Schedule H

Intravenous (IV) only

Powder for Injection (Lyophilised):

• Tigecycline 50 mg per vial (requires reconstitution)

Note: Tigecycline is available ONLY as injectable formulation. No oral formulation exists.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

⚠️ FDA Black Box Warning Equivalent: Increased all-cause mortality observed in meta-analyses compared to comparator antibiotics. Reserve for situations where alternative treatments are not suitable.

1. Complicated Intra-abdominal Infections (cIAI)

Parameter Dosing Details

Starting dose (Loading) 100 mg IV as single loading dose

Titration Not applicable

Usual maintenance dose 50 mg IV every 12 hours

Maximum dose 50 mg every 12 hours (standard); 100 mg every 12 hours in MDR infections (off-label)

Key Clinical Notes:

• Administer as IV infusion over 30–60 minutes

• Duration: 5–14 days based on infection severity and clinical response

• Covers Gram-positive, Gram-negative (including ESBL), and anaerobes

• Active against Enterococcus species including VRE

• NOT effective for Pseudomonas aeruginosa or Proteus species

1. Complicated Skin and Skin Structure Infections (cSSSI)

Parameter Dosing Details

Starting dose (Loading) 100 mg IV as single loading dose

Titration Not applicable

Usual maintenance dose 50 mg IV every 12 hours

Maximum dose 50 mg every 12 hours

Key Clinical Notes:

• Duration: 5–14 days

• Covers MRSA, VRE, and polymicrobial infections

• Consider for diabetic foot infections when MDR organisms suspected

• NOT first-line due to mortality concerns; use when alternatives unsuitable

1. Community-Acquired Bacterial Pneumonia (CABP)

Parameter Dosing Details

Starting dose (Loading) 100 mg IV as single loading dose

Titration Not applicable

Usual maintenance dose 50 mg IV every 12 hours

Maximum dose 50 mg every 12 hours

Key Clinical Notes:

• Duration: 7–14 days

• Use only when no suitable alternative available due to resistance pattern

• NOT recommended for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) — low serum and lung concentrations associated with poorer outcomes

• Avoid as monotherapy in severe pneumonia

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes

MDR Acinetobacter baumannii Infections (OFF-LABEL) Loading: 100 mg IV, then 100 mg IV every 12 hours (high-dose) 10–14 days Specialist/ID consultation mandatory. Often used in combination with colistin, aminoglycoside, or carbapenem (if susceptible). Evidence: Indian ICU observational studies, INICC data.

Carbapenem-Resistant Enterobacteriaceae (CRE) Infections (OFF-LABEL) Loading: 100 mg IV, then 100 mg IV every 12 hours (high-dose) Based on clinical response Specialist only. Use as part of combination therapy (with colistin, fosfomycin, or aminoglycoside). Evidence: Indian tertiary care protocols, observational data.

Severe Clostridioides difficile Infection (refractory) (OFF-LABEL) Loading: 100 mg IV, then 50 mg IV every 12 hours Until clinical improvement Specialist only. Third-line option for severe/refractory CDI. Evidence: Limited; case series and expert opinion.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

⚠️ NOT APPROVED for children in India

Tigecycline is NOT routinely approved for paediatric use due to:

• Risk of permanent tooth discoloration (yellow-grey-brown staining)

• Enamel hypoplasia

• Bone growth inhibition (tetracycline class effect)

Secondary Indications — Paediatric (Off-label)

May be considered ONLY for life-threatening MDR infections when no alternative exists

Age restriction: ≥8 years ONLY (under paediatric infectious disease specialist supervision)

8–11 years 1.2 mg/kg IV (max 50 mg) 1 mg/kg IV every 12 hours 50 mg/dose

12–17 years 1.2 mg/kg IV (max 100 mg) 1 mg/kg IV every 12 hours 50 mg/dose

≥18 years or ≥60 kg Adult dosing Adult dosing As per adult

Indications for off-label paediatric use:

• MDR Acinetobacter baumannii infections — Specialist only

• CRE infections with no alternative — Specialist only

Clear Statement: ABSOLUTELY CONTRAINDICATED below 8 years of age due to risk of permanent tooth discoloration and enamel hypoplasia. Use in children 8–17 years ONLY under paediatric infectious disease specialist supervision when no safer alternative exists.

