The oral LD50 of isotretinoin is greater than 4000 mg/kg in rats and mice (> 600 times the recommended clinical dose of 1 mg/kg/day after normalization of the rat dose for total body surface area and > 300 times the recommended clinical dose of 1 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1 mg/kg/day after normalization for total body surface area). In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness and ataxia. These symptoms quickly resolve without apparent residual effects.
Amnesteem causes serious birth defects at any dosage (see Boxed CONTRAINDICATIONS AND WARNINGS). Female patients of childbearing potential who present with isotretinoin overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the Boxed CONTRAINDICATIONS AND WARNINGS. Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in PRECAUTIONS
. Educational materials for such patients can be obtained by calling the manufacturer. Because an overdose would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a female patient who is or might become pregnant, for one month after the overdose. All patients with isotretinoin overdose should not donate blood for at least one month.
- Peck GL, Olsen TG, Yoder FW, et al. Prolonged remissions of cystic and conglobate acne with 13-cis-retinoic acid. N Engl J Med 300:329-333, 1979.
- Pochi PE, Shalita AR, Strauss JS, Webster SB. Report of the consensus conference on acne classification. J Am Acad Dermatol 24:495-500, 1991.
- Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acne with 13-cis-retinoic acid: evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol 3:602-611, 1980.
- Jones H, Blanc D, Cunliffe WJ. 13-cis-retinoic acid and acne. Lancet 2:1048-1049, 1980.
- Katz RA, Jorgensen H, Nigra TP. Elevation of serum triglyceride levels from oral isotretinoin in disorders of keratinization. Arch Dermatol 116:1369-1372, 1980.
- Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ. Isotretinoin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol 10:1024-1029, 1984.
- Dicken CH, Connolly SM. Eruptive xanthomas associated with isotretinoin (13-cis-retinoic acid). Arch Dermatol 116:951-952, 1980.
- Strauss JS, Rapini RP, Shalita AR, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 10:490-496, 1984.
OrthoNovum 7/7/7 is a registered trademark of Ortho-McNeil Pharmaceutical, Inc.
PATIENT INFORMATION/INFORMED CONSENT ABOUT BIRTH DEFECTS
(for female patients who can get pregnant)
To be completed by the patient (and her parent or guardian* if patient is under age 18) and signed by her doctor.
Read each item below and initial in the space provided to show that you understand each item and agree to follow your doctor's instructions. Do not sign this consent and do not take isotretinoin if there is anything that you do not understand.
* A parent or guardian of a minor patient (under age 18) must also read and initial each item before signing the consent.
- I understand that there is a very high chance that my unborn baby could have severe birth defects if I am pregnant or become pregnant while taking isotretinoin. This can happen with any amount and even if taken for short periods of time. This is why I must not be pregnant while taking isotretinoin.
- I understand that I must not get pregnant one month before, during the entire time of my treatment and for one month after the end of my treatment with isotretinoin.
- I understand that I must avoid sexual intercourse completely, or I must use two separate, effective forms of birth control (contraception) at the same time. The only exceptions are if I have had surgery to remove the uterus (a hysterectomy) or both of my ovaries (bilateral oophorectomy), or my doctor has medically confirmed that I am post-menopausal.
- I understand that hormonal birth control products are among the most effective forms of birth control. Combination birth control pills and other hormonal products include skin patches, shots, under-the-skin implants, vaginal rings and intrauterine devices (IUDs). Any form of birth control can fail. That is why I must use two different birth control methods at the same time starting one month before, during, and for one month after stopping therapy every time I have sexual intercourse, even if one of the methods I choose is hormonal birth control.
- I understand that the following are effective forms of birth control:
- tubal sterilization (tying my tubes)
- partner's vasectomy
- intrauterine device
- hormonal (combination birth control pills, skin patches, shots, under-the-skin implants or vaginal ring)
- male condom with or without spermicide
- diaphragm with spermicide
- cervical cap with spermicide
- vaginal sponge (contains spermicide)
A diaphragm and cervical cap must each be used with spermicide, a special cream that kills sperm
I understand that at least one of my two forms of birth control must be a primary method.
