EXALGO
Clinical safety rating
cautionComprehensive clinical and safety monograph for EXALGO (EXALGO).
Mu-opioid receptor agonist; inhibits ascending pain pathways and alters pain perception and emotional response to pain.
| Metabolism | Hepatic via CYP3A4 to hydromorphone and other inactive metabolites. |
| Excretion | Renal: primarily as hydromorphone-3-glucuronide and unchanged drug (~40% as glucuronide conjugates, ~3% as unchanged hydromorphone). Fecal: minimal. Total renal clearance accounts for ~50% of drug elimination. |
| Half-life | Terminal elimination half-life: approximately 15-18 hours in healthy adults. Steady state is achieved by 3-5 days. In patients with hepatic impairment, half-life may be prolonged up to 24-27 hours. |
| Protein binding | Approximately 20-30% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution (Vd): 90-120 L (approx. 1.3-1.7 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Extended-release tablet: approximately 40% oral bioavailability due to first-pass metabolism. Bioavailability relative to immediate-release hydromorphone is comparable. |
| Onset of Action | Extended-release oral: onset of analgesia within 30-60 minutes. Peak effect 4-6 hours post-dose. |
| Duration of Action | Duration of analgesia: 24 hours with once-daily dosing. Clinical note: Due to extended-release formulation, steady-state concentrations are maintained throughout the dosing interval; abrupt discontinuation may lead to withdrawal. |
| Molecular Weight | 285.8 |
Initial: 8 mg orally every 24 hours for opioid-naive patients; titration based on response; maximum 32 mg daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 50%; GFR <30 mL/min: start with 4 mg every 24 hours and titrate cautiously. |
| Liver impairment | Child-Pugh Class A or B: reduce dose by 25-50%; Child-Pugh Class C: avoid use or use with extreme caution with 50% dose reduction. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at lowest dose (4 mg every 24 hours) and titrate slowly due to increased sensitivity and risk of respiratory depression. |
| 1st trimester | Neonatal opioid withdrawal syndrome may occur with prolonged use. Consider risk of congenital malformations; data limited. |
| 2nd trimester | Prolonged use may cause fetal dependency and withdrawal. Use only if benefit outweighs risk. |
| 3rd trimester | May cause respiratory depression and withdrawal in neonate. Avoid use, especially near term. |
Clinical note
Comprehensive clinical and safety monograph for EXALGO (EXALGO).
| Placental transfer | Crosses placenta; demonstrated in animal and human studies. |
| Breastfeeding | Hydromorphone is excreted in breast milk in low amounts; monitor infant for drowsiness and respiratory depression. Use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited data, but opioids cross placenta; risk of neural tube defects not established. Second/third trimester: Prolonged use may cause fetal opioid dependence, neonatal abstinence syndrome (NAS). High doses near delivery may cause neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, bowel function. Fetal monitoring: Nonstress test or biophysical profile if prolonged use; assess for intrauterine growth restriction. Neonatal monitoring for NAS if maternal use >2-4 weeks. |
| Fertility Effects | Opioids may impair fertility in both sexes via hypothalamic-pituitary-gonadal axis suppression, causing hypogonadism, amenorrhea, and reduced sperm count. Reversible upon discontinuation. |
■ FDA Black Box Warning
Serious, life-threatening, or fatal respiratory depression; risk of opioid addiction, abuse, and misuse; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome.
| Serious Effects |
Respiratory depressionAcute or severe bronchial asthma in an unmonitored settingParalytic ileusKnown hypersensitivity to hydromorphone
| Precautions | Respiratory depression; addiction, abuse, and misuse; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; gastrointestinal obstruction; seizure-prone patients; head injury; impaired renal or hepatic function. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase hydromorphone levels. Avoid alcohol and any food containing alcohol, as it can potentiate CNS depression. No other significant food interactions reported; however, a high-fat meal may delay absorption but does not affect overall exposure. |
| Clinical Pearls | EXALGO (hydromorphone extended-release) is an opioid agonist indicated for pain severe enough to require daily, around-the-clock, long-term opioid treatment. Do not crush, chew, or dissolve tablets; this can cause rapid release and fatal overdose. Due to its high potency (5-7 times morphine), initiate cautiously in opioid-naïve patients. Use with naloxone available and educate on signs of respiratory depression. Avoid use in patients with significant respiratory depression, acute or severe bronchial asthma, or known or suspected paralytic ileus. Monitor for opioid-induced constipation and consider bowel regimen. EXALGO's QD dosing is convenient but requires strict adherence to 24-hour interval. |
| Patient Advice | Take EXALGO exactly as prescribed; do not take more than prescribed or more often than every 24 hours. · Swallow tablets whole; do not crush, chew, or dissolve them as this can cause a fatal overdose. · Avoid alcohol and any other central nervous system depressants (e.g., benzodiazepines, other opioids) unless directed by your doctor, as they increase risk of severe sedation and respiratory depression. · Store in a safe place out of reach of children and others; dispose of unused tablets via a drug take-back program. · Do not stop taking EXALGO abruptly without consulting your doctor; withdrawal symptoms may occur. · Seek emergency help if you experience trouble breathing, extreme drowsiness, or fainting. · Do not drive or operate heavy machinery until you know how EXALGO affects you. · Notify your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |
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