Hydromorphonedosage

Hydromorphone hydrochloride extended-release tablets 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.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of hydromorphone hydrochloride extended-release tablets 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 hydromorphone hydrochloride extended-release tablets. Consider this risk when selecting an initial dose and when making dose adjustments

For once daily administration IN OPIOID-TOLERANT PATIENTS.

Instruct patients to swallow hydromorphone hydrochloride extended-release tablets intact, and not to cut, break, chew, crush, or dissolve the tablets (risk of potentially fatal overdose).

Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with hydromorphone hydrochloride extended-release tablets, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose.

Dose may be increased using increments of 4 to 8 mg every 3 to 4 days as needed to achieve adequate analgesia.

Periodically reassess patients receiving hydromorphone hydrochloride extended-release tablets to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse.

Do not rapidly reduce or abruptly discontinue hydromorphone hydrochloride extended-release tablets in a physically-dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

Moderate Hepatic Impairment: Initiate treatment with 25% of the dose that would be prescribed for patients with normal hepatic function. Monitor closely for respiratory and central nervous system depression.

Moderate and Severe Renal Impairment: Initiate treatment in patients with moderate renal impairment with 50% and patients with severe renal impairment with 25% of the hydromorphone hydrochloride extended-release tablets dose that would be prescribed for patients with normal renal function. Monitor closely for respiratory and central nervous system depression.

2.1 Important

Dosage and Administration Instructions

To avoid medication errors, prescribers and pharmacists must be aware that hydromorphone is available as both immediate-release 8 mg tablets and extended-release 8 mg tablets.

Hydromorphone hydrochloride extended-release tablets 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.

Due to the risk of respiratory depression, hydromorphone hydrochloride extended-release tablets are only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other extended-release opioids when beginning hydromorphone hydrochloride extended-release tablets therapy. As hydromorphone hydrochloride extended-release tablets are only for use in opioid-tolerant patients, do not begin any patient on hydromorphone hydrochloride extended-release tablets as the first opioid.

Patients who are opioid-tolerant are those receiving, for one week or longer, at least 60 mg of oral morphine per day, at least 25 mcg transdermal fentanyl per hour, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 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 hydromorphone hydrochloride extended-release tablets 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 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 hydromorphone hydrochloride extended-release tablets. Consider this risk when selecting an initial dose and when making dose adjustments.

Hydromorphone hydrochloride extended-release tablets are administered orally once daily IN OPIOID-TOLERANT PATIENTS.

Instruct patients to swallow hydromorphone hydrochloride extended-release tablets whole. Crushing, chewing, or dissolving hydromorphone hydrochloride extended-release tablets will result in uncontrolled delivery of hydromorphone and can lead to overdose or death.

2.2 Patient

Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.

2.3 Initial

Dosage It is safer to underestimate a patient’s 24-hour oral hydromorphone dosage and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydromorphone dosage and manage an adverse reaction due to overdose. While useful tables of opioid equivalents are readily available, there is inter-patient variability in the potency of opioid drugs and opioid formulations. Frequently reevaluate patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to hydromorphone hydrochloride extended-release tablets. Conversion from Other Oral Opioid Analgesics to Hydromorphone Hydrochloride Extended-Release Tablets When hydromorphone hydrochloride extended-release tablets therapy is initiated, discontinue all opioid analgesics other than those used on an as needed basis for breakthrough pain when appropriate. In a hydromorphone hydrochloride extended-release tablets clinical trial with an open-label titration period, patients were converted from their prior opioid to hydromorphone hydrochloride extended-release tablets using the Table 1 as a guide for the initial hydromorphone hydrochloride extended-release tablets dose. The recommended starting dose of hydromorphone hydrochloride extended-release tablets is 50% of the calculated estimate of daily hydromorphone requirement. Calculate the estimated daily hydromorphone requirement using Table 1. 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 hydromorphone hydrochloride extended-release tablets.

The table cannot be used to convert from hydromorphone hydrochloride extended-release tablets to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose. Table 1. Conversion Factors to Hydromorphone Hydrochloride Extended-Release Tablets Prior Oral Opioid Approximate Oral Conversion Factor Hydromorphone 1 Codeine 0.06 Hydrocodone 0.4 Methadone 0.6 Morphine 0.2 Oxycodone 0.4 Oxymorphone

0.6 To calculate the estimated hydromorphone hydrochloride extended-release tablets 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 conversion factor to calculate the approximate oral hydromorphone daily dose.

For patients on a regimen of more than one opioid, calculate the approximate oral hydromorphone dose for each opioid and sum the totals to obtain the approximate total hydromorphone daily dose.

