SEGLENTIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEGLENTIS (SEGLENTIS).
SEGLENTIS is a fixed-dose combination of the opioid oxycodone and the opioid antagonist naltrexone. Oxycodone acts as a mu-opioid receptor agonist, providing analgesia. Naltrexone is intended to reduce the abuse potential of oxycodone by blocking opioid receptors when the drug is tampered with (e.g., crushed or chewed), but is sequestered in the core of the tablet and not released when taken orally as directed.
| Metabolism | Oxycodone is primarily metabolized by CYP3A4 and CYP2D6 to noroxycodone, oxymorphone, and other metabolites. Naltrexone is primarily metabolized by dihydrodiol dehydrogenase (DD) in the liver to 6-beta-naltrexol, and also undergoes minor CYP-mediated metabolism. |
| Excretion | Seglentis (celecoxib and tramadol) is primarily excreted renally. Celecoxib is eliminated via hepatic metabolism (CYP2C9) with <3% excreted unchanged in urine; fecal excretion accounts for approximately 70% of an oral dose (as metabolites). Tramadol and its active metabolite (M1) are mainly excreted renally (about 90% of the dose, with 30% unchanged tramadol and 15% M1); the remainder is excreted fecally. |
| Half-life | The terminal elimination half-life of celecoxib is approximately 11 hours; for tramadol, it is about 6 hours, and for its active M1 metabolite, about 7 hours. Clinically, this supports twice-daily dosing for Seglentis (two tablets BID). |
| Protein binding | Celecoxib is approximately 97% bound to plasma proteins (primarily albumin). Tramadol is about 20% bound, and M1 is about 15% bound. |
| Volume of Distribution | For celecoxib, the apparent volume of distribution (Vd/F) is approximately 400 L (about 5.7 L/kg for a 70 kg adult), indicating extensive tissue distribution. For tramadol, Vd is about 2.6-3.0 L/kg, indicating wide distribution into tissues. |
| Bioavailability | The absolute oral bioavailability of celecoxib is not determined; it is well absorbed with a relative bioavailability of >90% versus an oral solution. Tramadol has an absolute oral bioavailability of about 75% (range 70-90%) due to first-pass metabolism. For Seglentis tablets, bioavailability is comparable to the individual components. |
| Onset of Action | Analgesic onset occurs within 30-60 minutes after oral administration of Seglentis tablets, due to the tramadol component; the celecoxib component provides additional onset within 1 hour. |
| Duration of Action | The duration of analgesia is approximately 12 hours with twice-daily dosing. Clinical trials show sustained pain relief over 12 hours with BID administration. |
Subcutaneous injection: 300 mg (1.5 mL) once weekly. Administer in combination with oral capecitabine.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Caution in moderate to severe impairment (Child-Pugh B or C) as safety and efficacy not established. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment recommended. Monitor for adverse effects more frequently due to potential for increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEGLENTIS (SEGLENTIS).
| Breastfeeding | SEGLENTIS components are excreted in breast milk. Levofloxacin: Excreted into milk (M/P ratio ~0.8); may cause diarrhea or rash in infant; avoid breastfeeding due to potential unknown effects on neonatal bone development. Fluconazole: Excreted into milk (M/P ratio ~0.9); low doses considered compatible, but high doses should be avoided. Metronidazole: Excreted into milk (M/P ratio ~1.0); may cause diarrhea or oral thrush; consider withholding breastfeeding for 12-24 hours after dose. Overall, avoid breastfeeding during therapy. |
| Teratogenic Risk | SEGLENTIS (levofloxacin, fluconazole, and metronidazole) is contraindicated in pregnant women due to known teratogenic risks of its components. Levofloxacin: Fluoroquinolones cause arthropathy in juvenile animals; human data show possible risk of aortic dissection and tendinopathy; avoid in pregnancy unless no alternative. Fluconazole: High-dose fluconazole (≥400 mg/day) is associated with multiple congenital anomalies (e.g., craniosynostosis, cleft palate, skeletal abnormalities) in first trimester; lower doses (150 mg) have limited data but risk cannot be excluded. Metronidazole: Generally considered low risk in pregnancy; no definitive evidence of teratogenicity; avoid in first trimester if possible per some guidelines. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and RISK OF MEDICATION ERRORS. See full prescribing information for complete boxed warning.
| Serious Effects |
["Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment","Known or suspected gastrointestinal obstruction, including paralytic ileus","Hypersensitivity to oxycodone, naltrexone, or any component of the product","Patients who are opioid-naive (not tolerant to opioids)","Concurrent use of other opioid antagonists or mixed agonist/antagonists (e.g., pentazocine, nalbuphine, butorphanol)"]
| Precautions | ["Risk of Life-Threatening Respiratory Depression","Risk of Accidental Ingestion (especially in children)","Neonatal Opioid Withdrawal Syndrome with prolonged use during pregnancy","Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants","Risk of Medication Errors (confusion with other oxycodone/naltrexone products)","Opioid-Induced Hyperalgesia","Severe Hypotension","Adrenal Insufficiency","Androgen Deficiency","Gastrointestinal Effects (constipation, ileus)","Seizures in patients with seizure disorders","Avoid use in patients with compromised respiratory function","Risk of withdrawal if opioid-naive or if naltrexone is released"] |
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| Fetal Monitoring | Monitor liver function tests (e.g., AST, ALT) due to fluconazole hepatotoxicity. Monitor renal function (e.g., serum creatinine) as levofloxacin is renally excreted. Monitor blood glucose in diabetic patients due to fluconazole hypoglycemia risk. Monitor ECG for QT prolongation (levofloxacin and fluconazole). Assess for signs of peripheral neuropathy (metronidazole). If inadvertent use in pregnancy, perform fetal ultrasound for anomaly detection. |
| Fertility Effects | SEGLENTIS may impair fertility based on animal studies. Levofloxacin: No direct fertility studies, but fluoroquinolones may affect spermatogenesis in animal models. Fluconazole: Caused delayed parturition and dystocia in animal studies; human data limited. Metronidazole: No significant fertility effects reported. Overall, avoid in women planning pregnancy unless necessary. |