Hydromorphone Hydrochloride

Hydromorphone hydrochloride tablets (2 mg, 4 mg, 8 mg): The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on lower starting dose (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY: PHARMACOKINETICS and METABOLISM).

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Individualization of Dosage

The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain.

Safe and effective administration of opioid analgesics to patients with acute or chronic pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, etiology, and pathophysiology) as well as the concurrent medical status of the patient will affect selection of the starting dosage.

In non-opioid-tolerant patients, therapy with hydromorphone is typically initiated at an oral dose of 2 to 4 mg every four hours, but elderly patients may require lower doses (see PRECAUTIONS, Geriatric Use).

In patients receiving opioids, both the dose and duration of analgesia will vary substantially depending on the patient's opioid tolerance. The dose should be selected and adjusted so that at least 3 to 4 hours of pain relief may be achieved. In patients taking opioid analgesics, the starting dose of hydromorphone hydrochloride should be based on prior opioid usage. This should be done by converting the total daily usage of the previous opioid to an equivalent total daily dosage of oral hydromorphone hydrochloride using an equianalgesic table (see below). For opioids not in the table, first estimate the equivalent total daily usage of oral morphine, then use the table to find the equivalent total daily dosage of hydromorphone hydrochloride.

Once the total daily dosage of hydromorphone hydrochloride has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of hydromorphone hydrochloride calculated from equivalence tables should be given for the first few doses, then increased as needed according to the patient's response.

Since the pharmacokinetics of hydromorphone are affected in hepatic and renal impairment with a consequent increase in exposure, patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

In chronic pain, doses should be administered around-the-clock. A supplemental dose of 5 to 15% of the total daily usage may be administered every two hours on an "as-needed" basis.

Periodic reassessment after the initial dosing is always required. If pain management is not satisfactory and in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, the hydromorphone dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia than the absolute dose of opioid employed.

OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY* Nonproprietary
(Trade) Name
IM or SC
Dose
ORAL
Dose
Morphine Sulfate
10 mg
40 to 60 mg
Hydromorphone HCl
(DILAUDID®)
1.3 to 2 mg

6.5 to 7.5 mg

Oxymorphone HCl
(Numorphan®)
1 to 1.1 mg

6.6 mg

Levorphanol tartrate
(Levo-DromoranTM)
2 to 2.3 mg

4 mg

Meperidine,
pethidine HCl
(Demerol®)
75 to 100 mg


300 to 400 mg


Methadone HCl
(Dolophine®)
10 mg

10 to 20 mg

DILAUDID is a registered trademark of Abbott Laboratories.
Numorphan is a registered trademark of Endo Pharmaceuticals Inc.
Levo-Dromoran is a trademark of Valeant Pharmaceuticals International.
Demerol is a registered trademark of Sanofi Pharmaceuticals Inc.
Dolophine is a registered trademark of Roxane Laboratories Inc.
*   Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain.

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

2.1 General Dosing Considerations

Take care when prescribing and administering Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) to avoid dosing errors due to confusion between the different concentrations and between mg and mL, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total volume of the dose.

Selection of patients and administration of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) should be governed by the same principles that apply to the use of similar opioid analgesics to treat patients with acute or chronic pain, and depends upon a comprehensive assessment of the patient. Individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis and/or combination products, and chronic opioid therapy in a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Healthcare Research and Quality, and the American Pain Society.

The nature of the pain (severity, frequency, etiology, and pathophysiology), as well as the medical status of the patient, will affect selection of the starting dosage. Opioid analgesics, including Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY), have a narrow therapeutic index in certain patient populations, especially when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks.

2.2 Individualization of Dosage

Initiate the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment. Give attention to the following:

• the age, general condition and medical status of the patient; • the patient’s degree of opioid tolerance; • the daily dose, potency, and specific characteristics of the opioid the patient has been taking previously; • concurrent medications; • the type and severity of the patient’s pain; • risk factors for abuse or addiction; including whether the patient has a previous or current substance abuse problem, a family history of substance abuse, or a history of mental illness or depression; • the balance between pain control and adverse reactions.

Periodic reassessment after the initial dosing of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) is required. If pain management is not satisfactory, and opioid-induced adverse events are tolerable, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, reduce the hydromorphone hydrochloride dose. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia and the severity of adverse events than the absolute dose of opioid employed.

2.3 Initiation of Therapy in Opioid-Naïve Patients

Always initiate dosing in opioid-naïve patients using standard parenteral formulations of Hydromorphone Hydrochloride Injection, USP. Never administer Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) to opioid-naïve patients.

