Label: meperidine hydrochloride- Meperidine Hydrochloride solution
meperidine hydrochloride- Meperidine Hydrochloride tablet

Inactive ingredients

The oral solution contains glycerin, hydrochloric acid, maltol, sodium benzoate, sorbitol solution, and water.

The tablets contain starch (corn), lactose monohydrate, povidone, microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, and magnesium stearate.

Chemically meperidine hydrochloride is 1-Methyl-4-phenyl-4-piperidinecarboxylic acid, ethyl ester, hydrochloride, a white crystalline substance with a melting point of 186°C to 189°C. It is readily soluble in water and has a neutral reaction and a slightly bitter taste. The solution is not decomposed by a short period of boiling. Meperidine hydrochloride may be represented by the following structural formula:

C15H21NO2• HCl M.W. 283.80

Misuse, Abuse, and Diversion of Opioids

Meperidine is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Meperidine can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing meperidine in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Meperidine has been reported as being abused by crushing, chewing, snorting, or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose or death (see WARNINGS and DRUG ABUSE AND DEPENDENCE).

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.

Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

Interactions with Alcohol and Drugs of Abuse

Meperidine may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

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.

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 been compromised by a depleted blood volume or the administration of drugs such as the phenothiazines or certain anesthetics.

Usage in Ambulatory Patients

Meperidine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient should be cautioned accordingly.

Meperidine, like other narcotics, may produce orthostatic hypotension in ambulatory patients.

Usage in Pregnancy

Meperidine should not be used in pregnant women prior to the labor period, unless in the judgment of the physician the potential benefits outweigh the possible risks, because safe use in pregnancy prior to labor has not been established relative to possible adverse effects on fetal development.

Labor and Delivery

Meperidine crosses the placental barrier and can produce depression of respiration and psychophysiologic functions in the newborn. Resuscitation may be required (see OVERDOSAGE).

Nursing Mothers

Meperidine appears in the milk of nursing mother receiving the drug. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the potential benefits of the drug to the nursing woman.

General

Opioid analgesics can have a narrow therapeutic index in certain patient populations, particularly when combined with CNS depressant drugs. The use of these products should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension.

Use of meperidine may be associated with increased potential risks and should be used with caution in the following conditions: sickle cell anemia, pheochromocytoma, acute alcoholism; adrenocortical insufficiency (e.g., Addison’s disease); CNS depression or coma; delirium tremens; debilitated patients; kyphoscoliosis associated with respiratory depression; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; severe impairment of hepatic, pulmonary, or renal function; and toxic psychosis.

The administration of meperidine may obscure the diagnosis or clinical course in patients with acute abdominal conditions. All opioids may induce or aggravate seizures in some clinical settings.

Interactions with other CNS Depressants

Meperidine should be used with caution and consideration should be given to starting with a reduced dosage in patients who are concurrently receiving other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers, and alcohol. Drug-drug interactions may result in respiratory depression, hypotension, profound sedation, or coma if these drugs are taken in combination with the usual doses of meperidine.

Interactions with Mixed Agonist/Antagonist Opioid Analgesics

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, and buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as meperidine. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of meperidine and/or may precipitate withdrawal symptoms in these patients.

Supraventricular Tachycardias

Meperidine should be used with caution in patients with atrial flutter and other supraventricular tachycardias because of a possible vagolytic action which may produce a significant increase in the ventricular response rate.

Convulsions

Meperidine may aggravate preexisting 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.

Acute Abdominal Conditions

The administration of meperidine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

Tolerance and Physical Dependence

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

In general, opioids used regularly should not be abruptly discontinued.

Use in Drug and Alcohol Addiction

Meperidine is an opioid with no approved use in the management of addictive disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission, is for the management of pain requiring opioid analgesia. Meperidine should be used with caution in patients with alcoholism and other drug dependencies due to the increased frequency of narcotic tolerance, dependence, and the risk of addiction observed in these patient populations. Abuse of meperidine in combination with other CNS depressant drugs can result in serious risk to the patient.

