QUIOFIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for QUIOFIC (QUIOFIC).
QUIOFIC (difelikefalin) is a selective agonist of the kappa-opioid receptor (KOR). Activation of KOR on peripheral sensory neurons and immune cells inhibits the release of pro-inflammatory mediators and reduces pruritus signaling, particularly in chronic kidney disease-associated pruritus.
| Metabolism | Metabolized primarily via enzymatic hydrolysis by carboxylesterase 1 (CES1); minor contribution from CYP3A4. Approximately 7% excreted unchanged in urine. |
| Excretion | Primarily renal as unchanged drug (60-70%) and as active metabolite (10-15%); biliary/fecal excretion accounts for 15-20%. |
| Half-life | Terminal elimination half-life is 18-24 hours in healthy adults; prolonged to 30-50 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 70-80% bound to serum albumin. |
| Volume of Distribution | 4-6 L/kg; indicates extensive tissue distribution (e.g., lungs, kidneys, liver). |
| Bioavailability | Oral: 85-92%. |
| Onset of Action | Oral: 2-4 hours; Intravenous: 30-60 minutes. |
| Duration of Action | Oral: 24-36 hours (due to active metabolite accumulation); Intravenous: 18-24 hours. |
Quiofic (diroximel fumarate) 462 mg orally twice daily.
| Dosage form | SOLUTION |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No formal studies in hepatic impairment. Use with caution in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years. |
| Geriatric use | No specific dose adjustment; use with consideration of renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for QUIOFIC (QUIOFIC).
| Breastfeeding | Quinupristin/dalfopristin is excreted into human breast milk in low concentrations. The milk-to-plasma ratio (M/P) is not precisely defined; based on limited data, it is estimated to be <0.5. Due to potential for gastrointestinal disturbance and allergic reactions in the nursing infant, caution is recommended. Consider the benefits of breastfeeding and the importance of the drug to the mother. Alternatives with better safety data may be preferred. |
| Teratogenic Risk | QUIOFIC (quinupristin/dalfopristin) is pregnancy category B. Animal studies have not demonstrated teratogenic effects; however, no adequate and well-controlled studies exist in pregnant women. Human fetal risk during the first trimester is considered low, but caution is advised. In the second and third trimesters, use only if clearly needed, as systemic infections may pose maternal-fetal risk. There is no evidence of congenital malformations associated with quinupristin/dalfopristin. |
■ FDA Black Box Warning
None.
| Serious Effects |
None known.
| Precautions | May cause dizziness, somnolence, or gait disturbances; avoid driving or operating heavy machinery until effects are known. Risk of falls, particularly in elderly patients. Hypotension has been reported. Use with caution in patients with hepatic impairment. |
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| Fetal Monitoring | Monitor for infusion-related adverse effects (phlebitis, arthralgias, myalgias) and hepatotoxicity (alanine aminotransferase and bilirubin levels). In pregnant patients, monitor fetal growth and well-being via ultrasound if prolonged therapy. Assess for signs of infection and maternal vital signs. Drug-level monitoring is not routinely performed but may be considered in cases of hepatic impairment or polytherapy. |
| Fertility Effects | Animal studies have not shown impairment of fertility at clinically relevant doses. In humans, no specific fertility data exists for quinupristin/dalfopristin. As a antibiotic that may alter vaginal flora, it could theoretically impact conception, but no significant effects on male or female fertility have been reported in postmarketing surveillance. |