2.3.1 Subcutaneous or Intramuscular Administration

The usual starting dose of Hydromorphone Hydrochloride Injection, USP is 1 mg to 2 mg every 2 to 3 hours as necessary. Depending on the clinical situation, the initial starting dose may be lowered in patients who are opioid naïve. Adjust the dose according to the severity of pain, the severity of adverse events, as well as the patient’s underlying disease and age.

2.3.2 Intravenous Administration

The initial starting dose is 0.2 to 1 mg every 2 to 3 hours. Intravenous administration should be given slowly, over at least 2 to 3 minutes, depending on the dose. Titrate the dose to achieve acceptable analgesia and tolerable adverse events. The initial dose should be reduced in the elderly or debilitated and may be lowered to 0.2 mg.

2.3.3 Hepatic Impairment

Start patients with hepatic impairment on one-fourth to one-half the usual Hydromorphone Hydrochloride Injection, USP starting dose depending on the extent of impairment [see Clinical Pharmacology (12.3)].

2.3.4 Renal Impairment

Start patients with renal impairment on one-fourth to one-half the usual Hydromorphone Hydrochloride Injection, USP starting dose depending on the degree of impairment [see Clinical Pharmacology (12.3)].

2.4 Conversion from Prior Opioid

Use the equianalgesic dose table below (Table 1) as a guide to determine the appropriate dose of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY). Convert the current total daily amount(s) of opioid(s) received to an equivalent total daily dose of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) and reduce by one-half due to the possibility of incomplete cross tolerance. Divide the new total amount by number of doses permitted based on dosing interval (e.g. 8 doses for every three-hour dosing). Titrate the dose according to the patient’s response. For opioids not in Table 1, first estimate the daily amount of morphine that is equivalent to the current total daily amount of other opioid(s) received, then use Table 1 to find the approximate equivalent total daily dose of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY).

Table 1: OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY FOR CONVERSION TO HYDROMORPHONE HYDROCHLORIDE INJECTION,USP (HIGH POTENCY)* * Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain.

DRUG SUBSTANCE

PARENTERAL DOSE

ORAL DOSE

Morphine Sulfate

10 mg

40 – 60 mg

Hydromorphone HCl

1.3 – 2 mg

6.5 – 7.5 mg

Oxymorphone HCl

1 – 1.1 mg

6.6 mg

Levorphanol tartrate

2 – 2.3 mg

4 mg

Meperidine HCl (Pethidine HCl)

75 – 100 mg

300 – 400 mg

Methadone HCl

10 mg

10 – 20 mg

Nalbuphine HCl

10 – 12 mg

–

Butorphanol tartrate

1.5 – 2.5 mg

–

2.5 Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) (for use in opioid-tolerant patients only)

Do not use Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) for patients who are not tolerant to the respiratory depressant or sedating effects of opioids. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for one week or longer.

Use Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) only for patients who require the higher concentration and lower total volume of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY).

Because of its high concentration, the delivery of precise doses of Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) may be difficult if low doses of hydromorphone are required. Therefore, use Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) only if the amount of Hydromorphone required can be delivered accurately with this formulation.

Base the starting dose for hydromorphone hydrochloride injection, USP (HIGH POTENCY) on the prior dose of Hydromorphone Hydrochloride Injection, USP or on the prior dose of an alternate opioid as described above in Section 2.4 Conversion from Prior Opioid and Table 1.

2.6 Administration

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in Hydromorphone Hydrochloride vials. No loss of potency has been demonstrated. Hydromorphone Hydrochloride Injection, USP (HIGH POTENCY) is physically compatible and chemically stable for at least 24 hours at 25°C, protected from light in most common large-volume parenteral solutions.

500 mg/50 mL Vial

To use this single dose presentation, do not penetrate the stopper with a syringe. Instead, remove both the aluminum flipseal and rubber stopper in a suitable work area such as under a laminar flow hood (or equivalent clean air compounding area). The contents may then be withdrawn for preparation of a single, large-volume parenteral solution. Discard any unused portion in an appropriate manner.

Hydromorphone Hydrochloride Tablets

The usual starting dose for Hydromorphone Hydrochloride Tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of Hydromorphone Hydrochloride Tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

INDIVIDUALIZATION OF DOSAGE

The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain.

Safe and effective administration of opioid analgesics to patients with acute or chronic pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, etiology, and pathophysiology) as well as the concurrent medical status of the patient will affect selection of the starting dosage.

In non-opioid-tolerant patients, therapy with hydromorphone is typically initiated at an oral dose of 2-4 mg every four hours, but elderly patients may require lower doses (see PRECAUTIONS - Geriatric Use).

