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Potassium Increases Due to Drug Interactions Can Be Dangerous

Worst Pills, Best Pills Newsletter article November, 2008

One of the most common drug interactions occurs when patients take two or more drugs that can each increase blood potassium levels. The resulting condition, hyperkalemia (increased blood potassium levels), can cause nausea, fatigue, muscle weakness or tingling sensations, as well as heart abnormalities, showing up as an abnormal electrocardiogram. In some cases it can be fatal. If you are taking any combination of the drugs discussed below (and listed in the accompanying table), it is...

One of the most common drug interactions occurs when patients take two or more drugs that can each increase blood potassium levels. The resulting condition, hyperkalemia (increased blood potassium levels), can cause nausea, fatigue, muscle weakness or tingling sensations, as well as heart abnormalities, showing up as an abnormal electrocardiogram. In some cases it can be fatal. If you are taking any combination of the drugs discussed below (and listed in the accompanying table), it is important to monitor potassium levels at appropriate intervals to detect problems early. 

Who is at greater risk of excessive blood potassium?

Most of the people who have developed severe hyperkalemia due to drug interactions have had one or more of the following risk factors:

Diseases. Diabetes appears to be a significant risk factor for hyperkalemia from drug interactions. Reduced kidney function due to other factors such as dehydration or worsening heart failure also appears to be a risk factor. Because patients with diabetes are more prone to develop kidney problems, they may have a double whammy.

Age. Because most people taking these combinations of drugs are older, it is difficult to sort out whether age itself is a risk factor, but there is a normal age-related decrease in kidney function. Most patients who develop severe hyperkalemia from these drugs are elderly.

Elevated Spironolactone Dose. People taking larger doses of the diuretic spironolactone (ALDACTONE, 50 milligrams a day or more), especially if they are also using one of the other drugs discussed below, appear to be at increased risk of hyperkalemia. 

Other Drugs. While diuretics such as furosemide (LASIX) tend to decrease blood potassium, other drugs such as potassium-retaining diuretics, ACE inhibitors (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin receptor blockers) tend to increase potassium.

Many patients with heart failure are treated concurrently with a potassiumretaining diuretic such as spironolactone along with an ACE inhibitor or an ARB. Patients with hypertension and other cardiovascular diseases may also receive such combinations. Because of this, it may be necessary to monitor for alterations in blood potassium concentrations.

In patients taking a potassium-retaining diuretic or an ACE inhibitor or ARB, the presence of other drugs that also increase potassium levels can increase the risk: potassium supplements, non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors, trimethoprim and some beta-blockers.

In a subsequent issue of Worst Pills, Best Pills News we will discuss individual drugs that can cause hyperkalemia but here, because severe hyperkalemia is usually much worse and more common with these interactions, we limit the discussion to drugs that are the most common culprits when used in combination. 

What You Can Do

If you are taking these drug combinations:

• Be careful if you have risk factors. If you have diabetes or kidney disease you are at increased risk, so your doctor will have to weigh the risk of giving you these combinations. Also, the older you are, the more likely you are to develop hyperkalemia.

• Make sure you are receiving appropriate laboratory monitoring. Serum potassium and kidney function should be followed when taking these combinations. Of course, the intensity of monitoring will be different in different people, because some people are at high risk and others are at low risk.

• Avoid excessive drug doses. People should receive the lowest effective doses of the drugs. Excessive doses of spironolactone increase the risk hyperkalemia, and this probably applies to other drugs as well.

 

 Potassium-Retaining Diuretics
 eplerenone (INSPRA)***
 spironolactone (ALDACTONE)**
 triamterene (DYRENIUM)*
 Angiotensin-Converting Enzyme Inhibitors (ACE inhibitors)
 benazepril (ETHEX, LOTENSIN)**
 captopril (CAPOTEN)**
 enalapril (VASOTEC)**
 fosinopril (MONOPRIL)**
 lisinopril (PRINIVIL, ZESTRIL)**
 moexipril (UNIVASC)**
 quinapril (ACCUPRIL)
 ramipril (ALTACE)**
 trandolapril (MAVIK)**
 Angiotensin Receptor Blockers (ARBs)
 candesartan (ATACAND)**
 eprosartan (TEVETEN)**
 irbesartan (AVAPRO)**
 losartan (COZAAR)**
 olmesartan (BENICAR)***
 telmisartan (MICARDIS)**
 valsartan (DIOVAN)**
 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
 buffered aspirin (ASCRIPTIN, BUFFERIN)*
 celecoxib (CELEBREX)*
 diclofenac (VOLTAREN)**
 diflunisal (DOLOBID)*
 etodolac (LODINE)**
 fenoprofen (NALFON)**
 flurbiprofen (ANSAID, OCUFEN)
 ibuprofen (ADVIL, MEDIPREN, MOTRIN, NUPRIN)
 indomethacin (INDOCIN)*
 ketoprofen (ORUDIS)
 ketorolac (TORADOL)*
 meclofenamate (MECLOMEN)**
 mefenamic acid (PONSTEL)**
 meloxicam (MOBIC)*
 nabumetone (RELAFEN)**
 naproxen (ALEVE, ANAPROX, NAPROSYN)
 oxaprozin (DAYPRO)**
 piroxicam (FELDENE)*
 rofecoxib (VIOXX)*
 salsalate (DISALCID)*
 sulindac (CLINORIL)**
 tolmetin (TOLECTIN)**
 valdecoxib (BEXTRA)*
 Other Drugs
 potassium supplements
 levobunolol (BETAGAN)
 nadolol (CORGARD)
 pindolol (VISKEN)
 propranolol (INDERAL LA, INDERAL)
 sotalol (BETAPACE)
 timolol (BLOCADREN, TIMOPTIC)
 trimethoprim (PROLOPRIM, TRIMPEX)

* Do Not Use in Worst Pills, Best Pills
** Limited Use in Worst Pills, Best Pills
*** Do Not Use for Seven Years in Worst Pills, Best Pills – eplerenone - 2011; olmesartan - 2009