48. Keeping comfortable on isotretinoin

Doctor Jacob here today, and we're talking about keeping comfortable on isotretinoin. We're going to be talking about safety and side effects. If you haven't had a chance already, be sure and catch the previous episode in which we introduce isotretinoin.

This drug isotretinoin causes severe birth defects in women who become pregnant while taking this medication. It can cause both spontaneous abortions, as well as birth defects. The birth defects are severe and include skull and face malformations, problems with the heart, problems with the thymus and brain defects.

Children born to a mother taking isotretinoin who appear physically normal at birth may still have a higher rate of mental retardation and lower IQs. Fetal abnormalities have not been attributed to the use of isotretinoin in men, therefore men can safely father children while taking this medication.
Once women have stopped therapy for at least 30 days, a woman may then safely conceive with no additional risk of birth defects above the average level of risk. Despite stringent rules in the United States intended to prevent pregnancy with isotretinoin, certain women taking isotretinoin still become pregnant. Therefore, in 2006 the Food and Drug Administration of the USA established a computer-based risk management program to eliminate fetal exposure to isotretinoin, formally known as iPLEDGE. Prescribers, pharmacies and all patients receiving isotretinoin are required to comply with this registry. A detailed overview of the iPLEGE program will be discussed in a separate episode. Patients in other countries outside the United States may have additional government restrictions on their medications.

Now let's talk about side effects. Isotretinoin works for acne by shrinking the oil glands and increasing the rate of transit of cells through the epidermis. Almost all patients taking isotretinoin experience dry lips. An ointment like Aquaphor applied every couple hours, as well as right at bedtime before sleep makes this very tolerable. Lip dryness tends to increase with increasing doses, and many people breathing through their mouths at night while sleeping may also benefit from a humidifier placed near the bed. If the chore of applying the lip ointment becomes neglected, cracking can occur of the lips, as well as at the corners of the mouth. This crack can then be infected with a bacteria called staphylococcus aureus, leading to symptoms of irritation, pain and crusting. At that point you will need some prescription medication from your dermatologist such as Mupirocin ointment applied 4 to 6 times a day to the cracked areas, especially at the corners and especially applied before sleep. After one week the condition clears up. To prevent this from happening, diligent and frequent application of an ointment such as Aquaphor several times a day is needed.

Sometimes dry skin can result as well, in addition to dry lips, particularly at the face. A mild lotion such as Cetaphil lotion or Aveeno lotion is typically sufficient should dry skin occur. Only mild soaps or cleansers should be used. I recommend avoiding harsh soaps and medicated soaps and scrubs. Particularly avoid benzoyl peroxide based, salicylic acid based and glycolic acid based cleansers.

Occasionally the skin on the hands, forearms or arms becomes dry to the point that an itchy rash called eczema occurs. If this happens let your dermatologist know, as prescription-strength cortisone creams can help. Moisturizing with a thicker moisturizing cream after every shower or bath, such as Eucerin cream, Vanicream or CeraVe cream can really help control this problem.

Eyes can become dry, and it's more noticeable if a patient already has pre-existing dry eyes. Lubricating drops such as artificial tears are very helpful.

So if that wasn't enough, the inner lining of the nose can also become dry during isotretinoin therapy. If the dryness progresses, nose bleeds can occur due to cracks in the nasal lining. However, nose bleeds are easily prevented. Firstly, a small amount of ointment such as Aquaphor ointment is applied to the pinky finger, meaning the fifth finger, and inserted up the nose into the nostril. The ointment is then spread as the finger is rotated over the nasal lining, and this is done upon waking and before sleeping in each nostril. Secondly, a humidifier placed near the bed will help. If these are done, nose bleeds should not occur.

The skin may sunburn more easily during isotretinoin therapy, especially for fair-skinned individuals, or those people living in sunny areas. Sunscreen should be used regularly and reapplied every two hours as needed for continuous sun exposure. Sun protective clothing such as a hat is also very useful during isotretinoin therapy.

The skin doesn't heal as quickly and is more fragile while taking isotretinoin, because it thins out the skin. This effect goes away after isotretinoin therapy is completed, therefore waxing for hair removal is best avoided during isotretinoin therapy. Avoidance of elective surgery, dermabrasion procedures, chemical peels and laser treatments is also very wise for three to four months after stopping isotretinoin.

So we talked a lot about the effects of isotretinoin on the skin and mucus membranes. One final thought for patients who are very constipated while taking isotretinoin - the straining to pass stools through the rectum or very hard stools can sometimes cause rectal bleeding on isotretinoin. This is easily fixed by taking dietary fiber supplements or stool softeners.

