Estazolam TZF: composition and dosage form
One tablet contains 2 mg of estazolam. There is only one strength, and all the flexibility of treatment comes from splitting it: the usual adult dose runs from half a tablet to a whole one, and older people are advised to take half of that.
The tablet is taken by mouth with a little water, 30 minutes before sleep. The rule for choosing the dose fits in one line: the lowest effective dose is used and it is raised gradually.
How Estazolam TZF works
Estazolam belongs to the triazolo derivatives of the benzodiazepines. It acts on many structures of the central nervous system, above all on the limbic system and the hypothalamus — that is, on the structures involved in regulating the emotions. Like all benzodiazepines it enhances the inhibitory action of GABAergic neurons in the cortex, the hippocampus, the cerebellum, the thalamus and the hypothalamus.
The mechanism is described in detail. Estazolam alters the "sensitivity" of the GABAergic receptor, increasing its affinity for gamma-aminobutyric acid, the endogenous inhibitory neurotransmitter. Activating the benzodiazepine receptor or the GABA-A receptor results in an increased flow of chloride ions into the neuron through the chloride channel, hyperpolarisation of the membrane and, in the end, inhibition of neuronal activity. Clinically this looks like a hypnotic effect, and one detail matters here: estazolam shortens the time it takes to fall asleep, while it has less influence on the length of sleep and the number of night-time awakenings. It also has weak anticonvulsant properties and slightly reduces skeletal muscle tone.
Indications
There is a single indication and it fits in one line: occasionally and short-term in the treatment of sleep disorders — difficulty falling asleep, frequent night-time awakenings, early morning waking. Note the two qualifiers at the start: "occasionally" and "short-term". They are not a caveat but the substance of the indication itself.
Set that against the description of the mechanism and the picture sharpens: the medicine works most strongly where the problem is falling asleep, and influences night-time awakenings less, even though those are listed in the indication too.
Method of administration and dosage
The dose and the length of treatment are set individually for each patient, but the frame drawn around them is narrow.
- adults are usually given 1–2 mg, that is from half a tablet to a whole one, half an hour before sleep;
- patients over 65 are advised to halve the dose;
- in impaired kidney or liver function caution is needed, and a dose reduction may prove necessary;
- children and adolescents are not given the medicine: the safety and efficacy of estazolam in people under 18 have not been established;
- treatment is kept as short as possible — the reference point is 7–10 days; in individual cases it lasts longer, but it must not be extended without reassessing the patient.
The last rule weighs more than the others and is repeated three times in the product information: the medicine must not be stopped abruptly, the dose is always reduced gradually. The reason lies not in estazolam itself but in what happens when it is broken off suddenly — which the next section covers.
Contraindications
The first two prohibitions are the expected ones: hypersensitivity to estazolam, to other benzodiazepine derivatives or to the excipients, and poisoning with alcohol or with medicines that depress the central nervous system. Next come the respiratory ones — severe respiratory failure whatever its cause, and sleep apnoea syndrome. The second is worth remembering separately: a person with untreated apnoea comes complaining precisely of sleeping badly, and a hypnotic from this group is forbidden to them.
The remaining four contraindications look unexpected for a sleeping tablet. They are dizziness and balance disorders — exactly what the medicine is capable of making worse. They are disorders of consciousness. They are myasthenia, where relaxing the muscles becomes dangerous. And they are acute porphyria: estazolam can aggravate its manifestations.
Special warnings and precautions
The gravest warning concerns combining it with opioids: that can cause sedation, respiratory depression, coma and death. Such a combination is therefore reserved for patients in whom alternative forms of treatment are not possible, the lowest effective dose is used for the shortest possible time, and the signs of respiratory depression and sedation are watched closely, with both the patient and their carers warned about them.
| What happens | Why | What to do |
| Psychological and physical dependence | the risk grows with the dose and the duration and is higher with a history of dependence on alcohol, drugs or medicines | regular monitoring, no routine repeat prescribing, gradual dose reduction |
| Withdrawal symptoms on abrupt discontinuation | headache, muscle pain, anxiety, tension, agitation, confusion, sleep disturbance, irritability; in severe cases loss of the sense of reality, personality changes, hypersensitivity to sound and light, hallucinations, epileptic seizures | reduce the dose gradually and warn the patient in advance |
| Rebound effect | a temporary intensification of the very sleep disturbance the medicine was prescribed for, along with mood changes and anxiety | explain it to the patient at the start so the symptoms do not frighten them on withdrawal |
| Anterograde amnesia | possible even at therapeutic doses, with a higher risk at larger ones; appears a few hours after the dose and may be accompanied by behaviour inappropriate to the situation | ensure 7–8 hours of uninterrupted sleep |
| Paradoxical reactions | behaviour shifts in the direction opposite to the one expected — agitation instead of calm; more often in children and older people | stop treatment |
The paradoxical reactions are worth spelling out, because they are the hardest to recognise: with benzodiazepines, restlessness, agitation, irritability, aggression, anger, rage, delusions, nightmares, hallucinations, psychoses, personality changes and other unwanted effects on behaviour have been observed. Separately listed are the groups that need a lower dose. Older and debilitated patients, because of disturbed orientation and coordination and therefore falls and injuries; patients with chronic respiratory failure, because of respiratory depression. In severe liver failure benzodiazepines are not indicated at all: there is a risk of encephalopathy. There is also what estazolam is not: benzodiazepines are not indicated in psychotic disorders and are not used as the sole treatment for depression or for anxiety associated with depression — such monotherapy can intensify suicidal tendencies. With prolonged treatment a periodic blood count with a smear and a urine test are recommended. And finally: drowsiness, amnesia and reduced concentration limit the ability to drive and to operate machinery, and with insufficient sleep the risk is higher still.
