"The FDA is spelling out this and other precautions in class-wide boxed warnings on the labels of opioid painkillers such as oxycodone, prescription cough medicine containing opioids, benzodiazepines, which include alprazolam (Xanax, Pharma"...
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 [see WARNINGS AND PRECAUTIONS], 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
Important Dosage And Administration Information
ZOHYDRO ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
Daily doses of ZOHYDRO ER, a single dose of greater than 40 mg, or a total daily dose of greater than 80 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.
- Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS AND PRECAUTIONS].
- Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, 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 and following dosage increases with ZOHYDRO ER and adjust the dosage accordingly [see WARNINGS AND PRECAUTIONS].
Instruct patients to swallow ZOHYDRO ER capsules whole [see PATIENT INFORMATION]. Crushing, chewing, or dissolving the beads in ZOHYDRO ER capsules will result in uncontrolled delivery of hydrocodone and can lead to overdose or death [see WARNINGS AND PRECAUTIONS].
ZOHYDRO ER is administered orally twice daily (every 12 hours)
Use of ZOHYDRO ER as the First Opioid Analgesic (opioid-naïve patients)
Initiate therapy 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.
Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression. [see WARNINGS AND PRECAUTIONS].
Conversion From Oral Hydrocodone Formulations To ZOHYDRO ER
Patients receiving other oral hydrocodone-containing formulations may be converted to ZOHYDRO ER by dividing the patient’s total daily oral hydrocodone dose in half and administrating as ZOHYDRO ER every 12 hours.
Conversion From Other Oral Opioid To ZOHYDRO ER
Discontinue all other around-the-clock opioid drugs when ZOHYDRO ER therapy is initiated.
There is inter-patient variability in the relative potency of different opioid drugs and products. Therefore, a conservative approach is advised when determining the total daily dosage of ZOHYDRO ER. It is safer to underestimate a patient’s 24-hour oral hydrocodone dosage and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydrocodone dosage and manage an adverse reaction due to an overdose.
In a 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. To obtain the initial ZOHDYRO ER dose, first use Table 1 to convert the prior oral opioids to a total hydrocodone daily dose and then reduce the calculated daily hydrocodone dose by 25% to account for interpatient variability in relative potency of different opioids.
Consider the following when using the information in Table 1:
- This is not a table of equianalgesic doses.
- The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to 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 Equianalgesic Doses)
|Prior Oral Opioid||Oral Dose (mg)||Approximate Oral Conversion Factor|
|The conversion ratios in this table are only to be used for the conversion from current opioid therapy to 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 approximate oral conversion factor to calculate the approximate oral hydrocodone daily dose. Divide the daily dose in half for administration every 12 hours.
- For patients on a regimen of more than one opioid, calculate the approximate oral hydrocodone dose for each opioid and sum the totals to obtain approximate total hydrocodone daily dose. The daily dose should then be divided in half for administration every 12 hours.
- For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion.
- Reduce the calculated daily oral hydrocodone dose by 25%
Always round the dose down, if necessary, to the nearest ZOHYDRO ER strength(s) available and initiate therapy with that dose.
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 [see WARNINGS AND PRECAUTIONS]. 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 dosage adjustment 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 before increasing the ZOHYDRO ER dosage. 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, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
Dosage Modifications In Patients With Severe Hepatic Impairment
Patients with severe hepatic impairment may have higher plasma concentrations of hydrocodone than those with normal function. Therefore, initiate therapy with 10 mg every 12 hours and titrate carefully, while monitoring for respiratory depression, sedation, and hypotension. No adjustment in starting dose with ZOHYDRO ER is required in patients with mild or moderate hepatic impairment [see CLINICAL PHARMACOLOGY].
Discontinuation Of ZOHYDRO ER
Do not abruptly discontinue ZOHYDRO ER. When a patient no longer requires therapy with ZOHYDRO ER, taper the dose gradually, according to the schedule in Table 2, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these sign or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both.
Table 2. ZOHYDRO ER Taper Schedule Used in Phase 3 Study
|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.
Dosage Forms And Strengths
|10 mg||White opaque||“Z310 10 mg” in black ink|
|15 mg||Light green and white opaque||“Z315 15 mg” in black ink|
|20 mg||Light green opaque||“Z320 20 mg” in black ink|
|30 mg||Dark blue and white opaque||“Z330 30 mg” in black ink|
|40 mg||Dark brown and white opaque||“Z340 40 mg” in black ink|
|50 mg||Dark brown opaque||“Z350 50 mg” in black ink|
Storage And Handling
ZOHYDRO ER extended-release capsules are supplied in 60-count bottles with a child-resistant closure as follows:
|Strength||Capsule Color(s)||Capsule Text||NDC Number|
|10 mg||White opaque||“Z310 10 mg” in black ink||65224-310-60|
|15 mg||Light green and white opaque||“Z315 15 mg” in black ink||65224-315-60|
|20 mg||Light green opaque||“Z320 20 mg” in black ink||65224-320-60|
|30 mg||Dark blue and white opaque||“Z330 30 mg” in black ink||65224-330-60|
|40 mg||Dark brown and white opaque||“Z340 40 mg” in black ink||65224-340-60|
|50 mg||Dark brown opaque||“Z350 50 mg” in black ink||65224-350-60|
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].
Distributed by: Pernix Therapeutics, LLC., Morristown, NJ 07960. US. Revised: Dec 2016This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/6/2017
Additional Zohydro ER Information
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