Antibiotic, Streptogramin

Treatment of serious or life-threatening infections associated with vancomycin-resistant Enterococcus faecium bacteremia; treatment of complicated skin and skin structure infections caused by methcillin-susceptible Staphylococcus aureus or Streptococcus pyogenes

B

No evidence of impaired fertility or harm to the fetus in animal reproductive studies. Excretion in human breast milk is unknown; use caution in breast-feeding women.

Hypersensitivity to quinupristin, dalfopristin, pristinamycin, or virginiamycin

Use with caution in patients with hepatic or renal dysfunction. May cause pain and phlebitis when infused through a peripheral line (not relieved by hydrocortisone or diphenhydramine). Superinfection may occur. As with many antibiotics, antibiotic-associated colitis and pseudomembranous colitis may occur. May cause arthralgias, myalgias, and hyperbilirubinemia. May inhibit the metabolism of many drugs metabolized by CYP3A4. Concurrent therapy with astemizole, terfenadine, and cisapride (which may prolong QT_c interval and lead to arrhythmias) should be avoided.

>10%:

Hepatic: Hyperbilirubinemia (3% to 35%)

Local: Inflammation at infusion site (38% to 42%), local pain (40% to 44%), local edema (17% to 18%), infusion site reaction (12% to 13%)

Note: High baseline values were noted in many patients, contributing to the high incidence of this reaction in some studies

1% to 10%:

Central nervous system: Pain (2% to 3%), headache (2%)

Dermatologic: Pruritus (2%), rash (3%)

Endocrine and metabolic: Hyperglycemia (1%)

Gastrointestinal: Nausea (3% to 5%), diarrhea (3%), vomiting (3% to 4%)

Hematologic: Anemia (3%)

Hepatic: Increased LDH (3%), increased GGT (2%)

Local: Thrombophlebitis (2%)

Neuromuscular & skeletal: Arthralgia (<1% to 8%), myalgia (<1% to 5%), Increased CPK (2%)

<1%: Abdominal pain, allergic reaction, anaphylactoid reaction, anxiety, apnea, arrhythmia, bone pain, cardiac arrest, chest pain, coagulation disorder, confusion, constipation, dizziness, dysautonomia, dyspepsia, dyspnea, encephalopathy, fever, gastrointestinal hemorrhage, gout, hematuria, hemolysis, hemolytic anemia, hepatitis, hyperkalemia, hypertonia, hypoglycemia, hyponatremia, hypotension, hypoventilation, hypovolemia, increased BUN, increased serum creatinine, increased transaminases, infection, insomnia, leg cramps, maculopapular rash, mesenteric artery occlusion, myasthenia, neck rigidity, neuropathy, oral candidiasis, palpitation, pancreatitis, pancytopenia, paraplegia, paresthesia, pericarditis, peripheral edema, phlebitis, pleural effusion, pseudomembranous colitis, respiratory distress, seizures, shock, skin ulcer, stomatitis, sweating, syncope, thrombocytopenia, tremor, urticaria, vaginitis, vasodilation

Symptoms may include dyspnea, emesis, tremors and ataxia. Treatment is supportive. Not removed by hemodialysis or peritoneal dialysis.

CYP3A4 inhibitor

Store unopened vials under refrigeration (2°C to 8°C/36°F to 46°F). Reconstitute single dose vial with 5 mL of 5% dextrose in water or sterile water for injection. Swirl gently to dissolve - do not shake (to limit foam formation). After reconstitution, stability is ~5 hours at room temperature and 54 hours if refrigerated at 2°C to 8°C. Reconstituted solution should be added to at least 250 mL of 5% dextrose in water for peripheral administration (increase to 500 mL or 750 mL if necessary to limit venous irritation). An infusion volume of 100 mL may be used for central line infusions. Do not freeze solution.

Quinupristin/dalfopristin inhibits bacterial protein synthesis by binding to different sites on the 50S bacterial ribosomal subunit thereby inhibiting protein synthesis

Distribution: Quinupristin: 0.45 L/kg; dalfopristin: 0.24 L/kg

Protein binding: Moderate

Metabolism: To active metabolites via nonenzymatic reactions.

Half-life: Quinupristin: 0.85 hour, dalfopristin: 0.7 hour (mean elimination half-lives, including metabolites: 3 and 1 hours, respectively)

Elimination: Primarily by biliary excretion and fecal elimination (parent drug and metabolites 75% to 77%). Renal elimination accounts for 15% to 19% of a dose.

Adults: I.V.:

Vancomycin-resistant Enterococcus faecium: 7.5 mg/kg every 8 hours

Complicated skin and skin structure infection: 7.5 mg/kg every 12 hours

Dosage adjustment in renal impairment: No adjustment required in renal failure, hemodialysis, or peritoneal dialysis

Dosage adjustment in hepatic impairment: Pharmacokinetic data suggest dosage adjustment may be necessary; however, specific recommendations have not been proposed

Elderly: No dosage adjustment is required

Line should be flushed with 5% dextrose in water prior to and following administration. Incompatible with saline. Infusion should be completed over 60 minutes (toxicity may be increased with shorter infusion). Compatible (Y-site injection) with aztreonam, ciprofloxacin, haloperidol, metoclopramide or potassium chloride when admixed in 5% dextrose in water. Also compatible (Y-site injection) with fluconazole (used as undiluted solution). If severe venous irritation occurs following peripheral administration of quinupristin/dalfopristin diluted in 250 mL 5% dextrose in water, consideration should be given to increasing the infusion volume to 500 mL or 750 mL, changing the infusion site, or infusing by a peripherally inserted central catheter (PICC) or a central venous catheter.

No information available to require special precautions

No effects or complications reported

Monitor infusion site closely. If severe venous irritation occurs following peripheral administration of quinupristin/dalfopristin, consider changes to infusion volume, site, or administration via central line. Following infusion, flush with 5% dextrose in water to reduce vein irritation.

Powder for injection: 500 mg (350 mg dalfopristin and 150 mg quinupristin)

Bryson HM and Spencer CM, "Quinupristin/Dalfopristin," Drugs, 1996, 52(3):406-15.

Chant C and Rybak MH, "Quinupristin/Dalfopristin (RP 59500): A New Streptogramin Antibiotic," Ann Pharmacother, 1995, 29(10):1022-7.

Griswold MW, Lomaestro BM, and Briceland LL, "Quinupristin-Dalfopristin (RP 59500): An Injectable Streptogramin Combination," Am J Health Syst Pharm, 1996, 53:2045-53.