Piperacillin

Piperacillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Piperacillin has been approved to relieve symptoms and also for the treatment and maintenance of community-acquired pneumonia, severe infections including gynecologic, intra-abdominal, hospital-acquired/ventilator-associated pneumonia, bloodstream, and skin/soft tissue, urethritis, urinary tract infection, complicated & uncomplicated.

Piperacillin is not absorbed following oral administration. The volume of distribution of Piperacillin is 101 mL/kg intravenous administration of 50 mg/kg (5-minute infusion) in neonates. Piperacillin is not largely metabolized. Piperacillin is found to be eliminated primarily by glomerular filtration as well as tubular secretion.Piperacillin is excreted rapidly as an unchanged drug in high concentrations in the urine. As Piperacillin is excreted by the biliary route and renal route.Piperacillin can be used safely in appropriate dosage in patients with severely restricted kidney function.

The common side effects involving the use of Piperacillin are diarrhea, nausea, dizziness, oral thrush, vomiting, headache, and vaginal yeast infection.

Piperacillin is available in the form of Intramuscular and Intravenous Injections.

Piperacillin is available in the European Union, India, China, and Canada.

Piperacillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Piperacillin binds to and inhibits penicillin-binding proteins (PBPs). Piperacillin binds to specific penicillin-binding proteins (PBPs), which are located inside the bacterial cell wall. Piperacillin is found to inhibit the third and last stage of bacterial cell wall synthesis. Hence, the Cell lysis is then mediated by the bacterial cell wall autolytic enzymes such as autolysins.

Piperacillin has been approved to relieve symptoms and also for the treatment and maintenance of community-acquired pneumonia, severe infections including gynecologic, intra-abdominal, hospital-acquired/ventilator-associated pneumonia, bloodstream, and skin/soft tissue, urethritis, urinary tract infection, complicated & uncomplicated.

Following the intramuscular administration of Piperacillin, the peak plasma concentration is achieved in 30 minutes.

Piperacillin is available in the form of Intramuscular and Intravenous Injections.

Piperacillin can be used in the following treatment:

• Community-acquired pneumonia
• Severe infections, including gynecologic, intra-abdominal, hospital-acquired/ventilator-associated pneumonia, bloodstream, and skin/soft tissue
• Urethritis
• Urinary tract infection, complicated & uncomplicated

Piperacillin can help to relieve symptoms and also for the treatment and maintenance of community-acquired pneumonia, severe infections including gynecologic, intra-abdominal, hospital-acquired/ventilator-associated pneumonia, bloodstream, and skin/soft tissue, urethritis, urinary tract infection, complicated & uncomplicated.

Piperacillin is approved for use in the following clinical indications:

• Community-acquired pneumonia
• Severe infections, including gynecologic, intra-abdominal, hospital-acquired/ventilator-associated pneumonia, bloodstream, and skin/soft tissue
• Urethritis
• Urinary tract infection, complicated & uncomplicated

Community-acquired pneumonia

Intramuscular, Intravenous: Usual dosage: 6 to 8 g daily (100 to 125 mg/kg daily) in divided doses every 6 to 12 hours.

Severe infections, including gynecologic, intra-abdominal, hospital-acquired/ventilator-associated pneumonia, bloodstream, and skin/soft tissue

Usual dosage: 12 to 18 g daily (200 to 300 mg/kg daily) in divided doses every 4 to 6 hours (maximum: 24 g daily).

Urethritis

Intramuscular: 2 g once

Urinary tract infection, complicated

Intravenous: Usual dosage: 8 to 16 g daily (125 to 200 mg/kg daily) in divided doses every 6 to 8 hours.

Urinary tract infection, uncomplicated

Intramuscular, Intravenous: Usual dosage: 6 to 8 g daily (100 to 125 mg/kg daily) in divided doses every 6 to 12 hours.

Powder for IV injection: 2 g, 3 g, 4 g, 40 g

Powder for IM injection: 2 g, 3 g, 4 g

Powder for solution for injection: 2 g, 3 g, 4 g

Intramuscular and Intravenous Injection

• Dosage Adjustments in Kidney Patients

In patients with a creatinine clearance (CrCl) greater than 40 mL/minute or serum creatinine levels ranging from 1.5 to 3 mg/dL, no dosage adjustment is required. However, in patients with a CrCl between 20 to 40 mL/minute or serum creatinine levels ranging from 3.1 to 5 mg/dL, dosage adjustment may be necessary. In patients with a CrCl less than 20 mL/minute or serum creatinine levels greater than 5 mg/dL, significant dosage adjustments may be necessary.

• Dosage Adjustments in Pediatric Patients

Dosage adjustments for piperacillin in pediatric patients depend on the age, weight, and renal function of the child. The recommended dose for children over two months of age is 300 mg/kg/day, divided into 3 or 4 doses. For children weighing less than 40 kg, the dose should not exceed 4 g/day.

In children with renal impairment, dosage adjustments are necessary to avoid toxicity. For those with a creatinine clearance (CrCl) greater than 40 mL/min/1.73 m², no dose adjustment is necessary. However, in those with a CrCl between 20-40 mL/min/1.73 m², the dose should be reduced to 150-300 mg/kg/day. In children with a CrCl less than 20 mL/min/1.73 m², the dose should be reduced to 100-200 mg/kg/day.

In premature infants, the recommended dose is 60-90 mg/kg/day, divided into 2 or 3 doses. The dose should be adjusted based on gestational age and renal function. In neonates, the dose should not exceed 200 mg/kg/day.

Avoid high-acid foods like citrus fruits and juices like orange and grapefruit, soda, and chocolates.

