I know what you’re thinking…your doctor has probably been wrong more than ten times. I agree, but there have been times when the standard of care across the country has changed on a dime, and physicians went from routinely prescribing a medication to learning it may not be helpful at all.
Here are ten notable “whoops” times.
- Hormone replacement therapy (HRT). For years, physicians were initiating HRT in postmenopausal women praising its protection against stroke and heart disease. Well, the data showed otherwise. Hormone replacement therapy is the best treatment for relief of hot flashes and night sweats, vaginal dryness, and may protect against bone loss early in menopause. The problem? Combined hormone therapy is also linked to a small increased risk of heart attack. Some research suggests that women who start combined therapy within 10 years of menopause and who are younger than 60 years, may get some protection, but HRT should not be used solely to protect against heart disease.
- Digoxin (Digitek or Lanoxin). The warnings here keep getting stronger, and this year we learned that in patients with atrial fibrillation without heart failure, Digoxin was significantly associated with sudden cardiac death. The association between Digoxin use and poor clinical outcomes highlights the need to examine its use, particularly when prescribed to control heart rate in patients with atrial fibrillation. There are newer safer options.
- Bisphosphonates. This class includes medications like alendronate (Fosamax) and ibandronate (Boniva), which are indicated for the treatment of osteoporosis. When they were first approved, physicians prescribed these medications to women who had early signs of bone loss or bone thinning to prevent osteoporosis. The problem? Bisphosphonates inhibit bone remodeling and reduce the bone repair process which can lead to fractures. While they are still used for the treatment of osteoporosis and help prevent hip and spine fractures, they are not indicated for those with just mild thinning or mild bone loss.
- NSAIDS. Naproxen, Motrin, and Advil were believed to be relatively safe and effective even when used long term. Now we know that anyone who is at risk for or who has cardiovascular disease (coronary artery disease) may have a further increase in the risk of heart attacks when taking an NSAID. Let me be clear though, short-term intermittent use is fine.
- Proton pump inhibitors (PPI). The long-term use of proton pump inhibitors is also gathering more worrisome data. Turns out, you should try not to take proton pump inhibitors long-term. Medications in this class include omeprazole, esomeprazole, and pantoprazole. While they work well for reflux, esophagitis, gastritis and ulcer disease, it now appears that PPI use can lead to a higher risk of stomach cancer. Additionally, long-term use can also lead to vitamin B12 deficiency, increased risk of c-diff diarrhea, and some bone loss.
- Steroids. Physicians used to prescribe oral steroids for everything from poison oak, itchy rashes, allergies and ear congestion. A Medrol dose pack or prednisone for less severe illnesses is not recommended. Studies suggest that even short courses of oral steroids are associated with adverse effects that should be considered before prescribing
- Niacin, Tricor and gemfibrozil. Up until last year, physicians were prescribing these in combination with the cholesterol-lowering meds “statins.” However this combination showed little benefit, and the two are not recommended by the FDA for co-administration. This move also affected Niacin, fenofibric acid, Advicor, and Simcor. The FDA determined that the benefits of these medications along with statins no longer outweigh the risks.
- Avastin (bevacizumab). This was another medication that had its FDA approval yanked. Used for metastatic breast cancer, FDA approval was revoked when it was not shown to provide a benefit in terms of delay in the growth of tumors. Nor is there evidence that use of Avastin helped women with breast cancer live longer or improve their quality of life. Depressing.
- Epogen (epoetin alpha). This injection is given to stimulate red cells. Up until 2011, we were using it for the treatment of anemia (low red blood cell count) in people with kidney disease. That was until a study showed that the use of Epogen in these patients was associated with a 30% increased risk of acute stroke. Ugh.
- Diet meds. There has not been a great track record for weight loss medications. Fen Phen many of you remember was pulled from the market in 1997 after contributing to pulmonary hypertension and heart valve disease. Much later came Meridia (Sibutramine) for weight loss which was pulled in 2010 due to increased risk of stroke and heart disease. So, there’s that.
Abnormal urine color can be distressing to patients and their physicians. But did you know that discolored urine is usually harmless and is often due to medications?
If your urine comes out as an odd color, don’t panic until you’ve reviewed this list.