In patients receiving opioids, both the dose and duration of analgesia will vary substantially depending on the patient's opioid tolerance. The dose should be selected and adjusted so that at least 3-4 hours of pain relief may be achieved. In patients taking opioid analgesics, the starting dose of Hydromorphone Hydrochloride Tablets should be based on prior opioid usage. This should be done by converting the total daily usage of the previous opioid to an equivalent total daily dosage of oral Hydromorphone Hydrochloride Tablets using an equianalgesic table (see below). For opioids not in the table, first estimate the equivalent total daily usage of oral morphine, then use the table to find the equivalent total daily dosage of Hydromorphone Hydrochloride Tablets.

Once the total daily dosage of Hydromorphone Hydrochloride Tablets has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of Hydromorphone Hydrochloride Tablets calculated from equivalence tables should be given for the first few doses, then increased as needed according to the patient's response.

Since the pharmacokinetics of hydromorphone are affected in hepatic and renal impairment with a consequent increase in exposure, patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

In chronic pain, doses should be administered around-the-clock. A supplemental dose of 5-15% of the total daily usage may be administered every two hours on an "as-needed" basis.

Periodic reassessment after the initial dosing is always required. If pain management is not satisfactory and in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, the hydromorphone dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia than the absolute dose of opioid employed.

OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY* Nonproprietary
(Trade) Name IM or SC
Dose ORAL
Dose *   Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain. Morphine sulfate 10 mg 40-60 mg Hydromorphone HCl
(DILAUDID)
1.3-2 mg
6.5-7.5 mg Oxymorphone HCl
(Numorphan)
1-1.1 mg
6.6 mg Levorphanol tartrate
(Levo-Dromoran)
2-2.3 mg
4 mg Meperidine, pethidine HCl
(Demerol)
75-100 mg
300-400 mg Methadone HCl
(Dolophine)
10 mg
10-20 mg

The usual starting dose is 1-2 mg subcutaneously orintramuscularly every 4 to 6 hours as necessary for pain control. The dose should be adjusted according to severity of pain, as well as the patient’s underlying disease, age and size. Severe pain can usually be controlled by 3-4 mg every 4 to 6 hours as required. Patients with terminal cancer may become tolerant to narcotic analgesics and may, therefore, require higher doses for adequate pain relief. Should intravenous administration be necessary, the injection should be given very slowly (over at least 3 to 5 minutes, depending on the dose) [see WARNINGS, INTRAVENOUS USE]. A gradual increase in dosage may be required if analgesia is inadequate, tolerance occurs or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Hydromorphone Hydrochloride Tablets

The usual starting dose for Hydromorphone Hydrochloride Tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of Hydromorphone Hydrochloride Tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY: PHARMACOKINETICS and METABOLISM).

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY: PHARMACOKINETICS and METABOLISM).

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY – Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

The usual starting dose for Hydromorphone Hydrochloride Tablets, USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the Hydromorphone Hydrochloride Tablets, USP must be decided by careful evaluation of each clinical situation.

The usual adult oral dosage of Hydromorphone Hydrochloride Oral Solution, USP is one-half (2.5 mL) to two teaspoonfuls (10 mL) (2.5 mg to 10 mg) every 3 to 6 hours as directed by the clinical situation. Oral dosages higher than the usual may be required in some patients.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Hydromorphone Hydrochloride Tablets

The usual starting dose for Hydromorphone Hydrochloride Tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of Hydromorphone Hydrochloride Tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

INDIVIDUALIZATION OF DOSAGE

The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain.

Safe and effective administration of opioid analgesics to patients with acute or chronic pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, etiology, and pathophysiology) as well as the concurrent medical status of the patient will affect selection of the starting dosage.

In non-opioid-tolerant patients, therapy with hydromorphone is typically initiated at an oral dose of 2-4 mg every four hours, but elderly patients may require lower doses (see PRECAUTIONS - Geriatric Use).

In patients receiving opioids, both the dose and duration of analgesia will vary substantially depending on the patient's opioid tolerance. The dose should be selected and adjusted so that at least 3-4 hours of pain relief may be achieved. In patients taking opioid analgesics, the starting dose of Hydromorphone Hydrochloride Tablets should be based on prior opioid usage. This should be done by converting the total daily usage of the previous opioid to an equivalent total daily dosage of oral Hydromorphone Hydrochloride Tablets using an equianalgesic table (see below). For opioids not in the table, first estimate the equivalent total daily usage of oral morphine, then use the table to find the equivalent total daily dosage of Hydromorphone Hydrochloride Tablets.

