Synercid

quinupristin and dalfopristin

Synercid

Pharmacologic class: Streptogramin

Therapeutic class: Anti-infective

Pregnancy risk category B

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.

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.

quinupristin/dalfopristin

(kwin-oo-pris-tin/dal-foe-pris-tin) ,

Synercid

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: streptogramins
Pregnancy Category: B

Indications

Complicated skin/skin structure infections caused by Staphylococcus aureus (methicillin, susceptible) or Streptococcus pyogenes.

Action

Quinupristin inhibits the late phase of protein synthesis at the level of the bacterial ribosome; dalfopristin inhibits the early phase.

Therapeutic effects

Bacteriostatic effect against susceptible organisms.
Active against, S. aureus (methicillin-susceptible) and S. pyogenes.Not active against Enterococcus faecalis or Enterococcus faecium.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Protein Binding: Moderate.
Metabolism and Excretion: Both are converted to compounds with additional anti-infective activity; parent drugs and metabolites are mostly excreted in feces (75–77%); 15% of quinupristin and 17% of dalfopristin excreted in urine.
Half-life: Quinupristin—0.85 hr; dalfopristin—0.7 hr.

Time/action profile

ROUTEONSETPEAKDURATION
IVrapidend of infusion8–12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity.
Use Cautiously in: Concurrent use of other drugs metabolized by the cytochrome P450 3A4 enzyme system (serious interactions may occur);Hepatic impairment (dose adjustment may be necessary);Patients with a history of GI disease, especially colitis; Obstetric / Lactation / Pediatric: Pregnancy, lactation, or children <12 yr (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • headache

Cardiovascular

  • thrombophlebitis

Gastrointestinal

  • pseudomembranous colitis (life-threatening)
  • diarrhea
  • nausea
  • vomiting

Dermatologic

  • pruritus
  • rash

Local

  • edema/inflammation/pain at infusion site (most frequent)
  • infusion site reactions

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • pain

Interactions

Drug-Drug interaction

Inhibits the cytochrome P450 3A4 drug metabolizing enzyme system; inhibits metabolism of cyclosporine, midazolam, and nifedipine and ↑ risk of toxicity (careful monitoring required).Similar effects may be expected with concurrent use of delavirdine, nevirapine, indinavir, ritonavir, vinca alkaloids, docetaxel, paclitaxel, diazepam, verapamil, diltiazem, HMG CoA reductase inhibitors, tacrolimus, methylprednisolone, carbamazepine, quinidine, lidocaine, and disopyramide.

Route/Dosage

Intravenous (Adults and Children 12–17 yr) 7.5 mg/kg q 12 hr for at least 7 days.

Availability

Powder for injection: 500 mg/vial (150 mg quinupristin and 350 mg dalfopristin), 600 /vial (180 mg quinupristin and 420 mg dalfopristin)

Nursing implications

Nursing assessment

  • Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
  • Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
  • Monitor patient for pain or inflammation at the infusion site frequently throughout infusion. Increasing the volume of diluent from 250 mL to 500 mL or 750 mL or infusing via a peripherally inserted central catheter or central venous catheter may be required.
  • Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician or other health care professional immediately if these problems occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
  • Assess patient for myalgia and arthralgia after infusion. May be severe. Reducing dose frequency to every 12 hr may decrease pain. Symptoms usually resolve upon discontinuation of medication.
  • Lab Test Considerations: May cause ↑ serum total bilirubin concentrations.

Potential Nursing Diagnoses

Risk for infection (Indications,  Side Effects)
Diarrhea (Adverse Reactions)

