Flucloxacillin
Penicillin antibiotic for staphylococcal infections
📊 Quick Facts About Flucloxacillin
💡 Key Takeaways About Flucloxacillin
- Beta-lactamase resistant: Unlike standard penicillin, flucloxacillin is not broken down by staphylococcal beta-lactamase enzymes, making it effective against penicillin-resistant Staphylococcus aureus
- Take on an empty stomach: Flucloxacillin should be taken at least 1 hour before or 2 hours after meals for optimal absorption
- Complete the full course: Always finish the entire prescribed course, even if you feel better after a few days, to prevent antibiotic resistance
- Caution with paracetamol: Concurrent use carries a risk of high anion gap metabolic acidosis (HAGMA), especially in patients with kidney impairment or sepsis
- Monitor liver function: Risk of liver damage exists, particularly in patients over 50 and with prolonged treatment courses
What Is Flucloxacillin and What Is It Used For?
Flucloxacillin is a penicillin-type antibiotic that kills bacteria by preventing them from building a normal cell wall. It is specifically designed to resist breakdown by beta-lactamase enzymes, making it effective against staphylococcal bacteria that are resistant to standard penicillin.
Flucloxacillin belongs to the isoxazolyl penicillin group of antibiotics. Its primary distinguishing characteristic is its stability against staphylococcal beta-lactamase, an enzyme produced by many strains of Staphylococcus aureus that can inactivate ordinary penicillins such as phenoxymethylpenicillin (penicillin V) and amoxicillin. This makes flucloxacillin the antibiotic of choice for infections caused by penicillin-resistant staphylococci.
Like all beta-lactam antibiotics, flucloxacillin works by binding to penicillin-binding proteins (PBPs) on the bacterial cell surface. These proteins are essential for the construction and maintenance of the bacterial cell wall. When flucloxacillin binds to PBPs, the bacterium can no longer synthesize a functional cell wall, leading to osmotic instability and rapid bacterial death. This bactericidal mechanism means flucloxacillin actively kills bacteria rather than merely preventing their growth.
Peak plasma concentrations of flucloxacillin are typically reached within 1 to 2 hours after oral administration. The drug is partially metabolized in the liver and excreted primarily through the kidneys. Its plasma half-life is approximately 1 hour, which is why multiple daily doses are required to maintain effective blood levels throughout the treatment period.
Common Medical Uses
Flucloxacillin is prescribed for a range of infections caused by susceptible Gram-positive bacteria, particularly staphylococci. The most common indications include:
- Skin and soft tissue infections: Cellulitis, impetigo, wound infections, abscesses, infected eczema, and erysipelas
- Bone and joint infections: Osteomyelitis (bone infection) and septic arthritis
- Lung infections: Staphylococcal pneumonia and lung abscesses
- Endocarditis: Infection of the heart valves, typically as part of a combination antibiotic regimen
- Other infections: Infected surgical wounds, infected burns, and otitis externa (outer ear infection)
Flucloxacillin has a narrow spectrum of activity. It is primarily effective against Gram-positive bacteria, especially Staphylococcus aureus (including beta-lactamase-producing strains) and Streptococcus species. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative bacteria, or anaerobic organisms. Your doctor will determine whether flucloxacillin is the right antibiotic for your specific infection.
What Should You Know Before Taking Flucloxacillin?
Do not take flucloxacillin if you are allergic to flucloxacillin, penicillins, or any of the excipients. Tell your doctor if you have a history of liver problems, kidney impairment, or allergy to cephalosporins. Use caution when taking paracetamol concurrently due to the risk of metabolic acidosis.
Before starting treatment with flucloxacillin, it is essential to inform your healthcare provider about your complete medical history, current medications, and any known allergies. Several important factors must be considered to ensure safe and effective treatment.
Contraindications
You must not take flucloxacillin if:
- You are allergic to flucloxacillin or any other penicillin antibiotic
- You have had a previous severe allergic reaction (anaphylaxis) to any beta-lactam antibiotic, including cephalosporins
- You are allergic to any of the inactive ingredients in the tablet formulation
- You have a history of flucloxacillin-associated liver damage or jaundice
Warnings and Precautions
Talk to your doctor or pharmacist before using flucloxacillin if any of the following apply to you:
- Cephalosporin allergy: If you have a known hypersensitivity to cephalosporins (another group of antibiotics), there is a small risk of cross-reactivity. Your doctor will assess whether flucloxacillin is appropriate for you.
