Ampicillin + Flucloxacillin

Ampicillin + Flucloxacillin Should be taken on an empty stomach.

Hypersensitivity to ampicillin, flucloxacillin, or other β-lactam antibiotics (e.g. cephalosporins, penicillins). History of flucloxacillin-associated jaundice or hepatic dysfunction.

Patients with acute or chronic lymphocytic leukaemia; predisposition to hypokalaemia (e.g. renal tubule dysfunction, malnutrition, concurrent use of hypokalaemia-inducing diuretics); spirochaete infections (e.g. syphilis or leptospirosis). Not recommended in patients with infectious mononucleosis. Hepatic and renal impairment. Children. Pregnancy and lactation.

Significant: Bacterial or fungal superinfection (e.g. Clostridioides difficile-associated diarrhoea, pseudomembranous colitis) in prolonged use; flucloxacillin-induced hypernatraemia; Jarisch-Herxheimer reaction (particularly in patients with spirochaete infections). Rarely, high anion gap metabolic acidosis (HAGMA).
Blood and lymphatic system disorders: Rarely, haemolytic anaemia, leucopenia, reversible thrombocytopenia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea.
General disorders and administration site conditions: Fever.
Hepatobiliary disorders: Rarely, hepatitis, cholestatic jaundice.
Immune system disorders: Serum sickness-like reaction.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.
Psychiatric disorders: Rarely, hallucinations.
Renal and urinary disorders: Interstitial nephritis.
Respiratory, thoracic and mediastinal disorders: Bronchospasm, oropharyngeal pain, throat irritation.
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria.
Potentially Fatal: Hypersensitivity reactions, including anaphylactic or anaphylactoid reactions, and severe cutaneous adverse reactions (e.g. acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis); flucloxacillin-induced hypokalaemia (high doses).

Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor CBC, BUN, serum creatinine, AST, ALT, and urinalysis periodically (prolonged use). Assess for signs and symptoms of anaphylaxis during the 1st dose.

Symptoms: Diarrhoea, nausea, vomiting. Management: Symptomatic treatment. Ampicillin may be removed by haemodialysis.

Bacteriostatic drugs (e.g. erythromycin, chloramphenicol, tetracycline) may interfere with the bactericidal action of ampicillin and flucloxacillin. May decrease methotrexate excretion resulting in an increased risk of toxicity. May reduce the effectiveness of oral contraceptives. Prolonged and increased serum levels with probenecid.
Ampicillin: Increased risk of allergic skin reactions with allopurinol.
Flucloxacillin: Increased risk of HAGMA with paracetamol.

Decreased absorption with food.

May interfere with the results of urinary glucose tests using cupric sulfate (Clinitest^®, Benedict's solution) and some tests for urinary proteins. May result in a false-positive Coombs test.

Description:
Mechanism of Action: Ampicillin, a broad-spectrum penicillin, inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs). This blocks the final transpeptidation step of peptidoglycan synthesis in the bacterial cell walls resulting in bacterial lysis.
Flucloxacillin, a bactericidal antibiotic, interferes with bacterial cell wall synthesis causing cell wall destruction of susceptible bacteria during active multiplication. Additionally, it is resistant to staphylococcal penicillinase inactivation.
Synonym(s): Co-fluampicil.
Pharmacokinetics:
Absorption: Decreased absorption with food.
Ampicillin: Moderately well and incompletely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1-2 hours.
Flucloxacillin: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 79%. Time to peak plasma concentration: Approx 1 hour.
Distribution: Crosses the placenta and enters breast milk.
Ampicillin: Widely distributed throughout the body and can be found in ascitic, pleural, and joint fluids; penetrates the CSF when the meninges are inflamed. Plasma protein binding: 15-18%.
Flucloxacillin: Distributed into tissues, including bones; penetrates the CSF when meninges are not inflamed. Plasma protein binding: Approx 95%.
Metabolism: Metabolised to some extent into penicilloic acid.
Excretion: Ampicillin: Mainly via urine (approx 90%, as unchanged drug within 24 hours); faeces. Elimination half-life: 1-1.8 hours.
Flucloxacillin: Mainly via urine (65-76% as unchanged drug); faeces. Elimination half-life: 1 hour.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6249, Ampicillin. https://pubchem.ncbi.nlm.nih.gov/compound/Ampicillin. Accessed Feb. 25, 2025.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 21319, Floxacillin. https://pubchem.ncbi.nlm.nih.gov/compound/Floxacillin. Accessed Feb. 25, 2025.

Store below 25°C. Reconstituted susp: Store between 2-8°C. Protect the cap from heat, light and moisture.

Penicillins

J01CR50 - combinations of penicillins ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

Ampicillin and Flucloxacillin [Floxicillin]. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/12/2024.

Ampicillin. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/12/2024.

Brayfield A, Cadart C (eds). Ampicillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/12/2024.

Brayfield A, Cadart C (eds). Flucloxacillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/12/2024.

Co-Fluampicil 125/125 mg/5 mL Oral Suspension (Tillomed Laboratories Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/12/2024.

Co-fluampicil Capsules (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/12/2024.

Flucloxacillin [Floxicillin]. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/12/2024.

Joint Formulary Committee. Co-fluampicil. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/12/2024.

Magnapen Hard Capsules or Co-fluampicil 250 mg/250 mg Hard Capsules (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/12/2024.

Magnapen or Co-fluampicil 125 mg/125 mg/5 mL Powder for Oral Suspension (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/12/2024.