Pharmacology
Oharmacodynamics
faropenem is bactericidal, it has a strong affinity for the high molecular penicillin binding proteins (PBPs) of the cell wall, which is essential for multiplication of bacilli and thus acts by inhibiting the cell wall synthesis.Faropenem show broad antibacterial activity against both aerobic and anaerobic gram-positive and gram-negative bacteria. Faropenem is highly stable against various beta-lactamases and binds preferentially to the penicillin-binding protenis (PBPS) 2 and 1A of Escherichia coli.
Microbiology
Faropenem was found to be active against Enterococcus faecalis, Oxacillin-susceptible Staphylococci, Neisseria gonorrheae, Neisseria meningitides, Haemophillus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus saprophyticus, Staphylococcus epidermidis, Group A Streptococci, Group B Streptococci, Streptococcus milleri, Streptococcus viridans, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, E.coli, Klebsilla spp., Providentia stuartii, bacteroides fragilis, C.perfringens, Peptostreptococcus spp.
Faropenem was less active against the following:
Citrobacter freundii, Proteus mirabilis, Enterobacter spp., Proteus vulgaris and Morganella morganii.
Pharmacokinetics
Absorption
After single oral dose of faropenem in fasting healthy volunteers at 150,300 and 600 mg, the plasma levels of faropenem reached Cmax of 2.4,6.2 and 7.4 ug/ml, respectively at about 1 1.5 hours (Tmax) The AUCs of faropenem were 3.94,11.73 and 19.59 ug/ml. These Cmax and AUCs were proportional to the doses. The half-life of faropenem is about 1 hours irrespective of the dosage quantity.
At a single does of 300 mg in normal healthy adults after meals, the average Tmax was delayed by about 1 hours, but C, AUC and urinary recovery were not different from those in the fasting state. In the multiple dose study with 400 mg t.i.d., the C on day 1, 4 and 7 (1st,10th and 19th administration) were 5.5,4.3 and 4.8 ug/ml, respectively. The respective AUCs were 12.5,10.1 and 12.2 ug/ml, demonstrating no cumulative effect.
table: Average Pharmacokinetic Parameters of faropenem on single does administration on empty stomach in normal healthy adults (average +/- SD)
|
n |
C max(μg/ml) |
T max(h) |
T 1/2 (h) |
AUC μg.h/ml |
| 150 mg/person (empty stomach) |
6 |
2.36 ± 1.01 |
0.96 ± 0.46 |
0.76 ± 0.14 |
3.95 ± 2.06 |
| 300 mg/person (empty stomach) |
6 |
6.24 ± 2.86 |
1.04 ± 0.40 |
0.85 ± 0.23 |
11.73 ± 8.34 |
| 600 mg/person (empty stomach) |
6 |
7.37 ± 1.97 |
1.42 ± 0.49 |
1.08 ± 0.19 |
19.59 ± 6.37 |
Distribution
faropenem was found in the sputum of patients, fluid that oozes at the time of tooth extraction, tonsil tissues, maxillary sinus, mucous membrane tissues, female genital organ tissues, eyelids, subcutaneous cell tissues and prostate tissues.
Metabolism and Excretion
Before excretion in urine the absorbed faropenem gets metabolized by dehydropeptidase-I (DHP I) present in the kidney. The metabolites were found in blood and urine. The metabolites dont demonstrate antibacterial activity.
Faropenem is primarily excreted through kidneys and the rate of excretion in urine (0 ~ 24 hrs) of 150,300 and 600 mg (given on empty stomach to normal healthy adults) was 3.1 ~6.8% and the highest concentration in urine was 21.7,55.6 and 151.5 mg.ml respectively in 0-2 hours and after 12 hours it was almost nil.
INDICATIONS
Faropenem sodium tablets are indicated in the treatment of the following infections:
Lower respiratory tract infections: e.g acute bronchitis, pneumonia,pulmonary suppuration.
ENT infections: e.g. otitis externa, tympanitis, sinusitis
Upper respiratory tract infections: e.g. pharyngitis, tonsillitis
Skin and skin structure infections:e.g. pustular acne, folliculitis, contagious impetigo, erysipelas, lymphangitis, suppurative nail inflammation, subcutaneous abscess, hidradenitis (sweat gland inflammation), infective sebaceous cyst, chronic pyoderma, secondary infection of external wounds or surgical wound.
Gynaecological infections:e.g. adnexitis, bartholin gland inflammation.
DOSAGE AND ADMINISTRATION
| Indication |
Dosage |
| Lower respiratory tract infections |
200 mg t.i.d., can be increased to 300 mg t.i.d. |
| ENT infections |
200 mg t.i.d., can be increased to 300 mg t.i.d. |
| Genito-urinary infections |
200 mg t.i.d., can be increased to 300 mg t.i.d. |
| Upper respiratory tract infections |
150 mg t.i.d., can be increased to 200 mg t.i.d. |
| Skin and skin structure infections |
150 mg t.i.d., can be increased to 200 mg t.i.d. |
| Gynaecological infections |
150 mg t.i.d., can be increased to 200 mg t.i.d. |
Duration of treatment: the duration of treatment depends upon the severity of infection, clinical response and bacteriological findings.
