İHALE DÜNYASI
İHALE DÜNYASI
Meperidine hydrochloride is 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 tablet, for oral administration, contains 50 mg or 100 mg meperidine hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, pregelatinized starch, sodium starch glycolate and stearic acid. Chemically, meperidine hydrochloride is 4-Piperidinecarboxylic acid, 1-methyl-4-phenyl-, ethyl ester, hydrochloride and has the following structure: This is an image of the structural formula for meperidine hydrochloride.
Meperidine hydrochloride tablets are indicated for the relief of moderate to severe pain.
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 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. Adults The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary. Pediatric Patients The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary (see PRECAUTIONS: Pediatric Use ). | 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 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. Adults The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary. Pediatric Patients The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary (see PRECAUTIONS: Pediatric Use ). | Adults The usual dosage is 50 mg to 150 mg orally, every 3 or 4 hours as necessary. | Pediatric Patients The usual dosage is 1.1 mg/kg to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary (see PRECAUTIONS: Pediatric Use ).
Meperidine hydrochloride tablets are contraindicated in patients with hypersensitivity to meperidine or to any of its ingredients. 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. Serotonin syndrome with agitation, hyperthermia, diarrhea, tachycardia, sweating, tremors and impaired consciousness may also occur. 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 contraindicated in patients with severe respiratory insufficiency (see WARNINGS: Respiratory Conditions ).
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 lightheadedness, 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: Mood changes (e.g., euphoria, dysphoria), weakness, headache, agitation, tremor, involuntary muscle movements (e.g., muscle twitches, myoclonus), severe convulsions, transient hallucinations and disorientation, confusion, delirium, 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. Hypersensitivity reactions, anaphylaxis. Histamine release leading to hypotension and/or tachycardia, flushing, sweating, and pruritus.
Meperidine should not be used for treatment of chronic pain. Meperidine should only be used in the treatment of acute episodes of moderate to severe pain. Prolonged meperidine use may increase the risk of toxicity (e.g., seizures) from the accumulation of the meperidine metabolite, normeperidine. Meperidine hydrochloride tablets are opioid agonists 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. 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 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 ADDICTION ). 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. 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 ). Therefore meperidine is not recommended during labor. Nursing Mothers Meperidine appears in the milk of nursing mothers 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. | 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. | 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.
Interactions with Other CNS Depressants 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, coma, or death if these drugs are taken in combination with the usual doses of meperidine hydrochloride tablets. | 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 due to competitive blocking of receptors. | Drug Interactions Also see WARNINGS . Acyclovir Plasma concentrations of meperidine and its metabolite, normeperidine, may be increased by acyclovir, thus caution should be used with concomitant administration. Cimetidine Cimetidine reduced the clearance and volume of distribution of meperidine and also the formation of the metabolite, normeperidine, in healthy subjects and thus, caution should be used with concomitant administration. CNS Depressants Concomitant use of CNS depressants with usual doses of meperidine may result in respiratory depression, hypotension, profound sedation, coma or death (see PRECAUTIONS: Interactions with Other CNS Depressants ). Phenytoin The hepatic metabolism of meperidine may be enhanced by phenytoin. Concomitant administration resulted in reduced half-life and bioavailability with increased clearance of meperidine in healthy subjects, however, blood concentrations of normeperidine were increased, thus exercise caution when phenytoin is used concomitantly with meperidine. Ritonavir Plasma concentrations of the active metabolite normeperidine may be increased by ritonavir, thus concomitant administration should be avoided. Opioid analgesics, including meperidine hydrochloride tablets, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. | Acyclovir Plasma concentrations of meperidine and its metabolite, normeperidine, may be increased by acyclovir, thus caution should be used with concomitant administration. | Cimetidine Cimetidine reduced the clearance and volume of distribution of meperidine and also the formation of the metabolite, normeperidine, in healthy subjects and thus, caution should be used with concomitant administration. | CNS Depressants Concomitant use of CNS depressants with usual doses of meperidine may result in respiratory depression, hypotension, profound sedation, coma or death (see PRECAUTIONS: Interactions with Other CNS Depressants ). | Phenytoin The hepatic metabolism of meperidine may be enhanced by phenytoin. Concomitant administration resulted in reduced half-life and bioavailability with increased clearance of meperidine in healthy subjects, however, blood concentrations of normeperidine were increased, thus exercise caution when phenytoin is used concomitantly with meperidine. | Ritonavir Plasma concentrations of the active metabolite normeperidine may be increased by ritonavir, thus concomitant administration should be avoided. Opioid analgesics, including meperidine hydrochloride tablets, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.