As you might recall, we mentioned a problem called inflammatory bowel disease when we were talking about antianaerobic antibiotics such as full-strength doxycycline or minocycline. There has been some association of inflammatory bowel disease with isotretinoin, but I'll tell you why, and the association is not causative. I'll repeat that one more time - isotretinoin does not cause or induce inflammatory bowel disease. Many patients who get to taking isotretinoin had previously been treated with multiple courses of antianaerobic antibiotics such as doxycyline and minocycline, which through mechanisms we've already discussed in prior episodes, increase the risk of this serious intestinal problem. However, the actual increase of the risk seen in patients who have taken isotretinoin is typically attributed to the multiple courses of antibiotics taken prior in many patients' cases to starting isotretinoin. Symptoms would include abdominal pain, loose stools, blood in the stools, and unintended weight loss. If you are experiencing any of these symptoms, please consult your physician.

Next let's talk about depression and potentially suicide. Concerns of depression have been raised in association with isotretinoin. Studies have concluded that data on suicidal behavior and depression during treatment with isotretinoin are inadequate to establish causal relationships. Some doctors have proposed that psychological distress over severe acne rather than isotretinoin could be a contributing factor to suicide or depression in patients with this drug. More studies are needed to determine if there is a cause and effect relationship between isotretinoin and depression or suicide.

Based upon my clinical experience, high daily doses of isotretinoin can increase the chance of developing depressed mood, which is ameliorated by decreasing the daily dose to 10 or 20 mg daily. However, the risk of developing depressed mood even while taking high daily doses is low. The vast majority of patients are elated with the acne's improvement.

Patients should keep in mind that although isotretinoin improves acne, other aspects of their lives typically will not change. Stated in another way, the only aspect of life that isotretinoin improves is acne. For teenagers, this means that isotretinoin will not necessarily help to get the boyfriend or girlfriend or prom date of your dreams, the summer job that you want... It only fixes acne.

Also, this drug does not fix acne scarring. Scarring can be treated, but that's a separate discussion. Patients with active depression, bipolar disorder, schizoaffective disorder, or other psychiatric disorders should specifically discuss the state of their condition with their dermatologist. Typically, a therapist, counselor, psychologist or psychiatrist can be involved in monitoring the patient's condition during isotretinoin therapy.

If you feel depressed or suicidal thoughts during treatment with isotretinoin, discontinue the medication immediately and contact your dermatologist.

Other side effects can occur, but are not serious. Muscle aches can occur in patients taking isotretinoin, particularly those who engage in vigorous physical activity during the first few months. Reducing the vigor will cure this issue.

Liver damage may occur infrequently, but is more common if alcohol is used. Your dermatologist will monitor blood work for liver damage periodically while taking isotretinoin. Alcohol use should be limited to one or fewer drinks daily for patients who are of drinking age. Having more than a drink a day is not permitted. If your dermatologist discovers laboratory evidence of liver damage, he or she may temporarily or permanently discontinue your isotretinoin therapy.

Next, let's talk about high triglycerides. Triglycerides are a type of fat floating around in the blood. Elevation of triglycerides occurs in about 45% of patients on isotretinoin therapy. Elevation of cholesterol is also seen in a similar fraction. These elevations are transient in about 80% of the patients, and are rarely severe enough to require terminating therapy. Your doctor will monitor your blood tests periodically while you take this medicine. It's been shown that patients who develop high triglycerides while taking this medicine are at an increased risk for developing metabolic syndrome, which is a syndrome that includes obesity and type II diabetes.

Generally, people who are more heavy set, in my experience, have a higher than average risk of developing increased triglycerides while on this medication. Rarely, isotretinoin can cause high fluid pressure within the brain, called pseudotumor cerebri. Obese female patients are the most at risk.

Hormonal contraception, a.k.a. birth control also increases the risk of developing pseudotumor cerebri, as do tetracycline-type antibiotics. The symptom is severe and persistent headache. Some people say it's the worst, right behind the eyes. There may be short periods of vision loss, and this can happen in one or both eyes. They usually last a few seconds and might happen once in a while or several times a day. In rare cases, people with this condition can lose their vision forever.

If you experience severe headache or vision changes while taking isotretinoin, stop the medication immediately, contact your dermatologist and seek emergency care.

For patients taking more than two courses of isotretinoin, loss of bone density can be a problem. If a patient is going to embark upon a third course of isotretinoin, I will typically check a bone density test called DXA. This will allow me to monitor the patient's bone density relative to its baseline in the future, as the patient takes additional courses of isotretinoin.

I don't recommend taking supplemental vitamin A while you take isotretinoin. Isotretinoin is already a derivative of vitamin A and I think it's too much for the liver to process. That being said, eating carrots or foods that are high in vitamin A should not be a problem.

That's all for today. I'm Doctor Jacob, we'll see you next time.