Biapenem for Injection

Biapenem for Injection

Generic name: Biapenem for Injection
Brand name : Newanti
Composition: Biapenem without excipients
Chemical name: 6-[[(4R,5S,6S)-2-carboxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-
2-en-3-yl]thio]-6,7-dihydro-5H-pyrazolo[1,2-a]-s-triazol-4-ium hydroxide, inner salt
Structural Formula:

Molecular Formula: C15H18N4O4S
Molecular weight:  350.40
Strength: 0.3g
Appearance:
White to slight yellow crystalline powder
Indications:
Bacterial strain susceptible to the drug: staphylococcus, streptococcus, pneumococcus, enterococcus (except
enterococcus faecium), Moraxella, escherichia coli, Citrobacter, Klebsiella, enterobacter, Serratia, Proteus,
Haemophilus influenza,Pseudomonas aeruginosa, actinomyces, Peptostreptococcus, Bacteroides, Prevotella,
Fusobacterium, etc.epsis, pneumonia, lung abscess, superinfection in chronic respiratory disease, refractory
urocystitis, pyelonephritis, peritonitis, gynecology annexitis caused by susceptible bacteria
Dosage and administration
0.3g biapenem dissolved in 100ml of sodium chloride solution or glucose injection for intravenous drip. For
adults, Biapenem for Injection is administered by intravenous infusion over approximately 30 minutes to 60
minutes, 0.6g per day, 2 times per day. Appropriate increase and decrease of dose based on symptoms is
permitted. Maximum daily dose is not more than 1.2g.
Adverse Reactions
As reported in the foreign literature, most common adverse reactions are erythra/ pruritus, nausea, emesis,
diarrhea, etc. During 2348 clinical investigations, adverse reactions are observed in 64 (2.7%) patients, mainly
erythra (1.0%), diarrhea (0.7%), etc. During 2287 clinical investigations, 552 clinical indicators of 304 patients
(13.3%) are abnormal, mainly ALT (GPT) increase (144 patients, 6.3%), AST (GOT) increase (93 patients,
4.1%), eosinophilia (77 patients, 3.4%), etc.
Serious adverse events were as follows:
(1)Shock (<0.1%), allergy;
(2)Interstitial pneumonia (0.1%~5%), PIE syndrome;
(3)Serious enteritis like pseudomembranous colitis;
(4)Myospasm, psychogeny;
(5)Hepatic impairment, jaundice;
(6)Acute renal insufficiency.
[Contraindications]
(1)Allergy to this product;
(2)Co-administration of valproates.
Warnings and precautions
Caution should be exercised when Biapenem for Injection is administered to patients
(1)allergic to carbapenems, penicillins and cephalosporin antibiotics;
(2)Himself or herself and their relatives with allergic constitution to bronchial asthma, erythra, urticarial;
(3)with serious renal insufficiency;
(4)elderly patients (refer to elderly medication);
(5)with eating difficulties or systemic deterioration, and my with vitamin K deficiency symptoms, which should
be monitored closely.
(6)With a history of seizure or central nervous system disease;
Test paper reaction and GLU test by Benedict's reagent or Fehling's solution may produce false positive
results; Kevin test may produce positive results.
Pregnant or Lactating use
There is limited safety data available to support the use in Pregnant or Lactating Women.
Pediatric use
There is limited safety data available to support the use in Pediatric Patients.
Geriatric use
Due to reduced physiological function of elderly patients, dosage and dosing interval adjustment should be
paid attention.
Drug interactions
Co-administration of biapenem,  patients receiving valproic acid results in  reduction in serum concentrations
of valproic acid, therefore resulting in recurrence of seizures. Co-administration of valproic acid with biapenem
should be avoided.
Overdosage
There is no report on overdose in human.If overdosing occurs, regular monitoring and symptomatic treatment
is adopted.
Pharmacology and toxicology
Pharmacology
As a carbapenem antibiotics, the bactericidal activity of biapenem results from the inhibition of cell wall
synthesis. Biapenem has broad-spectrum antimicrobial activity, and display inhibiton against gram-positive
gram-negative and aerobic bacteria. Biapenem is stable to DHP-I, which can be administrated without
co-administration of DHP-Iinhibitor.
Toxicology
Multiple-dose toxicology: After intravenous injection of biapenem in rats and canine for continuous 3 months,
major toxic reaction is abnormal feces, watery stool, mucous stool, etc. After intraveneously administered with
biapenem 600mg/kg/d in rat, mild cloudy swelling was observed on the renal tubular epithelial cell; the spleen
and the cecum swell, and no pathological alteration occurs.
Genotoxicity: Biapenem was not mutagenic in bacterial reverse mutation assay, mammalian mutation assays
in mouse lymphoma, chromosomal aberration assays in hamster ovary cell, and the Mouse micronuclear test.
Reproductive toxicity:
Reproductive studies have been performed with biapenem in rats at doses of up to 300 mg/kg/day pre-
pregnancy and early pregnancy i.v, toxic reaction like reduction of food intake and body weight loss occurs
while fertility is not affected. Intraveneous injection of 300mg/kg/d biapenem at pregnant rat organ formation
stage result in weight loss of F1 generation fetal rats, but shows no lethal effect and teratogenic effect on fetal
rats. In perinatal toxicity test, delayed vagina open was observed in F1 generation female rats of 100mg/kg/d
and over dose group at 6 weeks age testing; but abnormal change of reproductive function was not observed
at 10 weeks age. Biapenem has no obvious influence on F2 generation fetal and newborn rats.
Pharmacokinetics
(1) Plasma concentration
At the end of three 60-minute intravenous infusion of a single dose (150mg, 300mg and 600mg) of biapenem
IV in 5 healthy volunteers, plasma concentration is linear with dose (figure 1).