Medications that cause orange urine
- Isoniazid is an antibiotic used for the treatment of tuberculosis.
- Sulfasalazine is an anti-inflammatory used for the treatment of rheumatoid arthritis and is also used in folks with ulcerative colitis.
- Riboflavin, also known as vitamin B2, is over the counter and included in many multivitamin formulations.
Medications that cause brown urine
- Metronidazole (Flagyl) is an antibiotic used to treat infections like c-diff diarrhea, bacterial vaginosis, and other gastrointestinal infections.
- Nitrofurantoin (Macrobid) is an antibiotic used for the treatment or prevention of urinary tract infection.
- Tylenol/Acetaminophen overdose may also cause brown urine.
Medications that cause blue or green urine
- Amitriptyline is a medication used to treat depression that may turn your urine blue or green.
- Cimetidine (Tagamet) is an acid blocker used for GERD (reflux) and heartburn symptoms.
- Indomethacin (Indocin) is an anti-inflammatory used for the treatment of Gout
- Zaleplon (Sonata) is an atypical benzodiazepine used as a sleep medication.
- Methocarbamol (Robaxin) is a good non-sedating muscle relaxant used for neck and back pain.
- Metoclopramide (Reglan) is a medication used to treat nausea.
- Oh, and Clorets breath mints. Random, but true.
Medications that cause red urine
- Warfarin (Coumadin) is a blood thinner used in patients with clots in the leg (DVT), atrial fibrillation, and for those who have had heart valve replacement.
- Rifampin is an antibiotic used for the treatment of tuberculosis and may be used as a second agent to treat folks with MRSA (methicillin-resistant staph aureus).
- Phenazopyridine (Azo, Pyridium) is over the counter and used for the pain related to urinary tract infections.
- Ibuprofen the nonsteroidal anti-inflammatory agent has been reported to cause red urine.
Many of the causes of abnormal urine color are benign effects of medications and foods. However, a change in urine color may be a sign of an underlying medical condition, so if it doesn’t go away when you stop your medication, see your doc.
More than one in ten visits to a primary care doctor is for fatigue. Fatigue is composed of three major components: generalized weakness (difficulty in initiating activities), easy fatigability (difficulty in completing activities), and mental fatigue (difficulty with concentration and memory). While certainly not the only answer, medications may cause fatigue. Here are some of the common culprits.
Beta-blockers wear many hats. They are commonly prescribed to improve survivability after a heart attack, lower blood pressure, help prevent a migraine headache, and control heart rate in atrial fibrillation. But, there is a downside. They can make you sleepy.
Carvedilol (Coreg), atenolol and metoprolol are common offenders when it comes to fatigue, occurring in more than 10% of people taking them. In fact, a quarter to half of the folks taking beta blockers discontinue their use during the first year of taking them, often for fatigue.
Pro tip, starting at low doses and titrating up will help with the fatigue so lower doses of beta blocker, increasing over time, is the way to go.
These are medications used for allergies, hives, nasal congestion, and itchy rashes. Benadryl, Atarax and cyproheptadine are all very sedating, and most available over-the-counter. Over the counter meds ending in ‘pm’ like Tylenol PM contain Benadryl and of course will cause drowsiness.
Many folks taking muscle relaxants for back or neck pain have no idea these may make them feel like Gumby for a few days. Commonly prescribed muscle relaxants cyclobenzaprine, Soma (carisoprodol) and Zanaflex (tizanidine) are hugely sedating.
Amitriptyline and Nortriptyline are also used to treat depression, chronic pain, and migraine and cause drowsiness and fatigue. In some studies, up to 40% of folks taking these two reported fatigue. That’s high.
Another good option? Studies have shown that bupropion SR and XL (Wellbutrin XL) are just as effective as SSRIs for the remission of major depressive symptoms. Those taking bupropion are less likely to suffer symptoms of sleepiness and fatigue than those treated with SSRIs.
Topiramate causes drowsiness and fatigue in up to 15% of people using it. Commonly used for prevention of seizures, migraine headache and weight loss (Qsymia contains topiramate), Topamax carried the nickname Dopamax because those taking it may feel ‘dopey.’
And last but not least
- Narcotics like hydrocodone, oxycodone, and acetaminophen/codeine may make you sleepy.
