Chemical formula: C₁₉H₂₁N₃O Molecular mass: 307.39 g/mol PubChem compound: 5732
Zolpidem interacts in the following cases:
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as Stilnoct with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited.
Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, antiepileptic drugs, anaesthetics and sedative antihistamines. Therefore, concomitant use of Stilnoct with these drugs may increase drowsiness and next-day psychomotor impairment, including impaired driving ability.
The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
Co-administration of zolpidem with ketoconazole (200 mg twice daily), a potent CYP3A4 inhibitor, prolonged zolpidem elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to zolpidem plus placebo. The total AUC for zolpidem, when co-administered with ketoconazole, increased by a factor of 1.83 when compared to zolpidem alone. A routine dosage adjustment of zolpidem is not considered necessary, but patients, should be advised that use of zolpidem with ketoconazole may enhance the sedative effects.
Zolpidem tartrate is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. The pharmacodynamic effect of zolpidem tartrate is decreased when it is administered with a CYP3A4 inducer such as rifampicin and St. John’s Wort. St. John’s Wort has been shown to have a pharmacokinetic interaction with zolpidem. Mean Cmax and AUC were decreased (33.7 and 30.0% lower, respectively) for zolpidem administered with St. John’s Wort compared to zolpidem administered alone. Co-administration of St. John’s Wort may decrease blood levels of zolpidem, concurrent use is not recommended.
As clearance and metabolism of zolpidem tartrate is reduced in hepatic impairment, dosage should begin at 5 mg in these patients with particular caution being exercised in elderly patients. In adults (under 65 years) dosage may be increased to 10 mg only where the clinical response is inadequate and the drug is well tolerated.
Also, isolated cases of visual hallucinations were reported in patients taking zolpidem with antidepressants including bupropion, desipramine, fluoxetine, sertraline and venlafaxine.
Co-administration of ciprofloxacin may increase blood levels of zolpidem tartrate, concurrent use is not recommended.
Co-administration of fluvoxamine may increase blood levels of zolpidem tartrate, concurrent use is not recommended.
Sleep walking and other associated behaviours such as “sleep driving”, preparing and eating food, making phone calls or having sex, with amnesia for the event, have been reported in patients who had taken zolpidem and were not fully awake. The use of alcohol and other CNS-depressants with zolpidem appears to increase the risk of such behaviours, as does the use of zolpidem at doses exceeding the maximum recommended dose. Discontinuation of zolpidem should be strongly considered for patients who report such behaviours (for example, sleep driving), due to the risk to the patient and othes.
The use of zolpidem is not recommended during pregnancy.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Zolpidem crosses the placenta.
A large amount of data on pregnant women (more than 1000 pregnancy outcomes) collected from cohort studies has not demonstrated evidence of the occurrence of malformations following exposure to benzodiazepines or benzodiazepine-like substances during the first trimester of pregnancy. However, certain case-control studies reported an increased incidence of cleft lip and palate associated with use of benzodiazepines during pregnancy.
Cases of reduced fetal movement and fetal heart rate variability have been described after administration of benzodiazepines or benzodiazepine-like substances during the second and/or third trimester of pregnancy.
Administration of zolpidem during the late phase of pregnancy or during labour has been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties (“floppy infant syndrome”) and respiratory depression due to the pharmacological action of the product. Cases of severe neonatal respiratory depression have been reported.
Moreover, infants born to mothers who took sedative/hypnotic agents chronically during the latter stages of pregnancy may have developed physical dependence and may be at risk of developing withdrawal symptoms in the postnatal period. Appropriate monitoring of the newborn in the postnatal period is recommended.
If zolpidem is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the product if she intends to become or suspects that she is pregnant.
Small quantities of zolpidem appear in breast milk. The use of zolpidem in nursing mothers is therefore not recommended.
Zolpidem has major influence on the ability to drive and use machines.
Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision and reduced alertness and impaired driving the morning after therapy. In order to minimise this risk a resting period of at least 8 hours is recommended between taking zolpidem and driving, using machinery and working at heights.
Driving ability impairment and behaviours such as “sleep-driving” have occurred with zolpidem alone at therapeutic doses.
Furthermore, the co-administration of zolpidem with alcohol and other CNS depressants increases the risk of such behaviours. Patients should be warned not to use alcohol or other psychoactive substances when taking zolpidem.
The following CIOMS frequency rating is used, when applicable: Very common ≥10%, Common ≥1 and <10%, Uncommon ≥0.1 and <1%, Rare ≥0.01 and <0.1%, Very rare <0.01%, Not known: cannot be estimated based on available data.
There is evidence of a dose-relationship for adverse effects associated with zolpidem tartrate use, particularly for certain CNS and gastrointestinal events. They should in theory be less if zolpidem tartrate is taken immediately before retiring, or in bed. They occur most frequently in elderly patients.
Not known: angioneurotic oedema
Common: hallucination, agitation, nightmare, depression
Uncommon: confusional state, irritability, restlessness, aggression, somnambulism, euphoric mood
Rare: libido disorder
Very rare: delusion, dependence (withdrawal symptoms, or rebound effects may occur after treatment discontinuation)
Not known: anger, psychosis, abnormal behaviour
Most of these psychiatric undesirable effects are related to paradoxical reactions
Common: somnolence, headache, dizziness, exacerbated insomnia, cognitive disorders such as anterograde amnesia (amnestic effects may be associated with inappropriate behaviour)
Uncommon: paraesthesia, tremor, disturbance in attention, speech disorder
Rare: depressed level of consciousness
Uncommon: diplopia, vision blurred
Very rare: visual impairment
Very rare: respiratory depression
Common: diarrhea, nausea, vomiting, abdominal pain
Uncommon: liver enzymes elevated
Rare: hepatocellular, cholestatic or mixed liver injury
Uncommon: appetite disorder
Uncommon: rash, pruritus, hyperhidrosis
Rare: urticaria
Common: back pain
Uncommon: myalgia, muscle spasms, muscular weakness
Common: upper respiratory tract infection, lower respiratory tract infection
Common: fatigue
Rare: gait disturbance, fall (predominantly in elderly patients and when zolpidem was not taken in accordance with prescribing recommendation)
Not known: drug tolerance
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