Drug class: Antitussives
ATC class: R05DA03
VA class: RE301

Medically reviewed by Drugs.com on Nov 9, 2023. Written by ASHP.

Introduction

Hydrocodone bitartrate is a phenanthrene-derivative opiate agonist antitussive and analgesic agent.¹⁰⁹

Uses for HYDROcodone Bitartrate (Antitussive)

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.

HYDROcodone Bitartrate (Antitussive) 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 for HYDROcodone Bitartrate (Antitussive)

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.

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

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.

HYDROcodone Bitartrate (Antitussive) 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.

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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