Sigmazidim (Ceftazidime) 500 mg & 1 g Vials for I.V./I.M. Injection
1. Disclaimer
This monograph is compiled for educational and professional information purposes for healthcare practitioners. It is not an alternative to the official package insert, clinical evaluation, or direct medical consultation. Ceftazidime is a parenteral, prescription-only antimicrobial requiring qualified medical supervision for prescription, reconstitution, and administration. Dosage must be tailored to the infection type, pathogen susceptibility, regional resistance trends, and patient renal clearance.
We do not guarantee the accuracy, currency or completeness of information regarding medications or medical products, and official sources should be verified before making any decisions. Readers are responsible for independently verifying the information before relying on it.
Excipients, formulation details, package configurations, and approved therapeutic indications can vary across countries and manufacturers; the Egyptian Drug Authority (EDA)-authorized leaflet accompanying the physical pack remains the primary authority for this brand.
2. Summary
Sigmazidim is an Egyptian commercial formulation of ceftazidime (supplied as ceftazidime pentahydrate), a third-generation parenteral cephalosporin available as sterile powder in 500 mg and 1 g vials for intravenous or intramuscular administration. Its primary clinical hallmark among cephalosporins is robust anti-pseudomonal coverage combined with broad-spectrum activity against Gram-negative bacilli and stability against many chromosomal beta-lactamases.
It exhibits bactericidal activity, undergoes no significant hepatic metabolism, and is cleared unchanged via glomerular filtration; consequently, dosage adjustment in renal impairment is vital and represents the foremost safety parameter. Standard adult regimens range from 1 to 2 g every 8 hours, expanding to 2 g every 8 hours in severe pathology and 100–150 mg/kg/day in cystic fibrosis (with doses up to 9 g daily utilized in adults with preserved renal function). Its key spectrum limitations include modest Gram-positive coverage, lack of activity against anaerobes (notably Bacteroides fragilis), enterococci, and MRSA, alongside susceptibility to degradation by extended-spectrum beta-lactamases (ESBLs).
3. Brand Name
Sigmazidim 500 mg vial for I.V./I.M. injection; Sigmazidim 1 g vial for I.V./I.M. injection.
International proprietary brand equivalents containing the identical molecule include Fortum, Fortaz, Tazicef, and Kefadim. Other ceftazidime brands authorized in Egypt include Fortum and Cefidime.
4. Category
Systemic antibacterial — Beta-lactam, third-generation anti-pseudomonal cephalosporin.
ATC Classification: J01DD02.
Legal Category: Prescription-only parenteral medicine for hospital and clinical administration.
5. Active Ingredient
Ceftazidime (as ceftazidime pentahydrate), delivering 500 mg or 1 g of active ceftazidime base per vial.
The sole inactive excipient is anhydrous sodium carbonate (approximately 118 mg per gram of active ceftazidime), which functions as a solubilising buffer. During reconstitution, it reacts to generate carbon dioxide, causing effervescence and internal positive pressure. Consequently, each gram of ceftazidime provides approximately 52 mg (2.26 mmol or ~2.3 mEq) of sodium (~2.6% of the WHO recommended adult daily limit per gram), an important consideration in sodium-restricted regimens and heart failure. The product contains no preservatives and is intended for single-dose use.
6. Pharmaceutical Form & Strength
Pharmaceutical Form: Sterile white to cream-coloured crystalline powder for solution for injection or infusion, presented in clear Type I glass vials (500 mg and 1 g), packaged with solvent ampoule(s).
Reconstituted Appearance: Clear solution ranging from pale yellow to light amber depending on concentration and diluent, without indicating loss of potency.
pH: Freshly reconstituted solutions exhibit a pH of approximately 5.0 to 8.0.
7. Manufacturer & Marketing Authorization Holder
Manufacturer: Sigma-Tec Pharmaceutical Industries S.A.E., Egypt (Sigma Group).
Marketing Distributor: Marketed in Egypt through the Pharco Group of Companies.
