quinupristin and dalfopristin

quinupristin and dalfopristin

Synercid

Pharmacologic class: Streptogramin

Therapeutic class: Anti-infective

Pregnancy risk category B

FDA Boxed Warning

• Drug combination is approved for treating serious or life-threatening infections related to vancomycin-resistant Enterococcus faecium bacteremia under the Food and Drug Administration's accelerated approval regulations that allow marketing of products for use in life-threatening conditions when other therapies aren't available.

Action

Synergistic effects of drug combination interfere with bacterial cell-wall synthesis by disrupting DNA and RNA transcription

Availability

Injection: 500 mg/10 ml (150 mg quinupristin, 350 mg dalfopristin), 600 mg/10 ml (180 mg quinupristin, 420 mg dalfopristin)

⊘Indications and dosages

➣ Serious or life-threatening infections caused by vancomycin-resistant Enterococcus faecium

Adults and adolescents ages 16 and older: 7.5 mg/kg by I.V. infusion over 1 hour q 8 hours

➣ Complicated skin and skin-structure infections caused by Staphylococcus aureus (methicillin-susceptible) or Streptococcus pyogenes

Adults and adolescents ages 16 and older: 7.5 mg/kg by I.V. infusion over 1 hour q 12 hours for at least 7 days

Dosage adjustment

• Hepatic impairment

Contraindications

• Hypersensitivity to drug or other streptogramins

Precautions

Use cautiously in:
• hepatic impairment
• breastfeeding patients
• children younger than age 16 (safety and efficacy not established).

Administration

☞ Don't mix with other drugs or saline solution.
• For intermittent infusion through a common I.V. line, flush line with dextrose 5% in water (D₅W) before and after giving drug.
• Add 5 ml of sterile water or D₅W to powdered drug in vial, and swirl gently by hand until powder dissolves; don't shake vial. Solution should be clear.
• Within 30 minutes of first dilution, draw up prescribed dosage and dilute further in D₅W to a final concentration of 2 mg/ml or less.
• Know that if patient has a central venous catheter and is fluid-restricted, drug may be given in 100 ml of D₅W.
• Administer by infusion pump over 60 minutes.
• If significant peripheral vein irritation occurs, dilute in 500 to 750 ml of D₅W.
• Be aware that duration of therapy depends on infection site and severity.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

Adverse reactions

CNS: headache

CV: thrombophlebitis

GI: nausea, vomiting, diarrhea

Musculoskeletal: joint pain, myalgia

Skin: rash, pruritus

Other: inflammation, pain, or edema at infusion site

Interactions

Drug-drug. Drugs metabolized by CYP450-3A4 (antiretrovirals; antineoplastics, such as vinca alkaloids, docetaxel, and paclitaxel; astemizole; benzodiazepines; calcium channel blockers; carbamazepine; cisapride; corticosteroids; disopyramide; HMG-CoA reductase inhibitors; immunosuppressants such as cyclosporine and tacrolimus; lidocaine; quinidine; terfenadine): increased therapeutic and adverse effects of these drugs

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased levels

Patient monitoring

• Monitor closely for infusion site reactions and thrombophlebitis. If these problems occur, consider increasing infusion volume, changing infusion site, or infusing through peripherally inserted central catheter or central venous catheter.
• Assess weight and fluid intake and output to help detect edema.
• Monitor bilirubin level.

Patient teaching

☞ Instruct patient to immediately report pain or redness at infusion site.
• Tell patient to report muscle aches and pains.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.