Resta

Uses

• * Anxiety disorder
• * Short term relief of anxiety
• * Anxiety associated with depression
• * Panic disorder, with or without agoraphobia.

Resta is also used to associated treatment for these conditions: Anxiety, Generalized Anxiety Disorder (GAD), Panic Disorder

How Resta works

Alprazolam is a triazolobenzodiazepine used to treat certain anxiety and panic disorders. Alprazolam acts on benzodiazepine receptors BNZ-1 and BNZ-2. The active metabolites 4-hydroxyalprazolam acts on these receptors with 0.20 times the potency of alprazolam and alpha-hydroxyalprazolam acts on these receptors with 0.66 times the potency.

The effect of alprazolam on BNZ-1 mediates the sedation and anti-anxiety effects of the drug while the action on BNZ-2 mediates effects on memory, coordination, muscle relaxation, and anticonvulsive activity.

Alprazolam also couple with GABA-A receptors to enhance GABA binding to its receptor. This interaction mediates inhibition of the nervous system and results in a calming effect.

The molecular mechanisms as well as the clinical effects of alprazolam have both been well demonstrated, however the means by which the molecular mechanism translates to a clinical effect is still not understood.

Dosage

Resta dosage

Treatment should be initiated with a dose of 0.25 to 0.5 mg three times daily. Depending on the response, dose may

be increased at intervals of 3 to 4 days in increments of no more than 1 mg per day. The maximum dose should not

exceed 4 mg/day. Occasional patients with panic disorder may need as much as 10 mg a day to achieve a

successful response and in these cases periodic reassessment and consideration of dosage adjustment is required.

Dosage should be individualized for maximum beneficial effect with a lowest possible dose. If side-effects occur at

starting dose, dose may be lowered. When discontinuing therapy, dosage should be reduced gradually by no more

than 0.5 mg every three days.

In elderly patients or in patients with advanced liver disease, the usual starting dose is 0.25 mg, two or three times

daily and may be gradually increased if needed and tolerated. Safety and effectiveness of Alprazolam in individuals

below 18 years of age have not been established.

Alprazolam XR 1 should be administered once daily, preferably in the morning by patients who are on multiple dosage

regimen of Alprazolam 0.25/0.5 mg. The tablets should be taken intact, they should not be chewed, crushed, or broken.

Side Effects

Side effects, if occur, are generally observed at the beginning of therapy and usually disappear upon continued medication. The most frequent side effects are drowsiness and light headedness. The other side effects, that may occur include depression, headache, confusion, dry mouth, constipation etc.

Toxicity

Alprazolam overdose can present as sleepiness, confusion, poor coordination, slow reflexes, coma, and death. Taking alprazolam with alcohol lowers the threshold for overdose. Patients should have their respiration, pulse, and blood pressure monitored. Patients can be treated by gastric lavage and intravenous fluids.. If hypotension occurs, patients may be treated with vasopressors. In known, or suspected overdoses, patients can be given the benzodiazepine receptor antagonist flumazenil in addition to other methods of management.

Oral LD50 in rats is 331-2171mg/kg.

Alprazolam is a pregnancy category D teratogen meaning there is evidence of risk to the fetus of a mother taking alprazolam but in some cases the benefit may outweigh the risk. Children born to these mothers are also at risk of withdrawal symptoms, flaccidity, and respiratory issues.

Benzodiazepines are expressed in human breast milk and so nursing is generally not recommended in mothers taking alprazolam.

Alprazolam is not associated with carcinogenicity, mutagenicity, or impairment of fertility.

Precaution

Because Alprazolam may produce psychological and physical dependence, increment of dose or abrupt discontinuation of Alprazolam therapy should not be done without physician's advice. Duration of therapy must be determined by the physicians. Alprazolam should be administered with caution to patients with hepatic or renal disease, chronic pulmonary insufficiency or sleep apnea.

Interaction

Alprazolam produces additive CNS depressant effects when co-administered with other psychotropic medications, anticonvulsants, antihistaminics, ethanol and other drugs which themselves produce CNS depression.

Volume of Distribution

Volume of distribution following oral administration is 0.8-1.3L/kg. Alprazolam crosses the blood-brain barrier.

Elimination Route

Oral bioavailability of a standard release tablet of alprazolam is 84-91% with a time to maximum concentration of 1.8 hours. A 1mg oral dose of alprazolam leads to a maximum plasma concentration of 12-22mcg/L. Alprazolam is rapidly absorbed in the gastrointestinal tract.

Data for the area under the curve and the effect of taking alprazolam with food are not readily available.

Half Life

11.2 hours in healthy patients. The half life is 16.3h in the elderly, 5.8-65.3h in patients with alcoholic liver disease, 9.9-40.4h in obese patients. The half life is 25% higher in Asian patients compared to Caucasians. Other studies have shown the half life to be 9-16h.

Clearance

Oral clearance is 0.90±0.21mL/min/kg but this increases to 2.13±0.54mL/min/kg when given with CYP3A inducers. Other studies have demonstrated a clearance of 0.70-1.5mL/min/kg.

Elimination Route

Alprazolam is mainly eliminated in the urine. A large portion of the dose is eliminated as unmetabolized alprazolam. 2

Pregnancy & Breastfeeding use

Pregnancy: Alprazolam has been categorized in pregnancy category D; that means, it should be avoided in pregnancy.

Lactation: Like other benzodiazepines, Alprazolam is assumed to be excreted in breast milk. Therefore, nursing should not be undertaken by mothers who must use Alprazolam.

Contraindication

Contraindicated in patients with hypersensitivity to alprazolam or other benzodiazepines. Alprazolam is also contraindicated in patients with myasthenia gravis, acute narrow angle glaucoma, during pregnancy and also in infants.

Special Warning

Use in Children: Safety and efficacy of Alprazolam in patients under the age of 18 years has not been established.

Acute Overdose

Manifestations of Alprazolam over dosage include somnolence, confusion, impaired coordination, diminished reflexes and coma. In such cases of over dosage general supportive measures should be employed along with immediate gastric lavage.

Storage Condition

Alprazolam tablets should be stored in a cool and dry place, protected from light and moisture.

Innovators Monograph

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