[FONT=Times New Roman, Times, serif]DEMEROL® .
[FONT=Times New Roman, Times, serif]Sanofi .
[FONT=Times New Roman, Times, serif]Meperidine HCl .
[FONT=Times New Roman, Times, serif]Analgesic .
[FONT=Times New Roman, Times, serif]Action And Clinical Pharmacology:. Meperidine is an opioid analgesic which acts predominantly as a mu-agonist.
In its effects on the CNS, meperidine resembles but is not identical to morphine. Analgesic effects are detectable within about 15 minutes following oral administration, reaching a peak within about 2 hours and subsiding gradually over several hours thereafter. Onset of analgesic effect is faster (within 10 minutes) after s.c. or i.m. administration, reaching a peak within about 1 hour that corresponds closely to the peak concentrations in plasma. In clinical use, the duration of effective analgesia is about 3 to 5 hours. Given parenterally, 75 to 100 mg of meperidine is approximately equivalent to 10 mg of morphine in analgesic effectiveness. At equianalgesic dosage, the 2 agents are comparable in the degree of sedation and of respiratory depression they produce. Given parenterally, meperidine is more than twice as effective as given orally in terms of the total analgesic response obtained. This is consistent with an oral bioavailability of about 40 to 60%.
In its effects on the cardiovascular system, meperidine generally resembles morphine, including its ability to release histamine upon parenteral administration. Heart rate is unlikely to be significantly affected with i.m. administration but may increase, with i.v. administration. As with morphine, respiratory depression leads to an accumulation of carbon dioxide which in turn produces cerebrovascular dilatation, increase in cerebral blood flow and elevation of cerebrospinal fluid pressure.
The effects of meperidine on smooth muscle are qualitatively similar, but in relation to analgesic effect less intense than those of other opioids. Meperidine does not cause as much constipation when given over prolonged periods of time. This may be related to its greater facility to enter the CNS, thereby producing analgesia at lower peripheral concentrations. At equianalgesic dosage, the rise in pressure in the common bile duct induced by meperidine is less than that by morphine, but greater than that by codeine. Clinical doses of meperidine nevertheless slow gastric emptying sufficiently to delay absorption of other drugs significantly. The uterus of nonpregnant women is usually mildly stimulated by meperidine. Therapeutic doses given during active labor do not delay the birth process; in fact, the frequency, duration and amplitude of uterine contractions may sometimes be increased. Meperidine does not interfere with normal postpartum contraction or involution of the uterus and does not increase the incidence of postpartum hemorrhage.
Following i.m. injection, peak plasma concentration is usually obtained at about 45 minutes, but the range in time is wide. After oral administration, only about 50% of meperidine escapes first-pass metabolism. Peak concentrations in the plasma are usually observed in 1 to 2 hours. Approximately 60% is bound to plasma proteins. Meperidine is metabolized chiefly in the liver. The plasma elimination half-life is normally 3 to 4 hours, but this may be extended considerably in the presence of significant hepatic disease. In patients with cirrhosis, bioavailability may be increased as much as 80%. Meperidine is hydrolyzed to meperidinic acid, which in turn is partially conjugated. Meperidine also undergoes N-demethylation to normeperidine, which may then be hydrolyzed to normeperidinic acid and subsequently conjugated. Normeperidine has a considerably longer plasma elimination half-life (15 to 20 hours) than its parent molecule. In the presence of renal insufficiency, normeperidine elimination is reduced.
At the usual values of urinary pH, or if the urine is alkaline, excretion of unchanged meperidine is negligible; urinary excretion of meperidine and normeperidine is enhanced by acidification of the urine. Meperidine crosses the placenta and appears in milk.
[FONT=Times New Roman, Times, serif]Indications And Clinical Uses:. The relief of moderate to severe pain in many medical, surgical, obstetrical and dental situations.
[FONT=Times New Roman, Times, serif]Contra-Indications:. Hypersensitivity to meperidine. Contraindicated in patients who are receiving MAO inhibitors or those who have received such agents within 14 days. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 14 days. The mechanism of these reactions is unclear, but may be related to a preexisting hyperphenylalaninemia. 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. (I.V. hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of i.v. chlorpromazine in those cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of narcotic antagonists in the treatment of these reactions is unknown.)
Solutions of meperidine and barbiturates are chemically incompatible.
[FONT=Times New Roman, Times, serif]Manufacturers' Warnings In Clinical States:. Drug Dependence: Meperidine can produce drug dependence of the morphine type and therefore has the potential for being abused. Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of meperidine, and it should be prescribed and administered with the same degree of caution appropriate to the use of morphine. Like other narcotics, meperidine is subject to the provisions of the Narcotic Control Act.
[FONT=Times New Roman, Times, serif]Drug Interactions:. Interactions with Other CNS Depressants: Meperidine should be used with great caution and in reduced dosage in patients who are concurrently receiving other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers (see Dosage), sedative-hypnotics (including barbiturates), tricyclic antidepressants, and other CNS depressants (including alcohol). Respiratory depression, hypotension, and profound sedation or coma may result.
Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of meperidine and its capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries. In such patients, meperidine must be used with extreme caution and only if its use is deemed essential.
I.V.: If necessary, meperidine may be given i.v., but the injection should be given very slowly, preferably in the form of a diluted solution. Rapid i.v. injection of narcotic analgesics, including meperidine, increases the incidence of adverse reactions; severe respiratory depression, apnea, hypotension, peripheral circulatory collapse, and cardiac arrest have occurred. Meperidine should not be administered i.v. unless a narcotic antagonist and the facilities for assisted or controlled respiration are immediately available. When meperidine is given parenterally, especially i.v., the patient should be lying down.
I.M.: Meperidine should be injected well within the body of a large muscle.
Asthma and Other Respiratory Conditions: Meperidine should be used with extreme caution in patients having an acute asthmatic attack, patients with chronic obstructive pulmonary disease or cor pulmonale, patients having a substantially decreased respiratory reserve, and patients with preexisting respiratory depression, hypoxia, or hypercapnia. In such patients, even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.
Hypotensive Effect: The administration of meperidine may result in severe hypotension in the postoperative patient or any individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or the administration of drugs such as the phenothiazines or certain anesthetics.
