Ampicillin + Sulbactam: Indication, Dosage, Side Effect, Precaution

This information is not country-specific. Please refer to the Indonesia prescribing information.

Generic Medicine Info

Indications and Dosage

Intramuscular, Intravenous
Bacterial septicaemia, Bone and joint infections, Gynaecological infections, Intra-abdominal infections, Lower respiratory tract infections, Pyelonephritis, Skin and skin structure infections, Upper respiratory tract infections, Urinary tract infection

Adult: Available preparations:
Ampicillin 250 mg and sulbactam 125 mg powder for solution for inj or infusion
Ampicillin 500 mg and sulbactam 250 mg powder for solution for inj or infusion
Ampicillin 1,000 mg and sulbactam 500 mg powder for solution for inj or infusion
Ampicillin 2,000 mg and sulbactam 1,000 mg powder for solution for inj or infusion

Recommended dose is expressed as a total of ampicillin/sulbactam combination. Dosage is individualised based on the type or severity of the infection and renal function of the patient. Usual dose range: 1,500-12,000 mg daily in divided doses 6 or 8 hourly via IV inj or IV infusion over 15-30 minutes, or via deep IM inj. Max: 4,000 mg sulbactam daily. In less severe cases, doses may be given 12 hourly. Treatment duration: 5-14 days, may be extended (or additional ampicillin may be given) in severely ill cases.
Child: Available preparations:
Ampicillin 250 mg and sulbactam 125 mg powder for solution for inj or infusion
Ampicillin 500 mg and sulbactam 250 mg powder for solution for inj or infusion
Ampicillin 1,000 mg and sulbactam 500 mg powder for solution for inj or infusion
Ampicillin 2,000 mg and sulbactam 1,000 mg powder for solution for inj or infusion

Neonates, infants, children 150 mg/kg daily (corresponding to 100 mg ampicillin/kg/day and 50 mg sulbactam/kg/day) in divided doses 6 or 8 hourly via IV inj or IV infusion over 15-30 minutes, or via deep IM inj. Neonates During the 1st week of life (particularly preterms): 75 mg/kg daily (corresponding to 50 mg ampicillin/kg/day and 25 mg sulbactam/kg/day) in divided doses 12 hourly. Alternatively, for skin infections: ≥1 year 300 mg/kg daily (corresponding to 200 mg ampicillin/kg/day and 100 mg sulbactam/kg/day) via IV infusion in divided doses 6 hourly for up to 14 days; ≥40 kg: Same as adult dose. Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).

Intramuscular, Intravenous
Prophylaxis of surgical infections

Intramuscular, Intravenous
Uncomplicated gonorrhoea

Renal Impairment

Intra-abdominal infections; Skin and skin structure infections; Bone and joint infections; Gynaecological infections; Upper and lower respiratory tract infections; Urinary tract infections; Pyelonephritis; Bacterial septicaemia; Prophylaxis of surgical infections:

CrCl (mL/min)	Dosage
≤30	Less frequent dose administration may be required (refer to detailed product guideline).

Reconstitution

Initially, reconstitute vial with the appropriate volume of sterile water for inj or any compatible diluent (e.g. 0.5% or 2% lidocaine hydrochloride may also be used for IM inj) to yield a final concentration of 375 mg/mL (250 mg ampicillin/125 mg sulbactam per mL). For IV infusion: Further dilute the reconstituted solution with a compatible diluent. Refer to specific product guidelines for further information on reconstitution.

Incompatibility

Incompatible with blood products or protein hydrolysates; aminoglycosides (avoid mixing in the same container or concurrent Y-site administration; reconstitute and administer separately).

Contraindications

Hypersensitivity (e.g. anaphylaxis, Stevens-Johnson syndrome [SJS]) to ampicillin, sulbactam, or β-lactam antibiotics (e.g. penicillins, cephalosporins). History of cholestatic jaundice or hepatic dysfunction associated with ampicillin/sulbactam combination use.

Special Precautions

Patient with history of atopic allergy (e.g. asthma, eczema, urticaria). Not recommended for use in patients with infectious mononucleosis. Renal and hepatic impairment. Neonates, infants and children. Pregnancy and lactation.

