Fixed dose combination of Amoxicillin and Flucloxacillin is available” in both oral and parenteral formulation. Their usage is determined on the basis of severity of infections. Flucloxacillin is an isoxazolyl penicillin of the beta-lactam group of antibiotics, which exerts a bactericidal effect upon many Gram positive organism including streptococci and beta lactamase producing staphylococci. It has a relatively narrow spectrum of antibacterial activity.
Each capsules contains:
Amoxicillin Trihydrate B.P. equivalent to……250 mg Amoxicillin
Flucloxacillin Sodium B.P. equivalent to…250 mg Flucloxacillin
Each Vial contains
Amoxicillin Sodium B.P.
equivalent to…………. 250 mg Amoxicillin
equivalent to………. 250 mg Flucloxacillin
Amoxicillin is similar to ampicillin in its bactericidal action against susceptible organisms during the stage of active multiplication; It acts though the inhibition of biosynthesis of cell wall mucopeptide.
Amoxicillin has been shown to be active against most strains of the following microorganism, both in vitro and in clinical infections.
Flucloxacillin is a narrow spoctrum antibiotic of the group of isoxazolylpenicillins: It is not inactivated by staphylococcal beta-lactamases.
Flumox exhibits in vitro and in experimental animals in vivo bactericidal activity against a wide rango, of Gram-positive and gram-negative bacteria. The following are among the more commonly encountered sensitive organism:
(ii) Synergism: Flumox oxhibits synergistic bacterial activity in vitro, and in experimetal animals in vivo against some ampicillin resistant organisms.
(iii) Additive effects: The two components of Flumox: amoxicillin and flucloxacillin generally exhibit an additive effect against sensitive bacteria and bacteria that are sensitive to amoxicillin or to flucloxacillin or remain sensitive to the combination, showing that antagonism does not occur when the two components are combined. Flucloxacillin, by its action on the synthesis of the bacterial wall, exerts a bactericidal effect on streptococci, staphylococci, induding the beta-lactamase-producing strains, clostridia neisseria. It is not active against methicillin resistant staphylococci.
Strains of the following organisms are generally sensitive to the bactericidal action of flucloxacillin in vitro: (The minimal inhibitory concenfration
(MIC) of flucloxacillin are quoted below.) Flucloxacillin is bactericidal with a mode of action similar to that of benzylpenicillin, but is resistant to staphylococcal penicillinase. It is active therefore against penicillinase-producingoand non-penicillinase-producing staphylococci, with minimum inhibitory concentration in range of 0.25 to 0.5 mcg per mlolts activity against streptococci such as Streptococci pneumoniae and S. Pyrogens is less than that of benzypenicillin but sufficient 1o be useful when these organisms are present with ponicillin-rosistant staphylococci. Flucloxacillin. is virtually ineffective against Enterococcus faecalis,
|Streptococcus aureus (beta-lactamase producing)
|0.25 – 0.5
|Streptococcus pyogenes (Group A beta-haemolytic)*
|Streptococcus viridans group
|Neisseria gonorrhoeae (beta-lactamase producing)
The Group A beta-haemolytic streptococci are less sonsitive to the isoxazolyl penicillins than to penicillin G or penicillin V.
Orally administered dosage of 250 mg amoxicillin capsule result in average peak blood levels one to two hours after administration in the range of 3.5 mcg/ml to 5.0 mcg/ml respectively. Flucloxacillin is stable in acid media and can therefore be administered either by the oral or parenteral route.” The peak serum of flucloxacillin reached after To hour are as follows.
– After 250 mg by the oral route (in fasting subjects): approximately 8.8 mg/I.
– After 500 mg by the oral route (in fasting subjects): approximately 14.5 mg/l.
Absorption is more efficient when taken on empty stomach. The total quantity absorbed by the oral route represents approximately 79% of the quantity administered.
Flucloxacillin sodium, like dicloxacillin sodium is about twice as well absorbed from the gastro-intestinal tract as cloxacillin sodium, but absorption is also reduced by the presence of food in the stomach. After an oral dose® of 250 mg to 1g in fasting subjects, peak plasma concentrations in about I hour are usually in the range of 5 to 15 mcg per ml. plasma concentrations following the intramuscular injection of Flucloxacillin sodium are similar,
but peak concentrations are achieved in about 30 minutes Doubling the dose can double the plasma concentration. About 95% of Flucloxacillin in the
circulation is bound to plasma proteins. In blood serum, amoxicillin is approximately 20% protein-bound. Flucloxacillin has boon reported to have plasma half-life of approximately 1 hour. The half life of amoxicillin is 61.3 minutes, The half life is prolonged in neonates.
