withdrawal syndrome and is not generally recommended in alcohol- or drug-dependent individuals or people with comorbid psychiatric disorders. The Dutch, British and French system called the System of Objectified Judgement Analysis for assessing whether drugs should be included in drug formularies based on clinical efficacy, adverse effects, pharmacokinetic properties, toxicity, and drug interactions was used to assess nitrazepam. A Dutch analysis using the system found nitrazepam to be unsuitable in drug-prescribing formularies. The use of nitrazepam during pregnancy can lead to intoxication of the newborn. A neonatal withdrawal syndrome can also occur if nitrazepam or other benzodiazepines are used during pregnancy with symptoms such as hyperexcitability, tremor, and gastrointestinal upset (diarrhea or vomiting) occurring. Breast feeding by mothers using nitrazepam is not recommended. Nitrazepam is a long-acting benzodiazepine with a risk of drug accumulation, though no active metabolites are formed during metabolism. Accumulation can occur in various body organs, including the heart; accumulation is even greater in babies. Nitrazepam rapidly crosses the placenta and is present in breast milk in high quantities. Therefore, benzodiazepines including nitrazepam should be avoided during pregnancy. In early pregnancy, nitrazepam levels are lower in the baby than in the mother, and in the later stages of pregnancy, nitrazepam is found in equal levels in both the mother and the unborn child. Internationally benzodiazepines are known to cause harm when used during pregnancy and nitrazepam is a category D drug during pregnancy. Benzodiazepines are lipophilic and rapidly penetrate membranes, so rapidly penetrate the placenta with significant uptake of the drug. Use of benzodiazepines such as nitrazepam in late pregnancy in especially high doses may result in floppy infant syndrome. Use in the third trimester of pregnancy may result in the development of a severe benzodiazepine withdrawal syndrome in the neonate. Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia, and reluctance to suckle, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. These symptoms may persist for hours or months after birth. Other precautions Caution in hypotension Caution in those suffering from hypotension, nitrazepam may worsen hypotension. Caution in hypothyroidism Caution should be exercised by people who have hypothyroidism, as this condition may cause a long delay in the metabolism of nitrazepam leading to significant drug accumulation. Contraindications Nitrazepam should be avoided in patients with chronic obstructive pulmonary disease (COPD), especially during acute exacerbations of COPD, because serious respiratory depression may occur in