Alprox: composition and presentation
One tablet contains 0.25 mg, 0.5 mg or 1.0 mg of alprazolam. Three strengths are needed because the dose here is raised and lowered in small steps, and the step is measured in quarters of a milligram.
This matters in principle: with alprazolam both the treatment and its ending come with set timeframes. The total duration of therapy should not exceed 8–12 weeks, and that figure includes the period of gradual withdrawal.
How Alprox works
Alprazolam has a high affinity for the benzodiazepine binding sites in the brain. It is that affinity which eases the inhibitory action of gamma-aminobutyric acid in the central nervous system, and it does so both presynaptically and postsynaptically.
The substance's principal property is anxiolytic. But beyond it alprazolam also has sedative, hypnotic, muscle-relaxing and anticonvulsant properties, and all four explain part of its adverse effects: drowsiness, muscle weakness and the risk of falls that goes with it arise not in spite of the mechanism but because of it.
Indications
The first indication is anxiety disorders with panic attacks, that is, panic anxiety. The second is symptomatic treatment of anxiety.
A limitation is attached to the indications that is worth reading literally: the medicine is indicated only in situations where the symptoms are severe, disturb normal functioning or are very distressing for the patient. In other words, anxiety on its own is not a reason to prescribe it — what counts is how much it gets in the way of living. It is not prescribed to children and adolescents under 18: safety and efficacy in them have not been shown.
Method of use and dosage
The dose is chosen individually, and it differs markedly between the two indications. In symptomatic treatment of anxiety it starts at 0.25–0.5 mg three times a day, with a maintenance dose of 0.5–3 mg a day in divided doses. In anxiety disorder with panic attacks it starts at 0.5–1 mg a day taken before sleep, and is raised by no more than 1 mg at intervals of three or four days.
| Situation | Doses |
| Symptomatic treatment of anxiety | starting 0.25–0.5 mg three times a day, maintenance 0.5–3 mg a day in divided doses |
| Panic disorder | starting 0.5–1 mg a day before sleep; maintenance from 3 to 6 mg a day in 3–4 doses, and in some cases up to 10 mg a day |
| Elderly, frail, with liver or kidney failure, sensitive to the sedative effect | starting and maintenance dose 0.25 mg two or three times a day; if needed it is raised gradually, to a maximum of 4.5 mg a day |
| Children and adolescents under 18 | the medicine is not used |
| Total duration | no more than 8–12 weeks, including the period of gradual withdrawal; it may be extended only after the patient's condition is reassessed |
| Stopping the medicine | the dose is lowered gradually: by no more than 0.5 mg a day at three-day intervals, and some patients need an even slower pace |
The patient's condition is assessed regularly, and it is especially important to decide whether treatment should continue once the symptoms of the illness have gone. Trial data cover half a year of treating anxiety and up to eight months of treating panic disorder — beyond those periods experience is limited.
Contraindications
The list is short, and every item is tied to a particular property of benzodiazepines: hypersensitivity to the active substance or to any excipient; myasthenia gravis, because the medicine relaxes muscle; severe respiratory failure and severe sleep apnoea, because it depresses breathing; severe liver failure, because in such patients benzodiazepines can contribute to encephalopathy.
From the same properties follow the situations that call not for a ban but for caution.
- persistent respiratory failure — the dose is taken lower than usual, because the medicine depresses breathing;
- mild and moderate liver failure, and impaired kidney function — the medicine is used with care;
- old age — because of excessive sedation and muscle weakness leading to falls with serious consequences; the general rule for elderly and frail patients is the lowest effective dose, so that ataxia and over-sedation do not develop.
Special warnings and precautions
The hypnotic effect of alprazolam may weaken after several weeks of regular use, and long-term use of benzodiazepines can cause physical and psychological dependence. The risk grows with the dose and the length of treatment, is higher in people who misuse medicines, drugs or alcohol, and increases when several benzodiazepines are taken at once — whether they were prescribed for anxiety or for sleep. But dependence also arises at therapeutic doses and in patients without risk factors, so everyone has to be warned about it.
- once physical dependence has developed, stopping treatment brings withdrawal symptoms: headache and muscle pain, heightened anxiety, tension, disturbed sleep, restlessness, confusion and irritability;
- severe cases include depersonalisation, loss of the sense of reality, sharpened hearing, numbness of the limbs, hypersensitivity to light, noise and touch, hallucinations and convulsions; they may appear several days after treatment ends;
- separately there are rebound symptoms: whatever the medicine was prescribed for comes back and at first seems stronger than before — mood swings, insomnia, restlessness;
- alprazolam may cause anterograde amnesia, usually within a few hours of a dose;
- if restlessness, agitation, irritability, fits of aggression, nightmares, insomnia, hallucinations, psychoses, inappropriate behaviour, confusion or other behavioural disturbances appear, the medicine is stopped; such paradoxical reactions are more common in children and in the elderly.
From all this follows a rule the leaflet states outright: the doctor must tell the patient at the very start that treatment will be limited in time, and explain in detail how the dose will be tapered. It is important to prepare the patient for possible withdrawal symptoms in advance, so that their appearance causes as little alarm as possible. There is also a technical point: benzodiazepines with a short half-life produce withdrawal symptoms even when the dose is changed, especially at high doses, which is why ones with a long half-life are not swapped for short-acting ones.
