Comprehensive Guide to Quinupristin/Dalfopristin: Uses, Dosage, Side Effects, and More
What is Quinupristin/Dalfopristin?
Overview of Quinupristin/Dalfopristin
Generic Name: Quinupristin/Dalfopristin
Brand Name: Synercid, generics
Drug Group: Streptogramin antibiotic (antibacterial)
Commonly Used For
- Treat vancomycin-resistant Enterococcus faecium (VRE) infections.
- Manage complicated skin and skin structure infections (cSSSI).
- Control nosocomial pneumonia caused by susceptible bacteria.
Key Characteristics
Form: Lyophilized powder for IV infusion (500 mg/vial, 150 mg quinupristin/350 mg dalfopristin) (detailed in Dosage section).
Mechanism: Synergistic action inhibits bacterial protein synthesis, effective against resistant Gram-positive pathogens.
Approval: FDA-approved (1999 for Synercid) and EMA-approved for specific resistant infections.
Indications and Uses of Quinupristin/Dalfopristin
Quinupristin/Dalfopristin is indicated for severe bacterial infections, particularly those resistant to standard therapies, leveraging its unique mechanism:
Vancomycin-Resistant Enterococcus faecium (VRE) Infections: Treats bacteremia and other serious infections caused by VRE, a critical option in hospital settings, per CDC guidelines, with efficacy demonstrated in clinical trials.
Complicated Skin and Skin Structure Infections (cSSSI): Manages cSSSI caused by methicillin-resistant Staphylococcus aureus (MRSA) or Streptococcus pyogenes, reducing morbidity, supported by infectious disease studies.
Nosocomial Pneumonia: Controls hospital-acquired pneumonia due to susceptible Gram-positive bacteria (e.g., MRSA), improving outcomes in ventilated patients, per pulmonary infection protocols.
Staphylococcal Endocarditis: Used off-label for MRSA endocarditis in patients intolerant to vancomycin, enhancing survival rates, with cardiology and infectious disease data.
Bone and Joint Infections: Investigated off-label for osteomyelitis or septic arthritis caused by resistant Gram-positive bacteria, improving bone healing, supported by orthopedic research.
Intra-Abdominal Infections: Employed off-label in complicated intra-abdominal infections with resistant pathogens, reducing sepsis risk, with surgical infectious disease evidence.
Central Nervous System Infections: Explored off-label for meningitis or brain abscesses due to resistant Streptococcus or Enterococcus, with cautious use under neurology supervision.
Pediatric Resistant Infections: Used off-label in children with VRE or MRSA infections, adjusting doses for safety, supported by pediatric infectious disease studies.
Prosthetic Joint Infections: Managed off-label for infections of prosthetic joints caused by resistant bacteria, improving implant retention, with orthopedic infectious disease data.
Dosage of Quinupristin/Dalfopristin
Dosage for Adults
VRE Infections or cSSSI: 7.5 mg/kg IV every 8–12 hours, infused over 60 minutes, until clinical improvement (typically 7–14 days).
Nosocomial Pneumonia: 7.5 mg/kg IV every 8 hours, with a minimum of 7 days, adjusted for severity.
Dosage for Children
VRE or MRSA Infections (off-label, 1 month–17 years): 7.5 mg/kg IV every 8–12 hours, based on weight, under pediatric infectious disease supervision.
Not recommended under 1 month due to limited safety data.
Dosage for Pregnant Women
Pregnancy Category B: Limited data; use only if benefits outweigh risks (e.g., life-threatening infection). Consult an obstetrician, with fetal monitoring.
Dosage Adjustments
Renal Impairment: No adjustment needed; monitor in severe cases (CrCl <30 mL/min).
Hepatic Impairment: Reduce dose to 5 mg/kg every 8–12 hours if Child-Pugh B; avoid if Child-Pugh C.
Elderly: Start with 5 mg/kg every 12 hours; increase to 7.5 mg/kg if tolerated.
