Fosmicin

Fosfomycin was first discovered in 1967 in a culture of Streptomyces fradiae, which was isolated from a Spanish soil sample. It is quite different from other antibiotics in that it has a very simple and unique chemical structure.
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.
Molecular Formula: C₃H₅Na₂O₄P.
Molecular Weight: 182.02.
As for pH and osmotic pressure ratio, see Table 1.

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Fosmicin is a sodium salt of fosfomycin and is given by IV administration. It is effective against infections due to Pseudomonas aeruginosa, Proteus sp, Serratia marcescens, E. coli and methicillin-resistant Staphylococcus aureus. Its mechanism of action is characteristic, and cross-resistance between fosfomycin and other antibiotics has not been demonstrated. Almost no binding to serum proteins has been reported. In animal studies, there has been no evidence of fosfomycin's antigenicity.
Pharmacology: Antibacterial Activity: Fosfomycin acts bactericidally on gram-positive and gram-negative pathogens. It is especially highly active against Pseudomonas aeruginosa, Proteus sp, Serratia marcescens, E. coli and methicillin-resistant Staphylococcus aureus.
Mechanism of Action: 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).
Pharmacokinetics: In Vivo Pharmacokinetic Behavior: 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 decreases 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, reaching 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 12 hrs.
Tissue Concentrations: Distribution to the cerebrospinal fluid was 54% observed in patients with meningitis after IV drip infusion.
Clinical Data: The results of 3 comparative clinical tests and general clinical trials using 1021 patients were as follows:
Clinical Efficacy: The efficacy rate was: 80.77% (21/26 cases) for septicemia and bacteremia; 94.4% (17/18 cases) for burn, 90.9% (30/33 cases) for adnexitis, 87% (47/54) for intrauterine infection, 86.7% (13/15) for pelvic dead space inflammation, 66.7% (6/9) for parametritis and 77.8% (10/13) for bone and joint infections.
**Results of Post-Marketing Surveillance.
The results of 5-year post-marketing surveillance since July 1994 to March 1999 are as follows: 100, 230 clinical case reports were obtained from 4737 medical facilities nationwide. There were 562 cases (0.56%) of side effects.
The principal side effects developed were as shown in Table 2. (See Table 2.)

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Toxicology: Non-Clinical Tests: Acute Toxicity: See Table 3.

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Subacute and Chronic Toxicities: In subacute toxicity tests using rats and rabbits, the maximum no-effect dose was surmised to be 500 mg/kg/day in rats and 400 mg/kg/day in rabbits. In chronic toxicity tests using rats and dogs, the maximum non-effect dose was surmised to be 250 mg/kg/day for both animals.
Teratogenicity: Neither teratogenic effect, toxicity to the fetus nor influence on the growth of neonates was observed in tests using pregnant rats and rabbits when they administered the drug intraperitoneally or IV during the organogenesis, perinatal and lactation periods.
Antigenicity: No antigenicity of fosfomycin was found in animal experiments using rabbits and mice, and investigation for induction of IgG and IgE antibodies.
Mutagenicity: Ames and dominant lethal tests using mice showed that the drug possesses no mutagenicity.
Distribution: The drug efficiently transferred to the kidney, liver, lung, spleen, heart, thymus gland, aqueous humor, etc, after administering it at 40 mg/kg to rabbits.

Infections due to fosfomycin-susceptible strains of Pseudomonas aeruginosa, Proteus sp, Serratia marcescens, Escherichia coli and methicillin-resistant Staphylococcus aureus: Septicemia, bronchitis, bronchiolitis, infected bronchiectasis, pneumonia, meningitis, UTI infections, suppurative diseases of the lung, pyothorax, peritonitis, pyelonephritis and cystitis.

IV Drip Infusion: Usual daily dosage of Fosmicin for IV use: Adults: 4 g/day (potency). Children: 100-200 mg/day (potency)/kg; both of these are given by IV drip infusion in 2 divided doses. Each dose is dissolved in 100-500 mL of IV fluid and infused over a period of 1-2 hrs.
IV Injection: Adults and children: The usual daily dosages are the same as for IV drip infusion, but given in 2 divided doses. As a solvent, 20 mL of water for injection or 5% glucose solution for injection is used to dissolve 1-2 g of Fosmicin for IV use. The IV injection must be performed over a period of >5 min.
The previously mentioned daily dosages may be adjusted according to the age of the patient and the severity of the infection.
Meningitis: 6-12 g/day divided 8 hrly.
Osteomyelitis or Bone and Joint Infections: 4 g every 12 hr.

Patients with a history of hypersensitivity to fosfomycin.

General Precautions: Sufficient history taking should be done to predict such adverse reactions as shock.
Careful Dosage: Fosmicin should be administered with caution to the following patients: Those who or whose parents or siblings have a predisposition to develop allergic reactions ie, bronchial asthma, rash and urticaria.
Those with liver disorders.
Other Precautions: In the case of patients who are put on long-term therapy using this drug, it is advisable to periodically perform liver and kidney function tests, as well as hematological tests. Fosmicin for IV use 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, etc.
Use in Pregnancy: The safety of Fosmicin for administration during the course of pregnancy has not yet been established. Therefore, it is advisable to avoid the use of this drug in females who are, or may be pregnant.

Use in Pregnancy: The safety of Fosmicin for administration during the course of pregnancy has not yet been established. Therefore, it is advisable to avoid the use of this drug in females who are, or may be pregnant.

Shock: Rarely, shock symptoms may occur, so sufficient observation is needed. When such symptoms as chest anxiety, dyspnea, decreased blood pressure, cyanosis, urticaria and discomfort, etc occur, administration should be discontinued and suitable countermeasures should be taken.
Liver: Occasionally, liver disorders eg, rise in the values for SGOT, SGPT, ALP, LDH r-GTP, bilirubin, etc may appear. Rarely, jaundice may appear, so sufficient observation is needed. When such symptom appears, discontinue Fosmicin and take suitable countermeasures.
Hematological Disorders: Rarely, agranulocytosis, granulocytopenia, anemia, eosinophilia, etc may appear.
Kidney: Renal disorders, edema, an elevated BUN value, proteinuria, abnormality in electrolytes, etc may rarely appear.
Gastrointestinal Tract (Digestive Tract): Such side effects as stomatitis, nausea, vomiting, abdominal pain, diarrhea and anorexia may occasionally appear.
Skin: Rarely, eruption, erythema, urticaria, a feeling of itching, etc may appear.
Respiratory Organs: A cough and asthma attacks may rarely appear.
Central and Peripheral Nervous Systems: Occasionally, patients may experience headache 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 appear.
Injection Site: Rarely, phlebitis develops and angialgia may occasionally appear.
Others: Rarely headache, oral dryness, redness, fever, feeling of fatigue, chest discomfort, a feeling of pressure on the chest, palpitation, etc may appear.

Fosmicin for IV use should be administered only by IV route. In addition, it is advisable for the administration to be performed by IV drip infusion whenever possible.
It is known that phlebitis and angialgia may occur following the IV administration of Fosmicin. Therefore, sufficient care should be taken with regard 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.
Note: When Fosmicin for IV use is dissolved, heat is released; this has no detrimental effect on the drug or its activity, and is therefore no cause for worry.
When 1 g of Fosmicin for IV use was dissolved in 20 and 100 mL each of distilled water for injection, physiological saline and 5% glucose solution, and the resultant solutions were preserved for 7 days, there were almost no change in the potency, pH or appearance, indicating that the solutions are stable.
The same results were obtained with 2 g of Fosmicin for IV use when tested by the previously mentioned method.

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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