Isotretinoin (Accutane)

ISOTRETINOIN (ACCUTANE^®)

Primary Use

Cystic acne, psoriasis and various other skin disorders.

Clinical Concerns

This drug, which competes with binding sites for retinoic acid and retinol in the retina, can cause decreased dark adaptation. However, only recently have data suggested the probability of permanent night blindness in rare cases (Fraunfelder, Fraunfelder and Edwards, 2001). Therefore, the Physicians’ Desk Reference (PDR) for 2001 lists a warning about this in the package insert. This drug can cause blepharitis, meibomitis and atrophy of the meibomian gland (in animals, complete destruction) (Mathers et al., 1991) and can increase the risk of staphylococcus disease. Any or all of these conditions may decrease tear film break-up time and increase tear osmolality. Therefore, isotretinoin can probably cause a permanent, ‘evapo-rative’ form of sicca.

Isotretinoin is secreted in the tears, causing irrita-tive conjunctivitis, superficial punctate keratitis, drug deposits in the superficial cornea and decreased toler-ance for contact lens wear. Some sicca patients are made worse, or latent sicca becomes manifest. This photosensitizer can cause or significantly aggravate existing lid diseases, especially blepharitis. Other known side effects include acute myopia, papilledema secondary to pseudotumor cerebri and optic neuritis. Recently, isotretinoin has been identified as the prob-able cause of reversible color vision defects.

Guidelines for Following Patients

It is not practical to examine the eyes of every patient beginning therapy with these agents. However, if the patient is younger than 40 and has not had an eye examination in the past few years, or older than 40 and has not had one in 1–2 years, baseline exami-nation is appropriate. This is especially important if the patient has had any other ocular problems before starting therapy, both to prevent aggravation of the above conditions and to avoid having the drug unfairly blamed for latent ocular disease.

Explain risk–benefit ratio in patients with

•   Retinitis pigmentosa

•   Dystrophic or degenerative retinal disease

•   Severe or chronic blepharoconjunctivitis

•   Significant tear film abnormalities

•   Pre-existing night blindness

In select patients with anterior segment or retinal pathology, consider prescribing UV-blocking lenses as this drug is a photosensitizer. Consider discontin-uing the use or delaying the fitting of contact lenses during therapy. Patients taking isotretinoin long term should have annual eye examinations. Suggest more frequent visits if patients experience ocular irritation or vision changes or if any significant ocular signs or symptoms occur. If progressive or persistent night blindness occurs, consider stopping the drug. As many cases of night blindness are transitory, this condi-tion is not in itself a reason to discontinue therapy. However, if night blindness persists for many weeks, consider closer monitoring and possibly further test-ing, i.e. electroretinography, visual field testing and dark adaptometry testing.

Therapy should be stopped if any of the following occur:

•   Pseudotumor cerebri

•   Optic neuritis

•   Persistent night blindness

Permanent night blindness, permanent sicca and transitory loss of color vision only occur in patients on long-term chronic therapy and are indeed rare events.