hydrocodone (Rx)

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Brand and Other Names:Zohydro ER, Hysingla ER

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule, extended-release (Zohydro ER): Schedule II

  • Abuse-deterrent product (BeadTek technology)
  • 10mg
  • 15mg
  • 20mg
  • 30mg
  • 40mg
  • 50mg

tablet, extended-release (Hysingla ER): Schedule II

  • Abuse-deterrent product (RESISTEC)
  • 20mg
  • 30mg
  • 40mg
  • 60mg
  • 80mg
  • 100mg
  • 120mg
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Chronic Pain

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate

Initial dosing

  • Should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain
  • 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
  • Monitor patients closely for respiratory depression, especially within the first 24-72 hr of initiating therapy

Opioid naïve or first opioid analgesic

  • Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
  • Zohydro ER: 10 mg PO q12hr initially
  • A single dose of Zohydro ER >40 mg, Zohydro ER 50 mg capsules, or a total daily dose greater than 80 mg are only for patients in whom tolerance to an opioid of comparable potency is established
  • Hysingla ER: Administer once daily as 20 mg PO q24h initially
  • Daily doses of Hysingla ER ≥80 mg/day are only for use in opioid tolerant patients

Opioid tolerant

  • See prescribing information for conversion table from existing opioid analgesic to hydrocodone extended-release
  • Opioid tolerance definition
    • Defined as patients who are receiving the following opioids (or an equianalgesic dose of another opioid) for 1 week or longer
    • morphine 60 mg/day PO
    • transdermal fentanyl 25 mcg/hr
    • oxycodone 30 mg/day
    • hydromorphone 8 mg/day PO
    • oxymorphone 25 mg/day PO

Titration, maintenance, discontinuation

  • Zohydro ER: Increase by increments of 10 mg q12hr q3-7d as needed to achieve adequate analgesia
  • Hysingla ER: Increase by increments of 10-20 mg/day q3-5d as needed to achieve adequate analgesia
  • Assess pain frequently for toxicity, breakthrough pain, or need for rescue analgesia
  • Discontinue by a gradual downward titration every 2-4 days; do not withdraw abruptly

Dosage Modifications

Hepatic impairment

  • Mild-to-moderate: No adjustment to starting dose required
  • Severe: Initiate with lowest dose, 10 mg (Zohydro ER) or 50% of initial dose (Hysingla ER) and monitor closely for signs of respiratory depression and excessive sedation

Renal impairment

  • Patients with renal impairment may have higher plasma concentrations than those with normal function
  • Initiate therapy with a low initial dose (Zohydro ER) or 50% of initial dose (Hysingla ER) and monitor closely for respiratory depression and sedation

Dosing Considerations

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 use for patients for whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain

Not indicated for acute pain or as an as-needed (prn) analgesic

Administration

Swallow capsule/tablet whole; crushing, chewing, or dissolving the extended-release dosage form will result in uncontrolled delivery of hydrocodone and can lead to overdose or death

Must be taken whole, 1 capsule/tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth

Safety and efficacy not established

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Interactions

Interaction Checker

and hydrocodone

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Zohydro ER

            • Constipation (8-11%)

            1-10%

            Zohydro ER

            • Nausea (7-10%)
            • Vomiting (3-5%)
            • Somnolence (1-5%)
            • UTI (1-5%)
            • Headache (4%)
            • Fatigue (1-4%)
            • Back pain (1-4%)
            • Dry mouth (3%)
            • Pruritus (3%)
            • Tremor (3%)
            • Dizziness (2-3%)
            • Peripheral edema (1-3%)
            • URI infection (1-3%)
            • Muscle spasms (1-3%)

            1-10% (Hysingla ER)

            • Nausea (8%)
            • Constipation (3%)
            • Vomiting (6%)
            • Dizziness (3%)
            • Insomnia (3%)
            • Influenza (3%)
            • Decreased appetite (2%)
            • Headache (2%)
            • Tinnitus (2%)
            • Somnolence (1%)
            • Fatigue (1%)
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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Long-acting hydrocodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess each patient’s risk prior to prescribing, and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase
            • Instruct patients to swallow capsules/tablets whole; crushing, chewing, or dissolving the extended-release dosage forms can cause rapid release and absorption of a potentially fatal dose of hydrocodone

