10 of the Most Unusual Medication Side Effects You Should Know About

Most people benefit from the therapeutic effects of medications, but adverse effects — commonly known as side effects — are always possible. Some of these side effects are common and expected. But others are more rare and not as well known to the average person. 

Below are 10 unusual reactions to medications, which you may not have heard about before but are worth knowing about. 

1. Toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a life-threatening skin reaction. By definition, TEN covers more than 30% of the body’s surface. It usually starts with fever, body aches, and other flu-like symptoms. A few days later, you’ll likely develop a painful rash in certain areas of the body, and your skin may start to blister and peel. 

Medications are the most common cause of TEN. Examples of medications that can cause this rare but serious condition are:

• Antibiotics like sulfa antibiotics, penicillins, and quinolones

• Seizure medications, such as carbamazepine (Tegretol, Tegretol XR), phenytoin (Dilantin, Phenytek), and lamotrigine (Lamictal)

• Piroxicam (Feldene)

• Allopurinol (Zyloprim)

• Oseltamivir (Tamiflu)

Treating TEN involves stopping the offending medication immediately and getting supportive care in an emergency setting until skin can recover. Supportive care can include IV fluids, pain management, and wound treatment. 

2. Stevens-Johnson syndrome

Stevens-Johnson syndrome (SJS) is another rare but serious skin condition. It’s less severe than TEN, but it can still be life-threatening. Like TEN, SJS usually starts with flu-like symptoms, which are followed by the appearance of a rash a few days later. The rash may evolve into blisters that erupt and cause the skin to start peeling. 

But SJS involves less than 10% of a person’s skin surface area, compared to 30% with TEN. The same medications that can cause TEN can cause SJS.

Like with TEN, the first step in treating SJS is to stop the medication that is thought to be causing it. You’ll likely also need to go to the hospital to receive IV fluids and other supportive care measures.

3. Hand-foot syndrome

Hand-foot syndrome is a side effect of some cancer medications that target blood vessels, including those in the hands and feet. These medications can leak out of the blood vessels and damage the surrounding tissues, causing the condition. 

This side effect usually presents as redness, swelling, and pain on the palms of the hands or soles of the feet. You may experience blisters in these areas, as well. Other symptoms include a tingling feeling, sensitivity to touch, and difficulty walking or using your hands.

Examples of medications that can cause hand-foot syndrome are:

• Capecitabine (Xeloda)

• Docetaxel (Taxotere)

• Doxorubicin

• Fluorouracil

• Axitinib (Inlyta)

• Sorafenib (Nexavar)

• Sunitinib (Sutent)

• Pazopanib (Votrient)

If you notice symptoms of hand-foot syndrome, try to avoid letting the affected areas come into contact with any heat. This is especially important when it comes to using hot water while bathing or doing dishes. And avoid putting any pressure on the affected areas. For example, avoid walking barefoot if you have a rash on the soles of your feet.

4. Nerve damage

Several medications are known to cause nerve damage (neuropathy). Common symptoms of neuropathy include sensitivity to touch, numbness, and tingling. Muscle weakness and muscle loss can also occur. 

Medications that may cause neuropathy include:

• Certain heart and blood pressure medications, such as amiodarone (Pacerone) and hydralazine

• Chemotherapy medications, such as docetaxel, cisplatin, and vincristine

• Antibiotics, such as metronidazole (Flagyl), nitrofurantoin (Macrobid), and isoniazid

• Biologic medications like infliximab (Remicade) and etanercept (Enbrel)

• Seizure medications like phenytoin and carbamazepine

• HIV antiretroviral medications like stavudine and those containing emtricitabine, such as Truvada (emtricitabine/tenofovir disoproxil fumarate)

• Colchicine (Colcrys)

• Disulfiram

If you have nerve pain or damage that is being caused by medication, stopping the medication often improves symptoms. If that isn’t an option, your healthcare provider may be able to safely lower your dose to help improve symptoms. Unfortunately, in some cases, damage from neuropathy isn’t reversible.  

If you have neuropathy, your provider may also recommend that you take certain seizure medications, including gabapentin, or tricyclic antidepressants (TCAs) for pain. 