Implementation

  • Intravenous Administration
  • pH: 5.0.
  • Intermittent Infusion: Reconstitute the 500-mg vial with 5 mL and the 600-mg vial with 6 mL of D5W or sterile water for injection, respectively, for a concentration of 100 mg/mL. Avoid shaking to prevent foam formation. Allow solution to sit until all foam has disappeared. Diluent: Dilute further with 250 mL of D5W (100 mL can be used for central line administration). May dilute in 500 mL or 750 mL of D5W if severe venous irritation occurs after peripheral administration. Reconstituted vials should be used within 30 min. Infusion is stable for 5 hr at room temperature or 54 hr if refrigerated.
  • Rate: Infuse over 60 min. Flush line before and after infusion with D5W.
  • Y-Site Compatibility: alemtuzumab, alfentanil, amikacin, amiodarone, anidulafungin, argatroban, aztreonam, bleomycin, buprenorphine, busulfan, butorphanol, carboplatin, carmustine, caspofungin, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, daptomycin, daunorubicin, dexmedetomidine, dexrazoxane, diltiazem, diphenhydramine, docetaxel, dolasetron, doxacurium, doxarubicin, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, epirubicin, esmolol, etoposide, etoposide phosphate, fenoldopam, fentanyl, fluconazole, gemcitabine, granisetron, haloperidol, hydromorphone, idarubicin, ifisfamide, isoproterenol, labetalol, levofloxacin, levorphanol, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, metoclopramide, metoprolol, midazolam, milrinone, mitomycin, mitoxantrone, morphine, mycophenolate, nalbuphine, naloxone, nesiritide, nicardipine, nitroglycerin, octreotide, ondansetron, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, pentamidine, phenylephrine, potassium chloride, procainamide, prochlorperazine, promethazine, propranolol, rocuronium, sodium phosphates, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, tirofiban, tobramycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, voriconazole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: acyclovir, amifostine, aminophylline, amphotericin B colloidal, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbacatam, azithromycin, bivalirudin, bumetanide, calcium chloride, calcium gluconate, cefazolin, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, clindamycin, dexamethasone sodium phosphate, diazepam, digoxin, ertapenem, fludarabine, fluorouracil, fosphenytoin, furosemide, ganciclovir, heparin, hydrocortisone, imipenem/cilastatin, insulin, ketorolac, leucovorin, meropenem, mesna, methotrexate, methylprednisolone sodium succinate, metronidazole, nitroprusside, pantoprazole, pemetrexed, pentobarbital, phenobarbital, phenytoin, piperacillin/tazobactam, potassium acetate, potassium phosphates, ranitidine, rituximab, sodium acetate, sodium bicarbonate, thiopental, ticarcillin/clavulanate, tigecycline, trimethoprim/sulfamethoxazole
  • Solution Incompatibility: 0.9% NaCl.

Patient/Family Teaching

  • Instruct patient to notify health care professional if signs and symptoms of anaphylaxis, fever, and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.

Evaluation/Desired Outcomes

  • Resolution of signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.

Synercid®

Quinupristin/dalfopristin Therapeutics An antibiotic effective against gram-positive multiresistant organism–eg, vancomycin-resistant and multiresistant Enterococcus faecium–VREF, nosocomial pneumonia, MRSA, methicillin-resistant S epidermidis–MRSE. See Antibiotic resistance, Methicillin-resistant Staphylococcus aureus.
References in periodicals archive ?
Antimicrobial susceptibility results for a novel Bacteroides genomospecies isolated from the bloodstream and intraabdominal abscesses of a patient with colon cancer, 2013 Antimicrobial drug MIC, [micro]g/mL * Ampicillin/sulbactam >256/128 Cefotetan 64 Clindamycin >256 Imipenem >32 ([dagger]) Linezolid 2 Metronidazole >256 ([dagger]) Minocycline 4 Moxifloxacin >32 Piperacillin/tazobactam >256 Synercid >32 Tetracycline 16 Ticarcillin/clavulanic acid >256/2 Tigecycline 1 * Antimicrobial susceptibility testing performed by using E-test (see online Technical Appendix, http://wwwnc.
At present the market has six approved therapies, out of which Vancomycin and Synercid (Quinupristin+Dalfopristin) are generic and rest four are branded drugs.
A concern now is that if Zyvox and Synercid are overused, resistance to those drugs may also develop.
Successful treatment of vancomycin-resistant Enteroeoccusfaecium bacteremia with linezolid after failure of treatment with Synercid (quinupristin/dalfopristin).
Virginiamycin is related to a new human drug called Synercid, which is an emerging replacement for one of the most valuable antibiotics in the clinician's arsenal, vancomycin.
It's almost identical to Synercid, which physicians recently began prescribing to patients.
But a few years ago, pharmaceutical companies developed a virginiamycin-like drug called Synercid to treat enterococcal infections in humans that were resistant to other antibiotics.
One of these, virginiamycin, is similar to an especially valuable antibiotic known as Synercid, which is the drug of last resort for about 70,000 potentially deadly infections every year.
A safety evaluation was conducted as part of the project coordinated by the Synercid Skin and Skin Structure Infection Group (18).
Comment: Because Synercid was approved under the FDA's accelerated approval program--applied to products that are used to treat serious or life-threatening conditions and that provide a "meaningful therapeutic" benefit over existing treatments--approval was based on trials using the surrogate end point of effectiveness, which in this case was clearance of VREF bacteremia.
RPR's choice of Catalytica for the manufacture of Synercid underscores our uncompromising commitment to quality and regulatory expertise.
Only a week ago did the Food and Drug Administration approve a new antibiotic - Synercid - for use against bacteria that can survive vancomycin.