Alprazolam: Uses, Indications, Dosages, Precautions, Contraindications, Side Effects & Interactions

Alprazolam

(al-praz-oh-lam)
Classification 
Pharmacotherapeutic: Benzodiazepine (Schedule IV)
Clinical: Antianxiety

Alprazolam Intensol, Niravam, Xanax, Xanax XR Apo-Alpraz, Xanax TS

CATEGORY AND SCHEDULE

Pregnancy Risk Category: D

Controlled Substance Schedule: IV

General Information

Alprazolam is an antianxiety drug used in the treatment of anxiety and panic disorders. Enhances the inhibitory effects of the neurotransmitter gamma-aminobutyric acid in the brain. It is available in the form of tablets. The tablets are used for the treatment of generalized anxiety disorders (GAD). Short-term relief from symptoms of anxiety, panic disorder, with or without agoraphobia. Anxiety associated with depression

Alprazolam can cause adverse reactions, such as sudden or too rapid withdrawal which can cause marked restlessness, irritability, insomnia, hand tremors, abdominal and muscle cramps, diaphoresis, vomiting and convulsions. Overdose causes somnolence, confusion, decreased reflexes and coma. Less commonly reported side effects include blood dyscrasias. They have rarely been reported

Action

May increase  the effects of gamma-aminobutyric acid (GABA) and other inhibitory neurotransmitters by binding to specific benzodiazepine receptors in limbic and cortical areas of the CNS. GABA inhibits excitatory stimulation, which helps control emotional behavior. The limbic system contains many benzodiazepine receptors, which may help explain the anxiolytic effects of the drug

Therapeutic Effect

Produces anxiolytic effect due to CNS depressant action

Availability (Rx)

Oral Solution: 1 mg/mL

Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Tablets (Extended-Release): 0.5 mg, 1 mg, 2 mg, 3 mg

Tablets (Orally Disintegrating): 0.25 mg, 0.5 mg, 1 mg, 2 mg

Uses

Anxiety, panic disorders with or without agoraphobia, anxiety with depressive symptoms

Unlabeled uses: Premenstrual dysphoric disorders, insomnia, PMS, alcohol withdrawal syndrome

Precautions

Geriatric, debilitated, hepatic disease, obesity, severe pulmonary disease

Make sure to tell your doctor if:

• You have a long-term Renal/hepatic disease

• You have pulmonary disease

• You are taking other medicines

Indications and Dosages

‣ To Treat Anxiety disorder

PO

• Adults: 0.25-0.5 mg tid, may increase q3-4days if needed, max 4 mg/day in divided doses

• Geriatric: 0.125-0.25 mg bid; increase by 0.125 mg prn

• Elderly, debilitated PTS, PTS with hepatic disease or low serum albumin: Initially, 0.25 mg 2–3 times/day. Gradually increase to optimum therapeutic response

‣ To Treat Panic disorder

PO (Immediate-Release, Oral Concentrate, ODT)

• Adults: Initially, 0.5 mg 3 times/day. May increase at 3- to 4-day intervals in increments of 1 mg or less a day. Range: 5–6 mg/day. Maximum: 10 mg/day. Elderly: Initially, 0.125–0.25 mg twice daily. May increase in 0.125-mg increments until desired effect attained

PO: (Extended-Release)

To switch from immediate-release to extended-release form, give total

daily dose (immediate-release) as a single daily dose of extended-release form.

• Adults: Initially, 0.5–1 mg once daily. May titrate at 3- to 4-day intervals.

Range: 3–6 mg/day. ELDERLY: Initially, 0.5 mg once daily

‣ To Treat Premenstrual dysphoric disorder PMS (unlabeled)

PO

• Adults: 0.25 mg bid-qid, starting on day 16-18 of menses cycle, taper over 2-3 days when menses occurs, max 4 mg/day

‣ To Treat Insomnia (unlabeled)

PO

• 0.25-0.5 mg at bedtime

‣ Dosage in Renal Impairment

• No dose adjustment

‣ Dosage in Hepatic Impairment

Severe Disease

• Immediate-Release: 0.25 mg 2–3 mg times/day

• Extended Release: 0.5 mg once daily

Pharmacokinetics

Well absorbed from GI tract. Protein binding: 80%. Metabolized in the liver primarily by CYP3A4. Primarily excreted in urine. Minimal removal by hemodialysis. Half-life: 11-16 h

Implementation

PO route

• Give with food or milk for GI symptoms; high-fat meal decreases absorption; tab may be crushed, if patient is unable to swallow medication whole, and mixed with foods or fluids; may divide total daily dose into more times/day, if anxiety occurs between doses

• Give sugarless gum, hard candy, frequent sips of water for dry mouth

• Discontinue, decrease by 0.5 mg q3days

• Place orally disintegrating tabs on tongue to dissolve and swallow, protect from moisture

• Give ext rel tab in am

Contraindications

Pregnancy D, breastfeeding, hypersensitivity to benzodiazepines, psychosis, addiction Hypersensitivity to ALPRAZolam. Acute narrow angleclosure glaucoma, concurrent use with ketoconazole or itraconazole or other potent CYP3A4 inhibitors

