Ocular Side Effects From Accutane
A new study confirms and ranks ocular adverse events associated with isotretinoin, providing dermatologists and other clinicians with guidelines for ocular exams, according to Frederick W. Fraunfelder and research colleagues with the Casey Eye Institute, Oregon Health Sciences University.
"We want to help clinicians make an informed decision as to whether the side effects reported by patients are real," said Dr. Fraunfelder, assistant professor of ophthalmology, Casey Eye Institute. For example, some patients may complain of double vision, which is classified in this study as unlikely and may not be drug induced.
In the September 2001 edition of the American Journal of Ophthalmology, the researchers describe 38 different signs and symptoms considered ocular abnormalities associated with isotretinoin.
Isotretinoin is indicated for severe recalcitrant nodule acne that has failed to respond to conventional therapy, including systemic antibiotics. It is strictly prohibited for pregnant women or those who may become pregnant because of the risk of major human fetal deformities.
According to Dr. Fraunfelder, side effects considered certain include decreased dark adaptation, decreased vision, ocular sicca, (dry eye), abnormal meibomian gland secretion, meibomian gland atrophy, blepharoconjunctivitis (inflammation of the eyelid), corneal opacities (only visible with a microscope), keratitis (corneal inflammation), decreased tolerance to contact lens, increase tear osmolarity, photophobia, myopia (near sightedness), ocular discomfort, as well as teratogenic ocular abnormalities.
Those on the probable/likely list include reversible decreased color vision and permanent loss of dark adaptation. Permanent keratoconjunctivitis sicca has a possible association with the drug.
"I would say the most serious would be anything that causes vision loss," Dr. Fraunfelder said. "Dermatologists need to ask patients on isotretinoin to talk about vision loss or dark adaptation problems. Does it take a long time for their eyes to adjust from sunlight when driving into a tunnel? It tells the dermatologist to refer to an ophthalmologist for more formal testing.
Package insert adverse events, which occurred in 80 percent of patients taking isotretinoin, include dry skin, skin fragility, pruritis, epistaxis, dry nose, and dry mouth. Up to 90 percent of patients in clinical trials reported cheilitis and 40 percent with conjunctivitis.
To establish a cause and effect relationship between the drug and side effects and then determine its classification, Dr. Fraunfelder and colleagues used the World Health Organization Causality Assessment Guide of Suspected Adverse Reactions criteria. To be labeled as a certain reaction, the side effect had to provide positive re-challenge data in several cases. "De-challenge data is when you stop the drug and the side effect goes away. But if you restart the drug and the side effect returns, that's a positive re-challenge and convincing evidence of an adverse drug event," he explained.
They are classified as certain, probably/likely, possible, unlikely or conditional/unclassifiable. The data is derived from 1,741 case reports received from various reporting systems, including the Food and Drug Administration, World Health Organization, the drug safety section of Roche Pharmaceuticals, and the National Registry of Drug-Induced Ocular Side Effects (based at the Casey Eye Institute).
"I think working closely with an ophthalmologist will help determine if isotretinoin should be continued," said Dr. Fraunfelder. "The dermatologist who is really well read in the area can look for more than 'the big three,'" which include problems with dark adaptation, color vision, and dry eye.
"I think dermatologists are aware of the (ocular) side effects from isotretinoin," he added. "It is known to cause dry eye and some photosensitivity. Many are probably aware that it could cause some vision changes, but it has never been reported until this journal article that there are certain associations."
Another recent study by the FDA supports previous data suggesting that serious clinical depression may result from taking isotretinoin.
The 18-year study is published in the October 2001 Journal of the American Academy of Dermatology. In 18 years, from 1982 to 2000, the FDA has records of 431 patients taking the drug who also developed depression-related complications. Some committed suicide (37); others were hospitalized for depression, suicide ideation or attempt (110), or suffered nonhospitalized depression (284). "Compared with all drugs in the FDA's Adverse Event Reporting System database to June 2000, isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt," the researchers concluded.
They also advise physicians to inform patients and their families to watch for signs of depression or worsening of depression. Reports about mood swings, loss of appetite, unusual fatigue, withdrawal, inability to concentrate, and other symptoms of depression should be addressed immediately, "including consideration of drug discontinuation and referral for psychiatric care."
For more information
Fraunfelder FT, Fraunfelder FW, Edwards R. Ocular side effects possibly associated with isotretinoin use. Am J Ophthalmol 2001 Sep;132(3):299-305.
www.ohsucasey.com (education links to National Registry)
Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 2001 Oct;54(4):515-519.
