Piperacillin Sodium - Uses, Dosage, Side effects, MOA

Piperacillin is a broad-spectrum Beta-lactam antibiotic that is usually administered in combination with tazobactam for the treating Gram-Negative Infections.

Piperacillin Uses:

Note: Not approved in the US

  • Infection:

    • Treatment for infections brought on by gram-negative, gram-positive, and anaerobic bacteria that are susceptible:
      • intra-abdominal infections,
      • septicemia,
      • lower respiratory tract infections,
      • skin and soft tissue infections,
      • bone and joint infections,
      • gynecological infections,
      • urinary tract infections (complicated and uncomplicated), and
      • uncomplicated urethritis
      • may also be used to treat mixed infections due to susceptible streptococci

Piperacillin dose in Adults

Piperacillin dose in the treatment of Community-acquired pneumonia:

  • IM, IV: Usual dosage: 6 to 8 g per day (100 to 125 mg/kg daily) every 6 to 12 hours in divided doses

Piperacillin dose in the treatment of severe infections (eg, gynecologic, intra-abdominal, nosocomial pneumonia, septicemia, skin/soft tissue):

  • IV: Usual dosage: Divided doses of 12 to 18 g per day (200 to 300 mg/kg per day) are given every 4 to 6 hours (maximum: 24 g daily)

Piperacillin dose in the treatment of gonococcal, uncomplicated Urethritis:

  • IM: 2 g once (Note: Administer probenecid 30 minutes prior to piperacillin)

Piperacillin dose in the treatment of complicated Urinary tract infection:

  • IV: Usual dosage: Every six to eight hours, 8 to 16 g (125 to 200 mg/kg) in divided doses

Piperacillin dose in the treatment of uncomplicated Urinary tract infection:

  • IM, IV: Usual dosage: Every six to twelve hours, 6 to 8 g (100 to 125 mg/kg) in divided doses

Piperacillin dose in Children

Refer to adults dosing.

Piperacillin Pregnancy Risk Category: B

  • Piperacillin crosses over the placenta, and is distributed into the amniotic liquid
  • Some pharmacokinetic parameters for piperacillin could be affected by pregnancy-induced physiological changes
  • Term-wise, piperacillin's apparent volume distribution is greater and its peak concentrations are much lower.
  • It is not unusual for total clearance to rise over time
  • These changes continue well into the first postpartum period.

Piperacillin can be used during breastfeeding

  • Breast milk contains small amounts of piperacillin.
  • Piperacillin should not be administered to nursing mothers, according to the manufacturer.
  • Modification of the bowel flora could also be a non-dose-related effect.

Piperacillin Dose in Kidney Disease:

  • CrCl >40 mL/minute or serum creatinine 1.5 to 3 mg/dL:

    • Dosage adjustment not necessary.
  • CrCl 20-40 mL/minute or serum creatinine 3.1 to 5 mg/dL:

    • uncomplicated Urinary tract infection:

      • No dosage adjustment is necessary.
    • complicated Urinary tract infection:

      • 3 g every 8 hours
    • Severe systemic infection:

      • 4 g every 8 hours
  • CrCl <20 mL/minute or serum creatinine >5 mg/dL:

    • Urinary tract infection (complicated/uncomplicated):

      • 3 g every 12 hours
    • Severe systemic infection:

      • 4 g every 12 hours
  • Hemodialysis:

    • Severe systemic infection: 2 g every 8 hours;
    • administer 1 g supplemental dose after each dialysis session; dialyzable (30% to 50%)

Piperacillin Dose in Liver Disease:

  • No dosage adjustment provided in drug manufacturer’s labeling.

Side effects of Piperacillin:

  • Cardiovascular:

    • Local Thrombophlebitis
  • Central Nervous System:

    • Confusion
    • Drowsiness
    • Myoclonus
    • Seizure
  • Dermatologic:

    • Skin Rash
    • Toxic Epidermal Necrolysis
    • Urticaria
  • Endocrine & Metabolic:

    • Electrolyte Disturbance
    • Hypokalemia
  • Hematologic & Oncologic:

    • Abnormal Platelet Aggregation (High Doses)
    • Agranulocytosis
    • Hemolytic Anemia
    • Pancytopenia
    • Positive Direct Coombs Test
    • Prolonged Prothrombin Time (High Doses)
  • Hypersensitivity:

    • Anaphylaxis
    • Hypersensitivity Reaction
  • Immunologic:

    • Jarisch-Herxheimer Reaction
  • Renal:

    • Acute Interstitial Nephritis
    • Acute Renal Failure
  • Miscellaneous:

    • Fever

Contraindications to Piperacillin:

  • Allergy or hypersensitivity to any of the penicillins, cephalosporins, or formulation ingredients;
  • Hypersensitivity to local anesthetics (amide-type)

Warnings and precautions

  • Anaphylactoid reactions and hypersensitivity reactions

    • Patients on penicillin therapy have had severe and sometimes fatal anaphylactic reactions.
    • If they have a history of beta-lactam hypersensitivity or sensitivity to several allergens, this is particularly true.
    • Asthmatic patients should be cautious.
    • If hypersensitivity develops, discontinue use and seek emergency treatment.
  • Bleeding disorders:

    • Patients with kidney impairment are more susceptible to bleeding disorders.
    • If bleeding or thrombocytopenia occurs, discontinue use.
  • Leukopenia, neutropenia