CONTRAINDICATIONS
faropenem is contraindicated in patients with known hypersensitivity to any of the components of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams.
WARNINGS AND PRECAUTIONS
faropenem should be administered withcaution in the following:
1. Patients with past history of hypersensitivity to penicillin, cephem or carbapenem drugs.
2. Patients with family history of atopy.
3. patients with renal insufficiency. The dosage should be reduced or the interval between doses should be increased.
4. Geriatric patients.
5. Patients with poor oral intake or poor general state (since there are cases that show symptoms of vitamin K deficiency, proper monitoring should be done).
Drug interactions
Imipenem and cilastatin sodium combination: It has been reported that in animal studies (rat), the concentration of faropenem in blood increases. It is due to obstruction of metabolic fermentation by cilastatin.
Furosemide It has been reported in animal studies (dog), that the kidney toxicity of faropenem increases.
Sodium valproate It has been reported that due to joint usage with carbapenem drugs (meropenem, panipenem and imipenem-cilastatin sodium), the concentration of valproic acid in blood reduces, and there is recurrence of epileptic fits.
Renal impairment
In patients with renal impairment, it was found that the plasma conncentration of the drug is increased and the half-life is extended.
Pregnancy
Safety regarding therapy during pregnancy has not been established. In pregnant women or expectant mothers, the medicine should be given only if the benefits of the treatment are greater than the risk involved.
Lactation
Faropenem is excreted in human milk. In lactating women faropenem should be given only if the benefit outweighs the risk.
Paediatric use
safety regarding therapy in infants has not been established.
Geriatric use
Half life of faropenem is prolonged in the elderly and this may be due to decline in kidney function and as a result there is high plasma concentration. In the elderly start with a dose of 150 mg and monitor the patient for any undesirable effects.
If diarrhoea and loose bowel movements appear, stop the medicine, monitor properly and take appropriate measures. There is a tendency of haemorrhage due to vitamin K deficiency in the elderly.
UNDESIRABLE EFFECTS
Faropenem is geberally well tolerated. The most frequently reported adverse reactions are diarrhoea, abdominal pain, loose bowel movements, nausea and rash.
The following adverse reactions have been observed:
Shock, pseudoanaphylactic symptoms: feeling of discomfort, wheezing, breathing trouble, dizziness, feeling of need to evacuate bowel, ringing in the ear, sweating, flushing of whole body, vascular edema, low blood pressure.
Acute renal insufficiency
Serious colitis accompanied by pseudomembranous colitis: bloody stool, stomach ache, frequent diarrhoea.
Mucocutaneous Ocular Syndrome (Steven-Johnson syndeome), Toxic Epidermal Necrosis (Lyell syndrome).
Interstital Pneumonia: pyrexia, cough, breathing trouble, abnormalities in the chest x-ray. If these symptoms appear, appropriate measures such as adrenal cortical hormone should be administered.
Liver function disorder, jaundice: an increase in AST (SGOT), ALT (SGPT), ALP etc.
Agranulocytosis.
Striated muscle softening: muscular pain, feeling of exhaustion, increase in CK (CPK), increase in myoglobin in blood and in urine, and subsequenyly,acute renal insufficiency.
Pulmonary infiltration with eosinophilia (PIE) syndrome: pyrexia, cough, breathing trouble, abnormalities in the chest x-ray and eosinophilia. If these symptoms appear, appropriate measures such as adrenal cortical hormone should be administered.
Hypersensitivity reactions: rash, pyrexia, redness, hives, red spots on skin, etc.
Abnormal laboratory findings: e.g. increases in liver function tests (ALT,AST, bilirubin, LDH etc), eosinophilia, increase in BUN-Creatinine, changes in granulocyte and platelets.
Vitamin deficiency: Symptoms of vitamin K deficiency (low prothrombin, tendency of haemorrhage etc), symptoms of vitamin B-group deficiency (inflammation of tongue,stomatitis, lack of appetite, neuritis etc) might occur rarely.
Gastrointestinal disorders: Vomiting, stomach ache, diarrhoea, lack of appetite, inflammation of corners of mouth and lips, gastritis, constipation, stomatitis.
Others: Burning sensation, headache, dizziness, drowsiness, edema, dryness of mouth and lips, change in nail color, washed out feeling occurs rarely.
OVERDOSAGE
No specific information is available on the treatment of overdosage with faropenem. Intertional overdosing of faropenem is unlikely. In the event of an overdose, faropenem should be discontinued and general supportive treatment given until renal elimination takes place.
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