Modafinil and Stevens-Johnson Syndrome 101

The company that first released modafinil, Cephalon Inc, lists Stevens Johnson Syndrome as a possible adverse reaction to the medication.

During a clinical trial, one patient was reported to have developed the condition.

Since this time, there have been no documented cases of the condition in response to modafinil. Nevertheless, the severity of this allergic reaction makes it important to know and understand the early signs and symptoms.

Here, we share some tips and tricks to make sure it doesn’t happen to you.

What is Stevens Johnson syndrome? How significant is it? What are my chances of developing it?

What is Modafinil?

Modafinil is a prescription medication prescribed in the treatment of narcolepsy and other sleep disorders.

It tells the brain to enter a state of wakefulness and vigilance. This has made it useful amongst students and highly productive individuals to further enhance their work efforts.

Modafinil essentially works to increase the quality of the working hours available in the day by delaying the onset of fatigue. When people take modafinil, they can easily churn out a dozen hours of non-stop work.

This makes it great for people who have a deadline coming up and need an extra boost in their productivity to get the project done. Others take it while they cram late into the evening for a tough exam.

Unlike popular “study drugs” such as Adderall and Concerta, modafinil has the added benefit of boosting dopamine levels in the brain.

This neurotransmitter is often found in low concentrations in people with difficulty focusing. It’s a common finding in people who have ADD or ADHD.

By increasing dopamine concentrations, modafinil can help boost our ability to focus on one task at a time without becoming so easily distracted or unmotivated.

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Modafinil is an excellent product; it really helps give me an extra boost when working two jobs; one late night job. It also helps my mood and overall well being. No side effects, works like a charm.

Where to Buy Modafinil

There are a few ways you can obtain some modafinil for yourself.

You can go to the doctor and get a prescription, however, you’ll need to have a valid reason before they prescribe it.

The second option is to buy your modafinil from an online vendor like ModafinilXL.com.

These sources offer modafinil ready for delivery without the need for a prescription.

Even people with valid prescriptions often use this method because it can save them thousands of dollars per year compared to local pharmacies. This is made possible by selling generic versions of the drug, which usually cost between $0.80 and $2.80 per tablet.

Conversely, brand names like Provigil or Nuvigil can cost between $30 and $50 per tablet.

What is Stevens-Johnson Syndrome?

Now that we’re familiar with WHY someone would use modafinil let’s go over Stevens Johnson Syndrome and how it’s connected to modafinil use.

Stevens Johnson syndrome (SJS) is a severe allergic skin reaction.

Early symptoms are flu-like, causing fever, burning eyes, sore throat, and body aches. The skin sometimes starts to burn a day or two after the condition begins developing [3].

Eventually, symptoms increase in severity to include skin ulcers and a painful rash spreading all over the body.

The rash covers the skin in blisters and can be very painful.

The ulcers start to form around the mucous membranes, almost always involving the mouth and tongue. This can make it extremely difficult for sufferers to eat and drink due to the pain involved with the ulcer formation.

The genital regions also develop similar ulcers around the same time.

What Causes Stevens Johnson Syndrome?

Stevens Johnson Syndrome is thought to be the result of immune system dysfunction. It’s an allergic reaction to certain medications or infectious organisms.

It’s considered a type IV hypersensitivity reaction, which means that it’s a delayed allergic reaction. These types of allergies can take several days to develop completely.

Symptoms usually start to show up about 4 to 28 days after initial exposure to the causative agent. This makes it particularly challenging to determine what triggered the condition.

Compared to other forms of allergies, type IV reactions don’t involve antibodies, which are the more common cause of allergic symptoms.

When someone is experiencing an allergic reaction to bee stings or peanuts, the symptoms that result are caused by an allergic antibody-mediated response.

Instead, Stevens Johnson Syndrome involves an issue with the cells themselves. They release chemical messengers that cause widespread destruction throughout the skin tissue.

The most common causes of this condition are medications [4]. As many as 100–200 different medications are associated with Stevens Johnson Syndrome [6].

Some common culprits include:

• Lamotrigine (Anticonvulsant)
• Tetracycline (Antibiotic)
• Carbamazepine (Anticonvulsant)
• Allopurinol (Anti-Gout medication)
• Barbiturates (Anxiolytics)
• Sulfonamide antibiotics (Antibiotic)
• Nevirapine (HIV medication)
• Modafinil (Narcolepsy medication)

See a complete list of drugs that have been connected to Stevens Johnson Syndrome.

Other causes for this condition include infection of Mycoplasma pneumonia or cytomegalovirus [1].

In many cases (roughly half of all cases), the cause is not determined.

Some factors can help predict the chances of developing the condition. This includes a few genetic links that researchers have made recently that can be used to help identify people who may develop this condition.

People who have autoimmune conditions (like multiple sclerosis, systemic lupus erythematosus, or asthma) or HIV are also at a much higher risk of developing the condition.

Is it Dangerous?

There are some complications that can arise from Stevens-Johnson syndrome, including dehydration, infections, pneumonia, and organ failure.