    • Leukopenia or neutropenia can be caused by prolonged use.
  • Superinfection

    • Long-term use may result in fungal or bacterial superinfection, including pseudomembranous colitis and C. difficile-associated diarrhoea (CDAD); CDAD was noted within two months of commencing antibiotic medication.
  • Cardiovascular disease

    • Take caution when using this product, especially if you are a sodium-restricted patient on long-term therapy. The formulation contains 42.5 mg sodium per gram.
    • With a longer treatment duration, monitor electrolyte status and cardiac function.
  • Cystic Fibrosis:

    • Patients with cystic Fibrosis have been known to experience an increase in fever and rash.
  • Infectious mononucleosis

    • Infectious mononucleosis patients have experienced a rash after receiving therapy with penicillins, such as amoxicillin and ampicillin.
  • Renal impairment

    • Patients with renal impairment should be cautious due to the sodium load and adverse effects (hematologic and neuropsychological changes). Dosage adjustment is recommended.
  • Seizure disorders:

    • High medication levels might cause more seizures, especially when there is renal impairment.
    • Patients who have a history of epilepsy should exercise caution.
  • Syphilis:

    • Patients receiving high-dose antimicrobial therapy for gonorrhea may experience symptoms of syphilis that are delayed or masked.
    • Patients with gonorrhea need to be tested for syphilis before initiating antimicrobial therapy. If syphilis has been suspected, serologic testing should continue for at least four months.

Piperacillin (United States: Not available): Drug Interaction

Risk Factor C (Monitor therapy)

Acemetacin

May increase the serum concentration of Penicillins.

BCG Vaccine (Immunization)

Antibiotics may reduce the BCG vaccine's therapeutic effect (Immunization).

Flucloxacillin

Piperacillin may increase the serum concentration of Flucloxacillin.

Lactobacillus and Estriol

The therapeutic effects of Lactobacillus and Estriol may be reduced by antibiotics.

Methotrexate

Penicillins may raise the level of methotrexate in the serum.

Mycophenolate

The serum levels of the active metabolite(s) of mycophenolate may drop when penicillins are used. Enterohepatic recirculation appears to be hindered, which has this impact.

Probenecid

Could raise the serum level of penicillins.

Vancomycin

Piperacillin might make Vancomycin's nephrotoxic effects worse.

Vecuronium

Vecuronium's ability to suppress neuromuscular activity may be improved by piperacillin.

Vitamin K Antagonists (eg, warfarin)

The anticoagulant impact of vitamin K antagonists may be strengthened by penicillins.

 

Risk Factor D (Consider therapy modification)

Aminoglycosides

Aminoglycoside serum levels may be lowered by penicillins. mainly found in patients with renal impairment and extended spectrum penicillins.

Sodium Picosulfate

Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic.

Tetracyclines

May diminish the therapeutic effect of Penicillins.

Typhoid Vaccine

The Typhoid Vaccine's therapeutic benefits may be reduced by antibiotics. The only strain impacted is the live attenuated Ty21a strain. Treatment: Patients receiving systemic antibacterial drugs should refrain from receiving the live attenuated typhoid vaccination (Ty21a). It is recommended to wait at least 3 days following the last dose of antibacterial medication before administering this vaccine.

Risk Factor X (Avoid combination)

BCG (Intravesical)

Antibiotics may lessen BCG's therapeutic effects (Intravesical).

Cholera Vaccine

Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics.

Monitoring Parameters:

  • Watch out for anaphylactic symptoms and indications once the initial dose is administered;
  • with extended therapy consider monitoring of electrolytes and cardiac status (patients with impaired cardiac function),
  • serum creatinine, BUN,
  • hepatic function, and
  • CBC.

How to administer Piperacillin?

  • IV: Rapid administration can lead to seizures.
  • Use an IV injection over three to five minutes or an intermittent infusion over twenty minutes to two hours to administer.
  • IM: IM injection should be administered into the upper outer quadrant of the buttocks.
  • Do not administer more than 2 g per IM injection site.

Mechanism of action of Piperacillin:

  • Attaches to penicillin-binding proteins (PBPs) and prevents the bacterial cell wall from being produced. This prevents the production of peptidoglycan at its ultimate stage in the walls of bacteria.
  • Bacteria eventually lyse as a result of ongoing cell wall autolytic enzyme activity, such as that caused by autolysins or murein hydrolases. Cell wall construction is now suspended (arrested).

Absorption:

  • IM: Rapid

Protein binding:

  • ~16%

Half-life elimination (dose-dependent; prolonged with renal impairment):

  • Adults: ~1 hour (decreased in patients with cystic fibrosis)

Time to peak, serum:

  • IM: 30 minutes

Excretion:

  • Primarily urine;
  • partially feces

International Brands of Piperacillin:

  • Acopex
  • Isipen
  • Pentcillin
  • Peracillin
  • Peracin
  • Picillina
  • Pipcil
  • Piperacillin
  • Pipracil
  • Pipraks
  • Pipril
  • Prisutomycin

Piperacillin Brand Names in Pakistan:

Piperacillin-Tazobactam (Na) Injection 4 g

Pipetazo Rotex Medica Pakistan (Pvt) Ltd

 

Piperacillin-Tazobactam (Na) Injection 4.5 g

Tanzo Bosch Pharmaceuticals (Pvt) Ltd.

 

Piperacillin-Tazobactam (Na) Injection 2.25 g

Tanzo Bosch Pharmaceuticals (Pvt) Ltd.