            Accidental exposure

            • Accidental consumption of even 1 dose of hydrocodone, especially by children, can result in a fatal overdose of hydrocodone

            Neonatal opioid withdrawal syndrome

            • For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome
            • Prolonged maternal use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening and requires management according to protocols developed by neonatology experts

            Interaction with alcohol

            • Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking hydrocodone (increased CNS depression)
            • Coingestion of Zohydro ER with alcohol may increase hydrocodone plasma levels and result in a potentially fatal overdose (alters release of drug from capsule)

            Interaction with CYP3A4 inhibitors

            • Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of hydrocodone from hydrocodone ER

            Contraindications

            Hypersensitivity

            Significant respiratory depression

            Acute or severe bronchial asthma or hypercarbia

            Suspected paralytic ileus

            Cautions

            Do not prescribe for acute pain or as needed (prn) pain relief; only for severe chronic pain requiring continuous, around-the-clock opioid analgesia

            Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone

            Coadministration with other CNS depressants may cause profound sedation, respiratory depression, and death; if coadministration is required, consider dose reduction of 1 or both drugs

            Monitor carefully in elderly, cachectic, debilitated patients, and those with chronic pulmonary disease because of increased risk for life-threatening respiratory depression

            Monitor patients with head injury or increased ICP for sedation and respiratory depression; avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of CO2 retention

            May cause severe hypotension, including orthostatic hypotension and syncope; added risk to individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone

            Prolonged gastric obstruction may occur

            Coadministration with CYP3A4 inhibitors may increase hydrocodone systemic exposure and result in toxicity; if co-administration with CYP3A4 necessary, monitor patients closely who are currently taking, or discontinuing, CYP3A4 inhibitors or inducers; evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved

            Caution must be used with potentially hazardous activities

            Avoid use of mixed agonist/antagonist analgesics (ie, pentazocine, nalbuphine, butorphanol) when taking full opioid agonist analgesics

            Hydrocodone ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings; monitor patients with a history of seizure disorders for worsened seizure control during hydrocodone ER therapy

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            Pregnancy & Lactation

            Pregnancy category: C

            Fetuses of rabbits administered oral doses of 75 mg/kg/day hydrocodone bitartrate (15 times an adult human dose of 100 mg/day on a mg/m² basis) during the period of organogenesis exhibited an increased number of malformations consisting of umbilical hernia, and irregularly shaped bones (ulna, femur, tibia and/or fibula)

            Lactation: Low concentrations of hydrocodone and hydromorphone in human breast milk of nursing mothers using hydrocodone for postpartum pain control have been reported in published literature

            Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue hydrocodone, taking into account the importance of the drug to the mother

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Mu opioid receptor agonist; interacts with other opioid receptors at higher doses; activates opioid receptors at sites in the peri-aquaductal and peri-ventricular gray matter, the ventro-medial medulla and the spinal cord to produce analgesia

            Also elicits euphoric, respiratory depressant, and physiologic dependence properties of mu receptors within the CNS

            Absorption

            Zohydro ER

            • Extended-release provided by spheroidal oral drug absorption system (SODAS) technology (ie, multi-particulate formulation of coated carrier beads in hard gelatin capsules); contains rate-controlling polymers and drug release by diffusion
            • Peak plasma time: 5 hr
            • Peak plasma concentration increased by 27% when administered with a high fat meal

            Hysingla ER

            • Peak plasma time (mean): 14-16 hr (range 6-30 hr)
            • AUC and peak plasma concentration increase linearly with doses
            • Peak plasma concentration (median): 14.6-110 ng/mL
            • AUC (median): 284-1787 ng•hr/mL
            • Peak plasma concentration increased by 20% when administered with a high fat meal

            Distribution

            Protein bound: ~19% (Zohydro ER); 36% (Hysingla ER)

            Vd: 402 L (Hysingla ER)

            Metabolism

            Metabolized in liver by CYP2D6 (minor) via O-demethylation, CYP3A4 (major) via N-demethylation, and 6-keto reduction

            Metabolites: CYP3A4 mediated N-demethylation to norhydrocodone is the primary metabolic pathway; CYP2D6 to hydromorphone (active metabolite with higher binding capacity to mu opioid receptor)

            Elimination

            Half-life: 8 hr (Zohydro ER); 7-9 hr (Hysingla ER)

            Excretion: Primarily by kidneys

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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