- Distribution: Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. Most: of the amoxicillin is excreted unchanged in the urine; Its excretion can be delayed by concurrent administration of probenecid Flucloxacillin diffuses well into most tissues Specifically, active concentration of Flucloxacillin have baen recovered in bones: 1156mg/l (Compact bone) and 156 mg /l (spongy bone), with a mean serum level of 8.9 mg /. Crossing the meningeal barrior: flucloxacillin diffuses in only small proportion into the cerebrospinal fluid of subjects whose meninges are not inflamed. Crossing into mother’s milk: flucloxacillin is excreted in small quantities in mother’s milk.
The distribution of Flucloxacillin into body tissues and fluids is similar to that of Cloxacillin.
- Metabolism: In normal subject approximately 10% of the flucloxacillin administered is metabolized to penicilloic acid. The elimination half-life of flucloxacillin is 30-60 minutes.
Flucloxacillin is metabolized to a limited extent and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion.
- Excretion: The drug is rapidly excreted by the kidney, about 50% within 6 hours of administration. A small portion of the dose administered is excreted in the bile. The excretion of flucloxacillin is slowed in cases of renal failure. Metabolites are excreted in the urine by glomerular filtration and renal tubular secretion: About 50% of a dose by mouth and up to 90% of an intramuscular dose is excreted in the urine within o hours.
Only small amounts are
excreted in the bile. Flucloxacillin is not removed by haemodialysis. Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxicillin. Following a 1-gram dose and utilizing a special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid.
Approximately 60% of an orally administrated dose of amoxicillin is excreted in the urine within 6 to 8 hours.
- Protein Binding: The serum protein binding rate is 95% in case of flucloxacillin whereas 20% of amoxicillin is protein bound.
Fixed dose combinations of Amoxicillin and Flucloxacillin is indicated for the treatment infections due Gram-positive organisms, including infections caused by B-lactamase producing staphylococci. Typical indications include:
Skin and Soft Tissue Infections: Boils, abscesses, carbuncles, furunculosis, cellulitis, infected wounds, infected burns, protection of skin grafts and impetigo.
Infected Skin Conditions: e.g. ulcer, eczema and acne.
Respiratory Tract Infections:
Pneumonia, lung abscess, empyema, sinusitis, pharyngitis tonsillitis, quinsy, otitis media and externa.
Other infections caused by amoxicillin & flucloxacillin-sensitive organisms such as osteomyelitis, enteritis, endocarditis, urinary tract infection, meningitis, septicemia.
Oral preparations of the B-lactamase-resistant penicillins (flucloxacillin alone or in combination with amoxicillin) should not be used as initial therapy in serious life-threatening infections. Oral therapy with fixed dose combination of amoxicillin & flucloxacillin, may be used to follow up the previous use of parenteral amoxicillin plus
flucloxacillin combination as soon as the clinical plus conditions warrants. Parenteral therapy is indicated caused by susceptible pathogens. Empirical therapy for infants with suspected negative staphylococcal sepsis. Drug may be administered combination or with netilmicin until culture results available.
Bone and joint infections
Dosage & Method of administration
Oral: Adults (including elderly patients): 2 capsules initially and then either 1 or 2 capsules 8-hourly, depending on severity of infection.
Children weighing 20 kg or more should be dosed according to the adult recommendations in severe infections or those caused by less susceptible organisms: 2 capsules every 6 hours for adults and 40 mg /kg/day in divided doses every 6 for children may be needed.
Desse should be administered 1 hour before
Parenteral Dose and Administration
25-50mg/kg/ dose by slow, IV injection.
|Weeks Postconception <29
|Days Postnatal 0 to 28
|30 to 36
|O to 14
|37 to 44
|O to 7
Flucloxacillin is administered by mouth as the sodium salt, in the form of capsules. Amoxicillin is available as amoxicillin trihydrate. It should be taken at least 30 minutes before meals as the presence of food in the stomach reduce absorption.
Both Amoxicillin & Flucloxacillin are administered parenterally as the sodium salt. In severe renal failure a reduction in dosage may be necessary.
Amoxicillin & Flucloxacillin are semisynthetic penicillin and should not be given to patients with a history of hypersensitivity to beta-lactam antibiotics (e.g. Penicillin, cephalosporins) or excipients. flucloxacillin is contraindicated in patients with a previous history of Flucloxacillin-associated jaundice/hepatic dysfunction.
Special Warnings and Special Precautions for use
Precautions: Dosage should be adjusted in renal impairment with other Medicaments and other forms of interactions. Bacteriostatic agents may interfere with the bactericidal actions of amoxicillin and flucloxacillin. Probenecid decrease the renal tubular secretion of both amoxicillin and flucloxacillin.
Concurrent administration of probenecid delays the renal excretion of amoxicillin and flucloxacillin.
Pregnancy and Lactation
Penicillins are generally considered safe for use in pregnancy. Animal studies with Amoxicillin and flucloxacillin have shown no teratogenic effects.
Limited information is available concerning the results of the use of Amoxicillin & Flucloxacillin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.
Trace quantities of amoxicillin and flucloxacillin are excreted in breast milk. Amoxicillin and Flucloxacillin may be administered during the period of lactation.
