Introduction ⬇
VA Class:RE301
ATC Class:R05DA03
AHFS Class:
Generic Name(s):
Notification REMS: FDA approved a REMS for hydrocodone to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of hydrocodone and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page ([Web]). |
Hydrocodone bitartrate is a phenanthrene-derivative opiate agonist antitussive and analgesic agent.109
Uses ⬆ ⬇
Cough 
Hydrocodone bitartrate and hydrocodone polistirex are used in combination with other antitussives or expectorants for the symptomatic relief of nonproductive cough. Since the cough reflex may be a useful physiologic mechanism that clears the respiratory passages of foreign material and excess secretions and may aid in preventing or reversing atelectasis, cough suppressants should not be used indiscriminately.
Antitussives containing hydrocodone should not be used in patients younger than 18 years of age.710 (See Cautions: Pediatric Precautions.)
Pain
For use of hydrocodone as an analgesic agent, see 28:08.08.
Dosage and Administration ⬆ ⬇
Administration
Hydrocodone bitartrate and hydrocodone polistirex are administered orally.109
When the extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex (e.g., Tussionex® Pennkinetic®) is used, patients and caregivers should be strongly advised to use an accurate, calibrated dosing device to measure doses of the suspension.109,112 Use of a household teaspoon as a measuring device could result in overdosage.109,112 The extended-release oral suspension should not be diluted with other liquids or mixed with other drugs, since this may alter resin binding, thereby altering the rate of hydrocodone absorption and possibly resulting in toxicity.109 The extended-release oral suspension should not be given more frequently than every 12 hours; if cough is not controlled, the clinician should be contacted.112 The extended-release oral suspension should be shaken well before each use.109
Dosage
Cough
Hydrocodone bitartrate and hydrocodone polistirex are currently commercially available only in combination products. Dosage of hydrocodone polistirex is expressed in terms of hydrocodone bitartrate.109
Hydrocodone preparations should be given in the smallest effective dose and as infrequently as possible to minimize the development of tolerance and physical dependence. Reduced dosage is indicated in debilitated or poor-risk patients and in very old patients.109
The recommended adult antitussive dosage of hydrocodone bitartrate conventional (immediate-release) preparations is 5 mg every 4-6 hours as needed, not to exceed 30 mg in a 24-hour period.113 However, recommended and maximum dosages of other drugs included in the combination preparations must be considered and may further limit the maximum hydrocodone bitartrate dosage given in a 24-hour period.114,115,116
In adults, the usual antitussive dosage of hydrocodone bitartrate using the extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex (e.g., Tussionex® Pennkinetic®) is 10 mg (5 mL) every 12 hours; the dosage should not exceed 20 mg (10 mL) daily.109
Cautions ⬆ ⬇
Adverse Effects
Adverse reactions occur infrequently with usual oral antitussive doses of hydrocodone. The most common adverse effects of hydrocodone are lightheadedness, dizziness, sedation, nausea, and vomiting.109 These adverse effects appear to be more prominent in ambulatory patients than in nonambulatory patients, and some of these effects may be alleviated if the patient lies down.109 Other adverse effects include constipation, rash, pruritus, euphoria, and dysphoria.109
Precautions and Contraindications
Hydrocodone shares the toxic potentials of the opiate agonists, and the usual precautions of opiate agonist therapy should be observed. See Cautions in the Opiate Agonists General Statement.
