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Alprazolam is primarily eliminated from the body by metabolism via cytochrome P450 3A (CYP3A). Most of the interactions that have been documented with alprazolam are with drugs that inhibit or induce CYP3A4. CYP3A4 is an important enzyme in the body, mainly found in the liver and the intestine. Its purpose is to oxidize small foreign organic molecules (xenobiotics), such as toxins or drugs so that they can be removed from the body.
Potent inhibitors of CYP3A may increase plasma concentrations of alprazolam. Drugs that have this effect include:
- Cimetidine (Tagamet)
- HIV protease inhibitors, e.g., ritonavir.
Benzodiazepines, including alprazolam, produce additive CNS depressant effects when co-administered with:
- Other psychotropic medications
- Other drugs that produce CNS depression.
Other drug interactions include:
- Digoxin - increased digoxin concentrations have been reported when alprazolam was given, especially in elderly older than 65 years of age
- Imipramine and desipramine - increased plasma concentrations of imipramine and desipramine by 31% and 20% respectively
- Fluoxetine - coadministration of fluoxetine with alprazolam increased the maximum plasma concentration of alprazolam by 46%, decreased clearance by 21%, increased half-life by 17%
- Propoxyphene - coadministration of propoxyphene decreased the maximum plasma concentration of alprazolam by 6%, decreased clearance by 38%, and increased half-life by 58%
- Birth control pills - coadministration of oral contraceptives increased the maximum plasma concentration of alprazolam by 18%, decreased clearance by 22%, and increased half-life by 29%.
Studies of benzodiazepines other than alprazolam suggest a possible drug interaction with alprazolam for the following:
- Antibiotics such as clarithromycin (Biaxin), erythromycin (EES, EryPed, Ery-Tab, Erythrocin, Pediazole), rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), rifapentine (Priftin), or telithromycin (Ketek)
- Grapefruit juice
- Ergotamine (Cafergot, Ergomar, Migergot)
- Cyclosporine (Gengraf, Neoral, Sandimmune)
- Heart or blood pressure medication such as amiodarone (Cordarone, Pacerone), diltiazem (Tiazac, Cartia, Cardizem), nicardipine (Cardene), nifedipine (Nifedical, Procardia), or quinidine (Quin-G)
- Dexamethasone (Cortastat, Dexasone, Solurex, DexPak)
- Imatinib (Gleevec)
- St. John's wort
- Antifungal medication such as miconazole (Oravig) or voriconazole (Vfend)
- Antidepressants such as fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), desipramine (Norpramin), imipramine (Janimine, Tofranil), or nefazodone
- A barbiturate such as butabarbital (Butisol), secobarbital (Seconal), pentobarbital (Nembutal), or phenobarbital (Solfoton)
- Seizure medications such as carbamazepine (Carbatrol, Equetro, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenytoin (Dilantin), or primidone (Mysoline).
This list is not complete, and other drugs may interact with Xanax. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin and herbal products.
Do not start a new medication without telling your doctor.
Xanax dependence and withdrawal
It is important to taper off Xanax gradually; otherwise there is a risk of benzodiazepine withdrawal syndrome.
To discontinue treatment of Xanax patient dosage should be reduced and tapered slowly. Because of the danger of withdrawal, abrupt discontinuation of treatment should be avoided. It is suggested that the daily dosage of Xanax be decreased by no more than 0.5 mg every three days. Reported withdrawal symptoms of discontinuation of Xanax include:4
Withdrawal symptoms may be experienced when Xanax is discontinued. These symptoms may include insomnia, light-headedness, anxiety, fatigue and headaches.
- Fatigue and tiredness
- Abnormal involuntary movement
- Weight loss
- Decreased appetite
- Decreased salivation
- Cognitive disorder
- Blurred vision
- Muscular twitching
- Impaired coordination
- Muscle tone disorders
- Memory impairment
- Confusional state.
Alprazolam is a safe and effective medication when used as directed.13