1. Dosage
In August 2014, the Drug Enforcement Administration published a final ruling to reschedule hydrocodone combination products from Schedule III to Schedule II due to their high potential of abuse. Beginning October 6, 2014, all hydrocodone combination products will be Schedule II. Single-entity hydrocodone products were already classified as Schedule II1.
Hydrocodone bitartrate, as combination therapy, is FDA-approved as an opioid antitussive and analgesic used for the relief of cough and moderate to moderately severe pain2-7. Hydrocodone bitartrate is available in fixed combinations with non-opiate drugs (e.g., acetaminophen, acetylsalicylic acid, chlorpheniramine, guaifenesin, ibuprofen, phenylephrine, and pseudoephedrine)2,3,6,7. This drug should be given in the smallest effective dose and as infrequently as possible to minimize the development of tolerance and physical dependence. Hydrocodone bitartrate is available in the United States as a single entity, extended-release capsule (Zohydro® ER), formulated with abuse-deterrent beads .2,3,8. This hydrocodone product is FDA-approved for managing pain requiring daily, long-term, around-the-clock opiate therapy not responsive to other treatment options. Hydrocodone bitartrate extended-release tablets with abuse deterrent properties (Hysingla® ER) have also been FDA-approved to manage severe pain requiring chronic, around-the-clock opiate treatment unresponsive to other treatment regimens 2,3,8,9.
The use of hydrocodone when prescribed by multiple physicians will be reviewed.
Hydrocodone/acetaminophen combination products containing greater than 325 mg of acetaminophen have been discontinued due to increased potential for liver toxicity.
1.1. Adults
Analgesic hydrocodone dosages should be determined based on pain severity and patient response/ tolerance. In individuals with severe pain or those who have become tolerant to the analgesic effects of hydrocodone, it may be necessary to exceed the usual dosage. Reduced hydrocodone dosages are indicated in high-risk patients and the elderly. The maximum daily dosage for the acetaminophen/ hydrocodone combination is restricted by the maximum acetaminophen dose of 4 g daily to limit the risk of hepatic damage and severe hypersensitivity reactions associated with acetaminophen use 2-4.
Hydrocodone exerts antitussive effects by directly acting on receptors in the cough center at dosages lower than those required for analgesia 2,3,6,7.
Recommended adult hydrocodone dosages as monotherapy and combination therapy are summarized in Tables 12,3,8,9 and 22-7,10. Dosages exceeding these recommendations will be reviewed.
Table 1: Recommended Adult Hydrocodone Dosages: Monotherapy
| Drug/Indication | Dosage Forms/Strengths | Usual Dosage Regimen | Maximum Recommended Dose |
|---|---|---|---|
| Analgesic hydrocodone extended-release capsule (Zohydro® ER, generics) | 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50 mg extended-release, abuse-deterrent capsules | 20 mg to 100 mg every 12 hours | maximum dose not defined; doses should be titrated per patient to maximize analgesia and minimize adverse drug reactions |
| Analgesic hydrocodone extended-release tablet (Hysingla® ER, generics) | 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg extended-release, abuse-deterrent tablets | 20 mg to 120 mg every 24 hours | maximum dose not defined; doses should be titrated per patient to maximize analgesia and minimize adverse drug reactions |
Table 2: Recommended Adult Hydrocodone Dosages: Combination Therapy
| Drug/Indication | Dosage Forms/Strengths | Usual Dosage Regimen | Maximum Recommended Dose |
|---|---|---|---|
| Analgesic hydrocodone bitartrate/ acetaminophen (Lortab®, Norco®, generics) | 5 mg/300 mg, 7.5 mg/300 mg, 10 mg/300 mg, 2.5 mg/325 mg, 5 mg/325 mg, 7.5 mg/325 mg, 10 mg/325 mg tablets; 7.5 mg/325 mg/15 ml or 10 mg/325 mg/15 ml solution; 10 mg/300 mg/15 ml elixir | 2.5-10 mg every 4-6 hours as needed | 60 mg/4000 mg daily* |
| Analgesic hydrocodone bitartrate/ ibuprofen (Vicoprofen®, Ibudone®, Reprexain®, generics) | 2.5 mg/200 mg, 5 mg/200 mg, 7.5 mg/200 mg, 10 mg/200 mg tablets | 2.5-10 mg every 4-6 hours as needed | 5 tablets per day [maximum hydrocodone dose (10mg/200 mg): 50 mg daily]** |
| Antitussive hydrocodone bitartrate/homatropine (Hydromet®, generics) | 5 mg/1.5 mg/5ml solution or 5 mg/1.5 mg tablet | 5 mg every 4-6 hours as needed | 30 mg daily |