Cautions: Renal/hepatic impairment, predisposition to urate nephropathy, obese pts. Concurrent use of CYP3A4 inhibitors/inducers and major CYP3A4 substrates; debilitated pts, respiratory disease, depression (esp. suicidal risk), elderly (increased risk of severe toxicity). History of substance abuse

Interactions

Individual drugs

Alcohol: increased CNS depression 

Cigarette smoking: decreased drug level

Levodopa: decreased action of levodopa

Rifampin: decreased action of ALPRAZolam

Drug classifications

• Anticonvulsants, antihistamines, opioids, sedatives/ hypnotics: increased CNS depression

• CYP3A4 inducers (barbiturates): decreased action of ALPRAZolam

• CYP3A4 inhibitors (cimetidine, disulfiram, erythromycin, fluoxetine, isoniazid, itraconazole, ketoconazole, metoprolol, propoxyphene, propranolol, valproic acid): increased action of ALPRAZolam

• Xanthines: decreased sedation

Drug/laboratory tests

• Increased: ALT, AST, alkaline phosphatase

Drugs/food

• Grapefruit, grapefruit juice: May inhibit alprazolam’s metabolism

• High-fat meal: May alter the rate, but not extent, of absorption

Herbal

• Gotu kola, kava kava, valerian: May increase CNS depressant effect of alprazolam

• St. John’s wort: Increases alprazolam clearance; decreases alprazolam half-life from 12 h to 6 h

Side effects

• CNS: Agitation, akathisia, confusion, depression, dizziness, drowsiness, fatigue, hallucinations, headache, insomnia, irritability, lack of coordination, lightheadedness, memory loss, nervousness, paresthesia, rigidity, speech problems, syncope, tremor, weakness

• CV: Chest pain, edema, hypotension, nonspecific ECG changes, palpitations, tachycardia

• EENT: Blurred vision, altered salivation, dry mouth, nasal congestion, tinnitus

• ENDO: Galactorrhea, gynecomastia, hyperprolactinemia

• GI: Abdominal discomfort, anorexia, constipation, diarrhea, elevated liver function test results, hepatitis, hepatic failure, nausea, vomiting

• GU: Altered libido, urinary hesitancy

• MS: Dysarthria, muscle rigidity and spasms

• RESP: Hyperventilation, upper respiratory tract infection

• SKIN: Dermatitis, diaphoresis, pruritus, rash, Stevens-Johnson syndrome

• Other: Weight gain or loss

 

Nursing considerations

Baseline assessment

• Assess degree of anxiety; assess for drowsiness, dizziness, light-headedness

• Assess motor responses (agitation, trembling, tension), autonomic responses

(cold/clammy hands, diaphoresis). Initiate fall precautions

Intervention/evaluation

• For pts on long-term therapy, perform hepatic/renal function tests, CBC

periodically

• Assess for paradoxical reaction, particularly during early therapy

• Evaluate for therapeutic response: calm facial expression, decreased restlessness, insomnia

• Monitor respiratory and cardiovascular status

Equipment must be available for anaphylaxis

• Assess mental status: mood, sensorium, anxiety, affect, sleeping pattern, drowsiness, dizziness, especially geriatric; physical dependency, withdrawal symptoms: anxiety, panic attacks, agitation, seizures, headache, nausea, vomiting, muscle pain, weakness; suicidal tendencies; withdrawal seizures may occur after rapid decrease in dose or abrupt discontinuation; short duration of action makes it the product of choice in the geriatric, suicidal thoughts,

behaviors

• Monitor B/P (with patient lying, standing), pulse; if systolic B/P drops 20 mm Hg, hold product, notify prescriber

• Monitor blood studies: CBC during long-term therapy; blood dyscrasias have occurred rarely; decreased hematocrit, neutropenia may occur

• Monitor hepatic studies: AST, ALT, bilirubin, creatinine LDH, alkaline phosphatase, if on long-term treatment

• Monitor I&O; indicate renal dysfunction if on long-term treatment

Evaluation

Positive therapeutic result

• Decreased anxiety, restlessness, sleeplessness (short-term treatment only)

Patient/family teaching

• Tell patient that product may be taken with food or fluids and tabs may be crushed or swallowed whole

• Tell patient not to use for everyday stress or longer than 4 mo unless directed by prescriber; not to take more than prescribed amount; may be habit forming; not to double doses or skip doses; memory impairment is a sign of longterm use

• Drowsiness usually disappears during continued therapy

• If dizziness occurs, change positions slowly from recumbent to sitting position before standing

• Avoid tasks that require alertness, motor skills until response to drug is

established

•Warn against stopping drug abruptly

because withdrawal symptoms may occur, include vomiting, cramping, tremors,

seizures

• Instruct patient never to increase prescribed dose because of risk of dependency

• Smoking reduces drug effectiveness

• Sour hard candy, gum, sips of water may relieve dry mouth

• Do not abruptly withdraw medication after long-term therapy

• Tell patient to avoid OTC preparations unless approved by prescriber; alcohol and CNS depressants increase CNS depression

• Do not take other medications without consulting physician

• Instruct female patient of childbearing age to notify prescriber immediately if she becomes or might be pregnant. Drug isn’t recommended during pregnancy

• Teach patient not to use during pregnancy (D), avoid breastfeeding

• Advise patient to avoid driving and activities that require alertness until alprazolam’s effects are known

Treatment of Overdose

Lavage, VS, supportive care, flumazenil