Registration details, pricing schedules, and packaging authorizations are periodically revised by the Egyptian Drug Authority (EDA).
8. Mechanism of Action
Ceftazidime exerts bactericidal activity by traversing Gram-negative outer membrane porins and binding covalently to essential penicillin-binding proteins (primarily PBP3 in Gram-negative bacilli). This inhibits the final transpeptidation cross-linking of bacterial peptidoglycan, resulting in cell wall weakening, osmotic lysis, and bacterial death.
Its antimicrobial killing is time-dependent; the primary pharmacodynamic driver correlating with clinical cure is the duration that free drug concentrations remain above the minimum inhibitory concentration (%fT > MIC), providing the scientific basis for 8-hourly dosing, prolonged infusions, or continuous infusions in severe sepsis. Resistance mechanisms include beta-lactamase hydrolysis (ESBLs, derepressed AmpC enzymes, carbapenemases), altered PBP affinities, porin loss, and multidrug efflux pumps.
9. Spectrum of Activity
The antibacterial spectrum predominantly targets aerobic Gram-negative bacilli:
- Susceptible Organisms: Pseudomonas aeruginosa (the defining distinction over ceftriaxone/cefotaxime), Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Neisseria meningitidis, Proteus mirabilis, Providencia spp., Citrobacter koseri, Pasteurella multocida, Streptococcus pyogenes, and Streptococcus agalactiae.
- Species with Potential Acquired Resistance: Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter freundii, Serratia spp., Morganella morganii, Acinetobacter baumannii, and Burkholderia cepacia.
- Inherently Inactive / Gaps: MRSA, Enterococci, Listeria monocytogenes, Clostridioides difficile, and anaerobes such as Bacteroides fragilis.
In vitro synergy is often observed with aminoglycosides. When anaerobic involvement is suspected, an agent like metronidazole must be co-prescribed. Current EUCAST interpretative criteria establish breakpoints of S ≤ 1 mg/L and R > 4 mg/L for Enterobacterales, while wild-type P. aeruginosa is categorized under increased exposure (requiring 2 g every 8 hours).
10. Pharmacokinetics
- Absorption: Complete bioavailability following intramuscular administration; peak serum levels reach 17–18 mg/L (500 mg dose) and 37–39 mg/L (1 g dose) at ~1 hour. Rapid 5-minute IV bolus yields peaks of ~45 mg/L (500 mg) and ~90 mg/L (1 g), while a 2 g IV infusion achieves ~170 mg/L.
- Distribution: Low serum protein binding (<10%). Widely distributed into bone, cardiac tissue, bile, sputum, aqueous humor, synovial fluid, and peritoneal fluid. CSF penetration is minimal through intact meninges but achieves 4–20 mg/L or higher during active meningeal inflammation. Crosses the placenta and distributes into breast milk in small quantities.
- Metabolism & Elimination: Unmetabolized. Approximately 80–90% of the dose is cleared unchanged in urine within 24 hours via glomerular filtration. Elimination half-life is ~1.9–2.0 hours in healthy adults, prolonged 3- to 4-fold in neonates ≤2 months, and substantially extended in renal impairment.
11. Indications
Indicated for the management of infections caused by susceptible pathogens in adults, children, and neonates:
- Nosocomial (hospital-acquired) pneumonia.
- Broncho-pulmonary infections in cystic fibrosis.
- Acute bacterial meningitis.
- Chronic suppurative otitis media and malignant otitis externa.
- Complicated urinary tract infections (including pyelonephritis).
- Complicated skin and soft tissue infections.
- Complicated intra-abdominal and biliary tract infections.
- Bone and joint infections.
- Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD).
- Empirical therapy for febrile neutropenia and associated bacteremia.
- Perioperative prophylaxis during transurethral resection of the prostate (TURP).
12. Administration
Administration Routes: Administered primarily via intravenous injection or infusion. Deep intramuscular injection into a large muscle mass is reserved for situations where intravenous access is unavailable. Intra-arterial administration must be strictly avoided due to risk of distal necrosis.