Interactions with other medicines
The first group of interactions is a strengthening of the depressant effect on the central nervous system. It happens when the medicine is taken with any psychotropic drug: antipsychotics, hypnotics, sedatives, antidepressants, narcotic analgesics, antiepileptics, anaesthetics and antihistamines with a sedative component. With narcotic analgesics euphoria may occur, and that increases psychological dependence. Alcohol strengthens the sedative effect of alprazolam, and during treatment it must not be drunk.
- with opioids — analgesics, cough medicines and substitution treatment — particular caution is needed because of respiratory depression, especially in the elderly;
- with clozapine an increased risk of respiratory arrest and cardiac arrest has been described;
- with muscle relaxants the relaxing effect is strengthened and the risk of falls rises, especially at the beginning of treatment with alprazolam.
The second group involves the liver: alprazolam is metabolised by liver enzymes, above all CYP3A4, so substances that inhibit those enzymes strengthen its action and may call for a lower dose. Taking it together with itraconazole, ketoconazole and other antifungal azoles is not recommended; caution is needed with HIV protease inhibitors, fluoxetine, dextropropoxyphene, oral contraceptives, sertraline, diltiazem and macrolide antibiotics such as erythromycin. How much this matters is shown by the experience with itraconazole: given at 200 mg a day together with 0.8 mg of alprazolam, the area under the curve grew two- to threefold and the elimination half-life lengthened to about 40 hours. Withdrawing itraconazole, conversely, may weaken the action of alprazolam.
Pregnancy and breastfeeding
Numerous cohort studies show that exposure to benzodiazepines in the first trimester is not linked to an increased risk of major malformations. Some early case-control studies did find an increased risk of a cleft in the oral cavity, but the figures show its size: fewer than 2 cases per 1000 newborns after prenatal exposure, against about 1 per 1000 expected in the general population.
The danger has more to do with the end of pregnancy. High doses of benzodiazepines in the second and third trimesters reduce the fetus's active movements and the variability of its heart rhythm. If for important medical reasons treatment is needed in the last phase of pregnancy, even small doses may cause floppy infant syndrome in the newborn: axial hypotonia and difficulty sucking, because of which the baby gains weight poorly. These are transient but last one to three weeks depending on the half-life. High doses may cause respiratory depression or apnoea in the newborn and a fall in body temperature, and in the postpartum period withdrawal symptoms with heightened excitability, agitation and tremor, even where there are no signs of floppy infant syndrome. Use in pregnancy is therefore considered only where the therapeutic recommendations are strictly followed, high doses are avoided in the last phase and the newborn is monitored, and women of childbearing age are told when the medicine is prescribed that if they are planning a pregnancy or suspect one they should see a doctor about stopping it. Alprazolam passes into human milk, and it is not given to breastfeeding mothers.
Adverse reactions
Adverse reactions, when they occur, usually fall at the start of therapy and as a rule pass as treatment continues or after the dose is reduced. In more than one person in ten there are drowsiness and sedation, ataxia, dizziness and headache, disturbances of memory and speech, constipation and a dry mouth, and also depression. In roughly one in a hundred there are confusion and disorientation, anxiety, insomnia and nervousness, changes of libido in both directions, reduced appetite, disturbances of balance and coordination, difficulty concentrating, an excessive need for sleep, lethargy, tremor, blurred vision, nausea and vomiting.
Less often mania, hallucinations, anger, agitation and amnesia have been described, and with unknown frequency hyperprolactinaemia, hypomania, aggressive and hostile behaviour, atypical thinking, increased psychomotor activity, imbalance of the autonomic nervous system and dystonia have been reported. It is worth noticing that depression and memory disturbance ended up in the commonest group: for a medicine prescribed in anxiety that is a material circumstance, and it is worth discussing with the doctor before starting rather than after.
Overdose
An overdose of alprazolam on its own should not create a threat to life — except where the medicine has been taken together with other substances acting on the central nervous system, alcohol included. With an overdose of any medicine it is borne in mind that the person may have taken several at once.
Depression of the central nervous system usually develops: from drowsiness to coma. Mild manifestations are drowsiness, confusion and lethargy; in more severe cases ataxia, hypotonia, a fall in blood pressure and respiratory depression appear; coma occurs rarely, and very rarely an overdose leads to death. If the person is conscious, vomiting should be induced quickly; if the level of consciousness falls, the stomach is washed out after the airway has been secured by intubation, and if that is not enough activated charcoal is given along with a laxative. Forced diuresis and haemodialysis are ineffective. The specific antidote is flumazenil, used strictly according to the guidance and with the contraindications in mind. In patients in a coma treatment is mainly symptomatic: what matters is preventing a lack of oxygen from the tongue falling back or from aspiration of stomach contents, and supporting breathing.
How to get an Alprox prescription online
The medicine is available on prescription, and the conversation with the doctor differs from the usual one: the prescription includes a plan for ending the treatment from the outset. The doctor should explain that the course is limited to 8–12 weeks including withdrawal, and describe exactly how the dose will be tapered, so it is worth asking about those two points in advance.
For the online consultation prepare an account of what is actually happening: how severe the anxiety is, whether it interferes with work and sleep, whether there are panic attacks. Mention myasthenia gravis, lung disease and sleep apnoea, severe liver and kidney disease, any past misuse of alcohol, medicines or drugs, depression, and also pregnancy and any plans for one. List separately the medicines you take: hypnotics, antidepressants, antipsychotics, opioid analgesics, muscle relaxants, antifungal azoles, macrolides, anti-HIV drugs and oral contraceptives. The doctor will assess these circumstances and, if there are no contraindications, will issue an electronic prescription.
