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Quetiapine (SEROQUEL) Interactions With Other Drugs

Worst Pills, Best Pills Newsletter article February, 2010

DANGEROUS INTERACTIONS

Quetiapine (SEROQUEL), a commonly used psychiatric drug used for schizophrenia, bipolar disorder and other psychiatric disorders, can interact with other drugs to cause dangerous side effects such as slowed breathing, dizziness and fainting.

Popular partly because it is somewhat less likely to cause involuntary movements than many older anti-psychotic drugs, quetiapine is metabolized, or processed, by the enzyme CYP3A4.

Many drugs either block or speed up...

DANGEROUS INTERACTIONS

Quetiapine (SEROQUEL), a commonly used psychiatric drug used for schizophrenia, bipolar disorder and other psychiatric disorders, can interact with other drugs to cause dangerous side effects such as slowed breathing, dizziness and fainting.

Popular partly because it is somewhat less likely to cause involuntary movements than many older anti-psychotic drugs, quetiapine is metabolized, or processed, by the enzyme CYP3A4.

Many drugs either block or speed up the activity of CYP3A4, which metabolizes drugs. Drugs that block CYP3A4 activity will cause increased blood levels of quetiapine. Drugs that speed up CYP3A4 activity will result in too little quetiapine in the blood. This article describes 36 drugs that can have one or the other of these effects.

Which drugs can increase the risk of quetiapine toxicity?

One patient on quetiapine developed a dramatic increase in quetiapine blood levels after the antibiotic clarithromycin (BIAXIN) was added to the patient’s prescriptions to treat an infection. This person suffered impaired consciousness (an inability to focus thoughts) and slowed breathing as a result of the interaction.

In a study of healthy subjects, adding the antifungal ketoconazole (NIZORAL), a potent CYP3A4 inhibitor, increased quetiapine blood levels by more than 500 percent, a level high enough to produce quetiapine toxicity in at least some patients.

Some of the more common adverse effects of excessive quetiapine blood levels include sedation, dizziness, confusion, respiratory depression, acute decrease in blood pressure and fainting. Because the side effects of quetiapine include sedation and lowered blood pressure, patients should be careful when taking quetiapine with other drugs that produce similar effects.

Which drugs can reduce the effect of quetiapine?

Quetiapine also is susceptible to interactions with medications that increase the activity of drug-metabolizing enzymes, such as CYP3A4. When quetiapine is metabolized too quickly, not enough remains in the blood to perform the drug’s intended function of treating psychiatric illnesses.

Of particular importance is the drug carbamazepine (CARBATROL, TEGRETOL), which may be used with quetiapine in the treatment of bipolar disorder and other psychiatric diseases. Carbamazepine can dramatically reduce quetiapine blood levels, and sometimes the effect is so large that no quetiapine can be detected in the blood.

Phenytoin (DILANTIN), an anticonvulsant drug, also has been shown to dramatically reduce quetiapine blood levels.

Are there other quetiapine interactions?

One recent report suggested that the combination of quetiapine and epilepsy drug valproate (DEPAKENE) may increase the risk of reduced bone marrow function over either drug alone, especially in African Americans.

This reaction results in reduced white cells in the blood and can increase the risk of serious infections.

More study is needed to determine whether this is a real interaction, but for now it would be prudent for people concurrently taking quetiapine and valproate to have their blood tested for reduced white blood cells.

What You Can Do

If you are taking quetiapine and a new drug is added, check with your physician or pharmacist to see if the new medication interacts with quetiapine.

If a new medication blocks quetiapine metabolism and a non-interacting alternative is not available, it may be possible to reduce the quetiapine dose to compensate for the interaction.

If the new drug stimulates quetiapine metabolism, however, the effect may be so large that it is not possible to compensate by increasing the quetiapine dose. In that case it may be necessary to avoid giving the combination.

If you are stabilized on chronic therapy with quetiapine and other medications, be alert for evidence of reduced quetiapine effect if an enzyme inhibitor drug is stopped and quetiapine is thus metabolized more quickly.

Conversely, if an enzyme inducer is stopped, one needs to be alert for quetiapine toxicity. Dramatic increases in quetiapine blood levels have been reported when enzyme inducers are stopped in patients on chronic quetiapine therapy because the drug will be metabolized more slowly.

Table 1. Drugs That Increase Risk of Quetiapine Toxicity

 

amiodarone (CORDARONE, PACERONE)***

amprenavir (AGENERASE)

aprepitant (EMEND)

atazanavir (REYATAZ)

clarithromycin (BIAXIN)**

conivaptan (VAPRISOL)

cyclosporine (NEORAL, SANDIMMUNE)

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 (FORTOVASE, INVIRASE)

tamoxifen (NOLVADEX)**

telithromycin (KETEK)*

verapamil (CALAN, CALAN SR, COVERA-HS, ISOPTIN, ISOPTIN SR, VERELAN)

voriconazole (VFEND)

* Do Not Use in "Worst Pills, Best Pills"
** Limited Use in "Worst Pills, Best Pills"
*** Last Choice in "Worst Pills, Best Pills"

Table 2. Drugs That Reduce Quetiapine Blood Levels

 

efavirenz (SUSTIVA)

nafcillin (NALLPEN, UNIPEN)

nevirapine (VIRAMUNE)

oxcarbazepine (TRILEPTAL)

phenobarbital (LUMINAL, SOLOFTEN)**

primidone (MYSOLINE)

rifabutin (MYCOBUTIN)

rifampin (RIFADIN, RIMACTANE)

rifapentine (PRIFTIN)

St. John’s wort*

* Do Not Use in "Worst Pills, Best Pills"
** Limited Use in "Worst Pills, Best Pills"