The death rate associated with it is about 5–10%.

In most cases, the skin will stop blistering and regrow as normal over a few months.

How Common Is Stevens Johnson Syndrome?

Luckily, Stevens Johnson syndrome is very rare, only affecting about 1 or 2 people per million. [2].

People at a Higher Risk of Developing this Condition Includes:

• Males (roughly twice as common as females) [1]
• People of Han Chinese origin
• People of Thai origin
• People suffering from an autoimmune disease
• HIV patients

Some tests can be done for some of these populations to determine risk (HLA-B*15:02 and CYP2C9*3 genetic testing).

Countries like Singapore, Hong Kong, Taiwan, mainland China, and Thailand are now performing genetic screening before placing people on at-risk drugs like modafinil or certain antibiotics.

How is Stevens Johnson Syndrome Treated?

Treatment for Stevens Johnson syndrome typically requires hospitalization.

Patients are placed in a specialty unit— like a burn unit or intensive care unit— and given symptomatic treatment for pain and to prevent secondary infection.

Antihistamines, antibiotics, immunoglobulin therapy, and pain medications are all used over the next couple of weeks until the condition starts to improve.

If the causative agent is identified and removed before rashes and blistering appear, it’s possible to avoid most of the symptoms of Stevens Johnson syndrome before hospitalization is required.

It can take as long as three months for treatment to conclude.

How to Prevent Stevens Johnson Syndrome

Although Stevens Johnson syndrome is extremely rare, there are a few things you can do to prevent the condition before it develops.

1. Risk Assessment

The best way to avoid the condition is to assess risk properly.

If you have HIV or any autoimmune conditions, it’s important to first speak with your doctor before trying modafinil, or any of the other drugs associated with risk of Stevens Johnson Syndrome.

Beyond this, there are some genetic tests available that researchers have identified as being a marker for the development of Stevens Johnson syndrome.

In East Asian populations, the best method is to test for a genetic variant called HLA-B*15:02 [7].

In Caucasians, a slightly different marker is investigated called HLA-B*57:01  or HLA-B*58:01 [7].

These markers can provide a good indication of the level of risk a person has for developing the condition before it happens.

Learn more about these tests here.

2. Start Small with Modafinil

If the symptoms of Stevens Johnson Syndrome are identified early (burning eyes, flu-like symptoms, fever, itchy skin), and you stop taking the medication, you can prevent the worst of the condition from ever developing.

For this reason, it’s recommended that you start with a smaller dose of modafinil if you’re trying it for the first time before gradually increasing the dose.

As soon as any symptoms of Stevens Johnson Syndrome present, stop taking the medication.

It’s recommended that you start with a dose of about 100mg modafinil for the first few days, then increasing to 200 mg or 400 mg per day depending on how you feel.

It’s also recommended that you don’t take modafinil every day for the first week.

Instead, try taking it every second day or less and then building up from there after you know how it affects you and how you tolerate it.

Should I Be Worried About Stevens Johnson Syndrome?

Although Stevens-Johnson syndrome is a very severe condition it’s unlikely to develop.

Unless you have a predisposing factor like an autoimmune disease, HIV, or have a specific genetic predisposing factor, you are more than likely NOT going to experience Stevens-Johnson syndrome.

If this is something that you are worried about and is preventing you from trying modafinil, speak with your doctor. They may be able to get you genetic testing that can screen for known genetic variations associated with the condition.

Remember, Stevens Johnson Syndrome comes on gradually, so you will need to wait several days before you know for sure if you’re completely free from risk.

 

References

1. Sartaj, S., & Swamy, A. (2018). Study of Stevens-Johnson syndrome. IJASRE, 4.
2. Dodiuk-Gad, R. P., Chung, W. H., Valeyrie-Allanore, L., & Shear, N. H. (2015). Stevens–Johnson syndrome and toxic epidermal necrolysis: an update. American journal of clinical dermatology, 16(6), 475-493.
3. Maverakis, E., Wang, E. A., Shinkai, K., Mahasirimongkol, S., Margolis, D. J., Avigan, M., … & Shear, N. H. (2017). Stevens-Johnson Syndrome and toxic epidermal necrolysis standard reporting and evaluation guidelines: results of a National Institutes of Health working group. JAMA dermatology, 153(6), 587-592.
4. Mockenhaupt, M., Bastuji-Garin, Salopek, Auquier-Dunant, Rzany, Ziemer, … & Rzany. (2011). The current understanding of Stevens–Johnson syndrome and toxic epidermal necrolysis. Expert review of clinical immunology, 7(6), 803-815.
5. Cephalon, Inc. (2017). Provigil prescribing information.
6. Cooper, K. L. (2012). Drug reaction, skin care, skin loss. Critical care nurse, 32(4), 52-59.
7. He, X. J., Jian, L. Y., He, X. L., Wu, Y., Xu, Y. Y., Sun, X. J., … & Zhao, L. M. (2013). Association between the HLA-B* 15: 02 allele and carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han individuals of northeastern China. Pharmacological Reports, 65(5), 1256-1262.