescription.
임신 가능성이 있는 여성환자는 적어도 2가지 이상의 효과적인 피임법을 동시에 하여 적어도 치료 전 1개월부터 치료 도중, 그리고 치료 종료 후 1개월 동안 사용하여야 한다.
[Effective Forms of Contraception]
Primary forms
- Tubal legation
- Partner's vasectomy
- Intrauterine devices
- Birth control pills
- Topical/injectable/implantable/insertable hormonal birth control products
Secondary forms
- Diaphragms
- Latex condoms
- Cervical caps
- Each must be used with a spermicide
Isotretinoin is found in the semen of male patients taking isotretinoin, but the amount delivered to a female partner would be about 1 million times lower than an oral dose of 40 mg.
Patients should not donate blood during therapy and for 1 month following discontinuance of the drug because the blood might be given to a pregnant woman whose fetus must not be exposed to isotretinoin.
It is not known whether this drug is excreted in human milk.
Because of the potential for adverse effects, nursing mothers should not receive isotretinoin.
Women ( 25 - 35 years) : highest pregnancy rate (3.7 pregnancies per 1000 courses of isotretinoin)
Women ( 15 - 24 years) : 2.8 pregnancies per 1000 isotretinoin courses
Pregnancies occurred in all age groups, but the rates were lower among women under 15 and over 34.
The pregnancy rates per 1000 courses of isotretinoin for ages 15 years, 35 to 44 years, and 45 years were 1.0, 1.7, and 0.5, respectively.
: CMAJ. 2004 May 11;170(10):1567-8.
The introduction of generic forms of isotretinoin, together with decreasing prices, will further increase the use of this drug by sexually active young women.
If, 20 years after the drug's introduction in clinical use, cases of fetal exposure continue to be reported, we see little reason to believe that the SMART program will be sufficient to reverse this trend.
We propose that certification and registration be required for physicians who wish to prescribe isotretinoin.