Because concomitant use of opiate agonists and benzodiazepines or other CNS depressants may result in profound sedation, respiratory depression, coma, and death, opiate antitussives should be avoided in patients receiving CNS depressants.700,704 (See Drug Interactions.) Patients receiving hydrocodone should be apprised of the risks associated with concomitant therapeutic or illicit use of benzodiazepines, alcohol, or other CNS depressants.700,703
In patients with asthma or pulmonary emphysema, indiscriminate use of antitussives may precipitate respiratory insufficiency resulting from increased viscosity of bronchial secretions and suppression of the cough reflex. Tolerance and physical dependence may occur following prolonged administration of hydrocodone preparations.109
Patients should be warned that hydrocodone may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).109
As with other opiate agonist antitussives, hydrocodone may cause respiratory depression in large doses, when given more frequently than recommended, or in sensitive patients; this effect seldom occurs with usual oral doses.109,112 Overdosage and toxicity (including fatal respiratory depression) have been reported in adults and children receiving hydrocodone.109,112,136,137,138 (See Cautions: Pediatric Precautions.) Patients should be advised to immediately seek medical attention if they have trouble breathing, slow heartbeat, severe sleepiness, dizziness, confusion, or cold, clammy skin.109,112 Severe respiratory depression resulting from acute toxicity may be reversed by administration of an opiate antagonist (e.g., naloxone hydrochloride).109
Hydrocodone should be used with caution in geriatric or debilitated patients and in those with hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture, pulmonary disease, or severe renal or hepatic impairment.109 Hydrocodone also should be used with caution in patients with head injury, other intracranial lesions, or preexisting increased intracranial pressure, since opiate agonists may increase CSF pressure and markedly exaggerate these conditions; in addition, adverse CNS effects of the drug may obscure the clinical course of the underlying condition.109 The drug should also be used with caution in patients who have undergone thoracotomies or laparotomies, since suppression of the cough reflex may lead to retention of secretions postoperatively in these patients.109
Hydrocodone may obscure the diagnosis or clinical course in patients with acute abdominal conditions.109
Long-term use of hydrocodone may result in obstructive bowel disease, especially in patients with an underlying intestinal motility disorder.109
Hydrocodone is contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation.109
Pediatric Precautions
Because the risks of respiratory depression, misuse, abuse, addiction, overdosage, and death outweigh the potential benefit in pediatric patients, FDA states that antitussive agents containing opiates, including hydrocodone, should not be used in pediatric patients younger than 18 years of age.710 In addition, use of hydrocodone for the management of cough and cold is contraindicated in children younger than 6 years of age.109,113,136,137,138
Geriatric Precautions
Clinical studies of hydrocodone polistirex and chlorpheniramine polistirex extended-release suspension did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently than younger adults.109 While other clinical experience generally has not revealed age-related differences in safety or response to the drug, care should be taken in dosage selection in geriatric patients.109 Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients, the manufacturer suggests that patients in this age group receive initial dosages of this preparation in the lower end of the usual range.109
Hydrocodone is substantially eliminated in urine and the risk of toxicity may be increased in patients with impaired renal function.109 Because geriatric patients are more likely to have decreased renal function, caution should be used when selecting dosages for such patients and monitoring of renal function should be considered.109
Pregnancy and Lactation
Pregnancy
Safe use of hydrocodone during pregnancy has not been established; therefore, the drug should not be administered to pregnant women unless the possible benefits outweigh the potential risks.109
Lactation
It is not known whether hydrocodone is distributed into human milk.109 A decision should be made to discontinue nursing or the drug, taking into account the importance of the drug to the woman.109
Drug Interactions ⬆ ⬇
Concomitant use of opiate agonists and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death.416,417,418,700,701,702,703,704 Opiate agonist antitussives should be avoided in patients taking benzodiazepines, other CNS depressants, or alcohol.700,704 Concurrent use of anticholinergic agents with hydrocodone may produce paralytic ileus.109 Concomitant use of opiate agonists with serotonergic drugs can cause serotonin syndrome.400 (See Drug Interactions in the Opiate Agonists General Statement 28:08.08.)
Other Information ⬆ ⬇
Pharmacology
Hydrocodone causes suppression of the cough reflex by a direct effect on the cough center in the medulla of the brain.109 The drug also appears to exert a drying effect on respiratory tract mucosa and to increase viscosity of bronchial secretions. On a weight basis, antitussive activity of hydrocodone is slightly greater than that of codeine. At equivalent therapeutic doses, hydrocodone is more sedating than codeine. The constipating effect of hydrocodone is less than that of morphine and not greater than that of codeine.
