Schedule H

Intravenous (IV)

Form Strengths (Piperacillin + Tazobactam)

Powder for IV Injection/Infusion 4 g + 500 mg (4.5 g vial)

Powder for IV Injection/Infusion 2 g + 250 mg (2.25 g vial)

Powder for IV Injection/Infusion 1 g + 125 mg (1.125 g vial) — limited availability

Reconstitution Note: Reconstitute with Sterile Water for Injection, Normal Saline, or 5% Dextrose. Administer as IV infusion over 30 minutes (standard) or 3–4 hours (extended infusion for severe infections).

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Nosocomial Pneumonia (Including Ventilator-Associated Pneumonia)

Adults:

Parameter Recommendation

Starting dose 4.5 g IV every 8 hours

Titration Increase frequency to every 6 hours for severe infections or high bacterial load

Usual maintenance dose 4.5 g IV every 6–8 hours

Maximum dose 4.5 g IV every 6 hours (18 g piperacillin/day)

Duration 7–14 days; guided by clinical response and cultures

Clinical Note: Combine with aminoglycoside or fluoroquinolone for suspected Pseudomonas aeruginosa infection. Not effective against MRSA — add vancomycin/linezolid if suspected.

1. Complicated Intra-Abdominal Infections (cIAI)

Adults:

Parameter Recommendation

Starting dose 4.5 g IV every 8 hours

Titration Increase to every 6 hours for severe peritonitis or sepsis

Usual maintenance dose 4.5 g IV every 6–8 hours

Maximum dose 4.5 g IV every 6 hours

Duration 4–7 days following adequate source control; extend if source control incomplete

Clinical Note: Provides coverage for gram-negative aerobes, gram-positive organisms, and anaerobes. Adequate surgical source control is essential.

1. Complicated Urinary Tract Infections (cUTI) / Pyelonephritis

Adults:

Parameter Recommendation

Starting dose 4.5 g IV every 8 hours

Titration Not routinely required

Usual maintenance dose 4.5 g IV every 8 hours

Maximum dose 4.5 g IV every 6 hours (in severe urosepsis)

Duration 7–14 days; step-down to oral therapy when clinically stable

1. Complicated Skin and Soft Tissue Infections (Including Diabetic Foot Infections)

Adults:

Parameter Recommendation

Starting dose 4.5 g IV every 8 hours

Titration Increase to every 6 hours for severe necrotising infections

Usual maintenance dose 4.5 g IV every 6–8 hours

Maximum dose 4.5 g IV every 6 hours

Duration 7–14 days for soft tissue infections; 2–4 weeks for osteomyelitis component in diabetic foot

Clinical Note: Add MRSA coverage (vancomycin/linezolid) if risk factors present. Surgical debridement critical for necrotising infections.

1. Febrile Neutropenia (Empirical Therapy in High-Risk Patients)

Adults:

Parameter Recommendation

Starting dose 4.5 g IV every 6 hours

Titration Not applicable

Usual maintenance dose 4.5 g IV every 6 hours

Maximum dose 4.5 g IV every 6 hours

Duration Until neutrophil recovery (ANC >500/µL) and afebrile for ≥48 hours; minimum 7 days

Clinical Note: Preferred empirical monotherapy for febrile neutropenia per AIIMS and Tata Memorial protocols. Add aminoglycoside if septic shock or suspected resistant Pseudomonas. Add vancomycin if catheter-related infection or skin/soft tissue focus suspected.

1. Sepsis / Septic Shock (Empirical Therapy for Healthcare-Associated Infections)

Adults:

Parameter Recommendation

Starting dose 4.5 g IV every 6 hours

Titration Not applicable

Usual maintenance dose 4.5 g IV every 6 hours

Maximum dose 4.5 g IV every 6 hours

Duration 7–14 days; de-escalate based on culture results

Clinical Note: Appropriate for suspected gram-negative sepsis including ESBL-producers (if local susceptibility >90%). Consider extended infusion (4 hours) for severe sepsis to optimise pharmacodynamics.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Nosocomial Pneumonia / Complicated Intra-Abdominal Infections / Complicated Skin and Soft Tissue Infections

