Anxiety neurosis, anxiety therapy supplement accompanying mental depression, anxiety disorders with other disorders, panic attacks and panic attacks, also in conjunction with the phobia, short-term treatment of insomnia caused by anxiety.

4.2 Posology and method of administration

It is intended for adults of 18 years.

Dosage is strictly individual, not only according to the nature and severity of symptoms, but also taking into account age and other illnesses the patient and has used drugs. The suppression of anxiety is given 3 times daily from 0.25 to 0.5 mg according to response and tolerance can be increased up to 3 to 4 mg daily. In elderly, debilitated persons, in patients with reduced liver or renal function or with hypoalbuminemia are given an initial dose of 0.25 mg two to three times daily and cumulative doses to be slower.

The damping of panic are given higher doses, initially three times a day and 0.5 mg dose may be increased to 10 mg per day. At high doses, has proved to be administered daily dose in 4-5 divided doses, in order to maintain sufficiently high plasma levels of alprazolam and avoid the possible occurrence of tolerance.

The administration of higher daily doses of the drug planted suddenly, but gradually tapering the daily dose should be reduced by more than 0.5 mg every 3 day, some patients still need to be slower reduction.

4.3 Contraindications

Hypersensitivity to any ingredients or to other benzodiazepines, myasthenia gravis, narrow angle glaucoma (benzodiazepines may act anticholinergic), chronic obstructive pulmonary disease with respiratory insufficiency, sleep apnea.

It is intended only for adults, children and adolescents under 18 years, the safety administration has so far demonstrated.

It shall not be made breast-feeding in the first trimester of pregnancy.

4.4 Special warnings and precautions for use

Intravenously to patients with drug addiction and alcoholism in the history of special caution. It is necessary to pay attention to depressive patients were described as episodes of mania and manic states. In cerebral ischemia and states of CNS depression are at increased risk of excessive sedation. In elderly, debilitated persons with hypoalbuminemia and reduced liver and renal function, lower doses are recommended (see section 4.2).

When drug use is inappropriate drinking alcoholic beverages.

Caution should be exercised in patients with parkinsonism, porphyria, in debilitated and exhausted patients.

If you experience withdrawal symptoms, it is necessary to reinstate the previous dosing schedule and to stabilize the patient and then start again slowly reducing the daily dose.

Long-term administration, especially higher doses, can cause somatic or psychological dependence.

Patients with rare hereditary problems of galactose intoleranice, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interactions

Alprazolam enhances the depressant effect of alcohol and drugs that suppress the central nervous system, such as: anodyne, antiepileptics, neuroleptics, hypnotics, sedatives, antidepressants, (sedating) antihistamines and the like. If concomitant use is necessary to reduce one or both drugs. If you are taking benzodiazepines concomitantly with opioids, it is necessary to reduce the dose by at least one third, and then slowly increase the dose. Concomitant use with imipramine or dezimipramínom increases the plasma concentration at steady state.

Alprazolam may decrease the clearance of digoxin and increase its plasma concentration.

Alprazolam may increase plasma levels of concomitant lithium.

Cimetidine reduced the clearance of alprazolam and prolongs its half-life.

Ethinylestradiol also prolongs half-life of alprazolam.

4.6 Pregnancy and lactation

Some benzodiazepines increase the risk of congenital malformations, because the administration of alprazolam in the first trimester is contraindicated. Alprazolam can penetrate the placental barrier, because its chronic administration in pregnancy may lead to the manifestation of the newborn and also according to withdrawal symptoms. Use of benzodiazepines in the last weeks of pregnancy may inhibit neonatal CNS. Safety of alprazolam throughout pregnancy is verified, the drug is therefore not recommended throughout pregnancy except in cases where the risk of serious consequences of untreated disease outweighs the potential risk to the fetus.

Alprazolam is excreted into breast milk and infants because it break down more slowly than adults, the infant could be an accumulation, sedation, and nutritional disorders.

During breast-feeding is therefore inappropriate administration of alprazolam.

4.7 Effects on ability to drive and use machines

With its sedative alprazolam can, especially at the start of administration and at each dose increase, adversely affect the activities that require attention, motor coordination and quick decision making (eg, driving, handling machinery, work at heights, etc.).

