Silenor is not an inhibitor of any CYP isozymes at therapeutically relevant concentrations. SILENOR ® is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines.
in2insulin natural dressings. The ability of Silenor to induce CYP isozymes is not known.Silenor exposure is doubled with concomitant administration of cimetidine, a nonspecific inhibitor of CYP isozymes. Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a hypnotic, with amnesia for the event) have been reported with hypnotics. Especially tell your healthcare provider if you take:Ask your doctor or pharmacist if you are not sure if your medicine is one that is listed above.Know the medicines you take. E assim foi. Important Safety Information. Doxepin is not a Pgp substrate.Doxepin is excreted in the urine mainly in the form of glucuronide conjugates.Less than 3% of a doxepin dose is excreted in the urine as parent compound or nordoxepin. However, data from the Silenor studies provide the physician with a basis for estimating the relative contributions of drug and non-drug factors to adverse reaction incidence rates in the populations studied.The percentage of subjects discontinuing Phase 1, 2, and 3 trials for an adverse reaction was 0.6% in the placebo group compared to 0.4%, 1.0%, and 0.7% in the Silenor 1 mg, 3 mg, and 6 mg groups, respectively. The primary metabolite is N-desmethyldoxepin (nordoxepin).The primary metabolite undergoes further biotransformation to glucuronide conjugates.In vitro studies have shown that CYP2C19 and CYP2D6 are the major enzymes involved in doxepin metabolism, and that CYP1A2 and CYP2C9 are involved to a lesser extent.Doxepin appears not to have inhibitory effects on human CYP enzymes at therapeutic concentrations.
The plasma exposures (AUC) at the no-effect dose for developmental effects (30 mg/kg/day) are approximately 6 and 18 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. Patients should avoid engaging in hazardous activities, such as operating a motor vehicle or heavy machinery, at night after taking Silenor, and should be cautioned about potential impairment in the performance of such activities that may occur the day following ingestion.When taken with Silenor, the sedative effects of alcoholic beverages, sedating antihistamines, and other CNS depressants may be potentiated [sThe following serious adverse reactions are discussed in greater detail in other sections of labeling:The pre-marketing development program for Silenor included doxepin HCl exposures in 1017 subjects (580 insomnia patients and 437 healthy subjects) from 12 studies conducted in the United States. Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center.Since overdose often is deliberate, patients may attempt suicide by other means during the recovery phase. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in treatment of tricyclic compound poisoning.In patients with central nervous system depression, early intubation is advised because of the potential for abrupt deterioration.
Silenor 3 mg was superior to placebo on objective WASO.The second randomized, double-blind study assessed Silenor 6 mg relative to placebo for 4 weeks in an outpatient setting in elderly subjects (N=254) with chronic insomnia.
If you would like more information, talk with your healthcare provider. To minimize the potential for next day effects, Silenor should not be taken within 3 hours of a meal [see Clinical Pharmacology (12.3)].The total Silenor dose should not exceed 6 mg per day.