Once the total daily dosage of Hydromorphone Hydrochloride Tablets has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of Hydromorphone Hydrochloride Tablets calculated from equivalence tables should be given for the first few doses, then increased as needed according to the patient's response.

Since the pharmacokinetics of hydromorphone are affected in hepatic and renal impairment with a consequent increase in exposure, patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

In chronic pain, doses should be administered around-the-clock. A supplemental dose of 5-15% of the total daily usage may be administered every two hours on an "as-needed" basis.

Periodic reassessment after the initial dosing is always required. If pain management is not satisfactory and in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, the hydromorphone dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia than the absolute dose of opioid employed.

OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY* Nonproprietary
(Trade) Name IM or SC
Dose ORAL
Dose *   Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain. Morphine sulfate 10 mg 40-60 mg Hydromorphone HCl
(DILAUDID)
1.3-2 mg
6.5-7.5 mg Oxymorphone HCl
(Numorphan)
1-1.1 mg
6.6 mg Levorphanol tartrate
(Levo-Dromoran)
2-2.3 mg
4 mg Meperidine, pethidine HCl
(Demerol)
75-100 mg
300-400 mg Methadone HCl
(Dolophine)
10 mg
10-20 mg

2.1 General Dosing Considerations

Selection of patients and administration of hydromorphone hydrochloride injection should be governed by the same principles that apply to the use of similar opioid analgesics to treat patients with acute or chronic pain, and depends upon a comprehensive assessment of the patient. Individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis and/or combination products, and chronic opioid therapy in a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Healthcare Research and Quality, and the American Pain Society.

The nature of the pain, (severity, frequency, etiology, and pathophysiology) as well as the medical status of the patient, will affect selection of the starting dosage. Opioid analgesics, including hydromorphone hydrochloride injection, have a narrow therapeutic index in certain patient populations, especially when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks.

2.2 Individualization of Dosage

Initiate the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment. Give attention to the following:

• the age, general condition and medical status of the patient; • the patient's degree of opioid tolerance; • the daily dose, potency, and specific characteristics of the opioid the patient has been taking previously; • concurrent medications; • the type and severity of the patient’s pain; • risk factors for abuse or addiction; including whether the patient has a previous or current substance abuse problem, a family history of substance abuse, or a history of mental illness or depression; • the balance between pain control and adverse reactions

Periodic reassessment after the initial dosing of hydromorphone hydrochloride injection is required. If pain management is not satisfactory, and opioid-induced adverse events are tolerable, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, reduce the hydromorphone hydrochloride dose. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia and the occurrence of adverse events than the absolute dose of opioid employed.

2.3 Subcutaneous or Intramuscular Administration

The usual starting dose is 1 mg to 2 mg subcutaneously or intramuscularly every 2 to 3 hours as necessary for pain. Depending on the clinical situation, the initial starting dose may be lowered in patients who are opioid naïve. Adjust the dose according to the severity of pain and occurrence of adverse events, as well as the patient's underlying disease and age.

2.4 Intravenous Administration

The initial intravenous starting dose is 0.2 mg to 1 mg every 2 to 3 hours as necessary for pain control.

Administer intravenous hydromorphone slowly, over at least 2 to 3 minutes, depending on the dose. Titrate the dose to achieve acceptable pain management and tolerable adverse events. Reduce the initial dose in the elderly or debilitated.

2.5 Hepatic Impairment

Start patients with hepatic impairment on one-fourth to one-half the usual dose of hydromorphone hydrochloride injection depending on the extent of impairment [see Clinical Pharmacology, Pharmacokinetics and Metabolism (12.3)].

2.6 Renal Impairment

Start patients with renal impairment on one-fourth to one-half the usual starting dose of hydromorphone hydrochloride injection depending on the degree of impairment [see Clinical Pharmacology, Pharmacokinetics (12.3)].

2.7 Conversion from Prior Opioid

Use the equianalgesic dose table below (Table 1) as a guide to determine the appropriate dose of hydromorphone injection. Convert the current total daily amount(s) of opioid(s) received to an equivalent total daily dose of hydromorphone injection and reduce by one-half due to the possibility of incomplete cross tolerance. Divide the new total amount by number of doses permitted based on dosing interval (e.g. 8 doses for every-three-hour dosing). Titrate the dose according to the patient's response. For opioids not in Table 1, first estimate the daily amount of morphine that is equivalent to the current total daily amount of other opioid(s) received, then use Table 1 to find the approximate equivalent total daily dose of hydromorphone injection. 

Table 1 OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY FOR CONVERSION TO HYDROMORPHONE INJECTION* * Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain.