Standard Dosage Guidelines:
- Adults & Children ≥40 kg: 1–6 g daily. Standard infections/UTIs: 500 mg–1 g every 12 hours or 1–2 g every 8 hours. Severe infections, febrile neutropenia, meningitis, and nosocomial pneumonia: 2 g every 8 hours. Cystic fibrosis: 100–150 mg/kg/day divided every 8 hours (maximum 9 g/day). Continuous infusion: 2 g loading dose followed by 4–6 g/24 hours.
- Children >2 months and <40 kg: 100–150 mg/kg/day divided every 8 hours (maximum 6 g/day).
- Neonates & Infants ≤2 months: 25–60 mg/kg/day divided into 2 equal doses (every 12 hours).
- Elderly (>80 years): Daily dosage should generally not exceed 3 g.
Renal Impairment Dosage Adjustments (Adults ≥40 kg): Initial 1 g loading dose, followed by maintenance based on creatinine clearance:
| Creatinine Clearance (mL/min) | Serum Creatinine Approx. µmol/L (mg/dL) | Recommended Unit Dose | Dosing Interval (Hours) |
|---|---|---|---|
| >50 | <150 (<1.7) | Standard Dose | — |
| 50–31 | 150–200 (1.7–2.3) | 1.0 g | Every 12 hours |
| 30–16 | 200–350 (2.3–4.0) | 1.0 g | Every 24 hours |
| 15–6 | 350–500 (4.0–5.6) | 0.5 g | Every 24 hours |
| <5 | >500 (>5.6) | 0.5 g | Every 48 hours |
Continuous Renal Replacement Therapy (CRRT) Adjustments:
Continuous Veno-Venous Haemofiltration (CVVH) — Maintenance Dose (mg) Every 12 Hours:
| Residual CrCl (mL/min) | Ultrafiltration 5 mL/min | Ultrafiltration 16.7 mL/min | Ultrafiltration 33.3 mL/min | Ultrafiltration 50 mL/min |
|---|---|---|---|---|
| 0 | 250 mg | 250 mg | 500 mg | 500 mg |
| 5 | 250 mg | 250 mg | 500 mg | 500 mg |
| 10 | 250 mg | 500 mg | 500 mg | 750 mg |
| 15 | 250 mg | 500 mg | 500 mg | 750 mg |
| 20 | 500 mg | 500 mg | 500 mg | 750 mg |
Continuous Veno-Venous Haemodialysis (CVVHD) — Maintenance Dose (mg) Every 12 Hours:
| Residual CrCl (mL/min) | Dialysate 1 L/h, UF 0.5 | Dialysate 1 L/h, UF 1.0 | Dialysate 1 L/h, UF 2.0 | Dialysate 2 L/h, UF 0.5 | Dialysate 2 L/h, UF 1.0 | Dialysate 2 L/h, UF 2.0 |
|---|---|---|---|---|---|---|
| 0 | 500 mg | 500 mg | 500 mg | 500 mg | 500 mg | 750 mg |
| 5 | 500 mg | 500 mg | 750 mg | 500 mg | 500 mg | 750 mg |
| 10 | 500 mg | 500 mg | 750 mg | 500 mg | 750 mg | 1000 mg |
| 15 | 500 mg | 750 mg | 750 mg | 750 mg | 750 mg | 1000 mg |
| 20 | 750 mg | 750 mg | 1000 mg | 750 mg | 750 mg | 1000 mg |
13. Method of Preparation
Because carbon dioxide is released upon dissolving, vials develop positive pressure. Reconstitution volumes and approximate resulting concentrations:
| Vial Strength | Intended Route | Diluent Volume Added | Approximate Final Concentration |
|---|---|---|---|
| 500 mg | Intramuscular (I.M.) | 1.5 mL | ~260 mg/mL |
| 500 mg | Intravenous Bolus | 5.0 mL | ~90 mg/mL |
| 1.0 g | Intramuscular (I.M.) | 3.0 mL | ~260 mg/mL |
| 1.0 g | Intravenous Bolus | 10.0 mL | ~90 mg/mL |
| 1.0 g | Intravenous Infusion | 50.0 mL | ~20 mg/mL |
For IM injection, 0.5% or 1% lidocaine HCl may be used as diluent to reduce local pain (never inject lidocaine IV). For IV infusions, add 10 mL diluent first, dissolve completely, vent with a gas-relief needle, and then add remaining infusion volume. Compatible IV fluids include 0.9% NaCl, 5% or 10% Dextrose, Hartmann's solution, and Dextran solutions. Do not mix in the same syringe or infusion line with aminoglycosides or vancomycin.
