Xanax®: composition and pharmaceutical form
Xanax® comes as tablets containing 0.25 mg, 0.5 mg, 1 mg or 2 mg of alprazolam. This set of strengths makes it possible to find the lowest effective dose and to reduce it gradually on withdrawal.
The tablets contain lactose, so the medicine is not suitable for people with the rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
How Xanax® works
The active substance of the medicine is alprazolam, a triazolobenzodiazepine. All benzodiazepines have qualitatively similar properties: anxiolytic, sedative and hypnotic, muscle-relaxing and anticonvulsant. They differ in their pharmacokinetics, and it is precisely this that determines the different uses of these medicines in medicine.
The action of the benzodiazepines is thought to rest on the strengthening of the inhibition of neurons mediated by gamma-aminobutyric acid. Tolerance to the sedative effect of alprazolam has been shown, but not to the anxiolytic one; at the same time, after several weeks of regular use the hypnotic effect of the benzodiazepines can weaken.
Indications
Xanax® is indicated for the short-term symptomatic treatment of anxiety states in adults.
The key restriction is that this means severe disorders only, in which the symptoms are marked, prevent the person from functioning normally or are extremely distressing for them. Ordinary anxiety and everyday tension are not treated with benzodiazepines, and in children and adolescents under 18 the medicine is not used.
Method of use and dosage
The medicine is used at the lowest effective dose and for as short a time as possible — a maximum of 2 to 4 weeks — and counting the period of dose reduction the total duration should not exceed 8–12 weeks. The patient's condition and the need to continue treatment are assessed often, especially if the symptoms have eased or gone; prolonged therapy is not recommended, since the risk of dependence grows with the dose and with the length of use.
| Group of patients | Scheme of use |
|---|---|
| Adults with anxiety states | A starting dose of 0.25 mg or 0.5 mg 3 times a day, if necessary an increase to a maximum of 4 mg a day divided into several doses |
| Elderly and debilitated patients | A starting dose of 0.25 mg 2–3 times a day, with a gradual increase according to tolerance |
| Patients who have not taken psychotropic medicines before | They need smaller doses than those who have already taken sedatives, antidepressants or hypnotics |
| Severe hepatic failure | The medicine is contraindicated |
| Impaired kidney function, mild and moderate hepatic failure | Caution is required |
How to end the treatment
The treatment is symptomatic in nature, so after it is stopped the symptoms may return. The dose is reduced gradually — an abrupt withdrawal threatens a withdrawal syndrome and a rebound phenomenon. If marked undesirable reactions have arisen after the starting dose, the dose is reduced; for the few patients who need doses above those recommended, the dose is raised gradually, with the larger part moved to the evening. The lowest effective dose matters also because it helps to avoid ataxia and excessive sedation — especially in elderly and debilitated people.
Contraindications
Xanax® is not prescribed in the following cases:
- hypersensitivity to alprazolam, to other benzodiazepines or to any excipient;
- myasthenia (myasthenia gravis);
- severe respiratory failure;
- sleep apnoea syndrome;
- severe hepatic failure;
- age under 18 — safety and efficacy in children and adolescents have not been confirmed.
Special warnings and precautions
The main risk in treatment with benzodiazepines is the formation of dependence. It can develop both on therapeutic doses and in people without risk factors, and the likelihood grows with the dose, the length of treatment and the concomitant use of several benzodiazepines. Particular caution is needed in patients prone to the abuse of medicines, drugs and alcohol. Abrupt discontinuation once dependence has formed produces a withdrawal syndrome: headache and muscle pain, extreme anxiety, tension, restlessness, disorientation, irritability, and sometimes derealisation, depersonalisation, sharpened perception of sounds, numbness and tingling in the limbs, increased sensitivity to light, noise and touch, hallucinations or convulsive fits. Similar symptoms have been described after the abrupt withdrawal of therapeutic doses too, so the dose is always reduced gradually.
- alprazolam can cause anterograde amnesia, more often several hours after the dose; in that case 7–8 hours of uninterrupted sleep must be ensured;
- paradoxical reactions are possible — motor restlessness, psychomotor agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychoses, inappropriate behaviour; they occur more often in children and older people and require the medicine to be withdrawn;
- in patients with depression and suicidal tendencies special precautions are needed and the amount of medicine prescribed is limited; benzodiazepines must not be used as the sole treatment for depression or mixed anxiety-depressive disorder — this can increase the risk of suicide attempts;
- in patients with depression, episodes of hypomania and mania have been described during treatment with alprazolam;
- elderly and debilitated patients are prescribed the lowest effective dose: sedation and muscle weakness raise the risk of falls with serious consequences;
- in chronic respiratory failure the dose is reduced because of the danger of respiratory depression;
- in acute angle-closure glaucoma the corresponding precautions are required, and in impaired kidney function and mild or moderate hepatic failure, caution;
- benzodiazepines are not suitable for the main treatment of psychoses.
