ZOHYDRO ER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOHYDRO ER (ZOHYDRO ER).
Zohydro ER is a pure opioid agonist with relative selectivity for mu-opioid receptors, although it can interact with other opioid receptors at higher doses. Its primary therapeutic action is analgesia via binding to mu-opioid receptors in the central nervous system, leading to activation of descending inhibitory pathways and modulation of pain perception.
| Metabolism | Hydrocodone is primarily metabolized by CYP3A4 and CYP2D6. CYP3A4 is the major enzyme responsible for N-demethylation to norhydrocodone, while CYP2D6 mediates O-demethylation to hydromorphone, a more potent opioid metabolite. |
| Excretion | Primarily renal excretion of hydromorphone-3-glucuronide (H3G, ~60%), unchanged hydromorphone (~15%), and other conjugates. Fecal excretion accounts for ~25%. |
| Half-life | Terminal elimination half-life is approximately 10.6 hours (range 8-17 hours) due to extended-release formulation; immediate-release hydromorphone half-life is 2-3 hours. Clinically, steady-state is achieved after 3-5 days of dosing. |
| Protein binding | Approximately 20-30% bound to plasma proteins (albumin). Low binding minimizes drug interactions from protein displacement. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 3.5 L/kg (range 2-5 L/kg), indicating extensive tissue distribution beyond total body water. |
| Bioavailability | Oral bioavailability is ~50% (range 40-60%) due to first-pass metabolism; extended-release formulation provides consistent absorption over 12 hours. |
| Onset of Action | Oral: Onset of analgesia occurs within 1-2 hours due to immediate-release component; peak effect at 3-4 hours. |
| Duration of Action | Duration of analgesia is 12 hours, allowing twice-daily dosing. Clinical note: Prolonged use may lead to tolerance, requiring dose titration. |
| Molecular Weight | 299.4 Da |
Initial: 20 mg orally every 24 hours; titrate in increments of 10-20 mg every 3-7 days as needed; maximum dose 200 mg every 24 hours.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 30-59 mL/min: Initiate at 50% of usual dose and titrate cautiously; GFR <30 mL/min: Not recommended due to accumulation of metabolites. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Initiate at 50% of usual dose; Child-Pugh Class C: Not recommended. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at 20 mg every 24 hours; titrate cautiously due to increased sensitivity and risk of respiratory depression. |
| 1st trimester | Risk of neural tube defects and congenital anomalies; use only if benefit outweighs risk. |
| 2nd trimester | Risk of miscarriage and fetal growth restriction; use only if clearly needed. |
| 3rd trimester | Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS); avoid use. |
Clinical note
Comprehensive clinical and safety monograph for ZOHYDRO ER (ZOHYDRO ER).
| Placental transfer | Hydrocodone and its active metabolite hydromorphone cross the placenta; fetal plasma levels may be similar to maternal. |
| Breastfeeding | Excreted into breast milk; monitor infant for drowsiness, respiratory depression, and withdrawal. Use lowest effective dose for shortest duration. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS.
| Serious Effects |
Significant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusHypersensitivity to hydrocodone or any component of the formulation
| Precautions | Addiction, Abuse, and Misuse, Life-Threatening Respiratory Depression, Neonatal Opioid Withdrawal Syndrome, Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants, Adrenal Insufficiency, Severe Hypotension, Gastrointestinal Effects: Constipation and Risk of Obstruction, Seizures in Patients with Seizure Disorders, Avoidance of Rapid Withdrawal, Driving and Operating Machinery |
| Food/Dietary | Take on an empty stomach (1 hour before or 2 hours after a meal) to prevent dose dumping. Avoid alcohol in any form (including medications containing alcohol, food prepared with alcohol, or alcoholic beverages) due to risk of rapid release and fatal overdose. Grapefruit juice may increase plasma hydrocodone levels; avoid concurrent use. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | ZOHYDRO ER contains hydrocodone, a Schedule II opioid. First trimester: Increased risk of neural tube defects (OR 2.2) and congenital heart defects (OR 1.8). Second and third trimesters: Chronic use may cause fetal opioid dependence, neonatal abstinence syndrome (NAS), and preterm birth. Avoid use during labor due to risk of neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal vital signs, respiratory rate, and sedation level. Assess fetal heart rate and uterine contractions. For prolonged use, monitor for neonatal abstinence syndrome (NAS) using standardized scoring tools. Consider umbilical cord drug testing at delivery if opioid use disorder suspected. |
| Fertility Effects | Chronic opioid use may cause hypothalamic-pituitary-adrenal axis suppression, leading to amenorrhea, anovulation, and decreased fertility in women. In men, may reduce libido, testosterone levels, and sperm quality. Effects are generally reversible upon discontinuation. |
| Clinical Pearls | Zohydro ER is an extended-release hydrocodone formulation that should be taken on an empty stomach (1 hour before or 2 hours after a meal) to avoid dose dumping. It is not bioequivalent to immediate-release hydrocodone; use caution when converting. Due to high alcohol content in the capsule (10% ethanol), patients with alcohol intolerance or liver disease may experience adverse effects. Prescribe only for opioid-tolerant patients requiring around-the-clock analgesia. Avoid in patients with significant respiratory depression, paralytic ileus, or MAOI use within 14 days. |
| Patient Advice | Swallow capsules whole; do not crush, chew, or dissolve as this can cause fatal overdose. · Do not consume alcohol while taking Zohydro ER; the capsule contains alcohol and additional alcohol may lead to rapid release and overdose. · Avoid grapefruit juice as it may increase hydrocodone levels. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not stop abruptly; withdrawal symptoms may occur. Taper under medical supervision. · Store securely out of reach of children and pets; dispose of unused medication via take-back programs. · Report severe drowsiness, slowed breathing, or difficulty breathing to a healthcare provider immediately. · Avoid driving or operating heavy machinery until you know how the medication affects you. |