Zovex

Alprazolam.

ZOVEX 0.5 mg tablet is a pink oval shaped tablet, with a score on one side and "CCP C60" on the other side.
Each tablet contains 0.5 mg Alprazolam.

Pharmacology: Pharmacodynamics: Alprazolam, like other benzodiazepines, has a high affinity for the benzodiazepine binding site in the brain. It facilitates the inhibitory neurotransmitter action of gamma-aminobutyric acid which mediates both pre- and post-synaptic inhibition in the central nervous system (CNS).
Pharmacokinetics: Following oral administration, peak plasma concentrations are reached in about 1.7 hours. After a single oral dose of 500 micrograms, the average maximal concentration was 7.1 nanograms/ml. There is a linear relationship between the dose and plasma concentration. At least 80% of the oral dose is absorbed. About 70% of the absorbed dose is bound to plasma proteins.
Alprazolam is extensively metabolised in the liver, primarily to hydroxylated metabolites, but about 20% of the dose is excreted as unchanged alprazolam. Elimination occurs mostly via the kidneys; 80% of the dose is excreted into the urine and only 7% into the faeces. The mean elimination half-life is 10-12 hours.

Zovex Tablets (alprazolam) are indicated for the treatment of: Anxiety states (anxiety neuroses): Symptoms which occur in such patients include anxiety, tension, agitation, insomnia, apprehension, irritability and/or autonomic hyperactivity resulting in a variety of somatic complaints.
Mixed anxiety-depression: Symptoms of both anxiety and depression occur simultaneously in such patients.
Neurotic or reactive depression: Such patients primarily exhibit a depressed mood or a pervasive loss of interest or pleasure. Symptoms of anxiety, psychomotor agitation and insomnia are usually present. Other characteristics include appetite disturbances, changes in weight, somatic complaints, cognitive disturbances, decreased energy, feeling of worthlessness or guilt, or thoughts of death or suicide.
Anxiety states, mixed anxiety-depression, or depression associated with other diseases such as the chronic phase of alcohol withdrawal and functional or organic disease, particularly certain gastrointestinal, cardiovascular, or dermatological disorders.
Panic related disorders: Zovex is indicated in the treatment of panic disorder with or without some phobic avoidance. Zovex is also indicated for the blocking or attenuation of panic attacks and phobias in patients who have agoraphobia with panic attacks. The effectiveness of Zovex in the treatment of anxiety, anxiety associated with depression and neurotic (reactive) depression for long-term use exceeding six months has not been established by systematic clinical trials; however, patients with panic-related disorders have been effectively treated for up to eight months. The physician should periodically reassess the usefulness of the drug for the individual patient.

The optimum dose should be individualized based upon the severity of the symptoms and individual patient response. In patients who require higher doses, dosage should be increased cautiously to avoid adverse effects. In general, patients who have not previously received psychotropic medications will require somewhat lower doses than those previously treated with minor tranquilizers, antidepressants, or hypnotics. It is recommended that the general principle of using the lowest effective dose be followed in elderly or debilitated patients to preclude the development of ataxia or oversedation.
Duration of Treatment: The overall duration of treatment should not be more than 8-12 weeks, including a tapering off process.
Discontinuation of Treatment: The dosage should be reduced slowly in keeping with the good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction (see Precautions).
Pediatric Use: Safety and efficacy have not been established in children under 18 years of age. (See table.)

Click on icon to see table/diagram/image

As with other benzodiazepines, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol). In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken.
Following overdose with any medicinal product, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage undertaken with the airway protected if the patient is unconscious. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. The value of dialysis has not been determined.
Special attention should be paid to respiratory and cardiovascular functions in intensive care. Flumazenil may be used as an adjunct to the management of respiratory and cardiovascular function associated with overdose.
Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, slurred speech, mental confusion and lethargy, in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.

Myasthenia gravis.
Hypersensitivity to benzodiazepines and any component of the product formulation.
Severe respiratory insufficiency.
Sleep apnoea syndrome.
Severe hepatic insufficiency.

Anaphylaxis (severe allergic reaction) and angiodema (severe facial swelling): which can occur as early as the first time the product is taken.
Complex sleep-related behaviors: which may include sleep driving, making phone calls, preparing and eating food while asleep.