Figure 1 Plasma concentration after single intravenous injection (healthy volunteers)


 Following intravenous doses, pharmacokinetics results show that no accumulation of biapenem in plasma
was observed compared with single intraveneous injection results.


(2) Distribution
After a single intravenous dose of 300mg biapenem IV, the highest concentration in pelvic fluid is 9.6µg/ml.
6 hours after administration drug concentration in saliva is 0.1~2.5μg/g.
(3) Metabolism
After a single intravenous dose of 150mg, 300mg and 600mg biapenem IV and multiple intravenous dose of
300mg,600mg biapenem IV in 5 healthy subjects,metabolites is not detected in the plasma and 9.7%~23.4%
of the metabolites are excreted in urine. Metabolites shows no bacteriostatic activity.
(4) Excretion
After a single 60-min intravenous dose of 150mg, 300mg and 600mg biapenem IV in 5 healthy subjects,
Average urinary concentrations of biapenem are 325.5, 584.8 and 1105.1μg/ml within 0~2 hours after
administration, and are 2.4, 4.7 and21.4μg/ml within 8~12 hours after administration. Accumulative urine
excretion rate within 0~12 hours is 62.1%, 63.4% and 64.0%, respectively.
(5) Renal Impairment
After a single 60-min intravenous dose of 300mg biapenem IV in 3 subjects with renal impairment, elimination
half-life is prolonged.
See figure 2.

Figure 2 Plasma concentration after single intravenous injection (subjects with renal impairment)

After twice single 30-min intravenous dose of 300mg biapenem IV per day for 7 days in 3 subjects with 
moderate renal impairment whose creatinine clearance are 50mL/min, no plasma and urine drug accumulation
occurred.After a single 60-min intravenous dose of 300mg biapenem IV per day in 5 subjects with severe 
renal impairment off hemodialysis period who need hemodialysis, elimination half-life is prolonged. 

See figure 3.

 

Storage: Protect from light, and keep air-tightly
Package: In vial, 1 vial per box.
Shelf-life:24 months