5. Loss of smell

Whether it’s temporary or permanent, loss of smell (anosmia) can have a big impact on a person’s quality of life. And certain medications may be the cause, including:

• Blood pressure medications, such as enalapril (Vasotec), diltiazem (Cardizem), and amlodipine (Norvasc)

• Antibiotics, such as azithromycin (Zithromax), amoxicillin (Amoxil), and ciprofloxacin (Cipro)

• Cholesterol medications like atorvastatin (Lipitor) and lovastatin

• Levothyroxine (Synthroid, Euthyrox)

If you think one of your medications is causing you to lose the ability to smell, talk to your healthcare provider. They may be able to prescribe an alternative.

6. Priapism

A rare side effect of some medications is a painful, prolonged erection that lasts for more than 4 hours, known as priapism. This condition is a potential side effect of:

• Antidepressants like trazodone and bupropion (Wellbutrin XR, Wellbutrin SR)

• Antipsychotics like clozapine (Clozaril) and chlorpromazine 

• Testosterone

• Prazosin (Minipress)

• Warfarin (Coumadin, Jantoven)

• Medications for ADHD (attention-deficit hyperactivity disorder) like methylphenidate (Ritalin)

Priapism is a medical emergency because it can lead to permanent damage if not treated. If you have a painful erection, or an erection that lasts 4 hours or longer, seek emergency care immediately. 

7. Unusual impulsive behavior

Some medications can cause changes in behavior. In rare and severe cases, medications can cause intense sexual or gambling urges or unusual impulses to spend money or binge eat. 

Some examples of medications that can cause behavioral changes are:

• Ropinirole 

• Aripiprazole (Abilify)

• Sinemet (carbidopa/levodopa)

• Amantadine (Gocovri)

If you notice any new urges or impulsive behaviors after starting a medication, talk to your healthcare provider immediately.

8. Abnormal dreams

Medications can affect your dreams — and not always in a good way. Some medications have the ability to cause nightmares or vivid dreams. Examples of these medications are:

• Dopamine agonists like cabergoline and Sinemet

• Beta blockers like labetalol (Trandate) and propranolol (Inderal LA)

• Some antidepressants, including venlafaxine (Effexor XR)

• Donepezil (Aricept)

• An allergy medication called montelukast (Singulair)

• Smoking-cessation products like varenicline (Chantix) and nicotine patches (Nicoderm CQ)

If you experience nightmares or bothersome dreams after taking medication, talk to your healthcare provider. In some cases, it may help to take the medication in the morning instead of at night. But don’t make adjustments without talking to your provider first.

9. Akathisia

Akathisia is the inability to be still, whether sitting or standing. It causes feelings of unease and inner restlessness. 

Akathisia is most commonly associated with antipsychotic medications like haloperidol (Haldol), ziprasidone (Geodon), and aripiprazole. But it may also occur with anti-nausea medications like prochlorperazine and metoclopramide (Reglan).

Medication-related akathisia can be treated by lowering the dose of the medication or switching to an alternative. Some medications, like propranolol, may be able to help treat akathisia. But there’s not a large amount of research to support this.

10. Onycholysis

Onycholysis is when fingernails or toenails separate from the nail bed. It can lead to infections under the nail, which can cause more serious damage if not treated. 

Certain medications can cause onycholysis, including:

• Tetracycline antibiotics like tetracycline

• Fluoroquinolone antibiotics like ciprofloxacin

• Nonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen (Aleve, Naprosyn)

• Taxanes, a class of chemotherapy medications, such as paclitaxel

Onycholysis can be reversed even without stopping the offending medication in some cases. Clipping the unattached nail, keeping the nail area dry, and trimming the nails daily until they start to reattach are all ways to prevent infection — and permanent damage — from onycholysis.

Why trust our experts?

Written by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Edited by:

Samvida Patel, MNSP, INHC

Samvida Patel, MNSP, INHC, is a health editor at GoodRx. She is a nutritionist and integrative nutrition health coach with over 8 years of experience in health communications.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Our editorial standards

Meet our experts