Quazepam

Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women. Administration of benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia, hypotonia, respiratory depression, and difficulty feeding. In addition, infants born to mothers who have taken benzodiazepines during the later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period. Although administration of quazepam to pregnant animals did not indicate a risk for adverse effects on morphological development at clinically relevant doses, data for other benzodiazepines suggest the possibility of adverse developmental effects (long-term effects on neurobehavioral and immunological function) in animals following prenatal exposure to benzodiazepines. Quazepam should be used during pregnancy only if the potential benefit justifies the potential risk.

Developmental toxicity studies of quazepam in mice at doses up to 400 times the human dose (15 mg) revealed no major drug-related malformations. Minor fetal skeletal variations that occurred were delayed ossification of the sternum, vertebrae, distal phalanges and supraoccipital bones, at doses approximately 70 and 400 times the human dose. A developmental toxicity study of quazepam in New Zealand rabbits at doses up to approximately 130 times the human dose demonstrated no effect on fetal morphology or development of offspring.

Quazepam and its metabolites are excreted in human milk. Caution should be exercised when administering quazepam to a nursing woman.

Carcinogenesis

Quazepam showed no evidence of carcinogenicity in oral carcinogenicity studies in mice and hamsters.

Mutagenesis

Quazepam was negative in the bacterial reverse mutation (Ames) assay and equivocal in the mouse lymphoma tk assay.

Impairment of Fertility

Reproduction studies in mice conducted with quazepam at doses equal to 60 and 180 times the human dose of 15 mg produced slight reductions in fertility rate. Similar reductions in fertility rate have been reported in mice dosed with other benzodiazepines, and is believed to be related to the sedative effects of these drugs at high doses.

Do not drive, operate machinery, do other dangerous activities or do anything that needs you to be alert until you know how quazepam affects you. You may still feel drowsy the next day after taking quazepam.

The following serious adverse reactions are discussed in greater detail in other sections of the label:

• CNS-depressant effects and next-day impairment
• Benzodiazepine withdrawal syndrome
• Abnormal thinking and behavior changes, and complex behaviors
• Worsening of depression

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.The table shows adverse reactions occurring at an incidence of 1% or greater in relatively short-duration, placebo-controlled clinical trials of quazepam.

A double-blind, controlled sleep laboratory study (N=30) in elderly patients compared the effects of quazepam 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.