"Young children have died or become seriously ill from accidental exposure to a skin patch containing fentanyl, a powerful pain reliever. As a result of this, the Food and Drug Administration (FDA) is issuing a Drug Safety Communication to warn pa"...
ZOHYDRO® ER (hydrocodone bitartrate) is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Limitations of Use
- Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve ZOHYDRO ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
- ZOHYDRO ER is not indicated as an as-needed (prn) analgesic.
DOSAGE AND ADMINISTRATION
ZOHYDRO ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
ZOHYDRO ER 50 mg capsules, a single dose of ZOHYDRO ER greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.
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]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with ZOHYDRO ER [see WARNINGS AND PRECAUTIONS].
ZOHYDRO ER must be taken whole [see PATIENT INFORMATION]. Crushing, chewing, or dissolving the pellets in ZOHYDRO ER capsules will result in uncontrolled delivery of hydrocodone and can lead to overdose or death [see WARNINGS AND PRECAUTIONS].
Use of ZOHYDRO ER as the First Opioid Analgesic
Initiate treatment with ZOHYDRO ER with one 10 mg capsule every 12 hours.
Use of ZOHYDRO ER in Patients Who Are Not Opioid Tolerant
The starting dose for patients who are not opioid tolerant is ZOHYDRO ER 10 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.
Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.
Conversion from Other Oral Opioids to ZOHYDRO ER
Discontinue all other around-the-clock opioid drugs when ZOHYDRO ER 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 preferable to underestimate a patient's 24-hour oral hydrocodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydrocodone requirements which could result in adverse reactions. In a ZOHYDRO ER clinical trial with an open label titration period, patients were converted from their prior opioid to ZOHYDRO ER using Table 1 as a guide for the initial ZOHYDRO ER dose.
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 ZOHYDRO ER.
- The table cannot be used to convert from ZOHYDRO ER 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 ZOHYDRO ER (not
|Prior Oral Opioid||Oral Dose (mg)||Approximate Oral Conversion Factor|
|The conversion ratios in this table are only to be used for the conversion from current opioid therapy to ZOHYDRO ER.|
To calculate the estimated daily ZOHYDRO ER 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 hydrocodone daily dose. The daily dose should then be divided in half for administration every 12 hours.
- For patients on a regimen of more than one opioid, calculate the approximate oral hydrocodone dose for each opioid and sum the totals to obtain approximate total hydrocodone daily dose. The daily dose should then be divided in half for administration every 12 hours.
- For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion.
Always round the dose down, if necessary, to the appropriate ZOHYDRO ER strength(s) available.
Example conversion from a single opioid to ZOHYDRO ER
Step 1: Sum the total daily dose of the opioid (in this case, extended-release oxymorphone); 15 mg oxymorphone twice daily = 30 mg total daily dose of oxymorphone.
Step 2: Calculate the approximate equivalent dose of oral hydrocodone based on the total daily dose of the current opioid using Table 1; 30 mg total daily dose of oxymorphone x 2 = 60 mg of oral hydrocodone daily. The daily dose should then be divided in half for administration every 12 hours.
Step 3: Calculate the approximate starting dose which is 30 mg ZOHYDRO ER every 12 hours. Round down, if necessary, to the appropriate ZOHYDRO ER capsule strengths available. Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity after converting patients to ZOHYDRO ER.
The dose of ZOHYDRO ER can be gradually adjusted preferably at increments of 10 mg every 12 hours every 3 to 7 days, until adequate pain relief and acceptable adverse reactions have been achieved.
Conversion from Methadone to ZOHYDRO ER
Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and tends to accumulate in the plasma.
Conversion from Transdermal Fentanyl to ZOHYDRO ER
ZOHYDRO ER treatment can be initiated 18 hours following the removal of the transdermal fentanyl patch. Although there has been no systematic assessment of such conversion, a conservative hydrocodone dose, approximately 10 mg every 12 hours of ZOHYDRO ER, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to ZOHYDRO ER, as there is limited documented experience with this conversion.
Titration And Maintenance Of Therapy
Individually titrate ZOHYDRO ER to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving ZOHYDRO ER 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. Patients who experience breakthrough pain may require a dose increase of ZOHYDRO ER, or may need a rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain while adjusting the ZOHYDRO ER dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, ZOHYDRO ER dosage adjustments, preferably at increments of 10 mg every 12 hours, may be done every 3 to 7 days. 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.
