For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
SODIUM FUSIDATE TABLETS (Sodium Fusidate) is the sodium salt of a substance having antibacterial activity produced by the growth of Fusidium coccineum. Chemically, Sodium Fusidate is Sodium (Z)-ent-16α-(acetyloxy)-3β,11β-dihydroxy-4β,8,14-trimethyl-18-nor-5β,10α-cholesta-17(20),24-dien-21-oate.The molecular formula is C31H47NaO6 and molecular weight is 538.7.
STRUCTURAL FORMULA :
Its structural formula is :
SODIUM FUSIDATE TABLETS is a white coloured, round film coated tablet.
Each film coated tablet contains :
Sodium Fusidate B.P. 250 mg
Colour : Titanium Dioxide B.P.
Fusidic acid is a steroidal antibacterial with a bacteriostatic or bactericidal activity, mainly against Gram-positive bacteria. Fusidic acid inhibits bacterial protein synthesis although, in contrast to drugs such as the macrolides or tetracyclines, it does not bind to the bacterial ribosome, but inhibits a factor necessary for translocation of peptide subunits and elongation of the peptide chain. It is capable of inhibiting protein synthesis in mammalian cells but exerts a selective action against susceptible infecting organisms because of poor penetration into the host cell. Fusidic acid is very active against staphylococci, notably Staph. aureus and Staph. epidermidis (including meticillin-resistant strains). Nocardia asteroides and many clostridial strains are also highly susceptible. The streptococci and enterococci are less susceptible. Most Gram-negative bacteria are intrinsically resistant but fusidic acid is active against Neisseria spp. and Bacteroides fragilis. It has some activity against strains of Mycobacterium tuberculosis and is highly active against M. leprae.
Fungi are resistant, but fusidic acid has some activity against a range of protozoa including Giardia lamblia and Plasmodium falciparum. High concentrations of SODIUM FUSIDATE are reported to inhibit viral growth in vitro, including that of HIV, although it is unclear whether this represents a surfactant effect, a general cytotoxic effect, or a genuine antiviral action. No synergy has been shown in vitro in most studies between fusidic acid and rifampicin or vancomycin, and antagonism of the effects of ciprofloxacin has been reported. Interactions with the penicillins are complex, with either antagonism of the effect of one or both drugs, or no interaction. However, use of an antistaphylococcal penicillin with fusidic acid may prevent the emergence of fusidic acid-resistant staphylococcal mutants, and such combinations may be clinically effective.
SODIUM FUSIDATE is well absorbed from the gastrointestinal tract, and a single oral 500-mg dose is reported to produce mean plasma concentrations of about 30 micrograms/ml within 2 to 4 hours, although there is considerable interindividual variation. Oral suspensions of fusidic acid are less well absorbed, with a bioavailability reported to be about 70 % of that for SODIUM FUSIDATE. Absorption may be delayed by food and may be more rapid in children than adults. Some accumulation occurs with repeated dosage and plasma concentrations of 100 micrograms/ml or more have been reported after 500 mg of SODIUM FUSIDATE given three times daily for 4 days. SODIUM FUSIDATE is widely distributed into tissues and body fluids, including bone, pus, and synovial fluid ; it penetrates cerebral abscesses but does not enter CSF in appreciable amounts. It has been found in the foetal circulation and in breast milk. About 95 % or more of SODIUM FUSIDATE in the circulation is bound to plasma proteins. SODIUM FUSIDATE has a plasma half-life of about 10 to 15 hours. It is excreted in the bile, almost entirely as metabolites, some of which have weak antimicrobial activity. About 2 % appears unchanged in the faeces. Little is excreted in the urine or removed by haemodialysis.
Treatment of localised as well as generalised staphylococcal infections (e.g. abscesses, furunculosis, wound infections, pneumonia, peritonitis, osteomyelitis, septicaemia, enteritis and otorhinolaryngeal infections). Cystic fibrosis : SODIUM FUSIDATE TABLETS is useful for elimination of staphylococci from the respiratory tract of patients with this condition. Endocarditis : when the infecting organism has been shown to be susceptible. If bacteriological diagnosis reveals methicillin-resistant Staphylococcus aureus, the use of SODIUM FUSIDATE TABLETS monotherapy is not appropriate and concurrent treatment with other anti-staphylococcal antibiotics is necessary.