14. Contraindications
- Hypersensitivity to ceftazidime, other cephalosporins, or sodium carbonate.
- History of severe, immediate hypersensitivity reactions (anaphylaxis) to any beta-lactam antibiotic (penicillins, carbapenems, monobactams).
- Known hypersensitivity to aztreonam, as ceftazidime and aztreonam share an identical R1 side chain, causing direct clinical cross-reactivity.
15. Warnings & Precautions
- Hypersensitivity & Anaphylaxis: Serious and fatal allergic reactions can occur. Immediate cessation and emergency intervention (epinephrine, airway management, IV fluids) are required upon occurrence.
- Severe Cutaneous Reactions (SCARs): SJS, TEN, DRESS, and AGEP have been reported. Permanently discontinue therapy if skin reactions emerge.
- Neurotoxicity Risk: Failure to reduce dosage in renal impairment results in elevated blood levels leading to myoclonus, asterixis, seizures, encephalopathy, and coma.
- Clostridioides difficile Colitis: Antibiotic-associated colitis ranging from mild diarrhea to fatal pseudomembranous colitis may develop during or after therapy.
- Resistance Selection: Inducible AmpC beta-lactamase derepression in Enterobacter, Citrobacter, and Pseudomonas can lead to treatment failure.
- Sodium Load: Contains 52 mg sodium per gram of drug, requiring caution in patients with congestive heart failure or strict sodium restrictions.
16. Drug Interactions
- Nephrotoxic Agents: Concomitant use with aminoglycosides or potent loop diuretics (e.g., furosemide) increases the risk of renal impairment; renal monitoring is advised.
- Chloramphenicol: In vitro antagonism exists; avoid combination when bactericidal action is essential.
- Laboratory Test Interferences: May produce false-positive urinary glucose results with copper reduction tests (Benedict's, Fehling's, Clinitest); use enzymatic glucose oxidase methods. Causes a positive direct Coombs' test in ~5% of patients, potentially confounding blood cross-matching.
- Live Vaccines: May attenuate the immune response to live oral typhoid and bacterial vaccines.
17. Side Effects
- Common (≥1/100 to <1/10): Phlebitis/thrombophlebitis at IV site, pain/inflammation at IM site, diarrhea, maculopapular/urticarial rash, eosinophilia, thrombocytosis, transient transaminase elevations (ALT, AST, LDH, GGT, ALP), positive Coombs' test.
- Uncommon (≥1/1,000 to <1/100): Candidiasis, leukopenia, neutropenia, thrombocytopenia, headache, dizziness, nausea, vomiting, abdominal pain, elevations in BUN and serum creatinine.
- Rare to Unknown Frequency: Anaphylaxis, angioedema, interstitial nephritis, acute renal failure, hemolytic anemia, agranulocytosis, SCARs (SJS/TEN), and neurotoxicity in unadjusted renal impairment.
18. Use in Special Populations
Pregnancy: Animal reproduction models demonstrate no teratogenicity. Clinical human data are limited; use only when clinically indicated and expected benefits outweigh potential risks.
Breastfeeding: Ceftazidime is excreted in breast milk in small concentrations (relative infant dose <1%). Compatible with breastfeeding; observe infant for loose stools or oral thrush.