Discontinuation Of ZOHYDRO ER
When a patient no longer requires therapy with ZOHYDRO ER, use a gradual downward titration of the dose every 2 to 4 days to prevent signs and symptoms of withdrawal in the physically-dependent patient. During the Phase 3 study, the following taper schedule was utilized for patients assigned to placebo in the treatment phase of the study (Table 2):
Table 2: ZOHYDRO ER Taper Schedule Used in Phase 3
|Stabilized Dose At Time of Taper Initiation||Taper Schedule|
|20 mg to 30 mg q12h*||
|40 mg to 70 mg q12h||
|80 mg to 100 mg q12h||
|*q12h = every 12 hours|
Doses above 100 mg every 12 hours (q12h) were not studied in the Phase 3 trial. For patients exceeding 100 mg q12h use a gradual downward titration of the dose every 2 to 4 days. Patients should be monitored closely for signs and symptoms of opioid withdrawal which may indicate a need to taper more slowly. Do not abruptly discontinue ZOHYDRO ER.
Administration Of ZOHYDRO ER
Instruct patients to swallow ZOHYDRO ER capsules whole. The pellets in the capsules are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of hydrocodone [see WARNINGS AND PRECAUTIONS].
Patients with hepatic impairment may have higher plasma concentrations of hydrocodone than those with normal function. No adjustment in starting dose with ZOHYDRO ER is required in patients with mild or moderate hepatic impairment. However, in patients with severe hepatic impairment, start with the lowest dose, 10 mg every 12 hours. Monitor these patients closely for adverse events such as respiratory depression [see CLINICAL PHARMACOLOGY].
Patients with renal impairment may have higher plasma concentrations of hydrocodone than those with normal function. Initiate therapy with a low initial dose of ZOHYDRO ER in patients with renal impairment and monitor closely for respiratory depression and sedation [see CLINICAL PHARMACOLOGY].
Dosage Forms And Strengths
ZOHYDRO ER (hydrocodone) extended-release capsules are available in 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, and 50 mg hard gelatin capsules, containing white to off-white beads, roughly spherical in shape, and uniform in appearance.
Storage And Handling
ZOHYDRO ER extended-release capsules are supplied in 100-count bottles with a child-resistant closure as follows:
|Strength||Capsule Color(s)||Capsule Text||NDC Number|
|10 mg||White opaque||“Zogenix 10 mg” in black ink||43376-210-10|
|15 mg||Light green and white opaque||“Zogenix 15 mg” in black ink||43376-215-10|
|20 mg||Light green opaque||“Zogenix 20 mg” in black ink||43376-220-10|
|30 mg||Dark blue and white opaque||“Zogenix 30 mg” in black ink||43376-230-10|
|40 mg||Dark brown and white opaque||“Zogenix 40 mg” in black ink||43376-240-10|
|50 mg||Dark brown opaque||“Zogenix 50 mg” in black ink||43376-250-10|
ZOHYDRO ER contains hydrocodone bitartrate which is a controlled substance and is controlled under Schedule II of the Controlled Substances Act. Hydrocodone, like all opioids, is liable to diversion and misuse and should be handled accordingly. Patients and their families should be instructed to dispose of any ZOHYDRO ER capsules that are no longer needed.
ZOHYDRO ER may be targeted for theft and diversion. Healthcare professionals should contact their State Medical Board, State Board of Pharmacy, or State Control Board for information on how to detect or prevent diversion of this product.
Healthcare professionals should advise patients to store ZOHYDRO ER in a secure place, preferably locked and out of the reach of children and other non-caregivers.
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].
Dispense in tight container as defined in the USP, with a child-resistant closure.
Advise patients to dispose of any unused capsules from a prescription as soon as they are no longer needed in accordance with local State guidelines and/or regulations [see PATIENT INFORMATION].
Manufactured by: Alkermes Gainesville LLC, Gainesville, GA.. Distributed by: Zogenix, Inc., San Diego, CA 92130, www.ZohydroER.com, www.ZohydroERREMS.com or call 1-866-ZOGENIX (1-866-964-3649). Issue: August 2014
Last reviewed on RxList: 8/28/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Zohydro ER Information
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