Presentation and Status in Health Basket
Film Coated Tablets
20 X 10 mg
Dosage in Adults: Use the lowest effective dose for the patient. The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness. The total dose of Stilnox should not exceed 10 mg once daily immediately before bedtime. The recommended initial doses for women and men are different because zolpidem clearance is lower in women.
Special Populations: Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of Stilnox in both of these patient populations is 5 mg (half tablet) once daily immediately before bedtime.
Use with CNS Depressants: Dosage adjustments may be necessary when Stilnox is combined with other CNS depressant drugs because of the potentially additive effects.
Indications are limited to treatment of severe sleep disorders in the following cases: Occasional insomnia, Transient insomnia. The short-term treatment of insomnia in situations where the insomnia is debilitating or is causing severe distress to the patient. As with all hypnotics long term use is not recommended and a course of treatment should not exceed 4 weeks. Hypnotics should generally be limited to 7 to10 days of use, and reevaluation of the patient is recommended if they are to be taken for more than 2 to 3 weeks.
Stilnox is contraindicated in patients with known hypersensitivity to zolpidem tartrate or to any of the inactive ingredients in the formulation. Observed reactions include anaphylaxis and angioedema.
As with all hypnotics long term use is not recommended and a course of treatment should not exceed 4 weeks. Hypnotics should generally be limited to 7 to10 days of use, and reevaluation of the patient is recommended if they are to taken for more than 2 to 3 weeks.
CNS Depressant Effects and Next-Day Impairment: Stilnox, like other sedative-hypnotic drugs, has central nervous system (CNS) depressant effects. Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. Dosage adjustments of Stilnox and of other concomitant CNS depressants may be necessary when Stilnox is administered with such agents because of the potentially additive effects. The use of Stilnox with other sedativehypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended. The risk of next-day psychomotor impairment, including impaired driving, is increased if Stilnox is taken with less than a full night of sleep remaining (7- to 8 hours); if a higher than the recommended dose is taken; if co-administered with other CNS depressants; or if coadministered with other drugs that increase the blood levels of zolpidem. Patients should be cautioned against driving and other activities requiring complete mental alertness if Stilnox is taken in these circumstances.
Need to Evaluate for Co-morbid Diagnoses: Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative/hypnotic drugs, including zolpidem.
Severe Anaphylactic and Anaphylactoid Reactions: Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including zolpidem. Some patients have had additional symptoms such as dyspnea, throat closing or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the throat, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should not be rechallenged with the drug.
Abnormal Thinking and Behavioral Changes: Abnormal thinking and behavior changes have been reported in patients treated with sedative/hypnotics, including Stilnox. Some of these changes included decreased inhibition (e.g. aggressiveness and extroversion that seemed out of character), bizarre behavior, agitation and depersonalization. Visual and auditory hallucinations have been reported. In controlled trials of Stilnox 10mg taken at bedtime <1% of adults with insomnia reported hallucinations. In a clinical trial, 7% of pediatric patients treated with Stilnox 0.25mg/kg taken at bedtime reported hallucinations versus 0% treated with placebo. Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons. Although behaviors such as “sleep-driving” have occurred with Stilnox alone at therapeutic doses, the co-administration of Stilnox with alcohol and other CNS depressants increases the risk of such behaviors, as does the use of Stilnox at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Stilnox should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with “sleep-driving”, patients usually do not remember these events. Amnesia, anxiety and other neuro-psychiatric symptoms may also occur. It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
Use in Patients with Depression: In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions (including completed suicides), have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed for the patient at any one time.
Respiratory Depression: Although studies with 10 mg zolpidem tartate did not reveal respiratory depressant effects at hypnotic doses in healthy subjects or in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD), a reduction in the Total Arousal Index together with a reduction in lowest oxygen saturation and increase in the times of oxygen desaturation below 80% and 90% was observed in patients with mild-to-moderate sleep apnea when treated with zolpidem compared to placebo. Since sedative/-hypnotics have the capacity to depress respiratory drive, precautions should be taken if Stilnox is prescribed to patients with compromised respiratory function. Post-marketing reports of respiratory insufficiency in patients receiving 10 mg of zolpidem tartate, most of who had pre-existing respiratory impairment, have been reported The risk of respiratory depression should be considered prior to prescribing Stilnox in patients with respiratory impairment including sleep apnea and myasthenia gravis.