Safety Monitoring in Children:

• Baseline and weekly LFTs

• Monitor for GI symptoms (high emesis rate)

• Document dental status before and after therapy

• CBC weekly

CRRT (CVVH/CVVHDF) No dose adjustment; monitor clinically

Note: Tigecycline is primarily eliminated via biliary/faecal route (~60%) with minimal renal excretion (~30%).

Note: Tigecycline clearance reduced by ~25% in moderate and ~55% in severe hepatic impairment. Monitor LFTs closely.

• Known hypersensitivity to tigecycline

• History of severe hypersensitivity (anaphylaxis, angioedema) to any tetracycline-class antibiotic

• Children below 8 years of age (risk of permanent tooth discoloration)

• Pregnancy (Category D — fetal harm documented)

• Increased mortality risk — FDA analysis and meta-analyses showed increased all-cause mortality versus comparator antibiotics; reserve for situations where alternatives not suitable

• NOT recommended for bloodstream infections/septicaemia — low serum concentrations result in poor outcomes; use only as part of combination therapy

• NOT recommended for HAP/VAP as monotherapy — inferior efficacy in trials; use only in combination for MDR organisms

• NOT effective against Pseudomonas aeruginosa, Proteus spp., Providencia spp., Morganella spp. — intrinsic resistance

• Severe hepatic impairment — requires dose reduction

• History of pancreatitis — tigecycline-associated pancreatitis reported; discontinue if suspected

• Prolonged use may lead to superinfection (fungal or resistant bacteria)

• High emetogenic potential — consider routine antiemetic prophylaxis

• Tetracycline class effects possible — photosensitivity, pseudotumor cerebri

• Coagulation abnormalities — may prolong PT/aPTT; monitor in patients on anticoagulants

Parameter Details

Risk Category Category D (documented fetal harm) — tetracycline class effect

Effects Crosses placenta; causes permanent tooth discoloration, enamel hypoplasia, and inhibition of bone growth in fetus

Preferred alternatives Carbapenems (meropenem), piperacillin-tazobactam, or other appropriate β-lactams based on sensitivity

When may be used ONLY for life-threatening MDR infections when no alternative exists AND benefit clearly outweighs fetal risk; specialist input mandatory

Monitoring If inadvertent exposure: detailed fetal anomaly ultrasound; maternal LFTs

Parameter Details

Compatibility NOT recommended during breastfeeding

Preferred alternatives Carbapenems, piperacillin-tazobactam (depending on infection)

Drug levels in milk Unknown; tetracycline class drugs are excreted in breast milk

Infant risks Potential for tooth discoloration, enamel hypoplasia, bone effects in nursing infant

Recommendation Discontinue breastfeeding during therapy and for 24 hours after last dose (based on half-life) OR use alternative antibiotic

Parameter Recommendation

Starting dose Standard loading dose (100 mg IV) if hepatic function preserved

Titration No specific adjustment for age alone; adjust for hepatic impairment if present

Special risks Higher incidence of nausea/vomiting; increased hepatotoxicity risk; frail elderly may have unrecognised hepatic dysfunction — monitor LFTs closely; dehydration risk from vomiting

Monitoring Baseline and serial LFTs; fluid/electrolyte status; antiemetic prophylaxis recommended

Interacting Drug Mechanism & Effect Management

Warfarin / Acenocoumarol Decreased prothrombin activity; may enhance anticoagulant effect Monitor INR closely (at baseline, day 3, and weekly); adjust anticoagulant dose as needed

Oral Contraceptives May reduce efficacy of oestrogen-containing contraceptives (tetracycline class effect) Advise additional non-hormonal contraception during therapy

Interacting Drug Effect Management

Calcineurin Inhibitors (Tacrolimus, Cyclosporine) Additive hepatotoxicity potential Monitor LFTs more frequently

Concurrent Hepatotoxic Drugs (paracetamol high-dose, ATT, azoles) Additive hepatotoxicity Monitor LFTs; avoid high-dose paracetamol

Digoxin Possible modest increase in digoxin levels (mechanism unclear) Monitor for digoxin toxicity; check levels if symptomatic

Live Vaccines Antibiotic may reduce vaccine efficacy Avoid live vaccines during therapy

Note: Tigecycline is NOT a significant CYP450 inducer or inhibitor — minimal pharmacokinetic interactions.

