Hydrocodonedosage

Hydrocodone bitartrate extended-release capsules should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Daily doses of hydrocodone bitartrate extended-release capsules, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of hydrocodone bitartrate extended-release capsules for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with hydrocodone bitartrate extended-release capsules. Consider this risk when selecting an initial dose and when making dose adjustments Instruct patients to swallow hydrocodone bitartrate extended-release capsules intact and not to cut, break, chew, crush, or dissolve the capsules (risk of potentially fatal overdose). Discuss availability of naloxone with the patient and caregiver and assess each patient’s need for access to naloxone, both when initiating and renewing treatment with hydrocodone bitartrate extended-release capsules. Consider prescribing naloxone based on the patient’s risk factors for overdose. For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg capsules orally every 12 hours. To convert to hydrocodone bitartrate extended-release capsules from another opioid, use available conversion factors to obtain estimated dose. Dose titration of hydrocodone bitartrate extended-release capsules may occur every 3 to 7 days, using increments of 10 mg every 12 hours (i.e., 20 mg per day). Patients with Severe Hepatic Impairment: Initiate dosing with 10 mg every 12 hours and titrate carefully, while monitoring for respiratory depression, sedation, and hypotension. No adjustment in starting dose with hydrocodone bitartrate extended-release capsules is required in patients with mild or moderate hepatic impairment. Do not abruptly discontinue hydrocodone bitartrate extended-release capsules in a physically dependent patient.

2.1 Important

Dosage and Administration Information Hydrocodone bitartrate extended-release capsules should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Daily doses of hydrocodone bitartrate extended-release capsules, a single dose of greater than 40 mg, or a total daily dose of greater than 80 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of hydrocodone bitartrate extended-release capsules for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with hydrocodone bitartrate extended-release capsules. Consider this risk when selecting an initial dose and when making dose adjustments. Instruct patients to swallow hydrocodone bitartrate extended-release capsules whole. Crushing, chewing, or dissolving the beads in hydrocodone bitartrate extended-release capsules will result in uncontrolled delivery of hydrocodone and can lead to overdose or death. Hydrocodone bitartrate extended-release capsules are administered orally twice daily (every 12 hours).

2.2 Patient

Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with hydrocodone bitartrate extended-release capsules. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.

2.3 Initial

Dosage Use of Hydrocodone Bitartrate Extended-Release Capsules as the First Opioid Analgesic (opioid-naïve patients) Initiate therapy with hydrocodone bitartrate extended-release capsules with one 10 mg capsule every 12 hours. Use of Hydrocodone Bitartrate Extended-Release Capsules in Patients Who Are Not Opioid Tolerant The starting dose for patients who are not opioid tolerant is hydrocodone bitartrate extended-release capsules 10 mg orally every 12 hours. Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression. Conversion from Oral Hydrocodone Formulations to Hydrocodone Bitartrate Extended-Release Capsules Patients receiving other oral hydrocodone-containing formulations may be converted to hydrocodone bitartrate extended-release capsules by dividing the patient’s total daily oral hydrocodone dose in half and administrating as hydrocodone bitartrate extended-release capsules every 12 hours. Conversion from Other Oral Opioids to Hydrocodone Bitartrate Extended-Release Capsules When hydrocodone bitartrate extended-release capsules therapy is initiated, discontinue all other opioid analgesics other than those used on an as needed basis for breakthrough pain when appropriate. There is inter-patient variability in the relative potency of different opioid drugs and products. Therefore, a conservative approach is advised when determining the total daily dosage of hydrocodone bitartrate extended-release capsules. It is safer to underestimate a patient's 24-hour oral hydrocodone dosage and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydrocodone dosage and manage an adverse reaction due to an overdose. In a hydrocodone bitartrate extended-release capsules clinical trial with an open label titration period, patients were converted from their prior opioid to hydrocodone bitartrate extended-release capsules using Table 1 as a guide for the initial hydrocodone bitartrate extended-release capsules dose. To obtain the initial hydrocodone bitartrate extended-release capsules dose, first use Table 1 to convert the prior oral opioids to a total hydrocodone daily dose and then reduce the calculated daily hydrocodone dose by 25% to account for interpatient variability in relative potency of different opioids. Consider the following when using the information in Table 1: This is not a table of equianalgesic doses. The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to hydrocodone bitartrate extended-release capsules. The table cannot be used to convert from hydrocodone bitartrate extended-release capsules to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and may result in fatal overdose. Table 1. Conversion Factors to Hydrocodone Bitartrate Extended-Release Capsules (Not Equianalgesic Doses) Prior Oral Opioid Oral Dose (mg) Approximate Oral Conversion Factor The conversion ratios in this table are only to be used for the conversion from current opioid therapy to hydrocodone bitartrate extended-release capsules. Hydrocodone 10 1 Oxycodone 10 1 Methadone 10 1 Oxymorphone 5 2 Hydromorphone 3.75 2.67 Morphine 15 0.67 Codeine 100

