Xanax® - (IR): composition and pharmaceutical form
Xanax® - (IR) are prolonged-release tablets containing 0.25 mg, 0.5 mg or 1 mg of alprazolam. The prolonged form makes it possible to take the medicine once a day, whereas ordinary alprazolam tablets are divided into several doses.
The tablets are swallowed whole: they must not be chewed, crushed or divided, otherwise the gradual release of the substance would be disturbed. For the 2 mg tablets the leaflet allows division into halves or quarters. The composition includes lactose, so the medicine is not suitable in hereditary galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption syndrome.
How Xanax® - (IR) works
Alprazolam belongs to the triazolobenzodiazepines. In all benzodiazepines the set of effects is qualitatively the same — anxiolytic, sedative and hypnotic, muscle-relaxing and anticonvulsant — and the differences between the medicines are determined by pharmacokinetics: by how quickly the substance is absorbed, distributed and eliminated.
The mechanism of action is linked to the strengthening of the inhibitory influence on neurons mediated by gamma-aminobutyric acid. Tolerance, that is the need to raise the dose, is rare with alprazolam: it has been shown for the sedative effect but not for the anxiolytic one, whereas the hypnotic action of the benzodiazepines can weaken after several weeks of use.
Indications
The medicine is prescribed for the short-term symptomatic treatment of generalised anxiety disorder, panic disorder, anxiety disorder in the form of a phobia and mixed anxiety-depressive disorder.
The indication is limited to situations in which the symptoms are marked, disturb normal functioning or are very distressing for the patient. Tension and unease linked to everyday problems are not an indication for prescribing it.
Method of use and dosage
If the medicine is taken once a day, it is better to do so in the morning. The dose is chosen individually according to the severity of the symptoms and the patient's response: those who have not taken psychotropic medicines before need smaller doses than people who have already received sedatives, antidepressants or hypnotics, and than those with alcohol dependence. If marked undesirable reactions appear after the first dose, the dose is reduced. The lowest effective dose helps to avoid ataxia and excessive sedation — this matters especially for elderly and debilitated patients.
| Indication or group of patients | Dosage |
|---|---|
| Generalised anxiety disorder, mixed anxiety-depressive disorder | A starting dose of 1 mg a day in one or two doses, if necessary up to 4 mg a day |
| Panic disorder and phobic disorders | A starting dose of 0.5–1 mg before sleep; an increase no faster than 1 mg every 3–4 days |
| Panic disorder, average doses in the studies | 4–8 mg a day; the maximum dose of 10 mg was needed only in isolated cases |
| Elderly and debilitated patients | 0.5–1 mg a day in one or two doses, increased according to tolerance |
| Children and adolescents under 18 | The medicine is not used |
How long the course lasts and how it is ended
Treatment must be as short as possible. The patient's mental state is assessed no later than 4 weeks after the start of therapy, in order to decide whether it needs to continue, and the total duration, including the period of dose reduction, should not exceed 8–12 weeks. Extending the course is possible only after an assessment of the condition by a specialist: with prolonged use the risk of drug dependence grows and the balance of benefit and risk becomes unfavourable. Since the treatment is symptomatic, after it is stopped the symptoms may return, so the dose is reduced gradually — no faster than 0.5 mg every three days, and some patients need an even slower withdrawal. In severe hepatic failure the medicine is contraindicated.
Contraindications
The medicine is not used in the following cases:
- hypersensitivity to alprazolam, to other benzodiazepines or to the excipients;
- myasthenia (myasthenia gravis);
- severe respiratory failure;
- sleep apnoea syndrome;
- severe hepatic failure;
- childhood and adolescence under 18 years.
Special warnings and precautions
Dependence is the key problem of the benzodiazepines, and alprazolam is no exception. The risk grows with the dose and the length of treatment, increases with the concomitant use of several benzodiazepines and is especially high in people prone to the abuse of medicines, drugs or alcohol, but dependence can develop even on therapeutic doses in a patient with no risk factors. Hence the rule: the minimum dose, the shortest possible course and gradual withdrawal. The patient is warned from the outset that treatment is limited in time and that withdrawal symptoms are possible when the dose is reduced — knowing this in itself reduces the anxiety if they appear.
- the withdrawal syndrome shows itself as headache and muscle pain, severe anxiety, tension, restlessness, disorientation and irritability, and sometimes as derealisation, depersonalisation, sharpened hearing, numbness of the limbs, increased sensitivity to light, noise and touch, hallucinations or seizures;
- in panic disorder the symptoms that return after withdrawal closely resemble the withdrawal symptoms, and to them are added mood swings, anxiety, sleep disturbances and restlessness;
- alprazolam can cause anterograde amnesia — most often several hours after the dose; to avoid this, 7–8 hours of uninterrupted sleep must be ensured;
- paradoxical reactions — restlessness, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychoses, inappropriate behaviour — require the medicine to be stopped; they arise more often in children and in older people;
- in patients with depression episodes of hypomania and mania have been described, and benzodiazepines must not be used as the only treatment in depression or mixed anxiety-depressive disorder: this can raise the risk of suicide attempts, so the amount of medicine prescribed is limited;
- elderly and debilitated patients need the lowest doses: sedation and muscle weakness increase the risk of falls with severe consequences;
- in chronic respiratory failure the dose is reduced because of the risk of respiratory depression, in acute angle-closure glaucoma special precautions are observed, and in kidney disease and mild or moderate impairment of liver function caution is needed;
- for the main treatment of psychoses benzodiazepines are not suitable.