4.8 Undesirable Effects

They occur mainly at the beginning of treatment, usually resolves spontaneously. Most often appears sleepy, which is somewhat dependent on the dose and disappears at a reduced, further fatigue, feeling of lightness or bias in the head, headache, dizziness, impaired coordination, blurred vision, irritability, increased and decreased appetite, constipation and diarrhea, and increase weight loss, sweating, feeling of nasal congestion, dry mouth, but also increased salivation, micturition disorders, skin allergies, skin rash, itching, blood dyscrasias, including agranulocytosis. Side effects are more common in the elderly and cachectic persons, children, at hepatikov, patients with hypoalbuminemia and persons with disabilities by organic CNS, which states ataxia, impaired memory and other functions of the intellect, rarely paradoxical affective response to the confusion, hallucinations and aggression. Long-term administration, especially higher doses, can cause somatic or psychological dependence. The risk of drug dependence is therefore higher in patients with panic disorder who are taking higher doses of alprazolam (4 mg daily). Similarly, (ie, at higher dosages for a long time - about 8 to 12 weeks of treatment) is more common syndrome of rebound and withdrawal symptoms. Withdrawal symptoms may occur with abrupt discontinuation of therapy within 2 to 3 days, manifested by insomnia, nervousness, irritability, less often, nausea, vomiting, and abdominal cramps in the muscles, with routes and increased sensitivity to sensory stimuli. (Rebound syndrome is a transient syndrome, in which the symptomatology, for which the benzodiazepine treatment began, recurs, and it increasingly. This symptomatology may occur on discontinuation of therapy).

4.9 Overdose

Toxic dose for humans after PO administration is about 0.33 mg / kg body weight. weight.

Symptoms of overdose: confusion, drowsiness and sleep, shortness of breath, severe weakness, slurred speech, titubácia, decreased reflexes, bradycardia.

Treatment: If the patient is conscious and there is no coma or convulsions when swallowing is suitable gastric lavage, activated charcoal or filing Emetics. No specific antidote is flumazenil. Hemodialysis and forced diuresis are not very effective. Of course there are general measures such as monitoring of basic vital signs (respiration, circulation, level of consciousness) and the correction of the anomalies detected.

5th Pharmacological Properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anxiolytic / antidepressant. Derivatives of benzodiazepine, alprazolam.

ATC code: N05BA12

Alprazolam is a short to intermediate acting benzodiazepine derivative as any benzodiazepines and operates at all levels of CNS depressant, depending on the dose, from mild sedation to sleep through the coma. Benzodiazepines promote or facilitate the inhibitory neurotransmitter gamma-aminobutyric acid activity (GABA), which is the main inhibitor of neurotransmission in the brain and mediates pre-and postsynaptic inhibition in all areas of the CNS.

Compared with other benzodiazepines alprazolam has significant anxiolytic effects and antipanické, but has also preserved the effects of myorelaxant, anticonvulsant and sedative-hypnotic.

5.2 Pharmacokinetic Properties

Alprazolam is after oral administration of GIT is rapidly and well absorbed, with peak plasma levels achieved in 1-2 hours. The plasma protein binding in the 70 to 80%. The plasma concentration at steady state is reached in about 2-3 days.

With multiple dosing, only a slight accumulation. Metabolised in the liver and its metabolites have very little to no pharmacological effect. The elimination half-life in adults 10 to 15 hours, than for alprazolam, and for its metabolites. Renal excretion is mainly in the form of conjugates, glucuronides. The elderly are the elimination and hence half-life prolonged.

5.3 Preclinical safety data

Acute toxicity (LD50) in mice is alprazolam after 1.02 g / kg, I. P. 540 mg / kg, PO in the rat  2 g / kg, I. P. 610 mg / kg.

In the 24 months duration in rats at dose 150 times the maximum recommended daily human dose showed no evidence of carcinogenicity. In tests on mice and bacteria showed no evidence of mutagenicity.

6th Pharmaceutical

6.1 List of excipients

Lactose, maize starch, microcrystalline cellulose, calcium stearate, colloidal anhydrous silica.

6.2 Incompatibilities

They are not known.

6.3 Shelf Life

2 years

6.4 Special precautions for storage

Store in a dry place at 10-25 C, protected from light.

Keep out of reach of children.