"The cystic fibrosis (CF) drug Orkambi (Vertex Pharmaceuticals) has received a green light from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP).
Orkambi is a fixed-dose oral combination "...
(Generic versions may still be available.)
Mepergan (meperidine and promethazine) Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes, in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Tolerance and Addiction Liability
Warning may be habit-forming
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 Federal narcotic laws.
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.
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.
INADVERTENT INTRA-ARTERIAL INJECTION
Due to the close proximity of arteries and veins in the areas most commonly used for intravenous injection, extreme care should be exercised to avoid perivascular extravasation or inadvertent intra-arterial injection of Mepergan (meperidine and promethazine) . Reports compatible with inadvertent intra-arterial injection suggest that pain, severe chemical irritation, severe spasm of distal vessels, and resultant gangrene requiring amputation is likely under such circumstances. Intravenous injection was intended in all the cases reported, but perivascular extravasation or arterial placement of the needle is now suspect. There is no proven successful management of this condition after it occurs, although sympathetic block and heparinization are commonly employed during the acute management because of the results of animal experiments with other known arteriolar irritants. Aspiration of dark blood does not preclude intra-arterial needle placement, because blood is discolored upon contact with promethazine. Use of syringes with rigid plungers or of small bore needles might obscure typical arterial backflow if this is relied upon alone.
If necessary, meperidine may be given intravenously, but the injection should be given very slowly, preferably in the form of a diluted solution. Rapid intravenous 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 intravenously unless a narcotic antagonist and the facilities for assisted or controlled respiration are immediately available. When meperidine is given parenterally, especially intravenously, the patient should be lying down.
When used intravenously, Mepergan (meperidine and promethazine) should be given at a rate not to exceed 1 mL (25 mg of each component) per minute. When administering any irritant drug intravenously, it is usually preferable to inject it through the tubing of an intravenous infusion set that is known to be functioning satisfactorily. In the event that a patient complains of pain during intended intravenous injection of Mepergan (meperidine and promethazine) , the injection should immediately be stopped to provide for evaluation of possible arterial placement or perivascular extravasation.
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.
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.
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.
Meperidine appears in the milk of nursing mothers receiving the drug.
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.
ACUTE ABDOMINAL CONDITIONS
The administration of meperidine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
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, hypothyroidism, Addison's disease, and prostatic hypertrophy or urethral stricture.
Antiemetics may mask the symptoms of an unrecognized disease and thereby interfere with diagnosis.
Patients in pain who have received inadequate or no analgesia have been noted to develop "athetoid-like" movements of the upper extremities following the parenteral administration of promethazine. These symptoms usually disappear upon adequate control of the pain.
Ambulatory patients should be cautioned against driving automobiles or operating dangerous machinery until it is known that they do not become drowsy or dizzy from promethazine hydrochloride therapy.
This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
Additional Mepergan Information
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