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Flucloxacillin + ampicillin Pregnancy: Animal studies with co-fluampicil have shown no teratogenic effects. The product has been in clinical use since 1971 and the limited number of reported cases of use in human pregnancy have shown no evidence of untoward effects. The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore co-fluampicil should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment. Lactation: Trace quantities of ampicillin and flucloxacillin can be detected in breast milk. The possibility of hypersensitivity reactions must be considered in breast-fed infants. Therefore co-fluampicil should only be administered to a breast-feeding mother when the potential benefit outweigh the potential risks associated with treatment.

Co-fluampicil

Brand names: Magnapen

Co-fluampicil is a fixed combination of flucloxacillin and ampicillin, providing penicillinase-stable cover for staphylococci together with broader activity against streptococci and some Gram-negative organisms.

Adult dose

Dose: Severe infections where the causative organism is unknown, and mixed infections involving beta-lactamase-producing staphylococci: usual adult dosage (including elderly patients and children over 10 years) 1 capsule (250 mg ampicillin as ampicillin trihydrate + 250 mg flucloxacillin as flucloxacillin sodium); may be doubled where necessary
Route: Oral
Frequency: Four times a day; oral doses half to one hour before meals
The pinned product is MAGNAPEN HARD CAPSULES / CO-FLUAMPICIL 250MG/250MG HARD CAPSULES (PL448530080, Kensington Pharma Ltd.), so ONLY THE ORAL CAPSULE is covered. NOT COVERED: the IV/parenteral route on the page - SPC §4.1 says 'Parenteral usage is indicated where oral dosage is inappropriate' but prints no parenteral dose; and Co-fluampicil Syrup, which §4.2 names for children under 10 but whose strength is not in this SPC. §2 (verbatim): 'Co-fluampicil Capsules contain 250mg ampicillin as ampicillin trihydrate with 250mg flucloxacillin as flucloxacillin sodium (co-fluampicil 250/250).' §4.1 (verbatim, abridged): 'indicated for the treatment of severe infections where the causative organism is unknown, and for mixed infections involving beta-lactamase-producing staphylococci.' Typical indications printed: in general practice chest infections, ENT infections, skin and soft tissue infections, and infections in patients whose underlying pathology places them at special risk; in hospital (prior to laboratory results) severe respiratory tract infections, post-operative chest and wound infections, septic abortion, puerperal fever, septicaemia, prophylaxis in major surgery, infections in patients receiving immuno-suppressive therapy. VERBATIM §4.2: 'Usual adult dosage (including elderly patients and children over 10 years): Oral: 1 capsule four times a day. Usual children's dosage: Oral: Under 10 years: half adult dose, using Co-fluampicil Syrup. The above dosages for adults and children may be doubled where necessary. Oral doses should be administered half to one hour before meals.' The SPC prints no maximum daily dose and no duration, so none is given. No paediatric block is written: the only under-10 instruction is 'half adult dose, using Co-fluampicil Syrup' (a relative figure for a different product whose strength is not printed here). Some sections of the product information we used were incomplete — check the full SPC.

Dose adjustments

Renal

No renal dose adjustment is printed in SPC §4.2. §4.4: care is necessary if very high doses of flucloxacillin are given, especially if renal function is poor, because of the risk of nephrotoxicity and/or neurotoxicity; care is also necessary if large doses of sodium (salts) are given to patients with impaired renal function or heart failure. Each capsule contains 13.0 mg sodium; patients at high risk of high anion gap metabolic acidosis with paracetamol include those with severe renal impairment.