- Benzodiazepines like Ativan (lorazepam), Valium (diazepam) and Xanax (alprazolam) often cause you to feel sleepy.
Pattern of Adverse Drug Reactions Reported with Cardiovascular Drugs in a Tertiary Care Teaching Hospital. J Clin Diagn Res. 2015 Nov;9(11)
Discontinuation of beta-blockers in cardiovascular disease: UK primary care cohort study. International Journal of Cardiology Vol 167 (6) 10 Sept 2012 pages 2695-2699.
A glycated hemoglobin (HbA1c) is a preferred screening test for diabetes. Done easily with a fingerstick in your physician’s office, it eliminates the need for fasting (not eating) prior to the test. The diagnosis of diabetes is confirmed if two consecutive A1c levels are greater than or equal to 6.5.
What is the HbA1c?
Red blood cells are permeable to glucose (sugar)—so after they enter your circulation, glucose becomes attached to them. The degree to which your red cells become “sugar coated” depends on your blood glucose level. The A1c indicates the average blood sugar level over the lifespan of the red cell—and it lines up with average blood sugar over the previous 2 – 3 months.
Take home message here: your HbA1c will not be affected if you had pizza the night before, unlike a random blood sugar test. But because the A1c is influenced by the total life cycle of your red cells, the levels can be inaccurate in some folks.
Here are some times the HbA1c will not be helpful:
A1c falsely elevated (HIGH)
Your test may tell you that you have diabetes, but you don’t.
- Untreated anemia from iron deficiency or vitamin B12 and folate deficiency can result in a HbA1c value that is falsely high because your red cell turnover is low. Because you have more “older” red cells instead of making new ones (due to lack of iron, or other vitamins) your HbA1c will be higher than it should be.
- Kidney failure or chronic kidney disease. If you have abnormal kidney function your HbA1c may be falsely high.
- Very high triglycerides (over 1,750) may also cause a falsely elevated HbA1c.
- Splenectomy (spleen surgically removed) will give you a falsely elevated HbA1c, due to decreased red cell turnover. This is because the spleen can’t remove the red cells from the bloodstream—which is the spleen’s normal job.
A1c falsely decreased (LOWER)
Your test may show that you aren’t diabetic, but you are.
- Donating blood or major bleeding. HbA1c levels are likely to be underestimated after blood donation. Donating blood, or major bleeding puts the red blood cells in a hyperkinetic (overactive) state—which shortens the life of the red blood cell.
- Treated iron deficiency anemia or treated vitamin B12 deficiency anemia may lead to a falsely low A1c due to rapid turnover of the red blood cells during treatment. In other words, if you have iron deficiency and are taking iron supplements, your A1c may be falsely low—but if you just have iron deficiency anemia NOT on treatment it will be falsely high.
- Pregnancy. Through the first and second trimester of your pregnancy, the HbA1c may be falsely low due to decreased red blood cell lifespan.
- Vitamin E supplements. If you are taking high doses of vitamin E supplements, your HbA1c may be falsely low due to reduced glycation (less glucose attached to your red blood cells).
- Hemolysis. Folks with hemolysis (red cells being chewed up) have rapid cell turnover and falsely low A1c. Hemolysis from autoimmune diseases, medications (ribavirin, interferon-alpha), or genetic problems like hereditary spherocytosis limits the use of A1c as a diabetes screening test in these folks.
- Erythropoietin treatment (Epogen or Procrit) during chemotherapy or for profound iron deficiency anemia will cause a falsely low HbA1c level, again, due to more rapid cell turnover (more younger red cells).
Your A1c will be inaccurate either way (HIGH or LOW):
- Recent blood transfusion makes the A1c of limited use because transfusion does many things to the measurement, including diluting your red cells with someone else’s red cells. HbA1c results in a recently transfused person should be considered uninterpretable.
Well, what can I be tested with if I can’t do HbA1C?
Fructosamine. Diabetes specialists will check blood concentration of a protein called fructosamine to get a longer-term estimate of your glycemic/sugar control. This gives them a better idea of your sugar levels, over random or fasting blood glucose.
