Dalfopristin Antimicrobial Drug

INTRODUCTION

Dalfopristin is a semi-synthetic streptogramin antibiotic analogue of ostreogyrcin A (virginiamycin M, pristinamycin IIA, streptogramin A).[1] The combination quinupristin/dalfopristin (marketed under the trade name Synercid) was brought to the market by Rhone-Poulenc Rorer Pharmaceuticals in 1999.[2] Synercid (weight-to-weight ratio of 30% quinupristin to 70% dalfopristin) is used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium

THERAPEUTIC USES:

• Treating infections caused by certain bacteria.

• It may also be used for other conditions as determined by your doctor.

• Quinupristin/dalfopristin is a streptogramin antibiotic.

• It works by blocking the production of proteins needed by the bacteria to survive.

SIDE EFFECTS:

More common:

• Swelling, redness, or pain at the injection site

Less common:

• Changes in skin color

• dry, red, hot, or irritated skin

• joint pain

• muscle pain

• pain

• redness, burning sensation, or pain under the skin usually in the injection site

• swelling of the foot or leg

• tenderness

Rare:

• Agitation

• anxiety

• back, leg, or stomach pains

• black, tarry stools

• bleeding gums

• bloating or swelling of the face, arms, hands, lower legs, or feet

• blood in the urine

• bloody, black, or tarry stools

• blue lips, fingernails, or skin

MECHANISM OF ACTION:

Both dalfopristin and quinupristin bind to sites located on the 50S subunit of the ribosome. Initial dalfopristin binding results in a conformational change of the ribosome, allowing for increased binding by quinupristin.A stable drug-ribosome complex is created when the two drugs are used together. This complex inhibits protein synthesis through prevention of peptide-chain formation and blocking the extrusion of newly formed peptide chains. In many cases, this leads to bacterial cell death.

ANTI MICROBIAL ACTIVITY

Alone, both dalfopristin and quinupristin have modest in vitro bacteriostatic activity. However, 8-16 times higher in vitro bactericidal activity is seen against many gram-positive bacteria when the two streptogramins are combined [5] . While quinupristin/dalfopristin is effective against staphylococci and vancomycin-resistant Enterococcus faecium, in vitro studies have not demonstrated bactericidal activity against all strains and species of common gram-positive bacteria.

PRECAUTIONS:

• if you are pregnant, planning to become pregnant, or are breast-feeding

• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

• if you have allergies to medicines, foods, or other substances

• if you have a history of liver or kidney problems, stomach or bowel problems (eg, colitis, severe diarrhea caused by antibiotic use), HIV infection, high blood bilirubin levels, or a heart condition

• if you are overweight

PHARMACOKINETICS:

Dalfopristin and quinupristin is most often given in a hospital setting. The medicine must be given slowly through an IV infusion, and can take up to 1 hour or longer to complete.

Dalfopristin and quinupristin is usually given for at least 7 days, or longer for more severe infections.

The elimination half-life is approximately 0.70 hours.

PHARMACODYNAMICS:

Dalfopristin is a streptogramin antibiotic, derived from pristinamycin IIA.

DRUG-DRUG INTERACTIONS:

Both dalfopristin and quinupristin are extensively hepatically metabolized, excreted from the feces, and serve as an inhibitor of cytochrome P450 (CYP) 3A4 enzyme pathway.[5] Caution should be taken with concommitent use with drugs metabolized by the CYP3A4 pathway. Concomitant use of quinupristin/dalfopristin with cyclosporine for 2–5 days has shown to result in a two-fold increase in cyclosporine levels.

No adverse effects have been seen in patients with hepatic impairment and no recommendations by the manufacturer have been made for dose reduction of quinupristin/dalfopristin in this patient population.

• amitriptyline +dalfopristin= can affect the rhythm of your hear

• Dalfopristin +ARIPiprazole=  drowsiness , Parkinson disease symptoms increase

• Dalfopristin +amlodipine= may increase the blood levels of amlodipine causing dizziness

REFERENCE: Tripathi K.D; "Essentials of medical pharmacology"; Page no-759