Zoldem
Sleep inducing agent
Go backPharmacokinetics
Zolpidem has both a rapid absorption and onset of hypnotic action. It has a bioavailability of about 70% following oral administration and demonstrates linear kinetics in the therapeutic dose range. Peak plasma concentration is reached between 0.5 and 3 hours. There is a short elimination half-life of mean 2.4 hrs (2-4) with a duration of action of upto 6 hours.
Total protein binding is 92.5% and remains constant independent of plasma concentration. First pass metabolism by the liver amounts to approximately 35%. All metabolites are pharmacologically inactive and are eliminated in the urine (56% and in the faeces 37%).
Plasma concentrations in elderly subjects and those with hepatic impairment are increased. In patients with renal insufficiency, zolpidem pharmacokinetics are not significantly different from those seen in the healthy population. As a general precaution however, renal patients should be closely monitored while being put nightly zolpidem.
Description
Contra-indications:
Hypersensitivity to zolpidem, Patients with psychotic illness, Patients with obstructive sleep apnea, myasthenia gravis, severe hepatic insufficiency, acute pulmonary insufficiency or respiratory depression.
Warnings and Precautions:
The cause of insomnia should be identified wherever possible and the underlying factors treated before a hypnotic is prescribed. The failure of insomnia to remit after a 7-14 day course of treatment may indicate the presence of a primary psychiatric or physical disorder which should be evaluated. Although studies have shown that during the day following medication with zolpidem, simulated vehicle driving is unaffected, vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of drowsiness the morning after therapy.
Use in depressed patients :
As with other sedative/hypnotic drugs, zolpidem should be administered with caution in patients exhibiting symptoms of depression. Suicidal tendencies may be present therefore the less amount of drug that is feasible should be supplied to these patients because of the possibility of intentional overdosage by the patient.
Use in patients prone to substance abuse :
Extreme caution should be exercised when prescribing for patients with a history of drug or alcohol abuse. These patients should be under careful surveillance when receiving zolpidem or any other hypnotic, since they are at risk of habituation and psychological dependence.
General precautions related to hypnotics usage :
General information relating to effects seen following administration of benzodiazepines and other hypnotic agents which should be taken into account by the prescribing physician are described below.
Tolerance :
Some loss of efficacy to the hypnotic effects of short–acting benzodiazepines and benzodiazepine-like agents may develop after repeated use for a few weeks.
Dependence :
Use of benzodiazepines or benzodiazepine-like agents may lead to the development of physical and psychological dependence on these products. The risk of dependence increases with dose and duration on treatment, it is also greater in patients with a history of alcohol or drug abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches or muscle pain, extreme anxiety and tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur, derealisation, depersonalization, hyperacusis, numbness and tingling of the extremities, hyper-reactiveness to light, noise and physical contact, hallucinations or epileptic seizures.
Rebound insomnia :
A transient syndrome, whereby the symptoms of sleeplessness that led to treatment with a benzodiazepines or benzodiazepine-like agent, may recur in an enhanced form on withdrawal of hypnotic treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. It is important that the patient should be aware of the possibility of rebound phenomena. It is helpful to minimize anxiety over such symptoms, should they occur when the medicinal product is discontinued. Since the risk of withdrawal phenomena or rebound insomnia has been shown to be greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually where clinically appropriate.
There are indications that, in the case of benzodiazepines and benzodiazepine-like agents with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
Amnesia :
Benzodiazepines or benzodiazepine-like agents may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product, and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours.
Psychiatric and ‘paradoxical‘ reactions :
Reactions like restlessness agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents. Should this occur, use of the product should be discontinued. These reactions are more likely to occur in the elderly.
Pregnancy & Lactation :
Safety in human pregnancy has not been established. As with all drugs, Zoldem should be avoided in pregnancy particularly during the first trimester. Infants born to mothers who took benzodiazepines or benzodiazepine-like agents chronically during late pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period. Small quantities of zolpidem appear in breast milk. Therefore, the use of zolpidem in nursing mothers is not recommended.
If the product is prescribed to a woman of child bearing potential, she should be warned to contact her physician about stopping the product if she intends to become or suspects that she is pregnant.
Drug Interactions:
Concomitant intake of zolpidem with alcohol is not recommended. The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), anxiolytics/sedatives, anti-depressant agents, narcotic analgesics, antiepileptic drugs, anaesthetics and sedative
antihistamines.
In the case of narcotic analgesics, enhancement of the euphoria may also occur leading to an increase in addiction potential.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines and benzodiazepine-like agents.
Side effects :
There is evidence of a dose-relationship for adverse effects associated with zolpidem use, particularly for certain CNS and gastrointestinal events. These occur most frequently in elderly patients.
In clinical trials side effects observed during treatment at doses up to 10 mg included drowsiness, dizziness, diarrhea, headache, nausea, asthenia and vertigo.
Memory disturbance (anterograde amnesia), nightmares, nocturnal restlessness depressive syndrome, episodes of confusion, perceptual disturbances or diplopia, tremor, unsteady gait and falls have been observed very rarely in long term clinical trials.
Overdosage :
In reports of overdose with zolpidem alone, impairment of consciousness has ranged from somnolence to light coma. Individuals have fully recovered from zolpidem overdoses upto 400 mg, 40 times the recommended dose.
General symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate; intravenous fluids should be administered as needed. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Sedating drugs should be withheld even if excitation occurs. Zolpidem has been shown to be non-dialysable. Use of flumazenil may be considered where serious symptoms are observed.
Use in hepatic impairment:
As clearance and metabolism of zolpidem is reduced in hepatic impairment, dosage should begin at 5 mg with particular caution being exercised in elderly patients. In adults (under 65 years) the dosage may be increased to 10 mg only where the clinical response is inadequate and the drug is well tolerated.
Children:
Not recommended for use in children.