- Liver problems: Flucloxacillin can cause liver damage (hepatotoxicity), which is rare but more likely in patients over 50 years of age and those on prolonged treatment courses (longer than 2 weeks). Your doctor may monitor your liver function during treatment.
- Kidney impairment: If you have severe kidney disease, dose adjustments may be needed and the risk of certain side effects may be increased.
- Concurrent paracetamol use: When flucloxacillin and paracetamol are taken together, there is a risk of high anion gap metabolic acidosis (HAGMA). This risk is particularly elevated in patients with severe kidney impairment, sepsis, or malnutrition, and when maximum daily doses of paracetamol are used.
- Signs of a severe allergic reaction: facial swelling, hives, difficulty breathing, dizziness
- Prolonged or severe diarrhea (may indicate Clostridioides difficile colitis)
- Skin rash with blistering, peeling, or target-shaped lesions (Stevens-Johnson syndrome or toxic epidermal necrolysis)
- Fever with swollen lymph nodes and rash (DRESS syndrome)
- Signs of reduced white blood cell count: fever with sore throat or mouth ulcers
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before taking flucloxacillin.
Pregnancy: There are no known risks associated with taking flucloxacillin during pregnancy. Penicillin antibiotics are generally considered safe during pregnancy and are among the most commonly prescribed antibiotics for pregnant women. However, as with all medications, flucloxacillin should only be used during pregnancy when clearly needed and as directed by your healthcare provider.
Breastfeeding: Flucloxacillin passes into breast milk in small amounts but is unlikely to affect the breastfed infant at therapeutic doses. However, there is a theoretical possibility of sensitization or disruption of the infant's gut flora. Consult your doctor if you require more than occasional use of flucloxacillin while breastfeeding.
Driving and Operating Machinery
Flucloxacillin has no or negligible effect on the ability to drive or operate machinery. However, if you experience dizziness as a side effect, you should not drive or operate machinery until the symptom resolves.
Sodium Content
Flucloxacillin tablets contain sodium as part of the active ingredient (flucloxacillin sodium monohydrate). The sodium content varies by strength:
- 125 mg tablet: Contains less than 1 mmol (23 mg) sodium – essentially sodium-free
- 500 mg tablet: Contains 29 mg sodium (1.5% of the WHO recommended maximum daily intake of 2 g for adults)
- 1 g tablet: Contains 58 mg sodium (3% of the WHO recommended maximum daily intake)
This should be considered by patients on a sodium-restricted diet, particularly those taking higher doses.
How Does Flucloxacillin Interact with Other Drugs?
Flucloxacillin can interact with several medications including methotrexate, probenecid, warfarin, paracetamol, and voriconazole. The most clinically significant interaction is with paracetamol, which can lead to dangerous metabolic acidosis. Always inform your doctor about all medications you are taking.
Drug interactions can alter how flucloxacillin works or increase the risk of serious side effects. It is critical to inform your healthcare provider about all medications you are currently taking, have recently taken, or plan to take, including over-the-counter medicines, vitamins, and herbal supplements.
Major Interactions
| Drug | Interaction | Clinical Significance | Action |
|---|---|---|---|
| Paracetamol (Acetaminophen) | Risk of high anion gap metabolic acidosis (HAGMA) | Very rare but potentially serious. Risk increased in patients with kidney impairment, sepsis, malnutrition, or using maximum paracetamol doses | Use paracetamol with caution; consider alternative analgesics. Monitor for symptoms of acidosis (rapid breathing, confusion, nausea) |
| Methotrexate | Reduced renal excretion of methotrexate, leading to increased methotrexate levels and toxicity risk | Potentially serious; risk of methotrexate toxicity including bone marrow suppression and mucositis | Monitor methotrexate levels closely. Doctor may adjust methotrexate dose |
| Warfarin | Altered anticoagulant effect; flucloxacillin may reduce warfarin efficacy or cause unpredictable INR changes | Risk of subtherapeutic anticoagulation or, less commonly, increased bleeding risk | Monitor INR closely during and after flucloxacillin treatment. Adjust warfarin dose as needed |
Minor Interactions
| Drug | Interaction | Action |
|---|---|---|
| Probenecid | Reduces renal excretion of flucloxacillin, resulting in higher and more prolonged blood levels | Sometimes used intentionally to increase flucloxacillin levels. Inform your doctor |
| Voriconazole | Flucloxacillin may reduce voriconazole blood levels, potentially decreasing antifungal efficacy | Monitor voriconazole levels. Alternative antifungal may be needed |
| Oral contraceptives | Antibiotics may theoretically reduce contraceptive efficacy (evidence is limited) | Consider additional contraception during treatment as a precaution |
The interaction between flucloxacillin and paracetamol leading to high anion gap metabolic acidosis (HAGMA) is very rare but can be serious. It occurs most commonly in patients who have underlying risk factors such as severe kidney impairment, sepsis (blood poisoning), or malnutrition. The risk increases when maximum daily doses of paracetamol (4 g/day) are used. HAGMA is a serious condition that requires urgent medical treatment. Symptoms may include rapid or deep breathing, confusion, nausea, and fatigue. If you experience these symptoms while taking both medications, seek medical attention immediately.