Weight-Based Dosing (≥2 months to <40 kg):

Parameter Recommendation

Starting dose 80 mg/kg (piperacillin component) IV

Titration May increase to 100 mg/kg/dose for severe infections

Usual maintenance dose 80–100 mg/kg (piperacillin component) every 6–8 hours

Maximum single dose 4 g piperacillin (4.5 g Pip-Tazo)

Maximum daily dose 16 g piperacillin/day (300–400 mg/kg/day)

Duration As per indication; typically 7–14 days

Dosing Table by Weight:

5 kg 400–500 mg (Pip component) Every 8 hours

10 kg 800–1000 mg (Pip component) Every 8 hours

20 kg 1.6–2 g (Pip component) Every 6–8 hours

30 kg 2.4–3 g (Pip component) Every 6–8 hours

≥40 kg Adult dosing (4.5 g) Every 6–8 hours

1. Febrile Neutropenia (Empirical Therapy)

Children ≥2 months:

Parameter Recommendation

Starting dose 80–100 mg/kg (piperacillin component) IV

Titration Not applicable

Usual maintenance dose 80–100 mg/kg every 6 hours

Maximum single dose 4.5 g

Maximum daily dose 18 g piperacillin/day

Duration Until ANC recovery and afebrile ≥48 hours

Clinical Note: Preferred empirical monotherapy for paediatric febrile neutropenia at major oncology centres. Add aminoglycoside if haemodynamically unstable.

1. Sepsis / Severe Bacterial Infections

Neonates (Specialist supervision mandatory):

Age Dose (Piperacillin component) Frequency

<7 days, <2 kg 50 mg/kg Every 12 hours

<7 days, ≥2 kg 50 mg/kg Every 8 hours

7–28 days, <2 kg 50 mg/kg Every 8 hours

7–28 days, ≥2 kg 50 mg/kg Every 6 hours

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Notes

Cystic Fibrosis Pulmonary Exacerbations 90–100 mg/kg (Pip component) every 6 hours 14–21 days OFF-LABEL. Specialist only. Anti-pseudomonal coverage required. Maximum 18 g/day

Age Restrictions and Safety Monitoring

Age Group Recommendation

<2 months Not recommended except under specialist supervision in NICU setting

2 months–12 years Weight-based dosing; requires paediatric infectious disease input for complex infections

≥12 years and ≥40 kg Adult dosing appropriate

Safety Monitoring in Paediatrics:

• Renal function monitoring (serum creatinine)

• Electrolytes (particularly potassium)

• CBC with differential if therapy >7 days

• Signs of hypersensitivity or infusion reactions

• Monitor IV site for phlebitis

Dose adjustment required based on creatinine clearance:

CrCl (mL/min) Dose Recommendation

40 4.5 g IV every 6–8 hours (no adjustment)

20–40 4.5 g IV every 8 hours

<20 2.25 g IV every 8 hours

Haemodialysis 2.25 g IV every 8 hours + supplemental dose of 2.25 g after each dialysis session

CAPD 2.25 g IV every 12 hours

CRRT (CVVH/CVVHD/CVVHDF) 4.5 g IV every 8 hours (adjust based on effluent rate and clinical response)

Clinical Note: Calculate CrCl using Cockcroft-Gault formula. In elderly patients, serum creatinine may underestimate renal impairment.

Note: Hepatic elimination is minimal. Main concern is coagulopathy risk in patients with advanced liver disease.

• Known hypersensitivity to piperacillin, tazobactam, or any penicillin

• History of severe hypersensitivity reaction (anaphylaxis, angioedema) to any beta-lactam antibiotic (penicillins, cephalosporins, carbapenems)

• History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam use

• History of non-severe penicillin or cephalosporin allergy — monitor closely for allergic reactions (cross-reactivity risk 1–2%)

• Renal impairment — dose adjustment essential to prevent drug accumulation, neurotoxicity, and seizures

• Pre-existing seizure disorder — high doses may lower seizure threshold; maintain appropriate dosing for renal function

