PALLADONE
Clinical safety rating
cautionComprehensive clinical and safety monograph for PALLADONE (PALLADONE).
Agonist at mu-opioid receptors, modulating pain perception via central and peripheral pathways.
| Metabolism | Hepatic via CYP3A4 and CYP2D6 to active metabolite hydromorphone; also via glucuronidation. |
| Excretion | Primarily renal (90%) as unchanged drug and glucuronide conjugate; ~10% biliary/fecal. |
| Half-life | Terminal elimination half-life is approximately 18 hours (range 12-24 h); supports extended dosing intervals. |
| Protein binding | Approximately 95-99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd ~4 L/kg (range 2-6 L/kg). Large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: ~40% (range 20-60%) due to first-pass metabolism; rectal: similar to oral. |
| Onset of Action | Immediate-release: 15-30 min; extended-release: 1-2 hours. Peak effect at 1-2 h (IR) and 3-6 h (ER). |
| Duration of Action | Immediate-release: 3-6 h; extended-release: 12-24 h. Duration is dose and formulation dependent. |
| Molecular Weight | 337.45 |
Immediate-release: 4-8 mg orally every 4-6 hours as needed for pain; extended-release: 8 mg orally every 12 hours, titrated based on response and tolerance.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | For CrCl 30-59 mL/min: start with 50% of recommended dose and titrate cautiously; for CrCl <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: start at 50% of usual dose and monitor; Child-Pugh Class C: not recommended. |
| Pediatric use | Weight-based dosing: 0.1-0.2 mg/kg orally every 4-6 hours as needed (immediate-release); maximum single dose 5 mg. Extended-release not recommended in children. |
| Geriatric use | Start at the low end of dosing range (e.g., 2-4 mg immediate-release every 4-6 hours) and titrate slowly; monitor for increased sensitivity and respiratory depression. |
| 1st trimester | Limited human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
| 2nd trimester | Use only if clearly needed; may cause fetal dependence with prolonged use. |
| 3rd trimester | Prolonged use may cause neonatal opioid withdrawal syndrome. Avoid high doses near term. |
Clinical note
Comprehensive clinical and safety monograph for PALLADONE (PALLADONE).
| Placental transfer | Crosses placenta; detected in fetal plasma. |
| Breastfeeding | Enters breast milk in low amounts; monitor infant for drowsiness and respiratory depression. Benefits usually outweigh risks for short-term use. |
| Lactation Rating | L2 |
| Teratogenic Risk | PALLADONE (hydromorphone) is an opioid agonist. Data in pregnancy are limited. First trimester: Use is associated with a small risk of congenital malformations, particularly neural tube defects, based on some epidemiologic studies; however, absolute risk is low. Second and third trimesters: Chronic use may lead to fetal dependence and neonatal opioid withdrawal syndrome (NOWS) after delivery. Additionally, use near term may cause neonatal respiratory depression, and use during labor may prolong labor. |
| Fetal Monitoring | Maternal monitoring: Assess pain control, respiratory rate, sedation level, and bowel function. Fetal/neonatal monitoring: During pregnancy, fetal heart rate monitoring may be indicated with chronic use. Newborns exposed in utero should be monitored for signs of neonatal opioid withdrawal syndrome (e.g., irritability, poor feeding, tremors) for 48-72 hours after birth. Neonatal respiratory monitoring is essential if opioids are used near term. |
| Fertility Effects | PALLADONE may reduce fertility in both males and females due to effects on hormonal regulation (e.g., suppression of gonadotropin-releasing hormone, reduced libido, and menstrual irregularities). In animal studies, hydromorphone caused decreased fertility in males and females. Reversibility upon discontinuation is possible but not well-characterized. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interaction with alcohol and CNS depressants.
| Serious Effects |
Hypersensitivity to hydromorphone or any excipientSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusSuspected surgical abdomenConcurrent use of MAOIs or within 14 days of stopping
| Precautions | Respiratory depression, Addiction and abuse potential, Risks from concomitant use of benzodiazepines or other CNS depressants, Neonatal opioid withdrawal syndrome, Adrenal insufficiency, Severe hypotension, Seizures, Serotonin syndrome with serotonergic drugs |
| Food/Dietary | Avoid grapefruit juice as it may increase hydromorphone levels. Avoid alcohol in any form (including beverages, cooking wines, and medications containing alcohol) due to risk of additive CNS depression and respiratory depression. High-fat meals may delay absorption; take consistently with or without food to maintain stable effects. |
| Clinical Pearls | PALLADONE (hydromorphone extended-release) is a potent mu-opioid agonist. Do not crush or allow patients to chew capsules; this can cause rapid release and fatal overdose. Use with extreme caution in patients with respiratory compromise, COPD, or sleep apnea. Initiate at the lowest effective dose and titrate slowly. Monitor for constipation and prescribe a bowel regimen prophylactically. Consider naloxone co-prescription for high-risk patients. Avoid use in patients with paralytic ileus or suspected GI obstruction. Renal impairment requires dose adjustment due to accumulation of hydromorphone-3-glucuronide. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Swallow capsules whole; do not crush, chew, or dissolve them as this can cause a fatal overdose. · Avoid alcohol and any medications containing alcohol while taking this drug as it increases risk of dangerous side effects. · Do not drive or operate heavy machinery until you know how PALLADONE affects you; it may cause dizziness or drowsiness. · This medication carries a risk of addiction, abuse, and misuse; store it securely out of reach of others. · Report any difficulty breathing, extreme drowsiness, confusion, or signs of allergic reaction immediately. · Do not stop suddenly; your doctor will help you taper off to prevent withdrawal symptoms. · Constipation is common; increase fluid and fiber intake and use laxatives as recommended by your doctor. |
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