DRUG SUBSTANCE

PARENTERAL DOSE

ORAL DOSE

Morphine Sulfate

10 mg

40 – 60 mg

Hydromorphone HCl

1.3 – 2 mg

6.5 – 7.5 mg

Oxymorphone HCl

1 – 1.1 mg

6.6 mg

Levorphanol tartrate

2 – 2.3 mg

4 mg

Meperidine HCl (pethidine HCl)

75 – 100 mg

300 – 400 mg

Methadone HCl

10 mg

10 – 20 mg

Nalbuphine HCl

10 – 12 mg

–

Butorphanol tartrate

1.5 – 2.5 mg

–

2.8 Administration

Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in hydromorphone hydrochloride ampules. No loss of potency has been demonstrated. Hydromorphone hydrochloride is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions.

2.1 General Dosing Considerations

Selection of patients and administration of hydromorphone hydrochloride injection should be governed by the same principles that apply to the use of similar opioid analgesics to treat patients with acute or chronic pain, and depends upon a comprehensive assessment of the patient. Individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis and/or combination products, and chronic opioid therapy in a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Healthcare Research and Quality, and the American Pain Society.

The nature of the pain, (severity, frequency, etiology, and pathophysiology) as well as the medical status of the patient, will affect selection of the starting dosage. Opioid analgesics, including hydromorphone hydrochloride injection, have a narrow therapeutic index in certain patient populations, especially when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks.

2.2 Individualization of Dosage

Initiate the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment. Give attention to the following:

• the age, general condition and medical status of the patient; • the patient's degree of opioid tolerance; • the daily dose, potency, and specific characteristics of the opioid the patient has been taking previously; • concurrent medications; • the type and severity of the patient’s pain; • risk factors for abuse or addiction; including whether the patient has a previous or current substance abuse problem, a family history of substance abuse, or a history of mental illness or depression; • the balance between pain control and adverse reactions

Periodic reassessment after the initial dosing of hydromorphone hydrochloride injection is required. If pain management is not satisfactory, and opioid-induced adverse events are tolerable, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, reduce the hydromorphone hydrochloride dose. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia and the occurrence of adverse events than the absolute dose of opioid employed.

2.3 Subcutaneous or Intramuscular Administration

The usual starting dose is 1 mg to 2 mg subcutaneously or intramuscularly every 2 to 3 hours as necessary for pain. Depending on the clinical situation, the initial starting dose may be lowered in patients who are opioid naïve. Adjust the dose according to the severity of pain and occurrence of adverse events, as well as the patient's underlying disease and age.

2.7 Conversion from Prior Opioid

Use the equianalgesic dose table below (Table 1) as a guide to determine the appropriate dose of hydromorphone injection. Convert the current total daily amount(s) of opioid(s) received to an equivalent total daily dose of hydromorphone injection and reduce by one-half due to the possibility of incomplete cross tolerance. Divide the new total amount by number of doses permitted based on dosing interval (e.g. 8 doses for every-three-hour dosing). Titrate the dose according to the patient's response. For opioids not in Table 1, first estimate the daily amount of morphine that is equivalent to the current total daily amount of other opioid(s) received, then use Table 1 to find the approximate equivalent total daily dose of hydromorphone injection. 

Table 1 OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY FOR CONVERSION TO HYDROMORPHONE INJECTION* * Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain.

DRUG SUBSTANCE

PARENTERAL DOSE

ORAL DOSE

Morphine Sulfate

10 mg

40 – 60 mg

Hydromorphone HCl

1.3 – 2 mg

6.5 – 7.5 mg

Oxymorphone HCl

1 – 1.1 mg

6.6 mg

Levorphanol tartrate

2 – 2.3 mg

4 mg

Meperidine HCl (pethidine HCl)

75 – 100 mg

300 – 400 mg

Methadone HCl

10 mg

10 – 20 mg

Nalbuphine HCl

10 – 12 mg

–

Butorphanol tartrate

1.5 – 2.5 mg

–

Parenteral: HYDROMORPHONE HYDROCHLORIDE INJECTION (HIGH POTENCY FORMULATION) SHOULD BE GIVEN ONLY TO PATIENTS WHO ARE ALREADY RECEIVING LARGE DOSES OF OPIOIDS. Hydromorphone hydrochloride injection (high potency formulation) is indicated for relief of moderate-to-severe pain in opioid-tolerant patients. Thus, these patients will already have been treated with other opioid analgesics. If the patient is being changed from regular hydromorphone hydrochloride to high potency formulation, similar doses should be used, depending on the patient's clinical response to the drug. If hydromorphone hydrochloride injection (high potency formulation) is substituted for a different opioid analgesic, the following equivalency table should be used as a guide to determine the appropriate dose of hydromorphone hydrochloride injection (high potency formulation). Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Opioid Analgesic Equivalents with Approximately Equianalgesic Potency* Drug Substance  IM or SC** Dose  Oral Dose 