• Concurrent nephrotoxic agents (aminoglycosides, vancomycin, NSAIDs, amphotericin B) — monitor renal function closely

• History of Clostridioides difficile infection or antibiotic-associated colitis

• Sodium load — each 4.5 g vial contains approximately 216 mg (9.4 mEq) sodium; use cautiously in patients with heart failure, cirrhosis, or sodium restriction

• Bleeding disorders or concurrent anticoagulation — may prolong bleeding time

• Prolonged therapy (>14 days) — increased risk of superinfection, haematological abnormalities

Parameter Recommendation

Overall safety Generally considered safe; widely used in pregnancy for severe infections

Risk category Category B (US legacy); no formal India classification

Preferred alternatives None required for severe infections; Pip-Tazo preferred when broad-spectrum IV coverage needed

When to use Appropriate for serious infections including pyelonephritis, chorioamnionitis, postpartum sepsis

Monitoring Maternal renal function, LFTs in prolonged courses; standard foetal monitoring

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low; minimal systemic absorption by infant expected

Preferred alternatives None required; acceptable during breastfeeding

Infant monitoring Observe for loose stools, oral thrush, or rash; temporary GI disturbance possible but usually mild

Parameter Recommendation

Starting dose 4.5 g IV every 8 hours (if renal function normal)

Titration Not applicable

Renal consideration Calculate CrCl; age-related decline in renal function common even with normal serum creatinine; dose reduce per renal adjustment table

Specific risks Increased susceptibility to nephrotoxicity, electrolyte disturbances (hypokalaemia), bleeding, and confusion/encephalopathy at higher doses

Monitoring Renal function before and during therapy; electrolytes; signs of neurotoxicity

Drug Interaction Recommendation

Methotrexate Reduced renal clearance of methotrexate → increased risk of haematological and GI toxicity AVOID combination if possible; if essential, monitor methotrexate levels and CBC closely; consider leucovorin rescue

Probenecid Inhibits tubular secretion → increased and prolonged piperacillin levels Avoid concurrent use; if used together, monitor for toxicity

Neuromuscular blocking agents (Vecuronium, Rocuronium, Atracurium) Prolonged neuromuscular blockade reported with aminopenicillins Monitor neuromuscular function closely; may require dose adjustment of paralytic agent

Oral anticoagulants (Warfarin, Acenocoumarol) Enhanced anticoagulant effect; mechanism includes vitamin K suppression via gut flora alteration Monitor INR closely during and after Pip-Tazo course; adjust anticoagulant dose as needed

Drug Interaction Recommendation

Aminoglycosides (Amikacin, Gentamicin, Tobramycin) Synergistic antibacterial effect but physical incompatibility if mixed; additive nephrotoxicity Administer via separate IV lines; never mix in same bag; monitor renal function and aminoglycoside levels

Vancomycin Increased risk of acute kidney injury when used in combination Monitor renal function every 24–48 hours; ensure adequate hydration; consider alternative if renal function deteriorating

Loop diuretics (Furosemide) Potential increased nephrotoxicity Monitor renal function; generally safe with hydration

Heparin Potential additive effect on bleeding time Monitor for bleeding; use standard coagulation monitoring

Phenytoin Possible decreased phenytoin levels Monitor phenytoin levels if used concurrently

• Diarrhoea (most frequent)

• Nausea and vomiting

• Skin rash (maculopapular)

• Injection site reactions (phlebitis, pain)

• Headache

• Insomnia

• Hypokalaemia

• Transient elevation of liver enzymes (AST, ALT)

• Fever

• Positive direct Coombs test (without haemolysis)

Adverse Effect Clinical Notes

Anaphylaxis Rare; discontinue immediately; manage with adrenaline and supportive care

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Very rare; discontinue immediately; requires hospitalisation

Clostridioides difficile-associated diarrhoea (CDAD) May occur during or after therapy; discontinue Pip-Tazo if confirmed; treat with oral vancomycin or fidaxomicin

Acute interstitial nephritis Presents with fever, rash, eosinophilia, rising creatinine; discontinue and consider corticosteroids

