Zolpidem adverse effects

More recently, non-BZD anxiolytics, such as buspirone, and nonbarbiturate, non-BZD hypnotics, such as zolpidem and zaleplon, have been developed. The more recent anxiolytics and hypnotics offer equal efficacy, fewer serious adverse effects, and less risk of a fatal consequence due to accidental or intentional overdose. Unfortunately, these compounds have not entirely eliminated the hazards of tolerance, dependency, and withdrawal syndromes, although they do have a lower abuse potential than their predecessors. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Zolpidem does not impair the psychomotor performance of patients the morning after administration. Adverse effects reported during its administration include dizziness and lightheadedness, somnolence, headache, and gastrointestinal upset. At doses of 10 mg there is no effect on anterograde memory [50, 82],... 

Zaleplon and zolpidem - stated to have little adverse effect on sleep profile. There is evidence that the therapeutic efficacy is maintained even after several months of treatment. 

From the published clinical studies, it would appear that the partial agonists bretazenil and abercamil are less likely to cause physiological dependence, have lower reinforcing effects and a lower incidence of subjective effects associated with abuse liability than the conventional 1,4-benzodiazepine sedative-hypnotics. It is presently unclear whether the full agonists for the GABA-A receptor, zolpidem and zopiclone, offer a real advance in the treatment of insomnia although their adverse effect profiles and abuse liability may be lower than that of the conventional benzodiazepines. 

Review of a Canadian adverse drug reactions database showed several cases of previously unreported benzodiazepine-induced adverse effects, including hallucinations and encephalopathy (97), although whether benzodiazepines alone were responsible is difficult to confirm. Visual hallucinations have also been reported in association with zolpidem (98). 

The adverse effects of zolpidem can be enhanced in hepatic cirrhosis (40). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

In a double-blind, placebo-controlled, crossover study, 10 patients with probable progressive supranuclear palsy took single oral doses of zolpidem (5 and 10 mg), co-careldopa (levodopa 250 mg plus carbidopa 25 mg), or placebo in four separate trials in random order (10). Zolpidem, unlike levodopa or placebo, reduced voluntary saccadic eye movements, and the 5 mg dose produced a statistically significant improvement in motor function. The adverse effects of zolpidem included drowsiness and... 

As measured by objective and subjective criteria, both zolpidem and flurazepam were effective hypnotics. Sleep stages were affected more by flurazepam than by zolpidem. The incidence of treatment-emergent adverse events was approximately the same for zolpidem (10 mg), flurazepam, and placebo. The 20-mgdose of zolpidem (twice the therapeutic dose) was associated with a higher incidence of adverse effects. It was concluded that no next day residual effects are associated with nightly intake (three nights) of the recommended dose of zolpidem. At this dose, zolpidem was an effective and safe hypnotic (75). 

The safety and efficacy of zolpidem for insomnia is similar to that of the benzodiazepines. As with other sedative medications, treatment optimally should not exceed 4 weeks to minimize tolerance and dependence. Zolpidem is less disruptive of sleep stages than benzodiazepines. The most common adverse effects include drowsiness, amnesia, dizziness, headache, and gastrointestinal complaints. Several cases of brief psychotic reactions have been reported in women. ... 

The recommended daily dose of zolpidem is 10 mg, but 5 mg is used in elderly patients and those with hepatic impairment. The dosage may be increased to 20 mg per night, but the incidence of adverse effects is dose related. ... 

Other adverse effects Barbiturates and carbamates (but not benzodiazepines, buspirone, zolpidem, or zaleplon) induce the formation of the liver microsomal enzymes that metabolize dmgs. This enzyme induction may lead to multiple drug interactions. Barbiturates may also precipitate acute intermittent porphyria in susceptible patients. Chloral hydrate may displace coumarins from plasma protein binding sites and increase anticoagulant effects. 

Valproate appears to increase the serum levels of diazepam lo-razepam and possibly midazolam, while clobazam appears to raise valproate levels. Clonazepam clearance may increase and valproate clearance decrease during concurrent use, and increased adverse effects have been seen. An isolated case describes sleepwalking in a patient taking valproate and zolpidem. 

However, a pharmacodynamic interaction may occur. Hallucinations have been seen with zolpidem alone, and they have also occurred, rarely, when zolpidem and some benzodiazepines were given with the SSRIs , (below), which are related to venlafaxine. However, adverse effects such as these seem rare and the concurrent use of these drugs need not be avoided, but bear this possible interaction in mind if hallucinations occur. 

In contrast, isolated cases of visual hallucinations lasting up to 7 hours have been reported in patients taking zolpidem who were also taking fluoxetine. Marked drowsiness occurred for a whole day in a patient taking fluoxetine 20 mg daily after being given cloral hydrate 500 mg the night before. She later tolerated cloral hydrate 1 g in the absence of fluoxetine without adverse effects. ... 

Visual hallucinations lasting 3 to 4 hours occurred in a 17-year-oid boy who had been taking bupropion 450 mg daiiy for one month and zolpidem 5 to 10 mg daily for about 6 months, when he increased the zolpidem dose to 60 mg. Note that the recommended dose of zolpidem is 10 mg daily and that zolpidem itself can cause psychiatric adverse effects such as hallucinations. Therefore an interaction is not established. Bupropion is contraindicated during abrupt withdrawal from any drug known to be associated with seizures on withdrawal, particularly benzodiazepines and benzodiazepine-like drugs. ... 

In chnical trials, zolpidem shortened sleep latency, improved the quahty of sleep, and accelerated the restoration of normal sleep patterns (Lee, 2004). In insomniac patients it increased the amount of slow wave, restorative sleep as seen in normal sleepers. Zolpidem has high oral bioavailability (70%), a short duration of action (tj /2 = 2 h), and is relatively highly bound to plasma proteins (92%). The recommended dose is generally 10 mg/day as needed. Zolpidem is extensively metabolized, mainly by CYP3A4 but also by CYP1A2 and CYP2C9, and its major metabolites do not appear to have pharmacological activity. It has minimal daytime residual effects, and a low risk for tolerance and abuse. The safety profile showed a low incidence of adverse events, close to that observed with placebo. The medicine is available in over 80 countries. 

Zaleplon and zolpidem have been compared in two concurrent multicenter, randomized, double-blind, placebo-controlled crossover studies in chronic insomniacs (12). In study 1, zaleplon 10 mg, zolpidem 10 mg, or placebo were given double-bhnd to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study (13). The subjects were gently awakened and given the medication at predetermined times, 5, 4, 3, or 2 hours before morning awakening, which occurred 8 hours after bedtime. When they awoke in the morning, subjective and objective assessments of residual effects of hypnotics were administered. There were no serious adverse experiences during the study all adverse events were mild to moderate. The most commonly reported adverse events associated with zaleplon were weakness and somnolence. Weakness, depersonalization, dizziness, and somnolence were the most frequent nervous system adverse events associated with zolpidem. 

Zolpidem 10 mg/day and zopiclone 7.5 mg/day, given at night, have been compared in a 14-day, double-blind study in 479 chronic primary insomniacs (17). With zolpidem 68% of the patients were rated at least moderately improved, versus 62% with zopiclone. However, with zolpidem sleep-onset latency improved in significantly more patients (86 versus 78%). In addition, significantly fewer patients who took zolpidem had drug-related adverse events (31 versus 45%) bitter taste accounted for 5.8% of such complaints with zolpidem compared with 40% with zopiclone. In conclusion, zolpidem was at least as effective as zopiclone but showed significantly less rebound on withdrawal overall it was better tolerated. 

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