Each tablet contains:
Zolpidem Hemitartrate .................10 mg
It is a -.white, oblong, biconvex tablet, a S|T is scored on the one side
and 385 on the other side.
Subunit modulation of the GABAa receptor chloride channel macromolecular
complex is hypothesized to be responsible for sedative, anticonvulsant,
anxiolytic, and myorelaxant drug properties. The major modulatory site of
the GABAa receptor complex is located on its alpha subunit and is referred
to as the benzodiazepine (BZ) or receptor. At least three subtypes of the
receptor have been identified.
While zolpidem is a hypnotic agent with a chemical structure unrelated to
benzodiazepines, barbiturates, or other drugs with known hypnotic
properties, it interacts with a GABA-BZ receptor complex and shares some of
the pharmacological properties of the benzodiazepines. In contrast to the
benzodiazepines, which non-selectively bind to and activate all three omega
receptor subtypes, zolpidem in vitro binds the receptor preferentially. The
receptor is found primarily on the Lamina IV of the sensorimotor cortical
regions, substantia nigra (pars reticulata), cerebellum molecular layer,
olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and
globus pallidus. This selective binding of zolpidem on the receptor is not
absolute, but it may explain the relative absence of myorelaxant and
anticonvulsant effects in animal studies as well as the preservation of deep
sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses.
The pharmacokinetic profile of zolpidem Hemitartrate is characterized by
rapid absorption from the GI tract and a short elimination half-life (T1/2)
in healthy subjects. In a single- dose crossover study in 45 healthy
subjects administered 5 and 10 mg Zolpidem Hemitartrate tablets, the mean
peak concentrations (Cmax) were 59 (range: 29 to 113) and 121 (range: 58 to
272) ng/ml, respectively, occurring at a mean time (Tmax) of 1.6 hours for
both. The mean Zolpidem Hemitartrate elimination half-life was 2.6 (range:
1.4 to 4.5) and 2.5 (range: 1.4 to 3.8) hours, for the 5 and 10 mg tablets,
respectively. Zolpidem Hemitartrate is converted to inactive metabolites
that are eliminated primarily by renal excretion. Zolpidem Hemitartrate
demonstrated linear kinetics in the dose range of 5 to 20 mg. Total protein
binding was found to be 92.5± 0.1% and remained constant, independent of
concentration between 40 and 790 ng/ml. Zolpidem did not accumulate in young
adults following nightly dosing with 20 mg zolpidem Hemitartrate tablets for
A food-effect study in 30 healthy male volunteers compared the
pharmacokinetics of zolpidem Hemitartrate 10 mg when administered while
fasting or 20 minutes after a meal. Results demonstrated that with food,
mean AUC and Cmax were decreased by 15% and 25% respectively, while mean
Tmax was prolonged by 60% (from 1.4 to 2.2 hr). The half-life remained
unchanged. These results suggest that, for faster sleep onset, zolpidem
Hemitartrate should not be administered with or immediately after a meal.
In the elderly, the dose for Zolpidem Hemitartrate should be 5 mg. This
recommendation is based on several studies in which the mean Cmax, T1/2, and AUC were significantly increased when compared to results in young adults.
In one study of eight elderly subjects (> 70
years), the means for Cmax, T1/2, and AUC significantly increased by
50% (255 vs 284 ng/ml), 32% (2.2 vs 2.9 hr), and 64% (955 vs 1,562 ng •
hr/ml), respectively, as compared to younger adults (20 to 40 years)
following a single 20 mg oral Zolpidem dose. Zolpidem Hemitartrate did not
accumulate in elderly subjects following nightly oral dosing of 10 mg for 1
DOSAGE AND ADMINISTRATION
Dose - The treatment should always be implemented at the lowest effective
dose and maximum dosage never exceeded.
The usual dose for adults is one 10mg tablet daily.
The medicinal product should always be taken just before going to bed.
In elderly subjects or subjects presenting with hepatic insufficiency,
dosage should be halved, i.e. 5mg.
Dosage must never exceeded 10mg per day.
In the absence of clinical studies, Zolpidem should not be given to
Zolpidem can be prescribed either continuously or on demand, depending on
the patient's symptoms.
Treatment duration - The treatment period should be as short as possible,
from a few days to four weeks, including the tapering period. The patients
should be advised to take the treatment as follows 2 to 5 days for
occasional insomnia (e.g. during a trip) 2 to 3 weeks for transient insomnia
(e.g. during a troubled period)
Very short treatment periods do not require any gradual treatment
For certain patients, it may be necessary to continue treatment for longer
than four weeks, in which case careful and repeated reassessment of the
patient's condition is necessary.
Mode of Administration
WARNING & PRECAUTIONS
ANAPHYLAXIS (SEVERE ALLERGIC REACTION) AND ANGIOEDEMA (SEVERE FACIAL
SWELLING) WHICH CAN OCCUR AS EARLY AS THE FIRST TIME THE PRODUCT IS TAKEN.
COMPLEX SLEEP-RELATED BEHAVIORS WHICH MAY INCLUDE SLEEP DRIVING, MAKING
PHONE CALLS, PREPARING AND EATING FOOD (WHILE ASLEEP).
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, and the patient
should be carefully re-evaluated at regular intervals.