The medicine noticeably affects the ability to drive and to operate machinery — through sedation, amnesia, reduced attention and muscle weakness; with a lack of sleep this is more marked. Alcohol and other agents that depress the central nervous system are excluded during treatment.
Drug interactions
With alcohol and other substances that depress the central nervous system the benzodiazepines act additively, so alcoholic drinks are forbidden during treatment. Increased sedation is possible in combination with antipsychotics, hypnotics, anxiolytics and sedatives, antidepressants, narcotic analgesics, anticonvulsants, anaesthetic agents and sedating antihistamines; with narcotic analgesics euphoria is additionally intensified and with it the risk of psychological dependence. Separate caution is needed with medicines that depress breathing — opioid analgesics, cough medicines and substitution therapy medicines — especially in elderly patients.
The second group of interactions is pharmacokinetic. Alprazolam is metabolised mainly by the enzyme CYP3A4, and its inhibitors raise the concentration of the medicine in the blood, enhancing its action. Combination with azole antifungals — ketoconazole, itraconazole, posaconazole, voriconazole — is not recommended. Nefazodone and fluvoxamine increase the area under the alprazolam concentration curve roughly twofold; when they are prescribed, as with cimetidine, particular caution and possibly a reduction of the dose are required.
Pregnancy and breastfeeding
The data on the teratogenicity of the benzodiazepines are contradictory: large cohort studies did not find an increase in the frequency of serious malformations with use in the first trimester, but in a number of early case-control studies the risk of cleft lip and palate was twice as high. Taking large doses in the second and third trimesters was accompanied by reduced motor activity of the foetus and a variable heart rhythm. That is why alprazolam is not recommended either during pregnancy or when planning one, and if the medicine is already being taken or a pregnancy has occurred during treatment, the doctor assesses the risk to the foetus.
Prescribing it in the late stages, even in small doses, carries the risk of floppy infant syndrome: reduced axial tone and difficulty sucking, because of which the newborn gains weight poorly. These disturbances are reversible but persist for one to three weeks. Large doses can cause respiratory depression or apnoea and hypothermia in the newborn and, a few days after birth, withdrawal symptoms in the form of increased excitability, restlessness and tremor. If use at the end of pregnancy is necessary, large doses are avoided and the newborn is monitored. Alprazolam passes into breast milk in small amounts, but it is not prescribed to breastfeeding women.
Adverse effects
Most of the undesirable reactions are a continuation of the pharmacological action of the medicine, and their severity depends on the dose and on individual sensitivity. They usually appear at the start of treatment and lessen with time or when the dose is reduced.
- very common — sedation and drowsiness, ataxia, disturbances of memory and speech, dizziness, headache;
- very common — depression, tiredness, irritability, dry mouth, constipation;
- common — confusion and disorientation, anxiety, nervousness, insomnia, changes of libido in both directions;
- common — disturbances of balance and coordination, worsening of concentration, increased drowsiness, apathy, tremor;
- common — blurred vision, nausea, reduced appetite, changes in weight, dermatitis, sexual disturbances;
- uncommon — mania, hallucinations, anger, agitation, amnesia, muscle weakness, urinary incontinence, disturbances of the menstrual cycle;
- frequency not known — hypomania, aggressive and hostile behaviour, disorders of thought, psychomotor agitation, dystonia, disturbances of the autonomic nervous system;
- frequency not known — hepatitis, impaired liver function and jaundice, angioedema, photosensitivity reactions, urinary retention, peripheral oedema, hyperprolactinaemia, raised intraocular pressure.
In many of the cases described the patients were at the same time taking other medicines that act on the central nervous system, so it is not always possible to link the reaction to alprazolam alone.
Overdose
An isolated overdose of benzodiazepines rarely threatens life; however, one must always bear in mind that alcohol or other agents depressing the central nervous system may have been taken along with the medicine, as well as the patient's concomitant illnesses. The symptoms follow from the pharmacological action of alprazolam.
The basis of care is the maintenance of breathing and circulation. In a coma the treatment is symptomatic, with prevention of asphyxia from the tongue falling back and of aspiration of the stomach contents; fluids are given intravenously so as to prevent dehydration. In a conscious patient vomiting is induced within the first hour; in an unconscious one the stomach is washed out with protection of the airway, after which activated charcoal and an osmotic laxative are given. After very large doses the effect of the medicine may last a long time; forced diuresis and haemodialysis are useless in this poisoning.
How to get a prescription for Xanax® - (IR) online
Alprazolam is dispensed on prescription, and the doctor prescribes it with a short course in mind: it is important to assess the severity of the anxiety disorder, any concomitant illnesses and the risk of dependence.
During the online consultation the doctor will go through the symptoms, will explain the rules for taking the prolonged-release form and the scheme of gradual withdrawal and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