| Antitussive hydrocodone polistirex/chlorpheniramine polistirex (TussiCaps®) | 10 mg/ 8 mg extended-release capsules | 1 capsule every 12 hours | 20 mg/16 mg every 24 hours |
| Antitussive hydrocodone polistirex/chlorpheniramine polistirex (Tussionex® Pennkinetic®, generics) | 10 mg/8 mg+/5 ml extended-release oral suspension | 10 mg/8 mg+ every 12 hours | 20 mg/16 mg+ daily |
Legend:
- *dosage limit based on maximum acetaminophen daily dose; varies by product
- **short-term use (less than 10 days) recommended
- +dosed as hydrocodone bitartrate and chlorpheniramine maleate
1.2. Pediatrics
Prior to 2018, Hydrocodone was not FDA-approved for use as an antitussive in pediatric patients younger than 6 years of age as safety and efficacy have not been established. In January 2018 the U.S. Food and Drug Administration changed the labeling to indicate that opioid cough and cold medicines containing codeine or hydrocodone are no longer indicated for patients less than 18 years of age.11 For analgesia, safety and efficacy of the hydrocodone/acetaminophen combination have not been established in children younger than 2 years of age, while the hydrocodone/ibuprofen combination is not indicated for use in children younger than 16 years of age due to lack of safety and efficacy data.2-5 The hydrocodone single-entity products, Zohydro® ER and Hysingla® ER are not FDA-approved in the pediatric population (less than 18 years of age) as safety and efficacy in this age group have not been established .2,3,8,9.
Analgesic hydrocodone dosages should be determined based on pain severity and patient response/ tolerance. In individuals with severe pain or those who have become tolerant to the analgesic effects of hydrocodone, it may be necessary to exceed the usual dosage. Reduced hydrocodone dosages are indicated in very young patients. Like adult patients, the maximum daily dosage for the acetaminophen/ hydrocodone combination is restricted by the maximum acetaminophen dose (as determined by age and weight – see Table 3) to limit the risk of hepatic damage and severe hypersensitivity reactions associated with acetaminophen use 2-10.
Recommended pediatric hydrocodone dosages as combination therapy are summarized in Table 32-5 . Dosages exceeding these recommendations will be reviewed.
Table 3: Recommended Pediatric Hydrocodone Dosages: Combination Therapy
| Drug/Indication | Usual Dosage Regimen | Maximum Recommended Dose |
|---|---|---|
| Analgesic hydrocodone bitartrate/acetaminophen (APAP) (Lortab®, Norco®, generics) |
|
|
| Analgesic hydrocodone bitartrate/ibuprofen (Vicoprofen®, Ibudone®, Reprexain®, generics) | 16 years and older: 2.5-10 mg/200 mg every 4-6 hours as needed | 5 tablets daily** |
Legend:
- +APAP = acetaminophen
- *dosage limit based on maximum acetaminophen daily dose
- **short-term use (less than 10 days) recommended
1.3. Opioid Reversal Agents
Naloxone is an opioid receptor antagonist that is FDA approved for reversal of opioid-induced respiratory and central nervous system depression. Naloxone is supplied as a nasal spray marketed as Narcan® 4 mg/0.1 mL nasal spray, Kloxxado® 8 mg/ 0.1 mL nasal spray, Evzio® 0.4 mg/ 0.4 mL auto-injector solution for injection, LifEMS Naloxone® 2 mg/ 2 mL solution for injection, and generic formulations of the solution for injection are available12-15.
In July 2020, the U.S. Food and Drug Administration made the recommendations that healthcare professionals should discuss the availability of naloxone products and consider prescribing naloxone to patients who are prescribed opioid pain relievers and are at increased risk of opioid overdose. Patients at risk of opioid overdose include patients who are co-prescribed benzodiazepines or other drugs that depress the central nervous system, patients with a history of opioid use disorder (OUD), or who have experienced a previous opioid overdose. Healthcare professionals should also consider prescribing naloxone to patients who have other household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.16 In 2016, the state of Texas, in association with the Texas Pharmacy Association, obtained a physician-signed standing order that allows pharmacists to dispense naloxone products to patients after completing Texas-accredited training17.