Product name
Clinical application
1. US FDA approves indications:
(1) Complex intra-abdominal infections caused by a variety of bacteria.
(2) Complex urinary tract infections (including pyelonephritis) caused by a variety of bacteria.
2. The Japanese Ministry of Health and Welfare approves the indications:
(1) Peritonitis, intra-abdominal abscess, cholecystitis, cholangitis.
(2) complicated cystitis, pyelonephritis, acute or chronic prostatitis, epididymitis, intrauterine infection, uterine annexitis.
(3) pharyngitis, laryngitis, tonsillitis (including perioral inflammation, periorbital abscess), pneumonia, lung abscess, empyema, chronic respiratory disease secondary infection.
(4) Secondary infections such as trauma, burns, and surgical trauma, deep skin infections (lymphitis, lymphadenitis).
(5) Eye socket infection, keratitis (including corneal ulcer), endophthalmitis (including full ocular inflammation), otitis media.
(6) Sepsis, infective endocarditis, osteophylactic inflammation, arthritis, honeycomb inflammation around the tibia, and gingivitis.
Pharmacology
Pharmacodynamics
This drug is a carbapenem antibiotic in β-lactams.
Mechanism of action This drug is linear in the dose range of penicillin-binding protein (PBP). AUC is elevated in patients with renal impairment and in the elderly. The average plasma protein binding rate of the drug is about 8.1%, and the binding rate is related to the blood drug concentration, and the volume of distribution is 16.8L (8.09-55.5L). This drug can be metabolized by dehydropeptidase-I to an inactive ring-opening metabolite (Donicene-M1), but it is mainly cleared by a prototype drug. The healthy adult receives 500mg of the drug, and the urine is in 48 hours. Recover 70% of the prototype drug and 15% of the open-loop metabolite. In healthy adults, the mean plasma terminal half-life of the drug was approximately 1 hour, with an average plasma clearance of 15.9 L/h and an average renal clearance of 10.8 L/h. Patients with normal renal function were given intravenous infusion of 500 mg or 1 g every 8 hours for 7 to 10 days. No accumulation of this drug was found.
Genetic and reproductive toxicity
(1) Genotoxicity: The drug showed no mutagenicity in the bacterial back mutation test, the chromosomal aberration test of Chinese rat mouse lung fibroblasts, and the mouse bone marrow micronucleus test.
(2) Reproductive toxicity: fertility of male and female rats at 1 g/kg per day for intravenous injection of rats (more than 500 mg per human dose, 1.5 times exposure at 8 hours, according to AUC) And the reproductive ability of the offspring has no adverse effects. The dose of this drug in rats is up to 1g/kg per day and the dose in rabbits is up to 50mg/kg per day (at least 500mg for human dose, 0.8 times for exposure at 8 hours, according to AUC), no Teratogenicity.
(3) Carcinogenicity: There is no long-term animal test research data of this drug.
Precautions
1. Cross-allergic β-lactam antibiotics have cross-allergy between them.
2. Contraindications for those who are allergic to this drug or to other β-lactam antibiotics (foreign data).
3. Use breastfeeding women with caution (foreign data).
4. The impact of drugs on children The safety and efficacy of drug use in children has not been established.
5. The effect of drugs on the elderly The exposure of the drug in the elderly is increased, and the elderly are prone to renal dysfunction or pre-renal azotemia, and the risk of adverse reactions is higher than other populations.
6. The effect of drugs on pregnancy There is no adequate and good control study data for pregnant women, and pregnant women can only use them when they are necessary. The US Food and Drug Administration (FDA) classifies the pregnancy safety of this drug as Class B.
7. The effect of drugs on breastfeeding is not clear whether the drug is secreted into breast milk, and breastfeeding women should be used with caution.
8. Renal function and moderate to severe renal impairment should be checked or monitored before and after treatment. Renal function should be checked regularly.