What Is the Correct Dosage of Flucloxacillin?
The typical adult dose of flucloxacillin is 250 mg to 1 g taken four times daily (every 6 hours), depending on the type and severity of infection. Tablets should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, with a full glass of water.
Your doctor will determine the appropriate dose of flucloxacillin based on the type and severity of your infection, your body weight, kidney function, and other individual factors. Always follow your doctor's instructions exactly. The dosages below are general guidelines and may differ from what your doctor prescribes.
Adults
Standard Adult Dosage
- Mild to moderate infections: 250–500 mg four times daily (every 6 hours)
- Severe infections: 1 g four times daily (every 6 hours)
- Bone and joint infections: 1–2 g four times daily; prolonged courses of 4–6 weeks or longer may be required
- Endocarditis: 2 g every 6 hours (usually intravenous initially, then switched to oral)
Children
Pediatric Dosage
Dosage for children is calculated based on body weight and the severity of infection. The following are general guidelines from the British National Formulary (BNF):
- Children under 2 years: Quarter of the adult dose
- Children 2–10 years: Half the adult dose
- Children over 10 years: Adult dose
Your child's doctor will calculate the exact dose based on the child's weight and the specific infection being treated. Liquid formulations (oral solution) are available for children who cannot swallow tablets.
Elderly
Dosage in Elderly Patients
Standard adult doses generally apply. However, elderly patients should be monitored more closely for liver function, particularly during prolonged treatment courses. The risk of flucloxacillin-induced liver damage is higher in patients over 50 years of age. Dose adjustment may be necessary in elderly patients with significantly impaired kidney function.
How to Take Flucloxacillin
Proper administration of flucloxacillin is important for optimal drug absorption and therapeutic efficacy:
- Take on an empty stomach: At least 1 hour before or 2 hours after a meal. Food significantly reduces the absorption of flucloxacillin from the gut.
- Swallow with a full glass of water: Use approximately 250 ml (a full glass) of water to reduce the risk of esophageal irritation and pain.
- Remain upright: Do not lie down immediately after taking the tablets to prevent esophageal irritation.
- Take at evenly spaced intervals: Try to maintain approximately 6-hour intervals between doses for consistent blood levels.
- The 500 mg and 1 g tablets can be split: The scored tablets can be divided into two equal halves if needed.
Missed Dose
If you forget to take a dose of flucloxacillin, take it as soon as you remember. Then continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If it is almost time for your next dose, skip the missed dose and take the next one at the usual time.
Overdose
If you or someone else has taken too much flucloxacillin, contact your doctor, hospital emergency department, or local poison control center immediately. Symptoms of overdose may include nausea, vomiting, and diarrhea. In severe cases, neurological symptoms such as seizures may occur, particularly in patients with kidney impairment. Treatment is generally supportive, and flucloxacillin can be removed from the blood by hemodialysis.
Even if you feel better after a few days of treatment, it is essential to complete the entire prescribed course of flucloxacillin. Stopping treatment early allows some bacteria to survive, potentially leading to a recurrence of the infection. Incomplete courses of antibiotics also contribute to the development of antibiotic resistance, which is a growing global health concern recognized by the World Health Organization (WHO) as one of the greatest threats to public health.
What Are the Side Effects of Flucloxacillin?
The most common side effects of flucloxacillin are gastrointestinal symptoms (nausea, diarrhea) and skin rash, affecting up to 1 in 10 people. Rare but serious side effects include liver damage, severe allergic reactions (anaphylaxis), and Clostridioides difficile colitis. Contact your doctor immediately if you experience severe diarrhea, skin blistering, or difficulty breathing.
Like all medicines, flucloxacillin can cause side effects, although not everyone experiences them. Most side effects are mild and resolve after treatment is completed. However, some side effects can be serious and require immediate medical attention.