Information for Patients/Caregivers

If clinically advisable, patients receiving meperidine hydrochloride tablets or their caregivers should be given the following information by the physician, nurse, pharmacist, or caregiver:

1. Patients should be aware that meperidine tablets contain meperidine, which is a morphine like substance.
2. Patients should be advised to report pain and adverse experiences occurring during therapy. Individualization of dosage is essential to make optimal use of this medication.
3. Patients should be advised not to adjust the dose of meperidine without consulting the prescribing professional.
4. Patients should be advised that meperidine may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
5. Patients should not combine meperidine with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because dangerous additive effects may occur, resulting in serious injury or death.
6. Women of childbearing potential who become, or are planning to become pregnant should be advised to consult their physician regarding the effects of analgesics and other drug use during pregnancy on themselves and their unborn child.
7. Patients should be advised that meperidine is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
8. Patients should be advised that if they have been receiving treatment with meperidine for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the meperidine dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms. Their physician can provide a dose schedule to accomplish a gradual discontinuation of the medication.
9. Patients should be instructed to keep meperidine in a secure place out of the reach of children. When meperidine is no longer needed, the unused tablets should be destroyed by flushing down the toilet.

Drug Interactions

Also see WARNINGS.

Special Risk Patients

Meperidine should be given with caution and the initial dose should be reduced in certain patients such as the elderly or debilitated, and those with severe impairment of hepatic or renal function, Sickle Cell Anemia, hypothyroidism, Addison’s disease, Pheochromocytoma and prostatic hypertrophy or urethral stricture. In patients with pheochromocytoma, meperidine has been reported to provoke hypertension.

Usage in Hepatically Impaired Patients

Accumulation of meperidine and /or its active metabolite, normeperidine, can occur in patients with hepatic impairment. Meperidine should therefore be used with caution in patients with hepatic impairment.

Usage in Renally Impaired Patients

Accumulation of meperidine and/or its active metabolite, normeperidine, can also occur in patients with renal impairment. Meperidine should therefore be used with caution in patients with renal impairment.

Carcinogenesis, mutagenesis, impairment of fertility

Studies to assess the carcinogenic or mutagenic potential of meperidine have not been conducted. Studies to determine the effect of meperidine on fertility have not been conducted.

Pregnancy

Labor and Delivery

See WARNINGS.

Nursing Mothers

See WARNINGS.

Pediatric Use

Literature reports indicate that meperidine has a slower elimination rate in neonates and young infants compared to older children and adults. Neonates and young infants may also be more susceptible to the effects, especially the respiratory depressant effects. Meperidine should therefore be used with caution in neonates and young infants, and any potential benefits of the drug weighed against the relative risk to a pediatric patient.

Geriatric Use

Clinical studies of meperidine during product development did not include sufficient numbers of subjects aged 65 and over to evaluate age-related differences in safety or efficacy. Literature reports indicate that geriatric patients have a slower elimination rate compared to young patients and they may be more susceptible to the effects of meperidine. A reduction in the total daily dose of meperidine may be required in elderly patients, and the potential benefits of the drug weighed against the relative risk to a geriatric patient.

Nervous System

Euphoria, dysphoria, weakness, headache, agitation, tremor, uncoordinated muscle movements, (e.g., muscle twitches, myoclonus), severe convulsions, transient hallucinations and disorientation, visual disturbances.

Gastrointestinal

Dry mouth, constipation, biliary tract spasm.

Cardiovascular

Flushing of the face, tachycardia, bradycardia, palpitation, hypotension (see WARNINGS), syncope.

Genitourinary

Urinary retention.

Allergic

Pruritus, urticaria, other skin rashes, wheal and flare over the vein with intravenous injection.

Symptoms

Serious overdosage 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.

Treatment

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. Therefore, an appropriate dose of this antagonist should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation.

An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.

Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.

In cases of overdosage with meperidine tablets, the stomach should be evacuated by emesis or gastric lavage.

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-fifth to one-tenth the usual initial dose administered.

For Relief of Pain

Dosage should be adjusted according to the severity of the pain and the response of the patient. Meperidine is less effective orally than with parenteral administration. The dose of meperidine hydrochloride should be proportionately reduced (usually by 25 to 50 percent) when administered concomitantly with phenothiazines and many other tranquilizers since they potentiate the action of meperidine.