The P-I-E-N-O Parkinsn's List Drug Database
alprazolam, XanaxTM
BENZODIAZEPINES:
Anti-anxiety, Anti-panic attack
Description: Alprazolam is an oral benzodiazepine used for the management of symptoms associated with panic disorder and anxiety disorders. Alprazolam is often preferable to other benzodiazepines, such as chlordiazepoxide, clorazepate, and prazepam, because alprazolam has a relatively shorter half-life and does not have active metabolites that can lead to accumulation, particularly in the elderly. Alprazolam was approved by the FDA in 1981 and became available as a generic in 1993.
Mechanism of Action: Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and coma. The action of these drugs is mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Central benzodiazepine receptors interact allosterically with GABA receptors, potentiating the effects of GABA and increasing the inhibition of the ascending reticular activating system. Benzodiazepines block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
Pharmacokinetics: Alprazolam is administered orally and is rapidly absorbed following an oral dose. The onset of action usually begins within 15-30 minutes. The drug is widely distributed and is 90% plasma protein-bound. Alprazolam may cross the placenta and distribute into breast milk (see Contraindications). The half-life of this benzodiazepine is 11-16 hours. Alprazolam undergoes oxidative metabolism in the liver, producing metabolites with little or no activity. Both the active and inactive derivatives of the drug are excreted in the urine.
Contraindications/precautions: Alprazolam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected, or a history of substance abuse.
Abrupt discontinuation of alprazolam after prolonged use can cause seizures in susceptible patients. The severity of withdrawal symptoms may be associated with the higher doses of alprazolam used to treat panic disorder. Abrupt discontinuation of benzodiazepine therapy has been reported to cause withdrawal symptoms including irritability, nervousness, and insomnia. Benzodiazepine withdrawal is more likely to occur following abrupt cessation after excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses administered for as few as 1-2 weeks. Benzodiazepine withdrawal also can be more intense if the benzodiazepine involved possesses a relatively short duration of action such as alprazolam. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea, vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but the incidence of these reactions is lower. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and slowly, using a very gradual dosage-tapering schedule.
Alprazolam should be used with extreme caution in patients with respiratory depression, pulmonary disease such as severe COPD (chronic obstructive pulmonary disease), or sleep apnea because the drug can exacerbate ventilatory failure.
Alprazolam should be used with extreme caution in patients with myasthenia gravis because the drug can exacerbate this condition.
The administration of alprazolam can exacerbate acute intermittent porphyria, so the drug should be used with caution in patients with this condition.
Alprazolam is occasionally beneficial for patients with major depression or psychosis. It can, however, induce paradoxical effects in these patients and in those with suicidal ideation. The drug should be administered to these patients with careful monitoring.
Alprazolam is classified as pregnancy category D because it could harm the fetus when administered to pregnant women. Positive evidence of human fetal risk exists based on investigational, marketing, or human studies, but the potential benefit to the mother may outweigh the potential risks to the fetus. Many benzodiazepines distribute into breast milk. Because of the potential for adverse effects in the nursing infant, such as sedation, feeding difficulties, and weight loss, alprazolam generally is not recommended during breast-feeding.
Alprazolam should be administered cautiously to patients with severe hepatic disease because the elimination half-life of the drug can be prolonged, possibly resulting in toxicity. Patients with hepatic disease are more likely to experience adverse CNS reactions and should receive reduced initial dosages. Patients with renal impairment should be carefully monitored during prolonged treatment with benzodiazepines to avoid the adverse reactions that may occur from drug accumulation.
The clearance and/or elimination of many drugs are reduced in the elderly. Delayed elimination can either intensify or prolong the actions of adverse reactions of the drug. Benzodiazepines have been associated with falls in the elderly and the consumer advocate group, Public Citizen, has recommended these drugs not be used in the elderly.
DRUG INTERACTIONS: Alprazolam undergoes oxidative metabolism in the liver. Inhibitors of this enzyme system can prolong the pharmacokinetics of alprazolam. Cimetidine, disulfiram, erythromycin, or fluvoxamineI can decrease the hepatic metabolism of alprazolam if administered concomitantly. Patients receiving alprazolam should be monitored for signs of altered benzodiazepine response when cimetidine, disulfiram, erythromycin, or fluvoxamine is initiated or discontinued.
Patients who are being treated with levodopa for Parkinson's disease can experience decreased control of the symptoms of this disease when benzodiazepines are added to their regimen. Benzodiazepines should be administered cautiously to such patients.
Concomitant administration of alprazolam with CNS-depressant drugs, including opiate agonists, phenothiazines, barbiturates, ethanol, HA-blockers, general anesthetics, and tricyclic antidepressants, can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
Oral contraceptives can increase the effects of alprazolam because oral contraceptives inhibit oxidative metabolism, thereby increasing serum concentrations of benzodiazepines that undergo oxidation. Patients receiving oral contraceptive therapy should be observed for evidence of increased response to alprazolam.
Diazepam reportedly has decreased the elimination of digoxin in some patients. Digoxin toxicity has occurred in a patient receiving alprazolam and digoxin. This interaction may be the result of increased protein binding of digoxin and/or an effect of benzodiazepines at the renal tubules that decreases the elimination of digoxin. Pending further clarification of this interaction, patients receiving a benzodiazepine and digoxin concurrently should be monitored for increased serum digoxin levels.
Flumazenil and benzodiazepines are pharmacological opposites. Flumazenil is specifically used to reverse the actions of benzodiazepines. Clinicians should note that the duration of action for some benzodiazepines may be much longer than that of flumazenil and repeat doses of flumazenil may be necessary.