Haematological toxicity (Thrombocytopenia, Leucopenia, Neutropenia) Usually with prolonged therapy (>14 days); monitor CBC weekly; typically reversible on discontinuation

Seizures Risk increased with high doses, renal impairment, or pre-existing CNS disease; ensure appropriate dose adjustment

Coagulopathy Vitamin K-dependent; more common with prolonged use or malnutrition; monitor PT/INR

Drug-induced liver injury Rare; cholestatic pattern; monitor LFTs if symptomatic

Phase Parameters

Baseline Serum creatinine, eGFR/CrCl, LFTs, CBC with differential, electrolytes (especially potassium), allergy history

During treatment (short course <7 days) Renal function (every 2–3 days in ICU/high-risk patients); clinical response; signs of hypersensitivity

During treatment (≥7 days) CBC weekly; LFTs weekly; renal function every 2–3 days; electrolytes (K+)

Prolonged therapy (>14 days) As above + coagulation profile (PT/INR); watch for superinfection (oral thrush, C. difficile); neurotoxicity signs

If on concomitant nephrotoxins Renal function daily or alternate days

Brand Name Manufacturer

Tazact Cipla

Pipzo Dr. Reddy's

Zosyn Pfizer

Piptaz Aristo

Tazopen Alkem

Pipracil Plus Lupin

Tazofast Hetero

Piperacillin + Tazobactam (Generic) Multiple manufacturers

Government/Jan Aushadhi Supply: Available under generic names at subsidised rates

4.5 g vial (Private brands) ₹150–₹350

4.5 g vial (Jan Aushadhi/Government supply) ₹50–₹100

2.25 g vial (Private brands) ₹80–₹180

2.25 g vial (Jan Aushadhi/Government supply) ₹30–₹60

Regulatory Note: Listed under NLEM 2022. NPPA price-controlled for scheduled formulations. Available through government hospital pharmacies and Jan Aushadhi kendras.

1. Extended infusion strategy: For severe infections (sepsis, VAP, febrile neutropenia), administer each dose over 3–4 hours instead of standard 30 minutes. This optimises time above MIC and improves pharmacodynamic outcomes. Widely adopted in Indian ICUs.

1. Spectrum limitations: Pip-Tazo does NOT cover MRSA, VRE, carbapenem-resistant Enterobacteriaceae (CRE), or Stenotrophomonas maltophilia. Add appropriate agents if these are suspected.

1. ESBL coverage caveat: Effective against many ESBL-producing organisms, but MIC creep reported. Use only if local antibiogram shows susceptibility >90%. Carbapenems preferred for serious ESBL infections with sepsis.

1. Sodium load awareness: Each 4.5 g vial contains ~9.4 mEq sodium. In patients receiving every-6-hour dosing, daily sodium from Pip-Tazo alone exceeds 37 mEq. Adjust total sodium intake in heart failure and cirrhosis.

1. De-escalation imperative: Pip-Tazo is a broad-spectrum reserve antibiotic. Always review cultures at 48–72 hours and de-escalate to narrower-spectrum agent when susceptibilities available. This aligns with ICMR AMR stewardship recommendations.

1. Vancomycin combination nephrotoxicity: Recent evidence shows increased AKI risk with Pip-Tazo + Vancomycin compared to other beta-lactam + vancomycin combinations. Use with close renal monitoring and consider alternatives if renal function declines.

piperacillin-tazobactam; beta-lactam; antipseudomonal; hospital-acquired-infection; febrile-neutropenia; sepsis; ESBL; renal-adjustment; NLEM-India; Schedule-H; ICU-antibiotic

RxIndia v1.0 — 30 Apr 2025

• CDSCO Drug Database and Product Inserts

• Indian Pharmacopoeia 2022

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine (11th Edition)

• AIIMS Antimicrobial Guidelines 2022

• ICMR Treatment Guidelines for Antimicrobial Use in Common Syndromes (2019)

• ICMR Antimicrobial Resistance Surveillance Network Reports

• Tata Memorial Hospital Febrile Neutropenia Protocols

• IAP Guidelines for Paediatric Antimicrobial Use

• Harrison's Principles of Internal Medicine (21st Edition)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics