<p>Serious or life-threatening reactions such as respiratory depression, coma, convulsions, possibly due to elevated levels of norpethidine and hypotension have been associated with the use of pethidine. Therefore the recommendations in the Warnings and Precautions sections should be carefully observed.<br />
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Pethidine should be used with caution in patients taking other CNS depressant drugs such as hypnotics and sedatives including barbiturates and benzodiazepines, phenothiazines, and other tranquillisers, anaesthetics, alcohol and antidepressants.<br />
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Patients with severe pain may tolerate very high doses of pethidine but may exhibit respiratory depression should their pain suddenly subside.<br />
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The elderly demonstrate an increased sensitivity to opioids relative to younger patients. Reduced liver function, renal function and plasma protein binding may contribute to the elevated plasma levels found in elderly subjects.<br />
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Since pethidine is metabolised in the liver and excreted via the kidneys, the possibility of accumulation of the toxic metabolic norpethidine should be considered in patients with hepatic and/or renal impairment<br />
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Reduced cardiac output may lead to reduced hepatic perfusion and diminished metabolism of pethidine leading to accumulation of pethidine with possible toxic results.<br />
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Pethidine may cause a transient rise in blood pressure and systemic vascular resistance and increased heart rate. Therefore, it is not recommended for pain relief in cardiac infarction.<br />
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Pethidine in patients with phaeochromocytoma may result in a hypertensive crisis.<br />
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In an individual physically dependent on opioids, the administration of the usual dose of an opioid antagonist will precipitate an acute withdrawal syndrome. The severity of this syndrome will depend on the degree of physical dependence and the dose of antagonist administered. The use of opioid antagonists in such individuals should be avoided if possible. If an opioid antagonist must be used to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with extreme care and only 10 to 20% of the usual initial dose administered.<br />
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Pethidine may aggravate pre-existing convulsions in patients with convulsive disorders. If dosage is escalated substantially above recommended levels because of tolerance development, convulsions may occur in individuals without a history of convulsive disorders.<br />
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In eclampsia the combination of pethidine with phenothiazines has been reported to induce recurrence of seizures rather than stopping them. Therefore, the use of pethidine in eclampsia and pre-eclampsia is not recommended.<br />
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Pethidine, while commonly used for pain relief in obstetrics, is known to pass the placenta and may cause neonatal depression, including respiratory depression. An opioid antagonist such as naloxone may be required to reverse such depression. In the neonate, pethidine is excreted and metabolised at a significantly reduced rate compared to adults.<br />
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Orthostatic hypotension has been reported in ambulatory patients administered pethidine.<br />
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Pethidine should be given with caution and the initial dose should be reduced in patients with hypothyroidism or Addison&rsquo;s disease.<br />
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Pethidine should be used with caution in patients with prostatic hypertrophy or urethral stricture.<br />
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As opiate agonists may produce hyperglycaemia, this effect should be considered when diabetics require pethidine.<br />
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There are conflicting reports about the effect of pethidine on the eye. Some reports state that pethidine and its congeners produce miosis, whereas others indicate that these drugs tend to produce mydriasis or no pupillary change. Until the effects are better defined intraocular tension should be monitored in patients with glaucoma who received pethidine.</p>