Hepatic

No hepatic dose adjustment is printed in SPC §4.2. §4.3: contraindicated in patients with a history of flucloxacillin-associated jaundice/hepatic dysfunction. §4.4: use with caution in patients with evidence of hepatic dysfunction. §4.8: hepatitis and cholestatic jaundice have been reported rarely and may be delayed for up to two months after withdrawal of treatment.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via MHRA Products — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • History of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins) or to excipients
  • History of flucloxacillin-associated jaundice/hepatic dysfunction
  • Should be avoided if infectious mononucleosis and/or acute or chronic leukaemia of lymphoid origin are suspected (ampicillin-associated skin rash) - SPC §4.4

Side effects

  • Minor gastrointestinal disturbances including occasionally nausea, vomiting and diarrhoea; pseudomembranous colitis reported rarely
  • Skin rash, pruritus and urticaria; incidence of rash is higher in infectious mononucleosis and acute or chronic leukaemia of lymphoid origin
  • Anaphylaxis and other hypersensitivity reactions (reported rarely); late sensitivity reactions may include serum sickness-like reactions, haemolytic anaemia and acute interstitial nephritis; bronchospasm from penicillin allergy
  • Hepatitis and cholestatic jaundice (rarely; may be delayed for up to two months after withdrawal); very rarely deaths from hepatic effects, mostly in patients with serious underlying disease; moderate transient increase in transaminases
  • Haematological effects (rare): reversible leucopenia, reversible thrombocytopenia, haemolytic anaemia
  • Electrolyte disturbances such as hypokalaemia due to large amounts of sodium
  • High anion gap metabolic acidosis when flucloxacillin is used with paracetamol, generally in the presence of risk factors (very rare)
  • With flucloxacillin: hallucinations (rare), coma with high doses, acute severe dyspnoea, erythema nodosum, pemphigoid reactions, non-thrombocytopenic purpura, vasculitis (all rare)
  • Severe skin reactions (rare): erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis; fever, arthralgia and myalgia can develop more than 48 hours after starting treatment
  • Reversible interstitial nephritis
  • This side-effect list may be incomplete — check the full SPC.

Interactions

  • Bacteriostatic antibacterials (chloramphenicol, erythromycins, tetracyclines): possible antagonism with penicillins, which may reduce effectiveness, particularly in pneumococcal meningitis and scarlet fever
  • Methotrexate (cytotoxics): penicillins reduce its excretion, increasing the risk of toxicity
  • Oral contraceptives: efficacy may be reduced, as with other oral broad-spectrum antibiotics; patients should be warned
  • Probenecid: decreases renal tubular secretion, giving increased and prolonged blood levels of both ampicillin and flucloxacillin
  • Allopurinol (with ampicillin): increased likelihood of allergic skin reactions
  • Paracetamol (with flucloxacillin): risk of high anion gap metabolic acidosis, especially in patients with risk factors
  • Diagnostic tests: false-positive direct antiglobulin (Coombs') test, falsely high urinary glucose with the copper sulphate test, falsely high urinary protein

Monitoring

  • Renal, hepatic and haematological status during prolonged and high-dose therapy (e.g. osteomyelitis, endocarditis)
  • After co-administration of flucloxacillin and paracetamol, close monitoring for acid-base disorders (high anion gap metabolic acidosis), including a search for urinary 5-oxoproline
  • Careful enquiry about previous beta-lactam hypersensitivity before starting
  • Sodium content (13.0 mg per capsule) counts toward the daily allowance in patients on sodium-restricted diets
  • Signs of pseudomembranous colitis in severe and persistent diarrhoea (discontinue flucloxacillin)

Clinical monograph

How it works

Both components are beta-lactams that inhibit bacterial cell-wall peptidoglycan synthesis, with flucloxacillin resisting staphylococcal penicillinase.

Prescribing in practice

  • The flucloxacillin component carries an MHRA-recognised risk of cholestatic jaundice and hepatitis that can occur up to two months after stopping, more commonly with prolonged courses or in older patients.
  • Contraindicated in penicillin allergy and in anyone with previous flucloxacillin-associated jaundice or hepatic dysfunction.
  • Best taken on an empty stomach as food reduces absorption of both penicillins.

Monitoring

Monitor for jaundice or hepatic symptoms during and after treatment, particularly with longer courses.

Counselling the patient

  • Take the doses before food, spaced through the day.
  • Report yellowing of the skin or eyes, dark urine or pale stools, even after the course has finished.
  • Complete the full course and report any rash or breathing difficulty.

Evidence & guidelines

MHRA advice on flucloxacillin hepatotoxicity informs the cautions for this combination.

Reference: Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Pathways