Fosmicin

Fosfomycin sodium.

Fosfomycin sodium is disodium(-)-(1R,2S)-(1,2-epoxypropyl) phosphonate. Its molecular formula is C₃H₅Na₂O₄P and its molecular weight is 182.02.
Fosfomycin sodium is a white crystalline powder having a slightly salty taste. It is very soluble in water, sparingly soluble in methanol, and practically insoluble in acetone, ethyl acetate, ether and chloroform. Decomposition Point: Over 300°C.
pH and Osmotic Pressure Ratio: See Table 1.


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Pharmacokinetics: Absorption and Excretion: In adult patients, IV injection of 1 g dissolved in 20 mL of 20% glucose solution produced a mean peak blood concentration of 74 mcg/mL at 30 min after injection which gradually declined to 8 mcg/mL by 6 hrs after injection. In healthy adult volunteers receiving 1-hr IV drip infusion of 2 g dissolved in 300 mL of 5% glucose solution, a mean peak blood concentration of 157.3 mcg/mL was attained at the time of completion of the infusion. This gradually decreased thereafter, approaching a level of 2.6 mcg/mL at 12 hrs after infusion.
The serum half-life was 1.8 hrs. The urinary recovery rate was 96% on an average within the first 2 hrs. It diffuses efficiently to the organs and tissues and is excreted in the urine in an active unchanged form.
Tissue Concentrations: In patients with respiratory tract infections, IV injection of 1 g produced a mean sputum concentration of 7 mcg/mL over the first 3 hrs after injection.
Distribution to the cerebrospinal fluid was observed in patients with meningitis after IV injection or continuous IV drip infusion.
In rabbits, good distribution to the kidney, liver, lung, pancreas, heart, spleen, thymus, aqueous humor, etc was confirmed.
Toxicology: Acute Toxicity: LD₅₀ of fosfomycin sodium (FOM-Na) (mg/kg): See Table 2.


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Subacute and Chronic Toxicities: Subacute toxicity tests revealed that the maximum nontoxic dose is 500 mg/kg/day in rats and 400 mg/kg/day in rabbits.
Chronic toxicity tests in rats and dogs indicated the maximum nontoxic dose to be 250 mg/kg/day for both animals.
Microbiology: The mode of action of fosfomycin is very unique. It is taken into bacterial cells in high concentration via the active transport system against a concentration gradient and inhibits the initial stage of cell wall synthesis (β-lactam antibiotics inhibit the final stage of cell wall synthesis).
Fosfomycin acts bactericidally on gram-positive and gram-negative pathogens. It is especially highly active against Pseudomonas aeruginosa, Proteus sp, Serratia marcescens and multidrug-resistant strains of Staphylococcus aureus and E. coli.
A synergistic effect has been reported between fosfomycin and other antibiotics eg, β-lactam antibiotics aminoglycosides, macrolide and tetracycline.
Teratogenicity: In animal studies, no adverse effects were observed in audiovisual or teratogenicity tests. No antigenicity of fosfomycin sodium has been found in experiments on the induction of IgG and IgE antibodies.
Fosfomycin has not been observed to show any antigenicity in animal studies.

Prevention of infections in abdominal surgery.

IV Drip Infusion: Usual Daily Dosage: Adults: 2-4 g (potency). Children: 100-200 mg (potency)/kg body weight. Both of these are given by IV drip infusion in 2-4 divided doses. Each dose is dissolved in 100-500 mL of IV fluid and infused over a period of 1-2 hrs.
Acute and Elective Abdominal Surgery: Adults and Children >12 years: 8 g as a single dose infused IV 0.5-1 hr preoperative.
Depending on the level of contamination and the length of the surgery, this dose can be repeated. Fosmicin should be given in combination with aerobic antibiotics.
Renal Insufficiency: Repeated doses should not be given if creatinine clearance is <20 mL/min.
The dose interval should be 16 hrs at 20-40 mL/min, Fosmicin 8 mg to be mixed with 500 mL isotonic glucose infusion liquid and to be given at an infusion rate 10-15 mL/min. Heat is generated when Fosmicin is dissolved. Other antibiotics or medicaments should not be added.

Fosmicin should be administered with caution in patients with liver disorders.
Fosmicin should be administered only by the IV route. In addition, it is desirable for the administration to be performed by IV drip infusion whenever possible.
It is known that phlebitis and angialgia may occur following IV administration of Fosmicin. Therefore, sufficient care should be taken with regards to the selection of the injection site and the technique to be employed for the administration and the rate at which the drug solution is injected should be as slow as possible.
In the case of patients who are on long-term therapy, it is desirable to periodically perform liver and kidney function tests as well as hematological tests.
Fosmicin contains 14.5 mEq of sodium/g (potency); accordingly, care should be taken when administering it to patients who need to reduce their sodium intake due to heart failure, kidney failure, hypertension.
Use in pregnancy: The safety of Fosmicin during pregnancy has not yet been established. Therefore, it is advisable to avoid its use in female who are or may be pregnant.

Use in pregnancy: The safety of Fosmicin during pregnancy has not yet been established. Therefore, it is advisable to avoid its use in female who are or may be pregnant.

Liver: Occasionally, the values for SGOT, SGPT and ALP, LDH, γ-GPT and bilirubin may increase.
Kidney: Proteinuria and abnormalities in the Fishberg test develop in rare cases, and occasionally an elevated BUN value and edema may develop.
Respiratory Organs: Cough and asthma attacks may develop on rare occasions.
Central and Peripheral Nervous Systems: Occasionally, patients may experience headaches and a feeling of numbness of the lips following the use of Fosmicin. Moreover, in the case of administration of large doses, spasms may occasionally occur.
Hematological Disorders: On rare occasions, agranulocytosis may develop, and occasionally, patients develop signs of anemia, eosinophilia, granulocytopenia and thrombocytopenia.
Gastrointestinal Tract: Stomatitis, nausea, vomiting, abdominal pain, diarrhea and anorexia may occasionally develop.
Skin: Eruption, urticaria, erythema and itching rarely develop.
Injection Site: Phlebitis develops on rare occasions and angialgia may occasionally occur.
Others: There are occurrences of dull headache, oral dryness, vertigo and chest discomfort and occasionally, patients may experience a feeling of pressure on the chest.

When Fosmicin is dissolved, heat is released; this has no detrimental effect on the drug or its activity and is therefore no cause for worry.

Store at room temperature.

Other Antibiotics

J01XX01 - fosfomycin ; Belongs to the class of other antibacterials. Used in the systemic treatment of infections.

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