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Oral Drugs for Diabetes: Avoiding Hypoglycemia

Worst Pills, Best Pills Newsletter article May, 2010

Millions of prescriptions are filled each year for oral diabetes medications such as rosiglitazone (AVANDIA). But what patients might not know is that many other commonly used medications may affect a patient’s response to oral diabetes drugs, sometimes with dangerous results.

Most diabetes drugs are metabolized by enzymes in the liver such as CYP2C9, CYP3A4 or CYP2C8. Many other drugs inhibit these enzymes and can cause increased levels of the diabetes drug in the blood. The result of...

Millions of prescriptions are filled each year for oral diabetes medications such as rosiglitazone (AVANDIA). But what patients might not know is that many other commonly used medications may affect a patient’s response to oral diabetes drugs, sometimes with dangerous results.

Most diabetes drugs are metabolized by enzymes in the liver such as CYP2C9, CYP3A4 or CYP2C8. Many other drugs inhibit these enzymes and can cause increased levels of the diabetes drug in the blood. The result of this increase may be serious hypoglycemia (very low blood sugar). See Tables 12 and 3 for lists of drugs that inhibit CYP2C9, CYP3A4 and CYP2C8, respectively, as well as the diabetes drugs that are metabolized by those respective enzymes.

With any of these diabetes drugs, using another drug that inhibits the metabolizing enzyme for your diabetes drug may increase the risk of hypoglycemia.

Two diabetes drugs that are less likely to interact

Some diabetes drugs are not metabolized by liver enzymes and thus would not undergo the kinds of drug interactions described here.

For example, diabetes drugs eliminated primarily by the kidneys rather than by undergoing metabolism in the liver include the relatively new drug sitagliptin (JANUVIA) and the very old drug metformin (GLUCOPHAGE). However, because both of these drugs are excreted by the kidneys, patients taking them may be vulnerable to interactions with drugs that affect the kidneys.

Also, some drugs (and alcohol) can affect blood sugar levels on their own without affecting the blood levels of diabetes medications. Such drugs would potentially affect any diabetes drug, including insulin.

What You Can Do

People who take oral diabetes drugs should be alert for the effects of other drugs on their blood sugar.

Make sure that the person who prescribed the diabetes drug knows all the medications you are taking (including nonprescription drugs and over-the-counter products). This is especially important when starting any new medications, because hypoglycemia is more likely during the initiation of the interacting drug.

If you are monitoring your own blood sugar levels, look for changes whenever you start or stop any other drug. Make sure you are aware of the symptoms of hypoglycemia (see Box, below) to increase your chances of detecting it before it gets too severe.

 

Symptoms of hypoglycemia include:

Nervousness
Trembling
Weakness
Sweating
Intense hunger
Palpitations
Trouble speaking

These symptoms are most quickly relieved by ingesting sugar-containing beverages such as regular soda or juice, or eating Life Savers or table sugar.


Table 1. CYP2C9

 

Diabetes Drugs Metabolized by CYP2C9

Generic Name

BRAND NAME

Chlorpropamide

DIABINESE*

Glyburide

DIABETA, GLYNASE, MICRONASE**

Glimepiride

AMARYL**

Glipizide

GLUCOTROL**

Nateglinide

STARLIX*

Rosiglitazone

AVANDIA*

Tolbutamide

ORINASE**

 

 

CYP2C9 Inhibitors (Drugs that can interact with drugs metabolized by CYP2C9)

Amiodarone

CORDARONE, PACERONE***

Capecitabine

XELODA

Co-trimoxazole

SEPTRA

Delavirdine

RESCRIPTOR

Efavirenz

SUSTIVA

Fluconazole

DIFLUCAN

Fluorouracil

ADRUCIL, CARAC, EFUDEX, FLUOROPLEX

Fluoxetine

PROZAC, SERAFEM**

Fluvastatin

LESCOL, LESCOL XL**

Fluvoxamine

LUVOX**

Metronidazole

FLAGYL**

Sulfinpyrazone

ANTURANE

Voriconazole

VFEND

 
Table 2. CYP2C8

 

Diabetes Drugs Metabolized by CYP2C8

Generic Name

BRAND NAME

Pioglitazone

ACTOS*

Repaglinide

PRANDIN*

 

CYP2C8 Inhibitors (Drugs that can interact
with drugs metabolized by CYP2C8)

Co-trimoxazole

SEPTRA

Gemfibrozil

LOPID*

Montelukast

SINGULAIR*

 
Table 3. CYP3A4

Diabetes Drugs
Metabolized by CYP3A4

Generic Name

BRAND NAME

Nateglinide

STARLIX*

Pioglitazone

ACTOS*

Repaglinide

PRANDIN*

Saxagliptin

ONGLYZA*

 

CYP3A4 Inhibitors (Drugs that can interact
with drugs metabolized by CYP3A4)

Amiodarone

CORDARONE, PACERONE***

Amprenavir

AGENERASE

Aprepitant

EMEND

Atazanavir

REYATAZ

Clarithromycin

BIAXIN**

Conivaptan

VAPRISOL

Cyclosporine

NEORAL

Darunavir

PREZISTA

Delavirdine

RESCRIPTOR

Diltiazem

CARDIZEM, CARDIZEM CD, DILACOR XR, TIAZAC**

Erythromycin

E-MYCIN, EES, ERYTHROCIN

Fluconazole

DIFLUCAN

Fluvoxamine

LUVOX**

Imatinib

GLEEVEC

Indinavir

CRIXIVAN

Itraconazole

SPORANOX*

Ketoconazole

NIZORAL

Nelfinavir

VIRACEPT

Posaconazole

NOXAFIL

Quinupristin

SYNERCID

Ritonavir

KALETRA, NORVIR

Saquinavir

INVIRASE

Tamoxifen

NOLVADEX**

Telithromycin

KETEK*

Verapamil

CALAN, CALAN SR, COVERA-HS, ISOPTIN, ISOPTIN SR, VERELAN

Voriconazole

VFEND

* Do Not Use on WorstPills.org
** Limited Use on WorstPills.org
*** Last Choice on WorstPills.org

Updated 4/4/2012