Withdrawal Effects: There have been reports of withdrawal signs and symptoms following the rapid dose decrease or abrupt discontinuation of zolpidem. Monitor patients for tolerance, abuse, and dependence.
Severe Injuries: Therapeutic dose of zolpidem gives somnolence, drowsiness, and reduced alertness shortly after intake. These pharmacologic effects may lead to gait disturbance, fall and consequently to severe injuries.especially in elderly patients. Zolpidem acts rapidly and therefore should be taken immediately before retiring or in bed. Age of 65 years or older, overdose (or high dose, i.e. 10 mg daily in elderly patient), concomitant intake of other central nervous system depressants, walking shortly after intake, and sleep walking increase the risk for fall and for severe injuries.
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: CNS-depressant effects and next-day impairment. Serious anaphylactic and anaphylactoid reactions. Abnormal thinking and behavior changes, and complex behaviors. Withdrawal effects.
CNS-active Drugs: Co-administration of zolpidem with other CNS depressants increases the risk of CNS depression. Zolpidem tartrate was evaluated in healthy volunteers in single-dose interaction studies for several CNS drugs.
Imipramine, Chlorpromazine: Imipramine in combination with zolpidem produced no pharmacokinetic interaction other than a 20% decrease in peak levels of imipramine, but there was an additive effect of decreased alertness. Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance.
Haloperidol: A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration does not predict the absence of an effect following chronic administration.
Alcohol: An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was demonstrated.
Sertaline: Concomitant administration of zolpidem and sertaline increases exposure to zolpidem.
Fluoxetine: After multiple doses of zolpidem and fluoxetine an increase in the zolpidem half-life (17%) was observed. There was no evidence of an additive effect in psychomotor performance.
Pregnancy and Lactation
Pregnancy Category C: There are no adequate and well-controlled studies of Stilnox in pregnant women. Studies in children to assess the effects of prenatal exposure to zolpidem have not been conducted; however, cases of severe neonatal respiratory depression have been reported when zolpidem was used at the end of pregnancy, especially when taken with other CNSdepressants. Children born of mothers taking sedative-hypnotic drugs may be at risk for withdrawal symptoms during the postnatal period. Neonatal flaccidity has also been reported in infants born of mothers who received sedative-hypnotic drugs during pregnancy. Stilnox should be used during pregnancy only if the potential benefit overweights the potential risk to the fetus Administration of zolpidem to pregnant rats and rabbits resulted in adverse effects on offspring development at doses greater than the Stilnox maximum recommended human dose (MRHD) of 10 mg/day (approximately 8 mg/day zolpidem base); however, teratogenicity was not observed. When zolpidem was administered at oral doses of 4, 20, and 100 mg base/kg/day to pregnant rats during the period of organogenesis, dose-related decreases in fetal skull ossification occurred at all but the lowest dose, which is approximately 5 times the MRHD on a mg/m2 basis. In rabbits treated during organogenesis with zolpidem at oral doses of 1, 4, and 16 mg base/kg/day, increased embryo-fetal death and incomplete fetal skeletal ossification occurred at the highest dose tested. The no-effect dose for embryo-fetal toxicity in rabbits is approximately 10 times the MRHD on a mg/m2 basis. Administration of zolpidem to rats at oral doses of 4, 20, and 100 mg base/kg/day during the latter part of pregnancy and throughout lactation produced decreased offspring growth and survival at all but the lowest dose, which is approximately 5 times the MRHD on a mg/m2 basis.
Labor and Delivery: Stilnox has no established use in labor and delivery.
Nursing Mothers: Zolpidem is excreted in human milk. Caution should be exercised when Stilnox is administered to a nursing woman.
Signs and Symptoms: In postmarketing experience of overdose with zolpidem tartrate alone, or in combination with CNS-depressant agents, impairment of consciousness ranging from somnolence to coma, cardiovascular and/or respiratory compromise and fatal outcomes have been reported.
Recommended Treatment: General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Zolpidem’s sedative hypnotic effect was shown to be reduced by flumazenil and therefore may be useful; however, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Sedating drugs should be withheld following zolpidem overdose, even if excitation occurs. The value of dialysis in the treatment of overdose has not been determined, although hemodialysis studies in patients with renal failure receiving therapeutic doses have demonstrated that zolpidem is not dialyzable. As with the management of all overdose, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-todate information on the management of hypnotic drug product overdose.