0.10 To calculate the estimated daily hydrocodone bitartrate extended-release capsule dose using

Table 1: For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total daily dose by the approximate oral conversion factor to calculate the approximate oral hydrocodone daily dose. Divide the daily dose in half for administration every 12 hours. For patients on a regimen of more than one opioid, calculate the approximate oral hydrocodone dose for each opioid and sum the totals to obtain approximate total hydrocodone daily dose. The daily dose should then be divided in half for administration every 12 hours. For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion. Reduce the calculated daily oral hydrocodone dose by 25%. Always round the dose down, if necessary, to the nearest hydrocodone bitartrate extended-release capsule strength(s) available and initiate therapy with that dose. Example conversion from a single opioid to hydrocodone bitartrate extended-release capsules Step 1: Sum the total daily dose of the opioid (in this case, extended-release oxymorphone); 15 mg oxymorphone twice daily = 30 mg total daily dose of oxymorphone.

Step 2: Calculate the approximate equivalent dose of oral hydrocodone based on the total daily dose of the current opioid using Table 1; 30 mg total daily dose of oxymorphone x 2 = 60 mg of oral hydrocodone daily. The daily dose should then be divided in half for administration every 12 hours.

Step 3: Calculate the approximate starting dose which is 30 mg hydrocodone bitartrate extended-release capsules every 12 hours. Round down, if necessary, to the appropriate hydrocodone bitartrate extended-release capsule strengths available. Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity after converting patients to hydrocodone bitartrate extended-release capsules. The dose of hydrocodone bitartrate extended-release capsules can be gradually adjusted preferably at increments of 10 mg every 12 hours every 3 to 7 days, until adequate pain relief and acceptable adverse reactions have been achieved. Conversion from Methadone to Hydrocodone Bitartrate Extended-Release Capsules Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and tends to accumulate in the plasma. Conversion from Transdermal Fentanyl to Hydrocodone Bitartrate Extended-Release Capsules Hydrocodone bitartrate extended-release capsules treatment can be initiated 18 hours following the removal of the transdermal fentanyl patch. Although there has been no systematic assessment of such conversion, a conservative hydrocodone dose, approximately 10 mg every 12 hours of hydrocodone bitartrate extended-release capsules, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to hydrocodone bitartrate extended-release capsules, as there is limited documented experience with this conversion.

2.4 Titration and

Maintenance of Therapy Individually titrate hydrocodone bitartrate extended-release capsules to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving hydrocodone bitartrate extended-release capsules to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During use of opioid therapy for an extended period of time, periodically reassess the continued need for use of opioid analgesics. Patients who experience breakthrough pain may require a dosage adjustment of hydrocodone bitartrate extended-release capsules, or may need a rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the hydrocodone bitartrate extended-release capsules dosage. Because steady-state plasma concentrations are approximated within 3 days, hydrocodone bitartrate extended-release capsules dosage adjustments, preferably at increments of 10 mg every 12 hours, may be done every 3 to 7 days. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.5 Dosage Modifications in

Patients with Severe Hepatic Impairment Patients with severe hepatic impairment may have higher plasma concentrations of hydrocodone than those with normal function. Therefore, initiate therapy with 10 mg every 12 hours and titrate carefully, while monitoring for respiratory depression, sedation, and hypotension. No adjustment in starting dose with hydrocodone bitartrate extended-release capsules is required in patients with mild or moderate hepatic impairment.

2.6 Safe Reduction or

Discontinuation of Hydrocodone Bitartrate Extended-Release Capsules Do not abruptly discontinue hydrocodone bitartrate extended-release capsules in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking hydrocodone bitartrate extended-release capsules, there are a variety of factors that should be considered, including the total daily dose of opioid (including hydrocodone bitartrate extended-release capsules) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co- morbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on hydrocodone bitartrate extended-release capsules who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.