Most diarrhea will resolve within 24 to 48 hours—if it’s caused by viral gastroenteritis (a stomach bug) or food borne illness. If your diarrhea is hanging on and not resolving, take a look at your medications. It can be challenging to identify which medication may be causing drug-induced diarrhea, especially if you’re taking multiple medications. Here are some well-known offenders commonly associated with drug-induced diarrhea.
- Antibiotics are a big one. They are associated with 25% of the cases of medication induced diarrhea. Though all antibiotics can cause diarrhea, it is more common with amoxicillin (Amoxil, and also in Augmentin); cephalosporins like cephalexin (Keflex), cefaclor (Ceclor), and cefdinir (Omnicef); and clindamycin (Cleocin).
- Metformin (Glucophage) is used to treat diabetes. It has a number of actions within the gut that may lead to diarrhea—which should resolve a few days after taking it. Pro tip: the extended release metformin (metformin ER, Glucophage XR) has fewer gastrointestinal effects than the regular release.
- Antidepressants. Diarrhea is a common side effect with certain kinds of antidepressants. The incidence of diarrhea is highest for sertraline (Zoloft) at 14%, followed by paroxetine (Paxil) at 8%. For other SSRI antidepressants like fluoxetine (Prozac), diarrhea occurs in 7% of folks taking it.
- Beta blockers are medications that end in -ol used for the treatment of heart disease and high blood pressure. Common examples are metoprolol, atenolol, and carvedilol, where diarrhea is a known side effect in the first week of use. Diarrhea is seen in up to 12% of folks taking carvedilol.
- ACE inhibitors and angiotensin receptor blockers (ARBS) are used to treat high blood pressure and heart failure, and all have diarrhea as a reported side effect. The ARB olmesartan (Benicar, Azor) is the biggest offender in this class of drugs and diarrhea can be severe and long lasting while you’re taking it. Others include ACE inhibitors lisinopril, benazepril, and enalapril, and ARBs losartan, irbesartan, and valsartan.
- Stomach meds. H2 “acid” blockers like cimetidine (Tagamet) and ranitidine (Zantac), along with the proton pump inhibitors (PPIs) like omeprazole (Prilosec), pantoprazole (Protonix), and esomeprazole (Nexium) may cause diarrhea because they inhibit gastric acid secretion in the gut (they decrease the amount of stomach acid).
- Digoxin is a medication used to control heart rate for people with atrial fibrillation. Digoxin inhibits ATPase, which affects the energy for the pump that regulates water and electrolyte transport, which may lead to diarrhea in folks taking it.
- Colchicine for gout is a common cause of diarrhea and abdominal pain, shortly after taking it. The cause of the diarrhea here is similar to digoxin where ATPase—the same enzyme inhibited by colchicine—affects water and electrolyte balance in the gut.
- Lithium. Diarrhea from Lithium usually occurs in the first 6 months of treatment and is seen in up to 10% of lithium-treated folks. Higher blood lithium levels (greater than 0.8 mEq/l) are associated with higher rates of diarrhea. Pro tip here is that rates of diarrhea are higher with sustained release lithium (lithium ER or Lithobid) than regular lithium.
- Levothyroxine (Synthroid) is synthetic thyroid hormone used for the treatment of hypothyroidism. Some studies suggest levothyroxine and Synthroid may disrupt the gut flora, causing small bowel bacterial overgrowth and potentially diarrhea. The tricky thing here is to make sure you are not over-replaced (hyperthyroid) with too high of a dose leading to diarrhea.
- Gemfibrozil (Lopid) and fenofibrate (Tricor) are used to lower triglycerides and raise HDL (the “good” cholesterol), and may lead to diarrhea by causing increased breakdown of fats.
- Magnesium-containing antacids like Maalox, Mylanta, and Gaviscon cause diarrhea. Magnesium is an “osmotic” agent so it sucks water into the gut which may lead to diarrhea.
- Vitamins like magnesium and vitamin C both pull water into the gut (they are osmotic agents), which may result in diarrhea.
- NSAIDs like ibuprofen (Advil, Motrin) and naproxen (Aleve) may cause both constipation and diarrhea.
The diagnosis of medication-induced diarrhea often relies on the absence of other obvious causes or the rapid disappearance of the diarrhea after stopping the suspected drug. Worth looking at . . .