Interaction with other medicines
The pharmacokinetic interactions come down to a single enzyme. Estazolam is metabolised with the participation of cytochrome P450, mainly by CYP3A, and medicines that affect the activity of those enzymes alter its action. Inhibitors — cimetidine, disulfiram, fluvoxamine, fluoxetine, omeprazole, erythromycin, ketoconazole — slow the biotransformation of estazolam and may intensify its effect; inducers — rifampicin, phenytoin, carbamazepine — speed it up and may weaken the effect. To that same group belongs an unexpected member: oral contraceptives accelerate the metabolism of estazolam, and taking them at the same time can weaken its effect.
The pharmacodynamic interactions are simpler in mechanism and more dangerous in consequence. Enhancement of the sedative effect, of the effect on breathing and on haemodynamic parameters is seen when benzodiazepines are combined with medicines that depress the central nervous system: neuroleptics and antipsychotics, anxiolytics and sedatives, antidepressants, hypnotics, antiepileptics, narcotic analgesics, anaesthetics, sedating antihistamines and skeletal muscle relaxants. Narcotic analgesics have a further feature: together with estazolam they intensify euphoria, and that leads to psychological dependence developing faster. Alcohol enhances the depressant effect of the medicine on the central nervous system, so it must not be drunk during treatment.
Pregnancy and breastfeeding
The wording about pregnancy is stern and hedged in two places at once. Use in pregnant women, especially in the first and third trimesters, is permissible only when it is absolutely necessary for the mother and when using a safer equivalent is impossible or contraindicated. Preclinical safety data and epidemiological data point to a teratogenic effect of estazolam.
What happens to the child is described separately. Use in the third trimester or in the perinatal period can cause a fall in body temperature and blood pressure in the newborn, disturbances of heart rhythm and breathing, and a weakened sucking reflex. In the children of mothers who took benzodiazepines long-term late in pregnancy, physical dependence develops, and withdrawal symptoms are possible after birth. Breastfeeding is not allowed during treatment, and if the mother needs the medicine, the child is weaned.
Adverse effects
The number and severity of unwanted effects depend on individual sensitivity and on the dose; they are usually mild and pass once the medicine is withdrawn. Most of what is described is neurological: drowsiness, slowed reactions, headache and dizziness, states of confusion and disorientation, ataxia. These appear more often at the start of treatment and in older people and generally pass as the course goes on, while a dose reduction helps if they intensify. Sometimes, especially after large doses, dysarthria with slurred speech, memory disturbances and disturbances of libido appear.
The rest is shorter. With unknown frequency, changes in the morphological composition of the blood are recorded; allergic skin reactions — rashes, itching, urticaria; loss of appetite; blurred and double vision; bradycardia and chest pain; a slight fall in blood pressure; a small rise in aminotransferases and liver dysfunction with jaundice; muscle tremor and muscle relaxation; urinary retention and incontinence; menstrual disturbances; weakness and fainting. Rarely there are nausea, gastric complaints and a dry mouth, and very rarely anaphylactic reactions. One line deserves separate attention: during treatment with estazolam a previously existing, undiagnosed depression may come to light.
Overdose
The usual signs of benzodiazepine overdose are drowsiness, incoordination of movement, impaired speech and nystagmus. An overdose of estazolam rarely threatens life if the medicine was taken on its own, but it can lead to diminished reflexes, apnoea, a fall in blood pressure, circulatory and respiratory depression and coma. The coma usually lasts several hours, though it sometimes drags on and recurs, particularly in older people, and respiratory depression is more marked in those with respiratory disease.
Vital signs are monitored and supportive measures applied according to the patient's condition, with symptomatic treatment if signs of respiratory and circulatory failure appear. Further absorption is prevented by activated charcoal given within 1–2 hours; sleeping patients who have been given charcoal must have their airway kept clear. In severe central nervous system depression, giving the benzodiazepine antagonist flumazenil is considered, but only under strict monitoring: its half-life is about an hour, so once its action ends the patient still needs observation, and alongside medicines that lower the seizure threshold, such as tricyclic antidepressants, it is used with great caution. And two separate rules: barbiturates are not given for seizures, and in treating any overdose it is borne in mind that the patient may have taken several different medicines.
How to get a prescription for Estazolam TZF online
The list of estazolam's contraindications contains an item that turns the usual logic on its head: sleep apnoea syndrome. A person with untreated apnoea comes complaining precisely of broken sleep and early waking — that is, of exactly what the indications describe — and a hypnotic from this group is forbidden to them. That is why the conversation about a prescription begins not with the insomnia but with its cause. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Describe the sleep itself in the questionnaire: what exactly is disturbed — falling asleep, night-time awakenings or early morning waking — how long it has been going on, and whether you snore loudly with pauses in breathing that those around you have noticed. Report separately any respiratory disease, myasthenia, porphyria, balance disorders and dizziness: these are direct contraindications. Say whether there was dependence on alcohol, drugs or medicines in the past and whether you have taken sleeping tablets before. List your medicines: opioid analgesics require a separate decision by the doctor, while neuroleptics, antidepressants, antiepileptics, sedating antihistamines and muscle relaxants strengthen the effect; name oral contraceptives separately — they weaken it. And bear in mind from the outset that the course is planned for 7–10 days and ends with a gradual dose reduction, not an abrupt stop.