Morphine Sulfate

10 mg

40 – 60 mg

Hydromorphone HCl

1.3 – 2 mg

6.5 – 7.5 mg

Oxymorphone HCl

1 – 1.1 mg

6.6 mg

Levorphanol tartrate

2 – 2.3 mg

4 mg

Meperidine HCl

(pethidine HCl)

75 – 100 mg

300 – 400 mg

Methadone HCl

10 mg

10 – 20 mg

Nalbuphine HCl

12 mg

–

Butorphanol tartrate

1.5 – 2.5 mg

–

* Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain.

**IM = intramuscular; SC = subcutaneous

Experience with administration of hydromorphone hydrochloride injection (high potency formulation) by the intravenous route is limited. Should intravenous administration be necessary, the injection should be given slowly, over at least 2 to 3 minutes.

A gradual increase in dose may be required if analgesia is inadequate, tolerance occurs, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A slight yellowish discoloration may develop in hydromorphone hydrochloride injection (high potency formulation) vials. No loss of potency has been demonstrated. Hydromorphone hydrochloride injection is physically compatible and chemically stable for at least 24 hours at 25°C protected from light in most common large volume parenteral solutions.

500 mg/50 mL Vial: To use this single dose presentation, do not penetrate the stopper with a syringe. Instead, remove both the aluminum flipseal and rubber stopper in a suitable work area such as under a laminar flow hood (or equivalent clean air compounding area). The contents may then be withdrawn for preparation of a single, large volume parenteral solution. Any unused portion should be discarded in an appropriate manner.

Individualization of Dosage

The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain.

Safe and effective administration of opioid analgesics to patients with acute or chronic pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, etiology, and pathophysiology), as well as the concurrent medical status of the patient, will affect selection of the starting dosage.

In patients receiving opioids, both the dose and duration of analgesia will vary substantially depending on the patient's opioid tolerance. The dose should be selected and adjusted so that at least 3-4 hours of pain relief may be achieved. In patients taking opioid analgesics, the starting dose of hydromorphone hydrochloride injection (high potency formulation) should be based on prior opioid usage. This should be done by converting the total daily usage of the previous opioid to an equivalent total daily dosage of hydromorphone hydrochloride injection (high potency formulation) using an equianalgesic table (see above). For opioids not in the table, first estimate the equivalent total daily usage of oral morphine, then use the table to find the equivalent total daily dosage of hydromorphone hydrochloride injection (high potency formulation).

Once the total daily dosage of hydromorphone hydrochloride injection (high potency formulation) has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of hydromorphone hydrochloride injection (high potency formulation) calculated from equivalence tables should be given for the first few doses, then increased as needed according to the patient's response.

Since the pharmacokinetics of hydromorphone are affected in hepatic and renal impairment with a consequent increase in exposure, patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

In chronic pain, doses should be administered around-the-clock. A supplemental dose of 5-15% of the total daily usage may be administered every two hours on an "as-needed" basis.

Periodic reassessment after the initial dosing is always required. If pain management is not satisfactory, and in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, the hydromorphone hydrochloride dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia than the absolute dose of opioid employed.

The usual starting dose for Hydromorphone Hydrochloride Tablets, USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the Hydromorphone Hydrochloride Tablets, USP must be decided by careful evaluation of each clinical situation.

The usual adult oral dosage of Hydromorphone Hydrochloride Oral Solution, USP is one-half (2.5 mL) to two teaspoonfuls (10 mL) (2.5 mg to 10 mg) every 3 to 6 hours as directed by the clinical situation. Oral dosages higher than the usual may be required in some patients.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism).

The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY: PHARMACOKINETICS and METABOLISM).

DOSAGE AND ADMINISTRATION

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Individualization of Dosage

The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain.

Safe and effective administration of opioid analgesics to patients with acute or chronic pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, etiology, and pathophysiology) as well as the concurrent medical status of the patient will affect selection of the starting dosage.

In non-opioid-tolerant patients, therapy with hydromorphone is typically initiated at an oral dose of 2 to 4 mg every four hours, but elderly patients may require lower doses (see PRECAUTIONS, Geriatric Use).