Administration : For Oral Use Only SODIUM FUSIDATE TABLETS should be taken without a meal to avoid a reduction in the extent and rate of absorption of SODIUM FUSIDATE TABLETS by a concomitant meal.
Dosage : For community acquired mild to moderate acute skin and skin structure infections likely to be caused by methicillin - sensitive staphylococci e.g. boils, carbuncles, furuncles, superficial abscesses, paronychia, superficial wound infections and impetigo.
Adults : 250 mg twice daily. For all other indications caused by Staphylococcus aureus. Adults 2 x 250 mg three times daily.
Children 5 to 12 years : 250 mg three times daily.
Over 12 years : as for adults.
In severe infections, deep-seated infections, infections due to methicillin-resistant staphylococci or when prolonged therapy may be required, SODIUM FUSIDATE TABLETS must be given concurrently with other anti-staphylococcal antibiotic therapy. Such combinations may produce enhanced activity, broaden the antibacterial spectrum and minimise the risk of less sensitive mutants. In general, full dosage of each antibiotic has been used and in severe infections, the dosage of SODIUM FUSIDATE TABLETS may also be doubled. The average duration of treatment is six days although more severe infection may indicate a longer period.
Dosage in Hepatic Insufficiency :
Dosage reduction may be necessary in patients with hepatic impairment, since fusidic acid is cleared from the blood via hepatic metabolism. Since SODIUM FUSIDATE TABLETS is excreted in the bile, no modifications are needed in renal impairement. The dosage in patients undergoing haemodialysis needs no adjustment as SODIUM FUSIDATE TABLETS is not significantly dialysed.
Contra-indicated in patients with known hypersensitivity to fusidic acid and its salts. SODIUM FUSIDATE TABLETS contains lactose which is contra-indicated in patients with galactosaemia, the glucose-galactose malabsorption syndrome, or lactase deficiency.
WARNINGS & PRECAUTIONS :
Liver function tests should be performed regularly in patients taking high doses, in patients taking the drug for prolonged periods and in patients with abnormal liver function. Risk-benefit should be considered when the following medical problems exist. Hepatic function impairment : SODIUM FUSIDATE TABLETS is metabolised in the liver; patients with impaired or immature hepatic function, especially neonates and infants or adults with impaired hepatic function, may require a reduction in dose or an alternative antibiotic should be considered. Caution should be exercised if SODIUM FUSIDATE TABLETS is administered with other drugs, including antibiotics (e.g. clindamycin and rifampicin), which have a similar biliary excretion pathway. Fusidic acid and its salts, when administered systemically, and concomitantly with oral anticoagulants such as warfarin, other coumarin derivatives or anticoagulants with similar action, may increase the plasma concentration of these anticoagulant agents, enhancing the anticoagulant effect. Downward adjustment of the oral anticoagulant dose, monitored by laboratory coagulation testing and clinical status, may be necessary in order not to exceed the desired level of anticoagulation. The mechanism of this suspected interaction remains unknown.
Specific pathways of SODIUM FUSIDATE TABLETS metabolism in the liver are not known, however, an interaction between SODIUM FUSIDATE TABLETS and drugs biotransformed via CYP-3A4 is suspected. The apparent mechanism of this interaction is a mutual inhibition of metabolism. The use of SODIUM FUSIDATE TABLETS systemically should be avoided in patients treated with CYP-3A4 biotransformed drugs. Common examples of CYP-3A4 biotransformed drugs are paracetamol, digitoxin and steroids. Co-administration of systemic SODIUM FUSIDATE TABLETS and HIV protease inhibitors, such as ritonavir and saquinavir, causes increased plasma concentrations of both agents, which may result in hepatotoxicity. Resistance has developed both in vitro and in vivo and physicians should be alert to this possibility. In spite of the ease with which staphylococci develop resistance to SODIUM FUSIDATE TABLETS in vitro, the development of resistance in clinical practice is not a frequent occurrence. SODIUM FUSIDATE TABLETS should be used cautiously in diabetic patients.
Pregnancy : Category C
Fusidic acid may cause kernicterus in babies during the first month of life by displacing bilirubin from plasma albumin. Fusidic acid should be avoided when possible during the last month of pregnancy.
Nursing mothers :
Safety in lactation has not been established. There is evidence that the drug can penetrate the placental barrier and is detectable in human milk. Caution is therefore required when SODIUM FUSIDATE TABLETS is used in mothers who wish to breast feed.