For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion. Always round the dose down, if necessary, to the appropriate hydromorphone hydrochloride extended-release tablets strength(s) available. Example conversion from a single opioid to hydromorphone hydrochloride extended-release tablets: Step 1: Sum the total daily dose of the opioid

30 mg of oxycodone 2 times daily = 60 mg total daily dose of oxycodone Step 2: Calculate the approximate equivalent dose of oral hydromorphone based on the total daily dose of the current opioid using Table 1

60 mg total daily dose of oxycodone x Conversion Factor of 0.4 = 24 mg of oral hydromorphone daily Step 3: Calculate the approximate starting dose of hydromorphone hydrochloride extended-release tablets to be given every 24 hours, which is 50% of the calculated oral hydromorphone dose. Round down, if necessary, to the appropriate hydromorphone hydrochloride extended-release tablet strengths available.

50% of 24 mg results in an initial dose of 12 mg of hydromorphone hydrochloride extended-release tablets once daily

Adjust individually for each patient Close observation and frequent titration are warranted until pain management is stable on the new opioid. Conversion from Methadone to Hydromorphone Hydrochloride Extended-Release Tablets 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 can accumulate in the plasma. Conversion from Fentanyl Transdermal System to Hydromorphone Hydrochloride Extended-Release Tablets Eighteen hours following the removal of the fentanyl transdermal system, hydromorphone hydrochloride extended-release tablets treatment can be initiated. To calculate the 24-hour hydromorphone hydrochloride extended-release tablets dose, use a conversion factor of 25 mcg/hr fentanyl transdermal system to 12 mg of hydromorphone hydrochloride extended-release tablets. Then reduce the hydromorphone hydrochloride extended-release tablets dose by 50%. For example: Step 1: Identify the dose of transdermal fentanyl.

75 mg of transdermal fentanyl Step 2: Use the conversion factor of 25 mcg/hr fentanyl transdermal system to 12 mg of hydromorphone hydrochloride extended-release tablets.

75 mg of transdermal fentanyl: 36 mg total daily dose of hydromorphone hydrochloride extended-release tablets Step 3: Calculate the approximate starting dose of hydromorphone hydrochloride extended-release tablets to be given every 24 hours, which is 50% of the converted dose. Round down, if necessary, to the appropriate hydromorphone hydrochloride extended-release tablet strengths available.

50% of 36 mg results in an initial dose of 18 mg, which would be rounded down to 16 mg of hydromorphone hydrochloride extended-release tablets once daily

Adjust individually for each patient

2.4 Titration and

Maintenance of Therapy Individually titrate hydromorphone hydrochloride extended-release tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving hydromorphone hydrochloride extended-release tablets 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. Plasma levels of hydromorphone hydrochloride extended-release tablets are sustained for 18 to 24 hours. Dosage adjustments of hydromorphone hydrochloride extended-release tablets may be made in increments of 4 to 8 mg every 3 to 4 days as needed to achieve adequate analgesia. Patients who experience breakthrough pain may require a dose increase of hydromorphone hydrochloride extended-release tablets, or may need 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 hydromorphone hydrochloride extended-release tablets dose. 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 Safe Reduction or

Discontinuation of Hydromorphone Hydrochloride Extended-Release Tablets Do not rapidly reduce or abruptly discontinue hydromorphone hydrochloride extended-release tablets in patients who may be physically dependent on opioids. Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt 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 hydromorphone hydrochloride extended-release tablets, there are a variety of factors that should be considered, including the total daily dose of opioid (including hydromorphone hydrochloride extended-release tablets) 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 comorbid 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 hydromorphone hydrochloride extended-release tablets 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.

2.6 Dosage Modifications in

Patients with Moderate Hepatic Impairment Start patients with moderate hepatic impairment on 25% of the hydromorphone hydrochloride extended-release tablets dose that would be prescribed for patients with normal hepatic function. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression during initiation of therapy with hydromorphone hydrochloride extended-release tablets and during dose titration. Use of alternate analgesics is recommended for patients with severe hepatic impairment.

2.7 Dosage Modifications in

Patients with Renal Impairment Start patients with moderate renal impairment on 50% of the hydromorphone hydrochloride extended-release tablets dose that would be prescribed for patients with normal renal function. Closely monitor patients with renal impairment for respiratory and central nervous system depression during initiation of therapy with hydromorphone hydrochloride extended-release tablets and during dose titration. As hydromorphone hydrochloride extended-release tablets are only intended for once daily administration, consider use of an alternate analgesic that may permit more flexibility with the dosing interval in patients with severe renal impairment.