Common Side Effects
May affect up to 1 in 10 people
- Gastrointestinal discomfort, primarily nausea or diarrhea
- Skin rash
Uncommon Side Effects
May affect up to 1 in 100 people
- Urticaria (hives)
- Eosinophilia (increased eosinophil white blood cells)
Rare Side Effects
May affect up to 1 in 1,000 people
- Liver damage (hepatotoxicity) – risk increases with age over 50 and prolonged treatment
Very Rare Side Effects
May affect up to 1 in 10,000 people
- Itching (pruritus)
- High anion gap metabolic acidosis (HAGMA) when taken with paracetamol, especially in patients with risk factors (see section on drug interactions)
Frequency Not Known
Reported but frequency cannot be estimated from available data
- Low potassium levels (hypokalemia) – may cause muscle weakness, twitching, or abnormal heart rhythm
- Dizziness, abdominal pain, vomiting
- Esophageal pain, difficulty swallowing, heartburn, throat irritation, chest pain
- Kidney inflammation (nephritis and interstitial nephritis)
- Genital itching caused by yeast overgrowth
- White coating in the mouth (oral thrush) caused by fungal infection
The following serious side effects have been reported with flucloxacillin. Stop taking the medicine and contact your doctor or emergency department immediately if you experience any of these:
- Severe allergic reaction (anaphylaxis): Skin flushing, itchy hives, difficulty breathing, and dizziness. This can be life-threatening.
- Severe skin reactions: Red scaly rash with bumps and blisters (acute generalized exanthematous pustulosis), target-shaped spots or lesions with blisters on the trunk, sores in the mouth and genital area (Stevens-Johnson syndrome), extensive skin peeling (toxic epidermal necrolysis), or fever with swollen lymph nodes (DRESS).
- Prolonged or severe diarrhea: This may indicate Clostridioides difficile colitis, a serious bowel infection that requires specific treatment.
- Reduced infection defense: Fever with severely deteriorated general condition, sore throat, or mouth ulcers. This may indicate agranulocytosis (dangerously low white blood cell count).
Flucloxacillin-induced liver damage typically manifests as cholestatic hepatitis, which may develop during treatment or up to several weeks after stopping the drug. Symptoms may include yellowing of the skin or eyes (jaundice), dark urine, pale stools, nausea, abdominal pain, and fatigue. The risk is increased in patients over 50 years of age, those treated for more than 2 weeks, and those with pre-existing liver disease. In most cases, the liver damage resolves completely after discontinuation of the drug, but in rare cases it can be severe or prolonged.
If you experience any side effects not listed here, or if any side effect becomes severe, inform your doctor or pharmacist. You can also report suspected adverse reactions directly to your national medicines regulatory authority to help monitor the benefit-risk balance of medicines.
How Should You Store Flucloxacillin?
Store flucloxacillin 1 g tablets below 30°C. Keep all tablets out of the sight and reach of children. Do not use after the expiry date printed on the packaging. For tablets in unit-dose blister packs, use within 6 months of opening the outer aluminum pouch.
Proper storage of flucloxacillin is important to ensure the medication remains effective throughout its shelf life. Follow these storage guidelines:
- Temperature: Store 1 g tablets at temperatures not exceeding 30°C (86°F). Do not freeze.
- Keep out of reach of children: Store the medication in a location that children cannot access.
- Expiry date: Do not use after the expiry date printed on the outer carton or label (marked "EXP"). The expiry date refers to the last day of that month.
- Unit-dose blister packs: Tablets in unit-dose blister packs (enclosed in an outer aluminum pouch) have a shelf life limited to 6 months after opening the outer pouch. Record the date you opened the pouch.
- Disposal: Do not dispose of medicines via wastewater or household waste. Return unused medication to your pharmacy for proper disposal to protect the environment.
What Does Flucloxacillin Contain?
The active substance is flucloxacillin (as flucloxacillin sodium monohydrate). Tablets are available in 125 mg, 500 mg, and 1 g strengths. Inactive ingredients include magnesium stearate, povidone, croscarmellose sodium, microcrystalline cellulose, and a film coating of titanium dioxide, macrogol, and hypromellose.
Active Ingredient
Each tablet contains flucloxacillin sodium monohydrate equivalent to the following amounts of flucloxacillin:
- 125 mg tablet: White, oblong, 5.2 x 10 mm
- 500 mg tablet: White, oblong with a score line on one side, 8 x 17 mm. Can be divided into two equal halves.