Pharmacokinetics
Hydrocodone is well absorbed from the GI tract. Following oral administration of a single 10-mg dose of hydrocodone to adult males in one study, a mean peak serum hydrocodone concentration of 23.6 ng/mL occurred after 1.3 hours. Following oral administration, antitussive action is maintained for 4-6 hours. Following multiple doses of the extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex (Tussionex® Pennkinetic®), a mean peak plasma hydrocodone concentration of 22.8 ng/mL occurred after 3.4 hours.109
The elimination half-life of hydrocodone is reportedly about 3.8 hours in healthy adults.109 Like other phenanthrene derivatives, hydrocodone is probably metabolized in the liver and excreted mainly in urine. Metabolism of hydrocodone includes O -demethylation, N -demethylation, and 6-keto reduction.
Chemistry and Stability
Chemistry
Hydrocodone bitartrate is a phenanthrene-derivative opiate agonist that is used as an antitussive and analgesic agent.109 Hydrocodone is a hydrogenated ketone derivative of codeine. Hydrocodone bitartrate occurs as fine, white crystals or crystalline powder and is soluble in water and slightly soluble in alcohol. Hydrocodone polistirex consists of hydrocodone with a cation-exchange resin copolymer complex of sulfonated styrene-divinylbenzene.109 Hydrocodone bitartrate and hydrocodone polistirex are currently commercially available only in combination products.
Stability
Hydrocodone bitartrate is affected by light. Hydrocodone bitartrate preparations should be stored in tight, light-resistant containers at 15-30°C.
Additional Information
For further information on the chemistry, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, and dosage and administration of hydrocodone bitartrate, see the Opiate Agonists General Statement 28:08.08 and Hydrocodone Bitartrate 28:08.08.
Preparations ⬆ ⬇
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Fixed-combination preparations containing hydrocodone in a concentration of 15 mg or less per dosage unit or 5 mL combined with a therapeutic amount of one or more nonopiate drugs or with a fourfold or greater quantity of isoquinolone opium alkaloid previously were subject to control under the Federal Controlled Substances Act of 1970 as schedule III (C-III) drugs. However, because of increasing concerns about misuse, abuse, and diversion, these preparations have been rescheduled and, effective October 6, 2014, are subject to control as schedule II (C-II) drugs.290 For additional information on the rescheduling of hydrocodone preparations, see Cautions: Misuse and Abuse, in Hydrocodone Bitartrate 28:08.08.
HYDROcodone Bitartrate Combinations
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Oral | Solution | 5 mg/5 mL with Chlorpheniramine Maleate 4 mg/5 mL | Vituz® (C-II) | Hawthorn |
| | 5 mg/5 mL with Chlorpheniramine Maleate 4 mg/5 mL and Pseudoephedrine Hydrochloride 60 mg/5 mL* | HYDROcodone Bitartrate, Chlorpheniramine Maleate, and Pseudoephedrine Hydrochloride Oral Solution (C-II) | |
| | | Zutripro® (C-II) | Hawthorn |
| | 5 mg/5 mL with Homatropine Methylbromide 1.5 mg/5 mL* | HYDROcodone Bitartrate and Homatropine Methylbromide Syrup (C-II) | |
| | | Hydromet® Syrup (C-II) | Actavis |
| | 5 mg/5 mL with Pseudoephedrine Hydrochloride 60 mg/5 mL* | HYDROcodone Bitartrate and Pseudoephedrine Hydrochloride Oral Solution (C-II) | |
| | | Rezira® (C-II) | Hawthorn |
| Tablets | 5 mg with Homatropine Methylbromide 1.5 mg* | HYDROcodone Bitartrate and Homatropine Methylbromide Tablets (C-II) | |
| | | Tussigon® (C-II; scored) | Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
HYDROcodone Polistirex Combinations
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
Oral | Suspension, extended-release | equivalent to HYDROcodone Bitartrate 10 mg/5 mL with Chlorpheniramine Polistirex equivalent to Chlorpheniramine Maleate 8 mg/5 mL* | HYDROcodone Polistirex and Chlorpheniramine Polistirex Extended-Release Suspension (C-II) | |
| | | Tussionex® Pennkinetic® (C-II) | UCB |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Copyright ⬆ ⬇
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions November 19, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
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