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
- Treatment for infections brought on by gram-negative, gram-positive, and anaerobic bacteria that are susceptible:
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
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 |
|
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. |