Meperidine and Promethazine Capsules

Meperidine HCl and Promethazine HCl capsules each contain 50 mg meperidine hydrochloride and 25 mg promethazine hydrochloride for oral administration. 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. Chemically, Meperidine hydrochloride is 4-Piperidinecarboxylic acid, 1-methyl-4-phenyl-, ethyl ester, hydrochloride and has the following structure:

Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is freely soluble in water and soluble in alcohol.

Chemically, Promethazine hydrochloride is (10H-phenothiazine-10-ethanamine, N,N,α-trimethyl-, monohydrochloride, (±)-) is a racemic compound and has the following structural formula:

Inactive Ingredients:

Black ink, FD&C Blue #1, FD&C Red #3, FD&C Yellow #6, gelatin, lactose, magnesium stearate, talc and titanium dioxide.

WARNING

PROMETHAZINE HYDROCHLORIDE SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION.

POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HYDROCHLORIDE IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HYDROCHLORIDE HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS.

CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HYDROCHLORIDE TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER.

IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HYDROCHLORIDE BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED.

Interaction with Other Central Nervous System 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, sedative-hypnotics, tricyclic antidepressants, and other CNS depressants (including alcohol). Respiratory depression, hypotension, and profound sedation or coma may result.

The sedative action of promethazine hydrochloride is additive to the sedative effects of central nervous system depressants; therefore, agents such as alcohol, barbiturates, and narcotic analgesics should either be eliminated or given in reduced dosage in the presence of promethazine hydrochloride. When given concomitantly with promethazine hydrochloride, the dose of barbiturates should be reduced by at least one-half and the dose of analgesic depressants, such as morphine or meperidine, should be reduced by one-quarter to one-half.

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 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 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 an individual whose ability to maintain his blood pressure has already been compromised by a depleted blood volume or concurrent 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 and Lactation

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 hazards, because safe use in pregnancy prior to labor has not been established relative to possible adverse effects on fetal development.

When used as an obstetrical analgesic, meperidine crosses the placental barrier and can produce respiratory depression in the newborn; resuscitation may be required (see OVERDOSAGE).

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. Meperidine appears in the milk of nursing mothers receiving the drug.

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

Central Nervous System: Euphoria, dysphoria, weakness, headache, agitation, tremor, uncoordinated muscle movements, transient hallucinations and disorientation, visual disturbances and, rarely, extrapyramidal reactions.

Gastrointestinal: Dry mouth, constipation, biliary-tract spasm.

Cardiovascular: Flushing of the face, tachycardia, bradycardia, palpitation, faintness, syncope.

Promethazine adverse reactions

Central Nervous System: Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported.

Cardiovascular: Increased or decreased blood pressure, tachycardia, bradycardia, faintness.

Dermatologic: Dermatitis, photosensitivity, urticaria.

Hematologic: Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.

Gastrointestinal: Dry mouth, nausea, vomiting, jaundice.

Respiratory: Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal).

Other: Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported.

Paradoxical Reactions: Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine hydrochloride. Consideration should be given to the discontinuation of promethazine hydrochloride and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients. Minor increases in blood pressure and occasional mild hypotension have been detected.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

To report SUSPECTED ADVERSE REACTIONS, contact ECI Pharmaceuticals, LLC at 954-486-8181 X-109

Symptoms

Serous 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, 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 patient airway and institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride, is a specific antidote against respiratory depression that may result from overdosage or unusual sensitivity to narcotics, including meperidine. Therefore, an appropriate dose of naloxone hydrochloride 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.

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.

NDC 51293-622-01

ECI Pharmaceuticals

Meperidine HCl and
Promethazine HCl
Capsules

Rx only
100 CAPSULES

50 mg/
25 mg