The medicine substantially affects the ability to drive and to operate machinery: sedation, amnesia, reduced concentration and muscle weakness worsen the reaction, and with a lack of sleep this is more marked. During treatment alcohol must not be consumed and other agents that depress the central nervous system must not be taken.
Drug interactions
Benzodiazepines act on the central nervous system additively with alcohol and with other agents that depress it, so alcohol is excluded during treatment. Caution is needed with medicines that depress breathing — above all with opioids (analgesics, cough medicines and those used in the treatment of dependence), especially in elderly patients. A strengthening of the depressant action on the nervous system 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 this raises the risk of psychological dependence.
The pharmacokinetic interactions relate to the metabolism of alprazolam through cytochrome CYP3A4: inhibitors of this enzyme raise its concentration and enhance its action. Concomitant use with ketoconazole, itraconazole, posaconazole, voriconazole and other azole antifungals is not recommended. Nefazodone and fluvoxamine increase the area under the alprazolam concentration curve roughly twofold, so in combination with them, and also with cimetidine, particular caution and possibly a reduction of the dose are needed.
Pregnancy and breastfeeding
The data on the teratogenic effect of the benzodiazepines and their influence on the development and behaviour of the child after birth are contradictory. Many cohort studies have shown no increase in the frequency of serious malformations with exposure in the first trimester; however, a number of early case-control studies found a twofold rise in the risk of cleft lip and palate. Large doses in the second and third trimesters led to a limitation of the active movements of the foetus and to a variable heart rhythm. Alprazolam is not recommended during pregnancy or when planning one; if it is nevertheless used or a pregnancy has occurred during treatment, the risk to the foetus is assessed.
Taking even small doses in the late stages can cause floppy infant syndrome in the newborn — axial hypotonia and difficulty sucking, because of which the child gains weight poorly. These manifestations are reversible but persist from one to three weeks, depending on the half-life of the medicine. With large doses, respiratory depression or apnoea and a fall in body temperature are possible in the newborn and, a few days after birth, withdrawal symptoms: increased excitability, restlessness and tremor, even if there was no floppy infant syndrome. Alprazolam passes into breast milk in small concentrations, but during breastfeeding it should not be used.
Adverse effects
The most distressing undesirable reactions are a consequence of an excessive pharmacological action of alprazolam. They usually appear at the start of therapy and lessen as treatment continues or when the dose is reduced.
- very common — sedation, drowsiness, ataxia, disturbances of memory and speech, dizziness, headache;
- very common — depression, tiredness, irritability, constipation, dry mouth;
- common — confusion and disorientation, anxiety, insomnia, nervousness, a decrease or increase in libido;
- common — disturbances of balance and coordination, reduced concentration, an increased need for sleep, apathy, tremor;
- common — blurred vision, nausea, reduced appetite, dermatitis, sexual disturbances, changes in weight;
- uncommon — mania, hallucinations, anger, agitation, amnesia, muscle weakness, urinary incontinence, irregular periods;
- frequency not known — hypomania, aggressive and hostile behaviour, disturbances of thought, increased psychomotor activity, dystonia;
- frequency not known — hepatitis, impaired liver function, jaundice, angioedema, photosensitivity, urinary retention, peripheral oedema, hyperprolactinaemia, raised intraocular pressure.
In many cases the patients with such symptoms were at the same time taking other medicines that act on the central nervous system.
Overdose
An overdose of benzodiazepines rarely threatens life, but one must remember that other agents depressing the central nervous system or alcohol may have been taken along with the medicine, and the patient's concomitant illnesses must also be taken into account. The manifestations of an overdose follow from the pharmacological action of the medicine.
Treatment comes down above all to maintaining breathing and circulation. In a coma the therapy is symptomatic, with prevention of complications — asphyxia from the tongue falling back or aspiration of the stomach contents; to prevent dehydration, fluids are given intravenously. If the patient is conscious, vomiting is induced within the first hour; if unconscious, the stomach is washed out with protection of the airway, after which activated charcoal is given to reduce absorption, together with an osmotic laxative. After very large doses the effect of the medicine may persist for a long time. Forced diuresis and haemodialysis are ineffective in this situation.
How to get a prescription for Xanax® online
Alprazolam is dispensed on prescription: prescribing it requires an assessment of the severity of the anxiety disorder, of any concomitant illnesses and of the risk of dependence, and the course is planned as a short one from the outset.
During the online consultation the doctor will discuss with you the symptoms, the permissible length of use 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.