Alcohol intake might lead to nausea, vomiting, and headache

Multivitamins and antacids contain minerals, primarily magnesium, calcium, aluminum, iron, or zinc, which bind to the antibiotic and refrain it from working. Spacing them at least for 2 hours after Piperacillin administration is recommended.

Piperacillin may is contraindicated under the following conditions:

• Patients with known hypersensitivity to Penicillin derivatives/ Cephalosporins.
  

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Serious/occasionally fatal hypersensitivity reactions had been reported in patients receiving therapy with penicillins. These reactions are more likely to occur in persons who have a history of sensitivity to multiple allergens. Cross-sensitivity of patients to penicillins as well as cephalosporins had been reported. Before initiating therapy with Piperacillin for Injection, a careful inquiry is to be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, as well as other allergens.

Antibiotic-associated pseudomembranous colitis had been reported with nearly all antibacterial agents, including piperacillin, and might range in severity from mild to life-threatening. It is important to consider this diagnosis if a significant diarrhea or colitis occurs during therapy. It is advised that treatment with an oral antibacterial drug effective against Clostridium difficile such as oral vancomycin should be considered.

Usage of alcohol should be avoided while on Piperacillin medication, as alcohol can worsen the effects of any underlying disease condition, including conditions such as dizziness, blurred vision, etc.

It is advised that caution should be exercised when Piperacillin for Injection is administered to the nursing mothers. Piperacillin is excreted in low concentrations in milk.

Category B

Although reproduction studies in mice as well as rats were performed at doses up to four times the human dose have shown no evidence of impaired fertility or harm to the fetus, the safety of Piperacillin for Injection use in pregnant women has not been determined.As the animal reproduction studies are not always predictive of human response, piperacillin should be used during pregnancy only if clearly needed. Piperacillin has been found to cross the placenta in rats.

No sufficient scientific evidence is traceable regarding the use and safety of Piperacillin in concurrent use with any particular food.

The adverse reactions related to Piperacillin can be categorized as follows:

• Injection site reactions
• Gastrointestinal disturbances
• Stevens-Johnson syndrome
• Headache
• Dizziness
• Fatigue
• Seizures
• Renal impairment
• Anaphylaxis
• Blood dyscrasias
• Bleeding

The clinically relevant drug interactions of Piperacillin are briefly summarized here:

• Simultaneous administration of probenecid reduces the excretion of penicillins and hence increases the blood level of the antibiotic.
• Piperacillin for Injection, when reconstituted with Lidocaine for intramuscular use, is contraindicated in patients with a known history of hypersensitivity to the local anesthetics of the amide-type.

The following are the side effects involving Piperacillin :

• Diarrhea
• Nausea
• Dizziness
• Oral thrush
• Vomiting
• Headache
• Vaginal yeast infection

• Pregnancy

Category B

Although reproduction studies in mice as well as rats were performed at doses up to four times the human dose have shown no evidence of impaired fertility or harm to the fetus, the safety of Piperacillin for Injection use in pregnant women has not been determined.As the animal reproduction studies are not always predictive of human response, piperacillin should be used during pregnancy only if clearly needed. Piperacillin has been found to cross the placenta in rats.

• Lactation

It is advised that caution should be exercised when Piperacillin for Injection is administered to the nursing mothers. Piperacillin is excreted in low concentrations in milk.

• Pediatric

Piperacillin has been used safely and effectively in pediatric patients for the treatment of various bacterial infections, including respiratory tract infections, skin and skin structure infections, and urinary tract infections. The recommended dose of piperacillin in pediatric patients is based on body weight and ranges from 200-400 mg/kg/day, divided into 3-4 doses.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Piperacillin.

Excessive serum levels of piperacillin may be reduced by hemodialysis. As with other penicillins, neuromuscular excitability or convulsions have occurred following large intravenous doses. General supportive measures, including the administration of phenytoin and barbiturates or other anticonvulsant drugs, might be considered. Daily doses of piperacillin of at least 24 g have been administered to humans without observation of adverse effects.

Pharmacodynamics

Piperacillin is said to have vitro activity against gram-positive as well as gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Piperacillin is said to result from the inhibition of cell wall synthesis and is mediated through Piperacillin binding to penicillin-binding proteins (PBPs). Piperacillin is foudn to be stable against hydrolysis by a variety of beta-lactamases, including cephalosporinases, penicillinases as well as extended-spectrum beta-lactamases.

Pharmacokinetics

• Absorption

Piperacillin is not absorbed following oral administration.

• Volume of distribution

The volume of distribution of Piperacillin is 101 mL/kg [intravenous administration of 50 mg/kg (5-minute infusion) in neonates]

• Metabolism

Piperacillin is not primarily metabolized.

• Route of elimination

Piperacillin is eliminated primarily by glomerular filtration and tubular secretion; it is excreted rapidly as an unchanged drug in high concentrations in the urine. Because Piperacillin is excreted by the biliary route as well as by the renal route, it can be used safely in appropriate dosage in patients with severely restricted kidney function.

• https://pdf.hres.ca/dpd_pm/00044150.PDF
• https://www.empr.com/drug/piperacillin/
• https://www.rxlist.com/pipracil-side-effects-drug-center.htm#overview
• https://www.mayoclinic.org/drugs-supplements/piperacillin-and-tazobactam-intravenous-route/side-effects/drg-20072716
• https://www.drugs.com/pregnancy/piperacillin.html
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050684s88s89s90_050750s37s38s39lbl.pdf
• https://go.drugbank.com/drugs/DB00319
• https://reference.medscape.com/drug/pipracil-piperacillin-342484
• https://www.pdr.net/drug-summary/Zosyn-piperacillin-tazobactam-629