ADVERSE REACTIONS: The most frequent adverse effects of alprazolam therapy are likely to be extensions of the drug's CNS-depressant effects, e.g., drowsiness or lightheadedness. The incidence and severity of these effects will vary with the dose used and condition being treated.
In some cases paradoxical stimulation can occur secondary to alprazolam. This is of particular significance in psychiatric patients who may be receiving other CNS-depressants, and have underlying behavioral problems. Alprazolam should be withdrawn if there is any evidence of agitation, rage, irritability, aggressive or hostile behavior.
According to the manufacturer's literature, more than 1% of patients treated with alprazolam for anxiety or panic disorder experienced the following adverse events at incidence rates 5% or greater than placebo: drowsiness; fatigue; ataxia; memory impairment or amnesia; learning impairment or cognitive disorder; dysarthria; libido increase or libido decrease (sexual dysfunction); akathisia; mood lability such as agitation, irritability, disinhibition, talkativeness, derealization, dream abnormalities, or fear; feeling warm; constipation; upper respiratory infection; rash; appetite stimulation or appetite loss (anorexia); weight gain or weight loss; dysuria; menstrual irregularity; incontinence; xerostomia; hypersalivation and hypotension.
Adverse events occurring in more than 1% of patients on alprazolam therapy, with incidence rates between 1 and 5% greater than placebo: confusion, blurred vision, muscle cramps, lightheadedness and dizziness.
Adverse events occurring in more than 1% of patients on alprazolam therapy, with incidence rates less than 1% greater than placebo: muscular twitching or muscle tone disorder, depression, anxiety, headache, insomnia, weakness, syncope, paresthesias, vasomotor disturbance, decreased salivation, nausea/vomiting, diarrhea, abdominal distress, nasal congestion, tachycardia, chest pain, hyperventilation, tinnitus, muscle stiffness, sweating, edema, infection and tremor.
Less common adverse events, occurring in less than 1% of patients on alprazolam therapy include: seizures, hallucinations, depersonalization, taste alterations, diplopia, elevated bilirubin, elevated hepatic enzymes, and jaundice.
Even after short-term use of alprazolam, there is evidence of physiological dependence and consequent adverse withdrawal symptoms. These symptoms may range from mild dysphoria and insomnia to a major withdrawal syndrome including abdominal and muscle cramps, vomiting, sweating, tremors and seizures. Higher doses and prolonged use are more likely to cause dependence. Withdrawal may lead to rebound of symptoms of panic disorder more severe than before treatment. The following symptoms have been identified as those associated with alprazolam withdrawal: heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitch, diarrhea, blurred vision, appetite decrease and weight loss. Anxiety and insomnia were also common, but may be associated with the underlying disease state and not a consequence of alprazolam withdrawal. If discontinuation of therapy is indicated, the dose of alprazolam should be reduced slowly and cautiously. According to data involving 641 patients receiving alprazolam for the treatment of panic disorder, adverse events emerging upon discontinuation of therapy occurred in the following percentage of patients: insomnia 29.5%, lightheadedness 19.3%, abnormal involuntary movement 17.3%, headache 17%, muscular twitching 6.9%, impaired coordination 6.6%, muscle-tone disorders 5.9%, weakness 5.8%, anxiety 19.2%, fatigue or tiredness 18.4%, irritability 10.5%, cognitive disorder 10.3%, memory impairment 5.5%, depression 5.1%, confusion 5%, nausea/vomiting 16.5%, diarrhea 13.6%, decreased salivation 10.6%, weight loss 13.3%, decreased appetite 12.8%, sweating 14.4%, tachycardia, 12.2% and blurred vision 10%.
Some hematological changes have been observed in patients receiving alprazolam. Few changes were considered to be of physiological significance. Patients receiving alprazolam over prolonged periods should have periodic blood counts.
PATIENT INFORMATION:
What do alprazolam tablets do?
Alprazolam (XanaxTM ) is a benzodiazepine. Benzodiazepines belong to a group of medicines that slow down the central nervous system. Alprazolam relieves anxiety and nervousness and helps to treat panic attacks. Federal law prohibits the transfer of alprazolam to any person other than the patient for whom it was prescribed. Do not share this medicine with anyone else. Generic alprazolam tablets are available.
What should my doctor or pharmacist know before I take alprazolam?
They need to know if you have any of these conditions:
alcohol or drug abuse problems asthma, lung disease or breathing difficulties kidney disease liver disease mental depression myasthenia gravis porphyria suicidal thoughts an unusual or allergic reaction to alprazolam, other benzodiazepines, foods, dyes, or preservatives pregnant or trying to get pregnant breast-feeding
How should I take this medicine?
Take alprazolam tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. If alprazolam upsets your stomach, take it with food or milk. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for children under 18 years old.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with alprazolam?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking alprazolam?
Serious side effects with alprazolam include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with alprazolam include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take alprazolam?
Visit your doctor for regular checks on your progress. Your body can become dependent on alprazolam, ask your doctor if you still need to take it. However, if you have been taking alprazolam regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or you may get severe side effects. Ask your doctor for advice. Even after you stop taking alprazolam it can still affect your body for several days.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how alprazolam affects you. To reduce the risk of dizzy and fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks.
Do not treat yourself for coughs, colds or allergies without asking your doctor or pharmacist for advice. Some ingredients can increase possible side effects.
If you are going to have surgery, tell your doctor or dentist that you are taking alprazolam.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Throw away any unused medicine after the expiration date.
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