With the exception of the risk of sensitization there are no detrimental effects for the breastfed infant.
Effect on Ability to Drive and Use Machines
Adverse effects on the ability to drive or operate machinery have not been observed
Before initiating therapy with amoxicillin and flucloxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactamas. Cross-sensitivity between penicillin and cephalosporins is well documented. If any hypersensitivity reaction occurs, the treatment should be discontinued. Rashes, urticaria, purpura, fever, eosinophilia: sometimes angioneurotic oedema, rarely anaphylatic shock (exceptional with oral administration) Certain reactions (fever, arthralgia, myalgia) sometimes develop more than 48 hours after the start of the treatment. Erythema multiforme has been reported rarely.
Serious and occasionally fatal, hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-lactam antibiotics, Although anaphylaxis is more frequently following parenteral therapy, it has occurred in patients on oral therapy.
These reactions are more likely to occur in individuals with a history of beta-lactam hypersensitivity. If an allergic reactions occurs, amoxicillin and flucloxacillin should be discontinued and appropriate therapy instituted. Serious anaphylactoid reaction may require immediate emergency treatment with adrenaline, with Oxygen, intravenous steroids and airway management including intubation, may also be required. As with other penicillin, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena, They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma hay fever or urticaria. The following adverse reactions have been reported as associated with the use of penicillins: Erythematous maculopapular rashes, erythema multiforme. Stevens-Johnson Syndrome, toxic epidermal necrolysis and urticaria have been reported.
NOTE: These hypersensitivity reactions may be controlled with antihistamine and, if necessary systemic corticosteroids. Whenever such reactions occur, amoxicillin and flucloxacillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threating and amenable only to amoxicillin and flucloxacillin therapy.
Gastrointestinal reactions: Nausea, vomiting and diarrhea. Minor gastrointestinal disturbances may occur during treatment. As with other antibiotic, pseudomembranous colitis has been reported rarely. If this condition develops, amoxicillin and flucloxacillin treatment should be discontinued and appropriate therapy. e.g. oral vancomycin should be initiated.
Hepatic and cholestatic jaundice have been reported. Hepatic and cholestatic jaundice have been reported occasionally with Flucloxacillin and may be delayed in onset older patients and those receiving Flucloxacillin for more than two weeks are at greater risk
These may be delayed for up to two months post-treatment. In some cases the course has been protracted and lasted for several months. Very rarely, deaths have been reported, almost always in patients with serious underlying disease.
Change in liver function test results may occur, but are reversible when treatment is discontinued.
A moderate rise in Serum glutamic oxaloacetic transaminase (SGOT) has been noted but the significance of this finding is unknown.
Neutropenia (including agranulocytosis) and thrombocytopenia may occur but are reversible when treatment is discontinued. Anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and agranulocytosis have been reported during therapy with penicillin. These reactions are usually, reversible on discontinuation of therapy and are believed to be hypersensitivity reactions.
no patients suffering from renal failure, neurological disorders with convulsions are possible with high doses (mainly parenteral), Reversible hyperactivity, agitation, anxiety, insomnia., confusion, bahavioral changes and / or dizzines: have been reported rarely.
Interstitial nephritis may occur but is reversible when
treatment is discontinued.
Like Amoxicillin, Flucloxacillin may decrease the efficacy of estrogen-containing oral contraceptives.
May reduce absorption of oral contraceptives leading to break through bleeding or pregnancy.
Parenteral therapy (Caution & Precautions).
Hypersensitivity to penicillins/ cephalosporins.
Cautions in preterm infants, especially extreme immaturity. Cautions in infants with liver, renal or gastrointestinal disease. Venous irritation, soft tissue injury at site of IV injection.
Pain soft tissue injury at site of IM injection.
(nausea, vomiting, diarrhoea). Non-specific rashes and skin eruptions.
Fever, Pruritis, urticaria.
Seizures (encephalopathy) with high doses greater than 400 mg/kg/day.
May be given concurrently with aminoglycoside for synergistic
effect. Administer separately as
simultaneous administration may cause inactivation and precipitation. Adjust dose in suspected renal dysfunction (usually by lengthening the dosing interval)
Gastrointestinal effect such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically. Flucloxacillin is not removed from the circulation by haemodialysis.
As for penicillin. Incompatible with colistin polymixin B sulphate.
Loss of potency after mixing with
Streptomycin has been reported.
Capsule: Store below 30°C. Protected from light.
Vial: Store below 25°C. Protected from light.
Medicine Classification: Prescription Medicine Only, Presentation:
Flumox Capsules: 2x 10’s
Flumox injection IM/IV: 1 Vial with WFI
Zifam Pyrex Myanmar Co., Ltd.
Lot C6, Zone-A, Thilawa SEZ, Thanlyin and Kyaut Tan Township, Yangon, Myanmar.
Zifam Pinnacle Pty.Ltd
The Healthcare Group
Updated on 9/Feb/2024