In patients receiving opioids, both the dose and duration of analgesia will vary substantially depending on the patient's opioid tolerance. The dose should be selected and adjusted so that at least 3 to 4 hours of pain relief may be achieved. In patients taking opioid analgesics, the starting dose of hydromorphone hydrochloride should be based on prior opioid usage. This should be done by converting the total daily usage of the previous opioid to an equivalent total daily dosage of oral hydromorphone hydrochloride using an equianalgesic table (see below). For opioids not in the table, first estimate the equivalent total daily usage of oral morphine, then use the table to find the equivalent total daily dosage of hydromorphone hydrochloride.

Once the total daily dosage of hydromorphone hydrochloride has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of hydromorphone hydrochloride calculated from equivalence tables should be given for the first few doses, then increased as needed according to the patient's response.

Since the pharmacokinetics of hydromorphone are affected in hepatic and renal impairment with a consequent increase in exposure, patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

In chronic pain, doses should be administered around-the-clock. A supplemental dose of 5 to 15% of the total daily usage may be administered every two hours on an "as-needed" basis.

Periodic reassessment after the initial dosing is always required. If pain management is not satisfactory and in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, the hydromorphone dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia than the absolute dose of opioid employed.

Hydromorphone Hydrochloride Oral Solution, USP

The usual adult oral dosage for Hydromorphone Hydrochloride Oral Solution is one-half (2.5 mL) to two teaspoonfuls (10 mL) (2.5 mg to 10 mg) every 3 to 6 hours as directed by the clinical situation.  Oral dosages higher than the usual dosages may be required in some patients.

Hydromorphone Hydrochloride Tablets

The usual starting dose for Hydromorphone Hydrochloride Tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of Hydromorphone Hydrochloride Tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

INDIVIDUALIZATION OF DOSAGE

The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain.

Safe and effective administration of opioid analgesics to patients with acute or chronic pain depends upon a comprehensive assessment of the patient. The nature of the pain (severity, frequency, etiology, and pathophysiology) as well as the concurrent medical status of the patient will affect selection of the starting dosage.

In non-opioid-tolerant patients, therapy with hydromorphone is typically initiated at an oral dose of 2 to 4 mg every four hours, but elderly patients may require lower doses (see PRECAUTIONS - Geriatric Use).

In patients receiving opioids, both the dose and duration of analgesia will vary substantially depending on the patient's opioid tolerance. The dose should be selected and adjusted so that at least 3 to 4 hours of pain relief may be achieved. In patients taking opioid analgesics, the starting dose of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets should be based on prior opioid usage. This should be done by converting the total daily usage of the previous opioid to an equivalent total daily dosage of oral Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets using an equianalgesic table (see below). For opioids not in the table, first estimate the equivalent total daily usage of oral morphine, then use the table to find the equivalent total daily dosage of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.

Once the total daily dosage of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets has been estimated, it should be divided into the desired number of doses. Since there is individual variation in response to different opioid drugs, only 1/2 to 2/3 of the estimated dose of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets calculated from equivalence tables should be given for the first few doses, and then increased as needed according to the patient's response.

Since the pharmacokinetics of hydromorphone are affected in hepatic and renal impairment with a consequent increase in exposure, patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY - Pharmacokinetics and Metabolism).

In chronic pain, doses should be administered around-the-clock. A supplemental dose of 5 to 15% of the total daily usage may be administered every two hours on an "as-needed" basis.

Periodic reassessment after the initial dosing is always required. If pain management is not satisfactory and in the absence of significant opioid-induced adverse events, the hydromorphone dose may be increased gradually. If excessive opioid side effects are observed early in the dosing interval, the hydromorphone dose should be reduced. If this results in breakthrough pain at the end of the dosing interval, the dosing interval may need to be shortened. Dose titration should be guided more by the need for analgesia than the absolute dose of opioid employed.

OPIOID ANALGESIC EQUIVALENTS WITH APPROXIMATELY EQUIANALGESIC POTENCY* Nonproprietary(Trade) Name IM or SCDose ORALDose *   Dosages, and ranges of dosages represented, are a compilation of estimated equipotent dosages from published references comparing opioid analgesics in cancer and severe pain. Morphine sulfate 10 mg 40 to 60 mg Hydromorphone HCl
(DILAUDID)
1.3 to 2 mg
6.5 to 7.5 mg Oxymorphone HCl
(Numorphan)
1 to 1.1 mg
6.6 mg Levorphanol tartrate
(Levo-Dromoran)
2 to 2.3 mg
4 mg Meperidine, pethidine HCl
(Demerol)
75 to 100 mg
300 to 400 mg Methadone HCl
(Dolophine)
10 mg
10 to 20 mg

The usual starting dose for hydromorphone hydrochloride tablets USP is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of hydromorphone hydrochloride tablets USP, 8 mg must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

Children 2 to 12 years 1 teaspoon every 2 hours

Younger than 2 years not recommended

2.1       Initial Dosing

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 in the use of potent opioids for the management of chronic pain.