Concomitant Medications: Adjust if combined with CYP3A4 inhibitors (e.g., ketoconazole), increasing toxicity risk.
Additional Considerations
- Administer this active ingredient via IV infusion over 60 minutes in dextrose 5%; avoid saline due to incompatibility.
- Premedicate with antihistamines or corticosteroids to reduce infusion reactions.
How to Use Quinupristin/Dalfopristin
Administration:
Reconstitute with 5% dextrose, dilute to 500 mL, and infuse IV over 60 minutes; avoid rapid injection.
Administer through a dedicated line to prevent drug interactions.
Timing: Use every 8–12 hours, maintaining a consistent schedule.
Monitoring: Watch for pain at infusion site, fever, or signs of allergic reaction (e.g., rash).
Additional Tips:
- Store at 20–25°C (68–77°F) before reconstitution; protect from light.
- Handle with gloves; dispose of waste per hazardous drug protocols.
- Report severe muscle pain, jaundice, or signs of infection immediately.
Contraindications for Quinupristin/Dalfopristin
Hypersensitivity: Patients with a known allergy to Quinupristin, Dalfopristin, or streptogramins.
Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to toxicity risk.
Concurrent Use with Certain Drugs: Avoid with CYP3A4 substrates with narrow therapeutic indices (e.g., astemizole).
Side Effects of Quinupristin/Dalfopristin
Common Side Effects
- Infusion Site Pain (40–60%, managed with premedication)
- Nausea (30–50%, reduced with antiemetics)
- Diarrhea (20–40%, transient)
- Rash (15–30%, monitor for severity)
- Arthralgia (10–25%, relieved with rest)
These effects may subside with dose adjustment or premedication.
Serious Side Effects
Seek immediate medical attention for:
- Hepatic: Jaundice, hepatitis, or liver failure.
- Musculoskeletal: Severe myalgia, arthralgia, or rhabdomyolysis.
- Infectious: C. difficile colitis or superinfections.
- Cardiovascular: QT prolongation or arrhythmias.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for liver function, muscle enzymes, and infection risk is advised.
- Report any unusual symptoms (e.g., severe abdominal pain, muscle stiffness) immediately to a healthcare provider.
Warnings & Precautions for Quinupristin/Dalfopristin
General Warnings
Infusion-Related Reactions: Risk of arthralgia, myalgia, or venous irritation; premedicate and use central lines.
Hepatotoxicity: Risk of elevated liver enzymes; monitor liver function regularly.
Superinfections: Risk of C. difficile-associated diarrhea; assess stools.
Antibiotic Resistance: Risk with improper use; ensure susceptibility testing.
Bone Marrow Suppression: Rare thrombocytopenia or neutropenia; monitor blood counts.
Additional Warnings
Cardiotoxicity: Rare QT prolongation; monitor ECG in at-risk patients.
Neurological Effects: Rare peripheral neuropathy; report numbness or weakness.
Renal Impairment: Monitor in severe cases; adjust if necessary.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
Hyperbilirubinemia: Increased risk; assess jaundice symptoms.
Use in Specific Populations
- Pregnancy: Category B; use only if essential with fetal monitoring.
- Breastfeeding: Excreted in breast milk; monitor infant for effects.
- Elderly: Higher risk of toxicity; start with lower doses.
- Children: Limited to 1 month+ off-label; supervise closely.
- Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about liver disease, muscle disorders, or medication history before starting this medication.
- Avoid abrupt cessation; complete the full course to prevent resistance.
Overdose and Management of Quinupristin/Dalfopristin
Overdose Symptoms
- Nausea, vomiting, or severe myalgia.
- Severe cases: Liver failure, renal impairment, or seizures.
- Fever, rash, or fatigue as early signs.
- Cardiac arrest with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer IV fluids, monitor vital signs, and provide antihistamines if allergic.