"We want to help clinicians make an informed decision as to whether the side effects reported by patients are real," said Dr. Fraunfelder, assistant professor of ophthalmology, Casey Eye Institute. For example, some patients may complain of double vision, which is classified in this study as unlikely and may not be drug induced.
In the September 2001 edition of the American Journal of Ophthalmology, the researchers describe 38 different signs and symptoms considered ocular abnormalities associated with isotretinoin.
Isotretinoin is indicated for severe recalcitrant nodule acne that has failed to respond to conventional therapy, including systemic antibiotics. It is strictly prohibited for pregnant women or those who may become pregnant because of the risk of major human fetal deformities.
According to Dr. Fraunfelder, side effects considered certain include decreased dark adaptation, decreased vision, ocular sicca, (dry eye), abnormal meibomian gland secretion, meibomian gland atrophy, blepharoconjunctivitis (inflammation of the eyelid), corneal opacities (only visible with a microscope), keratitis (corneal inflammation), decreased tolerance to contact lens, increase tear osmolarity, photophobia, myopia (near sightedness), ocular discomfort, as well as teratogenic ocular abnormalities.
Those on the probable/likely list include reversible decreased color vision and permanent loss of dark adaptation. Permanent keratoconjunctivitis sicca has a possible association with the drug.
"I would say the most serious would be anything that causes vision loss," Dr. Fraunfelder said. "Dermatologists need to ask patients on isotretinoin to talk about vision loss or dark adaptation problems. Does it take a long time for their eyes to adjust from sunlight when driving into a tunnel? It tells the dermatologist to refer to an ophthalmologist for more formal testing.
Package insert adverse events, which occurred in 80 percent of patients taking isotretinoin, include dry skin, skin fragility, pruritis, epistaxis, dry nose, and dry mouth. Up to 90 percent of patients in clinical trials reported cheilitis and 40 percent with conjunctivitis.
To establish a cause and effect relationship between the drug and side effects and then determine its classification, Dr. Fraunfelder and colleagues used the World Health Organization Causality Assessment Guide of Suspected Adverse Reactions criteria. To be labeled as a certain reaction, the side effect had to provide positive re-challenge data in several cases. "De-challenge data is when you stop the drug and the side effect goes away. But if you restart the drug and the side effect returns, that's a positive re-challenge and convincing evidence of an adverse drug event," he explained.
They are classified as certain, probably/likely, possible, unlikely or conditional/unclassifiable. The data is derived from 1,741 case reports received from various reporting systems, including the Food and Drug Administration, World Health Organization, the drug safety section of Roche Pharmaceuticals, and the National Registry of Drug-Induced Ocular Side Effects (based at the Casey Eye Institute).
"I think working closely with an ophthalmologist will help determine if isotretinoin should be continued," said Dr. Fraunfelder. "The dermatologist who is really well read in the area can look for more than 'the big three,'" which include problems with dark adaptation, color vision, and dry eye.
"I think dermatologists are aware of the (ocular) side effects from isotretinoin," he added. "It is known to cause dry eye and some photosensitivity. Many are probably aware that it could cause some vision changes, but it has never been reported until this journal article that there are certain associations."
Another recent study by the FDA supports previous data suggesting that serious clinical depression may result from taking isotretinoin.
The 18-year study is published in the October 2001 Journal of the American Academy of Dermatology. In 18 years, from 1982 to 2000, the FDA has records of 431 patients taking the drug who also developed depression-related complications. Some committed suicide (37); others were hospitalized for depression, suicide ideation or attempt (110), or suffered nonhospitalized depression (284). "Compared with all drugs in the FDA's Adverse Event Reporting System database to June 2000, isotretinoin ranked within the top 10 for number of reports of depression and suicide attempt," the researchers concluded.
They also advise physicians to inform patients and their families to watch for signs of depression or worsening of depression. Reports about mood swings, loss of appetite, unusual fatigue, withdrawal, inability to concentrate, and other symptoms of depression should be addressed immediately, "including consideration of drug discontinuation and referral for psychiatric care."
For more information
Fraunfelder FT, Fraunfelder FW, Edwards R. Ocular side effects possibly associated with isotretinoin use. Am J Ophthalmol 2001 Sep;132(3):299-305.
www.ohsucasey.com (education links to National Registry)
Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 2001 Oct;54(4):515-519.
posted by Nick Riley at 11:21 AM