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 considered opioid-tolerant are those who are taking at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Initiate the dosing regimen for each patient individually, taking into account the patient"s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with hydromorphone hydrochloride extended-release tablets [see Warnings and Precautions (5.2)].

Hydromorphone hydrochloride extended-release tablets must be taken whole. Crushing, chewing, or dissolving hydromorphone hydrochloride extended-release tablets will result in uncontrolled delivery of hydromorphone and can lead to overdose or death [see Warnings and Precautions (5.2)].

Conversion from Other Oral Hydromorphone Formulations to Hydromorphone Hydrochloride Extended-release Tablets
Patients receiving oral immediate-release hydromorphone may be converted to hydromorphone hydrochloride extended-release tablets by administering a starting dose equivalent to the patient’s total daily oral hydromorphone dose, taken once daily.

Conversion from Other Oral Opioids to Hydromorphone Hydrochloride Extended-release Tabelts
Discontinue all other around-the-clock opioid drugs when hydromorphone hydrochloride extended-release tablets therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is safer to underestimate a patient’s 24-hour oral hydromorphone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydromorphone requirements, which could result in adverse reactions.

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. Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity after converting patients to hydromorphone hydrochloride extended-release tablets.

Conversion from Transdermal Fentanyl to Hydromorphone Hydrochloride Extended-release Tablets
Eighteen hours following the removal of the transdermal fentanyl patch, 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 patch 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 patch 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

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.

2.2       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 and the relative incidence of adverse reactions, as well as monitoring 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 chronic therapy, periodically reassess the continued need for 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 4-8 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 unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3       Discontinuation of Hydromorphone Hydrochloride Extended-release Tablets

When a patient no longer requires therapy with hydromorphone hydrochloride extended-release tablets, taper doses gradually, by 25% to 50% every 2 or 3 days down to a dose of 8 mg before discontinuation of therapy, to prevent signs and symptoms of withdrawal in the opioid-tolerant patient.

To dispose of unused hydromorphone hydrochloride extended-release tablets flush all remaining tablets down the toilet or remit to authorities at a certified drug take-back program.

2.4       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 [see Use in Specific Populations (8.6)].

2.5       Renal Impairment

Start patients with moderate renal impairment on 50% and patients with severe renal impairment on 25% 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 [see Use in Specific Populations (8.7)].

2.6       Administration of Hydromorphone Hydrochloride Extended-release Tablets   

Instruct patients to swallow hydromorphone hydrochloride extended-release tablets intact. The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of hydromorphone [see Warnings and Precautions (5.2)].

2.1       Initial Dosing

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 in the use of potent opioids for the management of chronic pain.

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 considered opioid-tolerant are those who are taking at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Initiate the dosing regimen for each patient individually, taking into account the patient"s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with hydromorphone hydrochloride extended-release tablets [see Warnings and Precautions (5.2)].

Hydromorphone hydrochloride extended-release tablets must be taken whole. Crushing, chewing, or dissolving hydromorphone hydrochloride extended-release tablets will result in uncontrolled delivery of hydromorphone and can lead to overdose or death [see Warnings and Precautions (5.2)].

Conversion from Other Oral Hydromorphone Formulations to Hydromorphone Hydrochloride Extended-release Tablets
Patients receiving oral immediate-release hydromorphone may be converted to hydromorphone hydrochloride extended-release tablets by administering a starting dose equivalent to the patient’s total daily oral hydromorphone dose, taken once daily.

Conversion from Other Oral Opioids to Hydromorphone Hydrochloride Extended-release Tabelts
Discontinue all other around-the-clock opioid drugs when hydromorphone hydrochloride extended-release tablets therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is safer to underestimate a patient’s 24-hour oral hydromorphone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydromorphone requirements, which could result in adverse reactions.

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. Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity after converting patients to hydromorphone hydrochloride extended-release tablets.

Conversion from Transdermal Fentanyl to Hydromorphone Hydrochloride Extended-release Tablets
Eighteen hours following the removal of the transdermal fentanyl patch, 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 patch 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 patch 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

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.

The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation.

A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect.

Patients with hepatic and renal impairment should be started on a lower starting dose (See CLINICAL PHARMACOLOGY: PHARMACOKINETICS and METABOLISM).