• Nausea (up to 26–30%) — dose-related; most common adverse effect

• Vomiting (up to 18–20%)

• Diarrhoea

• Abdominal pain

• Headache

• Elevated hepatic transaminases (AST/ALT)

• Injection site reactions (phlebitis, pain)

• Dizziness

Adverse Effect Clinical Notes

Increased All-Cause Mortality Meta-analyses showed excess mortality versus comparator antibiotics (primarily in HAP/VAP, bloodstream infections). Reserve for appropriate indications; avoid for severe sepsis monotherapy.

Acute Pancreatitis Reported cases, including fatal; discontinue immediately if pancreatitis suspected (abdominal pain, elevated amylase/lipase)

Hepatotoxicity / Hepatic Failure Elevated LFTs common; rare cases of hepatic failure and jaundice. Monitor LFTs; discontinue if significant elevation.

Severe Hypersensitivity / Anaphylaxis Rare; discontinue immediately; cross-reactivity with tetracyclines possible

Coagulopathy Prolonged PT/aPTT reported; monitor in patients on anticoagulants or with baseline coagulopathy

Superinfection C. difficile-associated diarrhoea; fungal superinfections

Photosensitivity Tetracycline class effect; advise sun protection

During treatment (Days 3–5) LFTs; INR (if on warfarin); clinical assessment for GI tolerance; signs/symptoms of pancreatitis

Weekly (if therapy >7 days) LFTs; CBC; clinical assessment for superinfection

Clinical monitoring Nausea/vomiting — consider antiemetic prophylaxis; abdominal pain (pancreatitis risk); signs of hepatotoxicity (jaundice, RUQ pain); infection control and clinical response

• Tygacil® (Pfizer) — originator (limited availability; often import)

• Tiganex® (Glenmark)

• Tygan® (Cipla)

• Ticoz® (Zydus)

• Tigefax® (Lupin)

• Tigecy® (Sun Pharma)

• Tigecyn® (Hetero)

• Tigeron® (various generics)

Note: Availability may vary; often requires hospital pharmacy procurement or import channels for originator brand.

Note: Tigecycline is NOT listed in NLEM 2022. Not under NPPA price control. Prices vary significantly between brands and may require hospital/institutional procurement.

1. Reserve antibiotic — use judiciously — Due to increased mortality signal in meta-analyses, tigecycline should be reserved for situations where no suitable alternative exists. Avoid for bloodstream infections or HAP/VAP monotherapy.

1. High emetogenic potential — Nausea/vomiting occur in up to 30% of patients. Routine antiemetic prophylaxis (ondansetron 4–8 mg IV before infusion) significantly improves tolerance.

1. Slow infusion reduces GI side effects — Administer over 30–60 minutes; faster infusion increases nausea.

1. NOT for Pseudomonas — Tigecycline has NO activity against Pseudomonas aeruginosa, Proteus, Providencia, or Morganella. Do not use empirically when these organisms are suspected.

1. High-dose for MDR organisms — Standard dosing (50 mg every 12 hours) achieves low serum levels. For MDR Acinetobacter or CRE infections, high-dose (100 mg every 12 hours) regimens are commonly used off-label in Indian ICUs, usually in combination therapy.

1. Hepatic dosing matters — Unlike most antibiotics, tigecycline requires dose reduction in moderate-severe hepatic impairment. Check Child-Pugh score and adjust accordingly.

1. Broad spectrum but bacteriostatic — Active against MRSA, VRE, ESBL, anaerobes, and atypicals, but bacteriostatic mechanism may be suboptimal for severe infections with high bacterial burden.

glycylcycline; MDR-infections; Acinetobacter; CRE; ESBL; MRSA; VRE; intra-abdominal; skin-infection; hepatic-dose-adjust; renal-safe; increased-mortality-risk; pregnancy-contraindicated; ICU-antibiotic; Schedule-H; Tigecycline

RxIndia v1.0 — 06 Jun 2025

• CDSCO Drug Database and Import Permissions

• Indian Pharmacopoeia 2022

• API Textbook of Medicine (11th Edition)

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

• ICMR-AMR Guidelines (2022)

• NCDC National Treatment Guidelines for Antimicrobial Use in Infectious Diseases

• AIIMS Antibiotic Policy (2023)

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

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th Edition)

• Indian ICU protocols for MDR infections (AIIMS, PGIMER, CMC Vellore)

• FDA Safety Communication on Tigecycline (mortality data)

• Product package insert (Tygacil®)