Pediatrics: Authorized from birth with weight-adjusted dosing. Neonates (≤2 months) exhibit prolonged clearance half-lives.
Elderly: Age-associated reductions in renal clearance require dose reduction, typically not exceeding 3 g/day in patients over 80 years.
Renal Impairment: Mandatory dosage reduction based on creatinine clearance (see detailed dosage tables).
Hepatic Impairment: No dosage adjustment is necessary if renal clearance is preserved.
19. Storage Conditions
Store unopened vials at temperatures not exceeding 30 °C, protected from light in the original carton. Keep out of reach of children. Reconstituted solutions should ideally be administered immediately; if storage is unavoidable, follow hospital aseptic guidelines and local leaflet instructions (generally stable for up to 12 hours at room temperature or 3 days refrigerated).
20. Additional Sections
Packaging Configurations: 500 mg pack includes 1 vial + one 5 mL solvent ampoule; 1 g pack includes 1 vial + two 5 mL solvent ampoules.
Overdose Management: Manifests primarily as neurotoxicity and seizures in renal failure. Ceftazidime is dialyzable; hemodialysis accelerates clearance.
Antimicrobial Stewardship: Classified under the WHO AWaRe Watch Group. Empirical use should be guided by local susceptibility patterns and de-escalated following culture results.
Patient Counseling: Administered parenterally by medical staff. Patients should promptly report severe diarrhea, skin rashes, respiratory distress, facial swelling, or neuromuscular twitching.
21. Frequently Asked Questions (FAQ)
How does Sigmazidim differ from ceftriaxone?
Ceftazidime provides reliable bactericidal coverage against Pseudomonas aeruginosa, whereas ceftriaxone lacks anti-pseudomonal activity. Ceftriaxone offers superior Gram-positive activity and once-daily dosing, whereas ceftazidime is typically dosed every 8 hours.
Can Sigmazidim be injected intramuscularly?
Yes, via deep intramuscular injection into a large muscle mass. Reconstitution with 0.5%–1% lidocaine HCl alleviates injection pain (lidocaine solutions must never be given IV).
Why does the vial exhibit effervescence during reconstitution?
Sodium carbonate in the formulation releases carbon dioxide as the powder dissolves, generating internal positive pressure. This is normal and expected.
Is dose reduction required in renal impairment?
Yes, it is mandatory. Ceftazidime is cleared predominantly by the kidneys; failure to reduce the dose in renal disease can precipitate neurotoxicity, encephalopathy, and seizures.
Can it be mixed directly with aminoglycosides?
No. Ceftazidime and aminoglycosides are chemically incompatible and form precipitates; they must be infused separately with line flushes in between.
Does ceftazidime cover MRSA or anaerobes?
No. It lacks activity against MRSA (requiring agents like vancomycin) and Bacteroides fragilis (requiring anaerobic cover such as metronidazole).
Why does the reconstituted solution appear yellowish?
The solution naturally ranges from light yellow to amber depending on concentration and storage; this does not indicate loss of potency.
22. References
- Ceftazidime 1 g and 2 g Powder for Solution for Injection/Infusion — Summary of Product Characteristics (SmPC), Electronic Medicines Compendium (emc).
- DailyMed / U.S. FDA — Ceftazidime for Injection USP and FORTAZ Prescribing Information.
- British National Formulary (BNF) & BNF for Children — Ceftazidime Monograph.
- LactMed Database — Ceftazidime Maternal and Infant Safety Data.
- EUCAST — European Committee on Antimicrobial Susceptibility Testing Breakpoint Tables.
- ISPD Guidelines — Peritoneal Dialysis-Related Infections Recommendations (2022 Update).
- WHO AWaRe Antibiotic Categorization Framework.
- Egyptian Drug Authority (EDA) — Sigmazidim Registered Product Data and Authorized Insert, Sigma-Tec Pharmaceutical Industries S.A.E.