MEPERIDINE HYDROCHLORIDE TABLETS USP
(50 mg and 100 mg)

CII

Rx only

Meperidine 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.

Each MEPERIDINE HYDROCHLORIDE USP 50 mg tablet for oral administration contains:

      Meperidine Hydrochloride USP . . . . . . . . . . . . . . . . 50 mg

Each MEPERIDINE HYDROCHLORIDE USP 100 mg tablet for oral administration contains:

      Meperidine Hydrochloride USP . . . . . . . . . . . . . . . . 100 mg

Meperidine hydrochloride is a narcotic analgesic with multiple actions qualitatively similar to those of morphine; the most prominent of these involve the central nervous system and organs composed of smooth muscle. The principal actions of therapeutic value are analgesia and sedation.

There is some evidence which suggests that meperidine may produce less smooth muscle spasm, constipation, and depression of the cough reflex than equianalgesic doses of morphine. Meperidine, in 60 mg to 80 mg parenteral doses, is approximately equivalent in analgesic effect to 10 mg of morphine. The onset of action is slightly more rapid than with morphine, and the duration of action is slightly shorter. Meperidine is significantly less effective by the oral than by the parenteral route, but the exact ratio of oral to parenteral effectiveness is unknown.

Meperidine hydrochloride tablets USP are indicated for the relief of moderate to severe pain.

Meperidine hydrochloride tablets are contraindicated in patients with hypersensitivity to meperidine.

Meperidine is contraindicated in patients who are receiving monoamine oxidase (MAO) inhibitors or those who have recently received such agents. 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. (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.)

Meperidine hydrochloride tablets are an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine.

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

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 hydrochloride tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Meperidine hydrochloride tablets have 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.

Health care 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.

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.

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 hydrochloride tablets 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.

Meperidine hydrochloride tablets 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 hydrochloride tablets.

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.

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.

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.

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

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.

Meperidine hydrochloride tablets are 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 hydrochloride tablets 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 hydrochloride tablets in combination with other CNS depressant drugs can result in serious risk to the patient.

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

• Patients should be aware that meperidine hydrochloride tablets contain meperidine, which is a morphine-like substance.
• 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.
• Patients should be advised not to adjust the dose of meperidine hydrochloride tablets without consulting the prescribing professional.
• Patients should be advised that meperidine hydrochloride tablets may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
• Patients should not combine meperidine hydrochloride tablets 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.
• 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.
• Patients should be advised that meperidine hydrochloride tablets are 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.
• Patients should be advised that if they have been receiving treatment with meperidine hydrochloride tablets for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the meperidine hydrochloride tablets 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.
• Patients should be instructed to keep meperidine hydrochloride tablets in a secure place out of the reach of children. When meperidine hydrochloride tablets are no longer needed, the unused tablets should be destroyed by flushing down the toilet.

The major hazards of meperidine, as with other narcotic analgesics, are respiratory depression and, to a lesser degree, circulatory depression; respiratory arrest, shock, and cardiac arrest have occurred.

The most frequently observed adverse reactions include light-headedness, dizziness, sedation, nausea, vomiting, and sweating. These effects seem to be more prominent in ambulatory patients and in those who are not experiencing severe pain. In such individuals, lower doses are advisable. Some adverse reactions in ambulatory patients may be alleviated if the patient lies down.

Other adverse reactions include:

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.

Meperidine hydrochloride tablets contain meperidine, a mu-agonist opioid with an abuse liability similar to morphine and is a Schedule II controlled substance. Meperidine, like morphine and other opioids used in analgesia, can be abused and is

subject to criminal diversion.

Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

“Drug seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Meperidine hydrochloride tablets, like other opioids, have been diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Abuse of meperidine hydrochloride tablets poses a risk of overdose and death. This risk is increased with concurrent abuse of meperidine hydrochloride tablets with alcohol and other substances. Due to the presence of talc as one of the excipients in tablets, parenteral abuse of crushed tablets can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart disease. In addition, parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Dosage should be adjusted according to the severity of the pain and the response of the patient. Meperidine is less effective orally than on parenteral administration. The dose of meperidine hydrochloride tablets 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 hydrochloride tablets.

Each Meperidine Hydrochloride Tablet USP (50 mg) is available as a round, white to off-white scored tablet debossed with a semi-circle arc “7113” on one side and an on the other side.

                         Bottles of 100 . . . . . . . . . . . . . NDC 0406-7113-01

Each Meperidine Hydrochloride Tablet USP (100 mg) is available as a round, white to off-white tablet debossed with a semi-circle arc “7115” on one side and an on the other side.

                         Bottles of 100 . . . . . . . . . . . . . NDC 0406-7115-01

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Dispense in a well-closed, light-resistant container as defined in the USP.

Meperidine hydrochloride tablets are dosage forms that contain meperidine hydrochloride which is a controlled substance. Like morphine, meperidine is controlled under Schedule II of the Controlled Substances Act. Meperidine, like all opioids, is liable to diversion and misuse and should be handled accordingly. Patients and their families should be instructed to flush any meperidine hydrochloride tablets that are no longer needed.

Meperidine hydrochloride tablets have been targeted for theft and diversion by criminals. Health care professionals should contact their State Professional Licensing Board or State Controlled Substance Authority for information on how to prevent and detect abuse or diversion of this product.

is a registered trademark of Mallinckrodt Inc.

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Healthcare

Mallinckrodt

Mallinckrodt Inc
St. Louis, MO 63134, U.S.A.

Printed in the U.S.A.
Rev 122505