- 1 g tablet: White, elliptical with a score line, 9.6 x 21 mm. Can be divided into two equal halves.
Inactive Ingredients (Excipients)
The following inactive ingredients are present in flucloxacillin tablets:
- Tablet core: Magnesium stearate, povidone, croscarmellose sodium, microcrystalline cellulose
- Film coating: Titanium dioxide (E 171), macrogol (polyethylene glycol), hypromellose
Not all pack sizes may be available in your country. Flucloxacillin is manufactured by several pharmaceutical companies and is available under various brand names worldwide, including Flucloxacillin Orion, Flukloxacillin Viatris, Heracillin, Floxapen, and others. The active ingredient is the same regardless of the brand name.
Frequently Asked Questions About Flucloxacillin
Flucloxacillin is a penicillin-type antibiotic primarily used to treat infections caused by staphylococcal bacteria that are resistant to standard penicillin. Common uses include skin and soft tissue infections (such as cellulitis, impetigo, wound infections, and abscesses), bone and joint infections (osteomyelitis, septic arthritis), lung infections, and endocarditis. It works by preventing bacteria from building a normal cell wall, which causes them to die.
Paracetamol should be used with caution alongside flucloxacillin. There is a risk of high anion gap metabolic acidosis (HAGMA) when these drugs are taken together, particularly in patients with severe kidney impairment, sepsis, or malnutrition. The risk increases with higher doses of paracetamol, especially at maximum daily doses. If you need pain relief while taking flucloxacillin, consult your doctor for the safest option. Alternative analgesics such as ibuprofen may be considered, depending on your individual circumstances.
Flucloxacillin works best when taken on an empty stomach. Take your tablets at least 1 hour before or 2 hours after a meal. Food significantly reduces the absorption of flucloxacillin from the gastrointestinal tract, which can result in lower blood levels and reduced effectiveness. Swallow the tablets with a full glass of water (approximately 250 ml) and do not lie down immediately afterwards to reduce the risk of esophageal irritation.
The most common side effects of flucloxacillin (affecting up to 1 in 10 people) are gastrointestinal symptoms such as nausea and diarrhea, and skin rash. Uncommon side effects include hives (urticaria) and eosinophilia. Rare but serious side effects include liver damage (especially in patients over 50 and with prolonged treatment), severe allergic reactions (anaphylaxis), and Clostridioides difficile colitis. If you experience prolonged diarrhea, skin blistering, or difficulty breathing, contact your doctor immediately.
The duration of flucloxacillin treatment depends on the type and severity of infection. For most skin and soft tissue infections, treatment typically lasts 5 to 7 days. For bone infections (osteomyelitis), treatment may be required for 4 to 6 weeks or longer. For endocarditis, treatment may continue for several weeks. Always complete the full course prescribed by your doctor, even if you feel better after a few days, to prevent the infection from returning and reduce the risk of antibiotic resistance.
There are no known risks associated with taking flucloxacillin during pregnancy. Penicillin antibiotics are generally considered safe during pregnancy and are among the most commonly prescribed antibiotics for pregnant women. Flucloxacillin also passes into breast milk in small amounts but is unlikely to affect a breastfed infant at therapeutic doses. However, always consult your doctor or midwife before taking any medication during pregnancy or while breastfeeding.
References and Medical Sources
This article is based on the following evidence-based sources and international medical guidelines:
- European Medicines Agency (EMA). Flucloxacillin – Summary of Product Characteristics. Available at: ema.europa.eu
- British National Formulary (BNF). Flucloxacillin – Indications, Dose, Interactions, Side Effects. National Institute for Health and Care Excellence. Available at: bnf.nice.org.uk
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Available at: who.int
- National Institute for Health and Care Excellence (NICE). Antimicrobial Prescribing Guidelines. Available at: nice.org.uk
- Flucloxacillin sodium – DrugBank Online. Comprehensive Drug Database. Available at: drugbank.com
- Olsson S, et al. Flucloxacillin-induced liver injury – a systematic review. Journal of Hepatology. 2022.
- Berbari EF, et al. 2020 Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clinical Infectious Diseases. 2015;61(6):e26–e46.
- WHO. Global Action Plan on Antimicrobial Resistance. 2015. Available at: who.int
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians with expertise in clinical pharmacology, infectious diseases, and internal medicine.
Medical Review Process
- Reviewed by board-certified clinical pharmacologists
- Cross-referenced with EMA, BNF, and WHO guidelines
- Evidence level 1A (systematic reviews and RCTs)
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