One might blame Roche: the company has repeatedly gone to court demanding that material describing the development of Accutane be kept private.
But some believe that the Roche exploits that authority in order to keep certain details—details which might reflect poorly on the company—obscured. Werner Bollag first studied the chemical compound, cis retinoic acid at Roche laboratories in Switzerland during the s.
But Bollag also realized that the drug could cause serious birth defects. The compound derived from vitamin A, a known teratogen. When it proved ineffective as a cancer therapy he abandoned the project. In their research, Drs. Frank Yoder and Gary Peck accidentally discovered that the chemical also cleared up acne. Subjects who had been covered with pimples returned to the office with clear skin. Isotretinoin became Accutane, and in clinical trials researchers carefully avoided exposing pregnant women to the drug.
Hoffmann-La Roche had conducted animal studies, and offspring of subjects showed facial deformities much like the ones that have subsequently been seen in Accutane babies. Those researchers who did include women in trials required a negative pregnancy test and contraceptive use. FDA provides administrative support to the Dermatologic Drugs Advisory Committee, which includes several dermatologists, other medical experts and a consumer representative.
But the Committee also urged that the label be revised. There are no adequate and well-controlled studies in pregnant women. Drugs should be given only if the potential benefit justifies the potential risk to the fetus. Although FDA heightened the pregnancy risk rating for the drug, the original label did not suggest the careful precautions that Roche itself had used during clinical trials.
Instead, the label noted the fact that there had been no evidence of birth defects in humans. In May , nine months after the application had been submitted, FDA announced approval of Accutane.
According to a Hoffmann-La Roche spokeswoman quoted in the Washington Post , "Approval came through so fast that it came as quite a surprise to everyone The United States was the first country to approve Accutane. In September , Accutane arrived to a warm welcome. News and World Reports stated that Accutane could clear up most cases of acne within a few months.
At the same time, some of the doctors who had studied the drug began to voice alarm. Henry J. Roenigk had been chairman of the dermatology department at Northwestern University and participated as a researcher for Roche during clinical trials.
The potential toxicity of this drug has been seriously under-emphasized. Hoffmann-La Roche reproached the scientists for releasing information obtained while working for the company. Yoder claims that he received a hostile phone call from Roche executives. According to him, Roche representatives ''angrily told me I should not be writing that sort of confidential information. I didn't agree with them. I thought the public good must be served.
Shortly afterward the company sent letters to all scientists who had participated in clinical trials, stressing the confidentiality of information obtained during research sponsored by Hoffmann-La Roche. Within a few months, Hoffmann-La Roche began receiving stories about of babies born with severe birth defects to women who had taken Accutane.
In June —nine months after the drug had been released—three cases were reported to Roche. The company also revised the drug label to include more information about birth defects and a more prominently placed warning. In addition, Public Citizen asked FDA to require patient package inserts explaining the possible side-effects in non-technical language.
In the first 18 months of marketing, about , patients took Accutane. By March , Roche collected reports of 20 Accutane babies. The label explicitly suggested that patients use contraceptives beginning a month before therapy. In addition, FDA advised blood banks to refuse donations from Accutane users. Between and Roche delivered seven more Dear Doctor letters warning about Accutane. Practitioners have suggested that FDA requires a black box warning when it hopes to decrease sales of a drug.
On April 22, four days before the scheduled meeting, an account of the confidential FDA memo appeared on the front page of the New York Times. News of the large estimated number of Accutane babies—combined with the large number of abortions suggested to have been caused by the drug—sparked a craze of media attention. Journalists questioned whether the manufacturer and doctors had pushed the drug too far and whether FDA had approved the drug too quickly.
We must not allow the advisory committee process to be used as an excuse to permit such a seriously birth-deforming drug to remain on the market.
Yoder also described the firm safeguards that had been in place during testing to ensure that no pregnant women were exposed to the drug. This was very, very wrong. One source of controversy was the disparity between Accutane use in the U. As of April 30, only three Accutane babies had been born in Europe.
In Switzerland, doctors had to register with the government to prescribe it. In the United Kingdom, only dermatologist had authority to prescribe Accutane and only hospitals could dispense it. As a prerequisite to receiving the drug in Britain, a woman had to stipulate that she would be willing to have an abortion.
Sweden never approved Accutane for general use; dermatologists applied for special permission when a patient had a particular need. In Spain, the Ministry of Health kept the name and address of every woman taking Accutane in a special registry.
The European approach to Accutane reflected not just a different regulatory methodology, but also differing circumstances. In the wake of Thalidomide, Europeans treated all teratogenic drugs extremely cautiously.
The Committee meeting on April 26th was just as contentious as the public debate that preceded it. Hoffmann-La Roche proposed an aggressive education program to reduce the risk of pregnancy. The Committee recommended that only a limited number of certified physicians be permitted to dispense the drug.
In addition, women at high-risk of pregnancy would be required to procure a second opinion before receiving Accutane. Questioning whether it had the authority to dictate who could prescribe the drug, FDA instead mandated new warnings for the label. The agency required that Hoffmann-La Roche provide informed consent forms to be signed by patients and doctors. In addition the FDA directed the company to double the type size in the warning; include a picture of a baby deformed by Accutane in the material going to patients; dispense the drug in a blister-pack with warnings on every package; instruct doctors that they should give both written and oral warnings; add a symbol of a pregnant woman crossed out on the material given to doctors and patients; and conduct follow-up studies to determine the efficacy of the new program.
