Cefadroxil

Table of contents

• What is cefadroxil?
• How does cefadroxil work?
• Which conditions is it used or studied for?
• How is cefadroxil given?
• What do the clinical trials show?
• What side effects are known?

What is cefadroxil?

Cefadroxil is a semisynthetic cephalosporin antibiotic intended for oral administration.^[3] It is a white to yellowish-white crystalline powder that is soluble in water and acid-stable.^[3] The substance is classified as a chemically synthesised small-molecule medicine (ATC code J01DB05). It is already authorised as a medicine, with an authorisation record in Belgium held by Sandoz N.V. The product name in the registry is cefadroxil Sandoz 500 mg harde capsules. In the clinical trials listed here, cefadroxil appears as the test substance in one trial.^[1]

How does cefadroxil work?

Cephalosporins are bactericidal, meaning they kill bacteria, because they inhibit cell-wall synthesis.^[3] By blocking the construction of the bacterial cell wall, cefadroxil causes the bacteria to break down and die. In laboratory tests, cefadroxil has been shown to be active against beta-hemolytic streptococci, staphylococci including penicillinase-producing strains, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella species, and Moraxella catarrhalis.^[3] It is not active against most strains of Enterococcus faecalis, Enterococcus faecium, Enterobacter species, or Morganella morganii.^[3]

Which conditions is it used or studied for?

Cefadroxil is authorised as an antibiotic medicine and is being studied in two registered clinical trials for the following conditions:

• Staphylococcus aureus bacteremia — a bloodstream infection caused by the bacterium Staphylococcus aureus. A Phase 2 trial is studying how the body processes cefadroxil in people with this serious infection.^[1]
• Bone and joint infections — specifically pyogenic vertebral osteomyelitis, an infection of the bones of the spine. A Phase 3 trial is comparing an early switch from intravenous to oral antibiotic therapy, with cefadroxil as one of the oral options.^[2]

How is cefadroxil given?

Cefadroxil is given orally as hard capsules.^[3] The product used in the trials is cefadroxil Sandoz 500 mg hard capsules. In the Phase 2 bacteremia trial, the intervention is described as 4 grams taken orally.^[1] In the Phase 3 vertebral osteomyelitis trial, cefadroxil is listed as one of several oral antibiotics at a dose of 4000 mg.^[2] After oral administration, cefadroxil is rapidly absorbed, with average peak serum concentrations of approximately 16 mcg/mL after a 500 mg dose and 28 mcg/mL after a 1000 mg dose.^[3] Over 90% of the drug is excreted unchanged in the urine within 24 hours.^[3]

What do the clinical trials show?

Two clinical trials are registered for cefadroxil, both currently authorised. The first is a Phase 2 study in Staphylococcus aureus bacteremia with 25 participants.^[1] The second is a Phase 3 study in vertebral osteomyelitis with 280 participants.^[2]

What are the trials measuring?

The Phase 2 trial measures three things: pharmacokinetics (how the body processes the drug), pharmacodynamics (the drug's effect on the bacteria), and adverse events (side effects).^[1] The pharmacokinetic assessment aims to establish correct cefadroxil doses by checking that serum concentrations stay above the minimum inhibitory concentration (MIC) for at least 50% of the day.^[1] The pharmacodynamic assessment looks at therapeutic failure as a composite endpoint including relapsing bacteremia, deep-seated infection, switching to another antibiotic, rehospitalisation, or death within 90 days.^[1] The Phase 3 trial measures a composite clinical failure endpoint 24 weeks after stopping antibiotic therapy, including all-cause mortality, unplanned spine surgery, relapse of bacteraemia, relapse of infection, or renewed intravenous antibiotic therapy for more than 7 days.^[2]

Who can take part in these trials?

The Phase 2 trial includes patients with a bloodstream infection caused by Staphylococcus aureus.^[1] The Phase 3 trial includes patients with pyogenic vertebral osteomyelitis who are being treated with intravenous antibiotics and are candidates for an early switch to oral therapy after 7 days.^[2]

What side effects are known?

The provided product information does not list specific side effects for cefadroxil in the sections available. The Phase 2 trial includes monitoring and reporting of adverse events as one of its assessments.^[1] The Phase 3 trial includes adverse events leading to a switch to another antimicrobial regimen as part of its composite failure endpoint.^[2]