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Serious overdose with meperidine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.
Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride, is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including meperidine. The usual initial adult dose of naloxone is 0.4 to 2.0 mg, administered intravenously. If the desired degree of counteraction and improvement in respiratory functions is not obtained, this dosage can be repeated at two- to three-minute intervals while resuscitation efforts continue. If 10 mg of naloxone have been administered without an improvement in the clinical situation, the diagnosis of Mepergan (meperidine and promethazine) overdose should be questioned.
An antagonist should not be administered in absence of clinically significant respiratory or cardiovascular depression.
Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.
NOTE: In an individual physically dependent on narcotics, the administration of the usual dose of a narcotic 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 narcotic antagonists in such individuals should be avoided if possible. If a narcotic antagonist must be used to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with extreme care and only one-tenth to one-fifth the usual initial dose administered.
Attempted suicides with promethazine have resulted in deep sedation, coma, rarely convulsions and cardiorespiratory symptoms compatible with the depth of sedation present. Extrapyramidal reactions may be treated with anticholinergic antiparkinson agents, diphenhydramine, or barbiturates.
If severe hypotension occurs, levarterenol or phenylephrine may be indicated. Epinephrine is probably best avoided, since it has been suggested that promethazine overdosage could produce a partial alpha-adrenergic blockade.
A paradoxical reaction, characterized by hyperexcitability and nightmares, has been reported in children receiving large single doses of promethazine.
Hypersensitivity to meperidine or promethazine.
Under no circumstances should Mepergan (meperidine and promethazine) be given by intra-arterial injection, due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see " WARNINGS").
Mepergan (meperidine and promethazine) should not be given by the subcutaneous route; evidence of chemical irritation has been noted, and necrotic lesions have resulted on rare occasions following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection.
Meperidine is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOI) or those who have received such agents within 14 days. Therapeutic doses of meperidine have inconsistently precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 14 days. The mechanism of these reactions is unclear. Some have been characterized by coma, severe respiratory depression, cyanosis, and hypotension and have resembled the syndrome of acute narcotic overdose. In other reactions the predominant manifestations have been hyperexcitability, convulsions, tachycardia, hyperpyrexia, and hypertension. Although it is not known that other narcotics are free of the risk of such reactions, virtually all of the reported reactions have occurred with meperidine. If a narcotic is needed in such patients, a sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over the course of several hours while the patient's condition and vital signs are under careful observation.
(Intravenous hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of narcotic antagonists in the treatment of these reactions is unknown.)
This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
Additional Mepergan Information
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