In addition, the company offered to pay the costs of contraceptive counseling and pregnancy testing for any woman receiving a prescription of Accutane. Debates continued throughout Dermatologists presented pictures of patients who had suffered from extremely severe acne and had been cured by Accutane. In the fall a fight broke out in the back pages of the New England Journal of Medicine.
Robert Stern, a dermatologist in Boston, had written an article describing Accutane as a uniquely effective treatment for acne.
Likewise, Drs. Gerald Faich and Franz Rosa argued that there have probably been many more Accutane babies than have been reported. They lamented, "It is disappointing that little change has occurred in the rates of use of the drug in women, in spite of considerable publicity efforts to educate physicians.
FDA asked the two groups to address this question: had the pre adverse public health situation changed in a meaningful way and to a meaningful extent? The Committees found that it had not. The continued high level of Accutane use in the at risk population, prescriber non-compliance with important components of the program many reproductive-aged women had not even been given a pregnancy test before starting therapy , and relatively low levels of participation in the Slone survey posed significant concerns for the group.
It actually took twelve months for the committees to reconvene—the joint meeting was held in May —and by the time the groups came together, the media spotlight had disappeared.
Unlike the previous three Accutane-related meetings, this one received no coverage in the Washington Post or the New York Times. Roaccutane, a brand name of the drug isotretinoin, is used by about 30, people in the UK each year. Data from NHS Digital shows prescriptions for isotretinoin rose from 34, to 69, between and While studies have not found a clear or direct link with increased risk of psychiatric disorders and suicide, side-effects have been noted.
Since records began there have been 88 deaths. These people may not appear to be depressed. Two years ago, a new warning was added to say some people would be affected by problems getting or maintaining an erection and by lower libido.
The MHRA governs the safety of the drug. It said the safety of isotretinoin was kept under continuous review in the UK and across Europe. Use the medicine exactly as directed.
Each prescription of isotretinoin must be filled within 7 days of the date it was written by your doctor. You will receive no more than a day supply of isotretinoin at one time. Always take isotretinoin with a full glass of water.
Do not chew or suck on the capsule. Swallow it whole. Use this medicine for the full prescribed length of time. Your acne may seem to get worse at first, but should then begin to improve. Never share this medicine with another person, even if they have the same symptoms you have. Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time. Health Topics. Health Tools. Isotretinoin Accutane. Reviewed: June 23, These medicines should not be used with Accutane unless your doctor tells you it is okay.
Know the medicines you take. Keep a list of them to show to your doctor and pharmacist. Do not take any new medicine without talking with your doctor. If you get pregnant while taking Accutane, stop taking it right away and call your doctor. Doctors and patients should report all cases of pregnancy to:. Stop Accutane and call your doctor right away if you or a family member notices that you have any of the following signs and symptoms of depression or psychosis:.
Stop Accutane and call your doctor right away if you have muscle weakness. Muscle weakness with or without pain can be a sign of serious muscle damage. After stopping Accutane, you may also need follow-up mental health care if you had any of these symptoms. Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Accutane there are no specific foods that you must exclude from your diet when receiving Accutane.
Tell your doctor if you are pregnant or breastfeeding. Accutane must not be used by women who are pregnant or breastfeeding. Accutane must not be taken by patients who are pregnant or who may become pregnant. There is a high risk that Accutane will cause birth defects deformed babies , loss of a baby before birth miscarriage , death of the baby and early premature births. See "Drug Precautions" section. A program called iPLEDGE has been set up to make sure that pregnant women do not take Accutane and that women do not become pregnant while taking Accutane.
Before prescribing Accutane, your doctor will:. Female patients must not get pregnant:. Accutane should not be used by women who are breastfeeding. It is not known if Accutane is excreted in human breast milk or if it will harm your nursing baby. Tell your doctor if you are breastfeeding before you receive Accutane. You must take Accutane exactly as prescribed. You must talk about effective birth control methods with your doctor or go for a free visit to talk about birth control with another doctor or family planning expert.
Your doctor can arrange this free visit, which will be paid for by the company that makes Accutane. If you have sex at any time without using two forms of effective birth control, get pregnant or miss your expected period, stop using Accutane and call your doctor right away.
Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The recommended dosage range for Accutane isotretinoin is 0. If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away. If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur.
However, if an overdose is suspected, seek emergency medical attention. Accutane must not be used by female patients who are or may become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking Accutane in any amount, even for short periods of time. Potentially any fetus exposed during pregnancy can be affected.
There are no accurate means of determining whether an exposed fetus has been affected. Birth defects which have been documented following Accutane exposure include abnormalities of the face, eyes, ears, skull, central nervous system, cardiovascular system, and thymus and parathyroid glands. Cases of IQ scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion and premature births have been reported.
Documented external abnormalities include: skull abnormality; ear abnormalities including anotia, micropinna, small or absent external auditory canals ; eye abnormalities including microphthalmia ; facial dysmorphia; cleft palate. Documented internal abnormalities include: CNS abnormalities including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit ; cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency.
In some cases, death has occurred with certain of the abnormalities previously noted.
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