Paediatric Use :
SODIUM FUSIDATE TABLETS has been given to neonates from the day of birth and for periods of up to one year without adverse effects. Despite the immature enzyme system in the neonate, none of the children showed any evidence of hepatotoxicity, nor did they develop renal, blood, ocular or other toxicity.
Effects on ability to drive and use machines :
Sodium fusidate has no or negligible influence on the ability to drive and to use machines.
INTERACTIONS AND INCOMPATIBILITIES :
Specific pathways of SODIUM FUSIDATE TABLETS metabolism in the liver are not known, however, an interaction between SODIUM FUSIDATE TABLETS and drugs being CYP-3A4 biotransformed can be suspected. The mechanism of this interaction is presumed to be a mutual inhibition of metabolism. There is insufficient data to characterise the effect of fusidic acid on CYPs in-vitro. The use of SODIUM FUSIDATE TABLETS systemically should be avoided in patients treated with CYP-3A4 biotransformed drugs. SODIUM FUSIDATE TABLETS administered systemically and concomitantly with oral anticoagulants such as coumarin derivatives or anticoagulants with similar actions may increase the plasma concentration of these agents enhancing the anticoagulant effect. Anticoagulation should be closely monitored and a decrease of the oral anticoagulant dose may be necessary in order to maintain the desired level of anticoagulation. Similarly, discontinuation of SODIUM FUSIDATE TABLETS may require the maintenance dose of anticoagulant to be re-assessed. The mechanism of this suspected interaction remains unknown.
Co-administration of SODIUM FUSIDATE TABLETS systemically and HMG-CoA reductase inhibitors such as statins may cause increased plasma concentrations of both agents and rare cases of rhabdomyolysis have been reported for this combination. Patients on this combination should be closely clinically monitored. Co-administration of SODIUM FUSIDATE TABLETS systemically and ciclosporin has been reported to cause increased plasma concentration of ciclosporin.
SIDE EFFECTS :
Gastrointestinal Reactions : Nausea, vomiting, epigastric pain, anorexia, diarrhoea and dyspepsia. The incidence of these effects with the oral presentations can be lessened by taking the medication with food. SODIUM FUSIDATE TABLETS can cause disturbances of liver function including jaundice. Typically there is a predominant elevation of conjugated bilirubin. Elevations of alkaline phosphatase and transaminase levels are usually less marked. Recovery normally follows cessation of the use of SODIUM FUSIDATE TABLETS. The incidence of jaundice is higher with intravenous therapy. In some instances where the onset of jaundice was associated with the intravenous use of SODIUM FUSIDATE TABLETS , recovery followed a change to oral therapy but this was not invariable.
Skin rashes and pruritus have been observed on rare occasions. Dizziness, blurred vision and headaches have been generally mild and infrequent. Leukopaenia, thrombocytopaenia, pancytopaenia and anaemia. Haematological disorders affecting the white cell line (neutropaenia, granulocytopaenia, agranulocytosis) and more rarely disorders affecting the other two cell lines have been reported, either as isolated or associated events. This has been observed especially in cases of treatment duration of more than 15 days and is reversible upon drug withdrawal. Musculoskeletal, connective tissue and bone disorders : Frequency not known: Rhabdomyolysis (examples of signs and symptoms are muscle weakness (swelling and pain), dark urine, myoglobinuria, elevated serum creatine kinase, acute renal failure, cardiac arrhythmia). Severe allergic reactions including angioneurotic oedema have been reported rarely.
Early symptoms may include epigastric or gastric discomfort and possibly diarrhoea. Prolonged ingestion of high doses may produce jaundice and other abnormalities of liver function.
TREATMENT OF OVERDOSAGE :
There are no published reports of the treatment of accidental massive overdosage with SODIUM FUSIDATE TABLETS and there has been no experience with any specific treatment. Treatment should be restricted to symptomatic and supportive measures. Dialysis is of no benefit, because the drug is not significantly dialysed.
Store below 30°C(86°F), protected from moisture and light.
Do not refrigerate.
SHELF LIFE :
24 months from the date of manufacture.
SODIUM FUSIDATE TABLETS contain Sodium Fusidate B.P. 250 mg
2 Blisters of 10 Tablets in a carton.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.