SYMPROIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMPROIC (SYMPROIC).
SYMPROIC (naldemedine) is a peripherally acting mu-opioid receptor antagonist (PAMORA) that inhibits opioid binding at mu-opioid receptors in the gastrointestinal tract, thereby reversing opioid-induced constipation without affecting centrally mediated analgesic effects.
| Metabolism | Primarily metabolized by CYP3A4; also undergoes glucuronidation via UGT1A2, UGT1A3, UGT2B7, and UGT2B17. Naldemedine is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily fecal (approximately 77% of administered dose) via biliary excretion unchanged; renal excretion is negligible (<1%). |
| Half-life | Terminal elimination half-life is approximately 30–50 hours; due to extensive peripheral mu-opioid receptor binding, clinical duration exceeds half-life. |
| Protein binding | Approximately 93–94% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Mean Vd is approximately 100 L (about 1.4 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 5–7% due to P-glycoprotein efflux and extensive first-pass metabolism. |
| Onset of Action | Oral: median time to first bowel movement is approximately 1.5–3 hours after a single dose. |
| Duration of Action | Duration varies; sustained effect with continued dosing; clinical trials show laxation within 4 hours in many patients, and with daily dosing, bowel movements are maintained. |
0.2 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment (GFR 15-89 mL/min); not studied in ESRD (GFR <15 mL/min) or dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: not recommended due to lack of data. |
| Pediatric use | Safety and efficacy not established; no approved pediatric dosing available. |
| Geriatric use | No specific dose adjustment; monitor for increased sensitivity due to age-related changes in GI function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SYMPROIC (SYMPROIC).
| Breastfeeding | Data are limited. Naloxegol is excreted in rat milk but it is not known whether it is excreted in human breast milk. The molecular weight (651.75 g/mol) suggests possible excretion. The M/P ratio is unknown. Due to the potential for adverse effects in nursing infants (e.g., gastrointestinal effects), breastfeeding is not recommended during treatment. |
| Teratogenic Risk | SYMPROIC (naloxegol) is a peripherally acting mu-opioid receptor antagonist. In animal studies, no evidence of teratogenicity or fetal harm was observed at doses up to 200 times the human exposure. However, data in pregnant women are insufficient to establish risk. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is no known risk in any trimester based on animal data. |
■ FDA Black Box Warning
Not applicable
| Serious Effects |
["Known or suspected gastrointestinal obstruction","Concurrent use with opioid analgesics for treatment of opioid-induced constipation is contraindicated if the opioid analgesic is being tapered or discontinued abruptly."]
| Precautions | ["Gastrointestinal perforation: Cases of gastrointestinal perforation have been reported; discontinue immediately if symptoms suggestive of perforation develop.","Opioid withdrawal: Development of opioid withdrawal syndrome, especially in patients with disruption of blood-brain barrier; consider discontinuing treatment if symptoms occur.","Potential for decreased CYP3A4 substrate exposure when co-administered with strong CYP3A4 inducers."] |
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| Fetal Monitoring | No specific monitoring is required beyond standard prenatal care. However, monitor for gastrointestinal adverse effects (e.g., abdominal pain, diarrhea) which could cause maternal dehydration or electrolyte imbalances. Fetal monitoring is not routinely indicated. |
| Fertility Effects | In animal studies, no adverse effects on fertility or reproductive performance were observed in male or female rats at exposures up to 200 times the human exposure. Human data are not available, but based on mechanism of action (peripheral opioid antagonism), no direct impact on fertility is anticipated. |