Adverse reactions
[ Foreign adverse reaction reference]
Allergic reactions, Stevens-Johnson Syndrome, toxic epidermal necrolysis, interstitial pneumonia, seizures can be seen. In addition, the following adverse reactions occurred in clinical trials:
1. Cardiovascular system common phlebitis.
2. Vulvar fungal infection, kidney damage, and kidney failure can be seen in the genitourinary system.
3. Common headaches in the nervous system.
4. The liver showed an increase in alanine aminotransferase and an increase in aspartate aminotransferase.
5. Common nausea and diarrhea in the gastrointestinal tract, oral candidiasis, and diarrhea associated with Clostridium difficile (CDAD).
6. Anemia can be seen in the blood.
7. common skin rash, visible itching, macules, papules, urticaria, allergic dermatitis and bullous dermatitis, erythema, erythema multiforme.
8. The emergence of other visible resistant bacteria.
medicine interactions
Drug-drug interaction
1. Propane sulfonic acid can interfere with the active excretion of the drug by the renal tubule, resulting in an increase in plasma concentration of the drug, a 75% increase in AUC, and a 53% increase in plasma half-life.
2. This drug may inhibit the level of valproic acid glucuronide, so that the serum concentration of valproic acid is significantly reduced, so the serum concentration of valproic acid should be frequently monitored after the combination. If the serum concentration of valproic acid is not maintained within the scope of treatment or seizures, other antibacterial or anticonvulsant treatments should be considered.
3. The drug has no inhibitory effect on the metabolism of drugs via the cytochrome P450 isoenzyme metabolic pathway.
4. The drug has no antagonistic effect on other antibiotics (such as levofloxacin, amikacin, trimethoprim-sulfamethoxazole, daptomycin, linezolid and vancomycin).
Dosing instructions
1. Incompatibility: The compatibility of this drug with other drugs has not been determined. Do not mix this drug with a solution containing other drugs.
2. Preparation of injection:
(1) First formulated as a suspension: a suspension of 50 mg/mL was prepared using 10 mL of sterile water for injection or 0.9% sodium chloride injection. This suspension is not intended to be used directly.
(2) Prepare 500 mg for routine use: Add the suspension to an infusion bag containing 100 mL of normal saline or 5% glucose and gently shake until clear to obtain a solution for infusion (4.5 mg/mL). Formulation of 250 mg for patients with moderate to severe renal impairment: Prepare a solution for infusion according to the above method, remove 55 mL from the infusion bag and discard, and the remaining solution 250 mg (4.5 mg/mL) is available.
3. After the above suspension is prepared, it can be diluted into the infusion bag for at least 1 hour. The prepared suspension or infusion solution should not be frozen, and the infusion solution should not be placed too long.
4. It may not be administered in this way because it can cause pneumonia due to inhalation.
5. If the clinical symptoms are improved after at least 3 days of parenteral treatment, it can be changed to oral treatment.
6. Suspected or diagnosed as CDAD after administration, antibiotics in use that are not related to C. difficile need to be discontinued. If necessary, appropriate liquids and electrolytes or protein supplements can be administered, and antibiotics are used to control C. difficile.
7. Once an allergic reaction occurs, the acute allergic reaction requires adrenaline and other clinical first-aid measures, including oxygen delivery, intravenous infusion, intravenous infusion of antihistamines, administration of corticosteroids and amines. Medicine and respiratory treatment.
8. When overdose is used, general supportive care or hemodialysis should be discontinued.
Usage and dosage
[ Foreign usage and usage reference]
adult
Conventional dose
Intravenous drip
US FDA approved usage and dosage: for patients with bacteremia, the course of treatment can last for 14 days.
(1) Complex intra-abdominal infection: 500mg once, every 8 hours, 1 hour infusion, 5~14 days for a course of treatment.
(2) Complex urinary tract infections (including pyelonephritis): 500mg once every 8 hours, 1 hour infusion, 10 days for a course of treatment.
Elderly dose
Elderly patients with impaired renal function should be appropriately adjusted, and elderly patients with normal renal function are not recommended for dose adjustment.
Preparations and specifications
Doripenem for injection
(1) 250 mg.
(2) 500 mg.
Storage method:
Store at 25 ° C (15 ~ 30 ° C).
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