Specific Treatment: No antidote; manage symptoms and monitor organ function.
Monitor: Check liver enzymes, kidney function, and muscle enzymes for 24–48 hours.
Additional Notes
- Overdose risk is low; store securely.
- Report persistent symptoms (e.g., severe weakness, yellowing skin) promptly.
Drug Interactions with Quinupristin/Dalfopristin
This active ingredient may interact with:
- CYP3A4 Substrates: Increases levels (e.g., midazolam); monitor for toxicity.
- Statins: Enhances myopathy risk (e.g., simvastatin); use alternatives.
- Antiarrhythmics: Potentiates QT prolongation (e.g., quinidine); monitor ECG.
- Anticoagulants: Alters bleeding risk; monitor INR.
- Immunosuppressants: Increases levels (e.g., cyclosporine); adjust dose.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this streptogramin combination as prescribed to manage infections, following the exact schedule.
Monitoring: Report infusion site pain, jaundice, or muscle aches immediately.
Lifestyle: Avoid alcohol; maintain hydration to support kidney function.
Diet: Take with premedication; avoid heavy meals during nausea.
Emergency Awareness: Know signs of liver failure or allergic reaction; seek care if present.
Follow-Up: Schedule regular check-ups every 3–7 days during therapy to monitor liver, kidney, and muscle health.
Pharmacokinetics of Quinupristin/Dalfopristin
Absorption: Not orally bioavailable; administered IV (peak at end of infusion).
Distribution: Volume of distribution ~0.9 L/kg (quinupristin), 0.2 L/kg (dalfopristin); 55–78% protein-bound.
Metabolism: Hepatic via non-CYP pathways to active metabolites.
Excretion: Primarily biliary (70–80%) as metabolites; renal (15–20%); half-life 0.9–1.1 hours (quinupristin), 0.5–0.7 hours (dalfopristin).
Half-Life: Short, with prolonged tissue activity due to active metabolites.
Pharmacodynamics of Quinupristin/Dalfopristin
This drug exerts its effects by:
- Inhibiting bacterial protein synthesis at the 50S ribosomal subunit, with quinupristin and dalfopristin acting synergistically.
- Targeting resistant Gram-positive bacteria, including MRSA and VRE.
- Demonstrating bactericidal activity in high concentrations.
- Exhibiting dose-dependent risks of infusion reactions and hepatotoxicity.
Storage of Quinupristin/Dalfopristin
Temperature: Store at 20–25°C (68–77°F) before reconstitution; protect from light.
Protection: Keep in original container, away from heat.
Safety: Store in a locked container out of reach of children due to toxicity risk.
Disposal: Dispose of unused vials per hazardous drug regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Quinupristin/Dalfopristin treat?
A: This medication treats VRE and complicated skin infections.
Q: Can this active ingredient cause muscle pain?
A: Yes, muscle pain may occur; report if severe.
Q: Is Quinupristin/Dalfopristin safe for children?
A: Yes, for 1 month+ off-label with a doctor’s guidance.
Q: How is this drug taken?
A: Via IV infusion every 8–12 hours, as directed.
Q: How long is Quinupristin/Dalfopristin treatment?
A: Typically 7–14 days, depending on infection.
Q: Can I use Quinupristin/Dalfopristin if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 1999 (Synercid) for VRE and cSSSI.
European Medicines Agency (EMA): Approved for resistant Gram-positive infections.
Other Agencies: Approved globally for specific resistant infections; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Synercid (Quinupristin/Dalfopristin) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Quinupristin/Dalfopristin Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Quinupristin/Dalfopristin: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Quinupristin/Dalfopristin.
- WHO’s consideration of Quinupristin/Dalfopristin for resistant infections.
- Clinical Infectious Diseases. (2022). Quinupristin/Dalfopristin in VRE Infections.
- Peer-reviewed article on Quinupristin/Dalfopristin efficacy (note: access may require a subscription).