Adverse Reactions

Significant: Fungal or bacterial superinfection, including Clostridium difficile-associated diarrhoea (CDAD) and pseudomembranous colitis (prolonged use); rash or severe cutaneous reactions (e.g. toxic epidermal necrolysis, SJS, dermatitis exfoliative, erythema multiforme, acute generalised exanthematous pustulosis).
Blood and lymphatic system disorders: Anaemia, thrombocytopenia, eosinophilia, leucopenia, neutropenia.
Cardiac disorders: Chest pain.
Gastrointestinal disorders: Diarrhoea, vomiting, nausea, flatulence, abdominal distension, glossitis, mucosal bleeding.
General disorders and administration site conditions: Inj site pain, fatigue, malaise, chills, oedema.
Hepatobiliary disorders: Hyperbilirubinaemia.
Investigations: Increased ALT, AST; decreased plasma concentration of total conjugated estriol, conjugated estrone, estradiol, and estriol-glucuronide (in pregnant women).
Nervous system disorders: Headache.
Renal and urinary disorders: Urine retention, dysuria.
Respiratory, thoracic and mediastinal disorders: Epistaxis, throat tightness.
Skin and subcutaneous tissue disorders: Pruritus.
Vascular disorders: Phlebitis, thrombophlebitis.
Potentially Fatal: Hypersensitivity reaction (e.g. anaphylaxis), hepatotoxicity (e.g. hepatitis, cholestatic jaundice).

Pregnancy Category (US FDA)

Parenteral/PO: B

Monitoring Parameters

Assess the allergy history of the patient before starting treatment. Evaluate for signs of anaphylaxis during the 1st dose and signs and symptoms of opportunistic infections. Monitor haematologic, renal, and hepatic function with prolonged use. Perform culture and susceptibility tests prior to treatment initiation; consult local institutional recommendation before treatment initiation due to antibiotic resistance risks.

Drug Interactions

Increased and prolonged serum concentrations with probenecid.
Ampicillin: Increased incidence of rashes with allopurinol. May enhance the effect of anticoagulants. May inactivate the effect of aminoglycosides. Bacteriostatic drugs (e.g. chloramphenicol, erythromycin, sulfonamides, tetracyclines) may interfere with the bactericidal effect of ampicillin. Diminished therapeutic efficacy of estrogen-containing oral contraceptives. Decreased clearance of methotrexate thus increase the risk of toxicity.

Lab Interference

May cause false-positive result with urinary glucose tests using cupric sulfate (e.g Benedict’s solution, Fehling’s solution, Clinitest^®).

Action

Description:
Mechanism of Action: Ampicillin prevents bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins resulting in the inhibition of the final transpeptidation step of peptidoglycan synthesis in the bacterial cell walls.
Sulbactam extends the spectrum of ampicillin activity due to its irreversible inhibition of β-lactamases that are found in penicillin-resistant organisms. It has limited antibacterial activity to Neisseriaceae.
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed following IM inj.
Ampicillin: Time to peak plasma concentration: 30-40 minutes (IM).
Sulbactam: Time to peak plasma concentration: 30-52 minutes (IM).
Distribution: Crosses the placenta, enters breast milk (small amounts). Penetrates the CSF with inflamed meninges.
Ampicillin: Distributed into the bile. Plasma protein binding: 15-18%.
Sulbactam: Widely distributed in the bile, blister, and tissue fluids. Plasma protein binding: 38%.
Metabolism: Ampicillin: Metabolised to penicilloic acid.
Excretion: Ampicillin: Via urine (approx 90%); faeces. Elimination half-life: 1-1.8 hours.
Sulbactam: Via urine (approx 75-85% as unchanged drug). Elimination half-life: 1-1.3 hours.

Chemical Structure

Storage

Store intact vials below 30°C. IM: Concentrated solution must be used within 1 hour of reconstitution. IV infusion: Storage recommendations after reconstitution and dilution may vary depending on the diluent used and the final concentration of the solution. Refer to specific product guidelines.

MIMS Class

Penicillins

ATC Classification

J01CR01 - ampicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

References

Anon. Ampicillin and Sulbactam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 15/01/2021.

Anon. Ampicillin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 15/01/2021.

Anon. Ampicillin/Sulbactam. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 15/01/2021.

Bactacin (Shin Poong Pharm, Co. Ltd.). MIMS Philippines. http://www.mims.com/philippines. Accessed 15/01/2021.

Buckingham R (ed). Ampicillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/01/2021.

Buckingham R (ed). Sulbactam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/01/2021.

Joint Formulary Committee. Ampicillin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/01/2021.

Unasyn 375 mg, 750 mg, 1.5 g Sterile Powder for Injection (Pfizer, Inc.). MIMS Philippines. http://www.mims.com/philippines. Accessed 20/04/2021.

Unasyn for Intravenous or Intramuscular Use (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 15/01/2021.

Unasyn Injection, Powder, for Solution (Roerig). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 15/01/2021.

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