Hydrocodone Bitartrate; Potassium Guaiacolsulfonate
Indications: Cough
DESCRIPTION:
Hydrocodone (dihydrocodeinone) bitartrate is a semi-synthetic centrally acting narcotic antitussive and potassium guaiacolsulfonate, an expectorant for oral administration. Chemically, hydrocodone bitartrate is 4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5).
Its empirical formula is C18H21NO3Β·C4H6O6*21/2H2O. It has a molecular weight of 494.50.
Chemically, potassium guaiacolsulfonate is benzenesulfonic acid, hydroxy- methoxy-, monopotassium salt, hemihydrate.
Its empirical formula is C7H7KO5S*1/2H2O. It has a molecular weight of 251.29.
Atuss EX: Each teaspoonful (5 ml) contains hydrocodone bitartrate, 5 mg and potassium guaiacolsulfonate, 300 mg. Inactive Ingredients: Citric acid, flavoring, menthol, purified water, sodium benzoate, sodium saccharin, and sorbitol.
CLINICAL PHARMACOLOGY:
Clinical trials have proven hydrocodone bitartrate to be an effective antitussive agent which is pharmacologically 2 to 8 times as potent as codeine. At equi-effective doses, its sedative action is greater than codeine. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act by directly depressing the cough center. In excessive doses, hydrocodone, like other opium derivatives, can depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system is insignificant. The constipation effects of hydrocodone are much weaker than that of morphine and no stronger than that of codeine. Hydrocodone can produce miosis, euphoria, physical and psychological dependence. At therapeutic antitussive doses, it does exert analgesic effects. Following a 10 mg oral dose of hydrocodone administered to five male human subjects, the mean peak concentration was 23.6 Β± 5.2 ng/ml. Maximum serum levels were achieved at 1.3 Β± 0.3 hours and half-life was determined to be 3.8 Β± 0.3 hours. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-demethylation and 6-ketoreduction to the corresponding 6-alpha- and 6-beta-hydroxymetabolites.
Potassium guaiacolsulfonate has been used empirically for many decades as an expectorant.
INDICATIONS AND USAGE:
Hydrocodone bitartrate; potassium guaiacolsulfonate is indicated for the symptomatic relief of irritating non-productive cough associated with upper and lower respiratory tract congestion.
CONTRAINDICATIONS:
Hydrocodone bitartrate; potassium guaiacolsulfonate is contraindicated in patients hypersensitive to hydrocodone or potassium guaiacolsulfonate. Patients known to be hypersensitive to other opioids may exhibit cross sensitivity to this product. Hydrocodone is contraindicated in the presence of an intracranial lesion associated with increased intracranial pressure; and whenever ventilatory function is depressed.
WARNINGS:
May be habit forming. Hydrocodone 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 hydrocodone bitartrate; potassium guaiacolsulfonate, and it should be prescribed and administered with the same degree of caution appropriate to the use of other narcotic drugs (see DRUG ABUSE AND DEPENDENCE).
Respiratory Depression: Hydrocodone bitartrate; potassium guaiacolsulfonate produces dose-related respiratory depression by directly acting on the brain stem respiratory centers. If respiratory depression occurs, it may be antagonized by the use of naloxone hydrochloride and other supportive measures when indicated.
Head Injury and Increased Intracranial Pressure: The respiratory depressant properties of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in the intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries.
Acute Abdominal Conditions: The administration of this product or other opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
PRECAUTIONS:
Before prescribing medication to suppress or modify cough, it is important to ascertain that the underlying cause of cough is identified, that modification of cough does not increase the risk of clinical or physiologic complications, and that appropriate therapy for the primary disease is provided.
Usage in Ambulatory Patients: Hydrocodone, like all narcotics, may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, and patients should be warned accordingly.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: Carcinogenicity, mutagenicity, and reproduction studies have not been conducted with hydrocodone bitartrate; potassium guaiacolsulfonate.
Pregnancy, Teratogenic Effects, Pregnancy Category C: Animal reproduction studies have not been conducted with hydrocodone bitartrate; potassium guaiacolsulfonate. It is also not known whether hydrocodone bitartrate; potassium guaiacolsulfonate can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Hydrocodone bitartrate; potassium guaiacolsulfonate should be given to a pregnant woman only if clearly needed.
Nonteratogenic Effects: Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose. There is no consensus on the best method of managing withdrawal. Chlorpromazine 0.7-1.0 mg/kg q 6 h, phenobarbital 2 mg/kg q 6 h, and paregoric 2-4 drops/kg q 4 h, have been used to treat withdrawal symptoms in infants. The duration of therapy is 4 to 28 days, with the dosages decreased as tolerated.
Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from hydrocodone bitartrate; potassium guaiacolsulfonate, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
DRUG INTERACTIONS:
Patients receiving other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative hypnotics or other CNS depressants (including alcohol) concomitantly with hydrocodone may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced (see WARNINGS).
ADVERSE REACTIONS:
Respiratory System: Hydrocodone produces dose-related respiratory depression by acting directly on brain stem respiratory centers.
Cardiovascular System: Hypertension, postural hypotension, and palpitations.
Genitourinary System: Ureteral spasm, spasm of vesical sphincters, and urinary retention have been reported with opiates.
Central Nervous System: Sedation, drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, dizziness, psychic dependence, mood changes, and blurred vision.
Gastrointestinal System: Nausea and vomiting occur more frequently in ambulatory than in recumbent patients.
DRUG ABUSE AND DEPENDENCE:
Special care should be exercised in prescribing hydrocodone for emotionally unstable patients and for those with a history of drug misuse. Such patients should be closely supervised when long-term therapy is contemplated.
Hydrocodone bitartrate; potassium guaiacolsulfonate is a Schedule III narcotic. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of narcotics; therefore, hydrocodone bitartrate; potassium guaiacolsulfonate should always be prescribed and administered with caution. Physical dependence is the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome.
Patients physically dependent on opioids will develop an abstinence syndrome upon abrupt discontinuation of the opioid or following the administration of a narcotic antagonist. The character and severity of the withdrawal symptoms are related to the degree of physical dependence. Manifestations of opioid withdrawal are similar to, but milder than, that of morphine and include lacrimation, rhinorrhea, yawning, sweating, restlessness, dilated pupils, anorexia, gooseflesh, irritability, and tremor. In more severe forms, nausea, vomiting, intestinal spasm and diarrhea, increased heart rate and blood pressure, chills, and pains in bones and muscles of the back and extremities may occur. Peak effects will usually be apparent at 48 to 72 hours.
Treatment of withdrawal is usually managed by providing sufficient quantities of an opioid to suppress severe withdrawal symptoms and then gradually reducing the dose of opioid over a period of several days.
OVERDOSAGE:
Signs and Symptoms: Serious overdosage with hydrocodone bitartrate; potassium guaiacolsulfonate 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 re-establishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote for respiratory depression which may result from overdosage or unusual sensitivity to narcotics including hydrocodone. Therefore, an appropriate dose of naloxone hydrochloride should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. For further information, see full prescribing information for naloxone hydrochloride. An antagonist should not be administered in the absence of clinically significant respiratory depression. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Gastric emptying may be useful in removing unabsorbed drug. Activated charcoal may be of benefit.