I will talk with my doctor about any medicines including herbal products I plan to take during my isotretinoin treatment because hormonal birth control methods may not work if I am taking certain medicines or herbal products.
I may receive a free birth control counseling session from a doctor or other family planning expert. My isotretinoin doctor can give me an isotretinoin Patient Referral Form for this free consultation.
I must begin using the birth control methods I have chosen as described above at least one month before I start taking isotretinoin.
I cannot get my first prescription for isotretinoin unless my doctor has told me that I have two negative pregnancy test results. The first pregnancy test should be done when my doctor decides to prescribe isotretinoin. The second pregnancy test must be done in a lab during the first 5 days of my menstrual period right before starting isotretinoin therapy treatment or as instructed by my doctor. I will then have one pregnancy test; in a lab.
at the end of treatment
and 1 month after stopping treatment
- every month during treatment
I must not start taking isotretinoin until I am sure that I am not pregnant, have negative results from two pregnancy tests, and the second test has been done in a lab.
I have read and understand the materials my doctor has given to me, including The iPLEDGE Program Guide for Isotretinoin for Female Patients Who Can Get Pregnant, The iPLEDGE Birth Control Workbook and The iPLEDGE Program Patient Introductory Brochure
My doctor gave me and asked me to watch the DVD containing a video about birth control and a video about birth defects and isotretinoin.
I was told about a private counseling line that I may call for more information about birth control. I have received information on emergency birth control.
I must stop taking isotretinoin right away and call my doctor if I get pregnant, miss my expected menstrual period, stop using birth control or have sexual intercourse without using my two birth control methods at any time.
My doctor gave me information about the purpose and importance of providing information to the iPLEDGE program should I become pregnant while taking isotretinoin or within one month of the last dose. I understand that if I become pregnant, information about my pregnancy, my health, and my baby’s health may be shared with the makers of isotretinoin, authorized parties who maintain the iPLEDGE program for the makers of isotretinoin and government health regulatory authorities.
I understand that being qualified to receive isotretinoin in the iPLEDGE program means that I:
have chosen and agreed to use two forms of effective birth control at the same time. At least one method must be a primary form of birth control, unless I have chosen never to have sexual contact with a male (abstinence), or I have undergone a hysterectomy. I must use two forms of birth control for at least one month before I start isotretinoin therapy, during therapy and for one month after stopping therapy. I must receive counseling, repeated on a monthly basis, about birth control and behaviors associated with an increased risk of pregnancy.
have signed a Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) that contains warnings about the chance of possible birth defects if I am pregnant or become pregnant and my unborn baby is exposed to isotretinoin.
have interacted with the iPLEDGE program before starting isotretinoin and on a monthly basis to answer questions on the program requirements and to enter my two chosen forms of birth control.
- have had two negative urine or blood pregnancy tests before receiving the first isotretinoin prescription. The second test must be done in a lab. I must have a negative result from a urine or blood pregnancy test done in a lab repeated each month before I receive another isotretinoin prescription.
My doctor has answered all my questions about isotretinoin and I understand that it is my responsibility not to get pregnant one month before, during isotretinoin treatment, or for one month after I stop taking isotretinoin.
I now authorize my doctor ____________________to begin my treatment with isotretinoin.
Patient Signature:________________________________________ Date: _____________
Parent/Guardian Signature (if under age 18):___________________ Date:_____________
Please print: Patient Name and Address_________________________________________
_________________________________________ Telephone ______________________
I have fully explained to the patient, ________________________________, the nature and purpose of the treatment described above and the risks to female patients of childbearing potential. I have asked the patient if she has any questions regarding her treatment with isotretinoin and have answered those questions to the best of my ability.
Doctor Signature: ________________________________________ Date: _____________
PLACE THE ORIGINAL SIGNED DOCUMENTS IN THE PATIENT’S MEDICAL RECORD. PLEASE PROVIDE A COPY TO THE PATIENT.