Tolerance: Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Dependence: Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of alcohol or drug abuse.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealization, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.
Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, mild dysphoria, anxiety or sleep disturbances, abdominal and muscle cramps, vomiting, sweating, tremor and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually.
Duration of treatment: The duration of treatment should be as short as possible (see Dosage & Administration) but should not exceed eight to twelve weeks including tapering off process. Extension beyond these periods should not take place without re-evaluation of the situation.
It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur while the medicinal product is being discontinued.
There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high. When benzodiazepines with a long duration of action are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.
During discontinuation of Zovex treatment, the dosage should be reduced slowly in keeping with good medical practice. It is suggested that the daily dosage of alprazolam be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.
Amnesia: Benzodiazepines may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours (see also Adverse Reactions).
Psychiatric and 'paradoxical' reactions: Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines. Should this occur, use of the drug should be discontinued. They are more likely to occur in children and the elderly.
Effects on ability to drive and use machines: Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If sufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see also Interactions).
These effects are potentiated by alcohol (see also Interactions). Patients should be cautioned about operating motor vehicles or engaging in other dangerous activities while taking Zovex.
Specific patient groups: Benzodiazepines should not be given to children without careful assessment of the need to do so; the duration of treatment must be kept to a minimum. Elderly should be given a reduced dose (see Dosage & Administration).
Use Zovex with caution in elderly patients as there is a risk of falls secondary to the myorelaxant effects of benzodiazepines.
A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression. Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy.
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patient). Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse.
Administration to severely depressed or suicidal patients should be done with appropriate precautions and appropriate size of the prescription.

Benzodiazepines including Zovex should only be used during pregnancy or lactation if considered essential by the physician. Animal studies with benzodiazepines have shown minor effects on the foetus while a few studies have reported late behavioural disturbance in offspring exposed in utero.
If the product is prescribed to a woman of childbearing potential, the patient should be warned to contact a physician regarding discontinuance of the product if the patient intends to become or suspects that the patient is pregnant. If, for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour, effects on the neonate, such as hypothermia, hypotonia, and moderate respiratory depression, can be expected, due to the pharmacological action of the compound. Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Since benzodiazepines are found in the breast milk, benzodiazepines should not be given to breast feeding mothers.

Sedation/drowsiness, light-headedness, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, memory impairment, muscle weakness, ataxia, double or blurred vision, insomnia, nervousness/anxiety, tremor, change in weight. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.
Side effects also decrease with decreased dosage. Other side effects like gastrointestinal disturbances, changes in libido or skin reactions have been reported occasionally.
In addition, the following adverse events have been reported in association with the use of Zovex: dystonia, anorexia, slurred speech, jaundice, sexual dysfunction/changes in libido, menstrual irregularities, incontinence, urinary retention, abnormal liver function and hyperprolactinaemia.
Increased intraocular pressure have been rarely reported.
Withdrawal symptoms have occurred following rapid decrease or abrupt discontinuance of benzodiazepines including Zovex. These can range from mild dysphoria and insomnia to a major syndrome, which may include abdominal and muscle cramps, vomiting, sweating, tremor and convulsions. In addition, withdrawal seizures have occurred upon rapid decrease or abrupt discontinuation of therapy with Zovex.
Amnesia: Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesic effects may be associated with inappropriate behaviour (see Precautions).
Depression: Pre-existing depression may be unmasked during benzodiazepine use.
Psychiatric and 'paradoxical' reactions: Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepine or benzodiazepine-like agents. They may be quite severe with this product. They are more likely to occur in children and the elderly.
Dependence: Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena (see Precautions). Psychic dependence may occur. Abuse of benzodiazepines has been reported.

Not recommended: Concomitant intake with alcohol.
The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
Take into account when in combination with CNS depressants.
Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines.
In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychic dependence.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines that are metabolised only by conjugation. Based on the degree of interaction and the data available currently, the following recommendations are made: The co-administration of Zovex with ketoconazole, itraconazole, or other azole-type antifungals is not recommended.
Caution and consideration of dose reduction is recommended when Zovex is co-administered with nefazodone, fluvoxamine, and cimetidine.
Caution is recommended when Zovex is coadministered with fluoxetine, propoxyphene, oral contraceptives, diltiazem, or macrolide antibiotics such as erythromycin and troleandomycin.
Interactions involving HIV protease inhibitors (eg, ritonavir) and Zovex are complex and time dependent. Low doses of ritonavir resulted in a large impairment of Zovex clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of Zovex.

Store below 30°C. Protect from light and moisture.

Anxiolytics

N05BA12 - alprazolam ; Belongs to the class of benzodiazepine derivatives anxiolytics. Used in the management of anxiety, agitation or tension.

B