Approval date: 2013
Morinidazole Sodium Chloride Injection Instructions
Please read the instructions carefully and use under the guidance of a physician
Warning
To reduce the formation of drug-resistant bacteria and to ensure the effectiveness of morinidazole and other antibacterial drugs, morinidazole should be used only for the prevention or treatment of infections caused by sensitive anaerobic bacteria.
This product may pose a potential carcinogenic risk.
Morpholinidazole is a nitroimidazole, and carcinogenicity has been observed in another drug with structurally related and similar biological effects, metronidazole, when used for long-term treatment of rats and mice. Although similar findings have not been observed in the available data of morinidazole studies, they should be taken seriously.
Drug Name
Generic name: Morinidazole sodium chloride injection
English name: Morinidazole and Sodium Chloride Injection
Hanyu Pinyin: Malinxiaozuo LühuanaZhusheye
Ingredients
The main component of this product is morinidazole. Its chemical name is 1-[3-(4-morpholinyl)-2-hydroxypropyl]-2-methyl-5-nitro-1H-imidazole.
The chemical structure formula is
Molecular formula: C11H18N4O4
Molecular weight: 270.29
The excipients are sodium chloride, water for injection.
【Properties】.
This product is slightly yellowish green to yellowish green clear liquid.
Indications
To reduce the formation of drug-resistant bacteria and to ensure the effectiveness of morinidazole and other antibacterial drugs, morinidazole should be used only for the treatment or prevention of infections caused by proven or suspected susceptible pathogens.
Information on bacterial cultures and drug susceptibility testing, if available, should be consulted to select or modify antimicrobial regimens. If this information is not available, local experience such as epidemiologic and bacterial susceptibility data may be helpful in selecting a treatment regimen.
It is important to note that bacterial culture and drug sensitivity testing should be performed prior to administration to identify the causative organism and its susceptibility to morinidazole. Morpholinidazole can be started after specimen collection and adjusted accordingly when the sensitivity results are known.
Based on the current clinical trial data, this product is indicated for the following infections in adults (≥18 years of age) caused by sensitive bacteria.
1, gynecological pelvic inflammatory disease (including endometritis, tubal inflammation, tubo-ovarian abscess, pelvic peritonitis, etc.): caused by including Streptococcus alginolyticus, Streptococcus fragilis, Veronococcus, G. jirovecii, etc.
2, combined surgical treatment of purulent appendicitis, gangrenous appendicitis: caused by the genus including Aspergillus (fragile Aspergillus, ovoid/polytype Aspergillus, monomorphic Aspergillus, common Aspergillus, Aspergillus spp.), Clostridium (Clostridium perfringens, Clostridium bifidum, Clostridium butyricum and other Clostridium), Clostridium (Clostridium nucleatum, Clostridium variabilis), anaerobic cocci (Streptococcus digestiveis, Clostridium welchii), etc.
Since pelvic inflammatory disease and appendicitis are mixed infections of anaerobic and aerobic bacteria, other adjuvant therapeutic measures should be taken according to clinical needs, such as combining drugs that are effective against aerobic bacteria.
Specification
100ml: morpholinidazole 0.5g and sodium chloride 0.9g
Dosage
Dosage and administration method.
1. Gynecological pelvic inflammatory disease (including endometritis, tubal inflammation, tubo-ovarian abscess, pelvic peritonitis, etc.)
Intravenous drip, 500mg each time, drip time is not less than 45 minutes, 2 times a day, dosing interval is 6 to 8 hours, continuous dosing for 14 days.
2.Purulent appendicitis, gangrenous appendicitis
Intravenous drip, 500mg each time, drip time is not less than 45 minutes, 2 times a day, dosing interval is 6 to 8 hours, continuous dosing 5 to 7 days.
Start administration within 30 minutes before completion of surgical preparation and preparation for opening the abdomen.
Directions for use.
This product is filled in 100 ml single dose soda lime glass infusion vials, each vial contains 0.5 g morpholinizole with 0.9 g sodium chloride.
This product should be kept in a cool place (not more than 20℃) under shade and airtight.
Please check the packaging carefully before use, it should be intact; the solution inside should be clarified and free from visible particles. As long as the solution and container packaging allow, the infused drug should be inspected visually for particulate matter and discoloration before administration.
After removing the outer packaging when using, it should be visually inspected for minor leakage. If leakage is found, the sterility of the product has been destroyed and its use should be prohibited.
This product is a ready-to-use isotonic solution and does not need to be diluted before use.
Preparation before use.
1. Hang the infusion bottle through the hanging hole.
2.Remove the protective cap of the infusion port.
3. Connect the infusion set.
Note for use:
This product should only be administered as a continuous or intermittent infusion by slow intravenous drip. No additive should be added to this product. If the original intravenous infusion system is used, the original solution should be discontinued during the morinidazole infusion.
Adverse reactions]
1.The following adverse reactions may occur during the administration of this product.
(1) Digestive system: including nausea, bitter mouth, dry mouth, gastrointestinal discomfort, indigestion, etc..
2) Nervous system: including dizziness, headache, drowsiness, sleepiness, vertigo, weakness, mouth numbness, etc..
3) laboratory tests: including elevated transaminases, decreased white blood cell count, abnormal TBIL, etc.
(4) Others: allergic rash, streptococcal vaginitis, facial yellowing, palpitations, etc.
2. Adverse reactions observed in randomized controlled clinical trials of this product
In a phase III clinical trial study, the subject population was patients with gynecological pelvic inflammatory disease. 338 cases were included in the SAS analysis, and the incidence of adverse reactions was 31.95%. Major adverse reactions (incidence >2%): elevated transaminases, dizziness, nausea, decreased white blood cells, and allergy. The details are shown in Table 1.
Table 1 Symptoms and incidence of adverse reactions in patients with gynecological pelvic inflammatory disease
Symptoms or signs Incidence of adverse reactions (%) P value Control drug morpholine nizole sodium chloride injection Neurological dizziness 12.35% (21/170) 5.95% (10/168) 0.0582 Drowsiness 5.29% (9/170) 1.19% (2/168) 0.0612 Headache 4.12% (7/170) 1.19% (2/168) 0.1739 sleepiness2.35% (4/170) 1.19% (2/168) 0.6847 fatigue2.35% (4/170) 0.60% (1/168) 0.3713 mouth numbness0% (0/170) 0.60% (1/168) 0.4970 dizziness0% (0/170) 0.60% (1/168) 0.4970 Digestive nausea 3.53% (6/170) 2.38% (4/168) 0.7502 Gastrointestinal upset 1.76% (3/170) 1.19% (2/168) 1.0000 Bitter mouth 0.59% (1/170) 1.19% (2/168) 0.6217 Indigestion 0% (0/170) 0.60% (1/168) 0.4970 Dry mouth 1.18% (2/170) 0.60% (1/168) 1.0000 Cardiovascular system Palpitations 0% (0/170) 0.60% (1/168) 0.4970 Other symptoms Allergic reactions 2.35% (4/170) 2.98% (5/168) 1.0000 Facial yellowing 0% (0/170) 0.60% (1 /168) 0.4970 Streptococcal vaginosis 0.59% (1/170) 0.60% (1/168) 1.0000 Laboratory tests Elevated transaminases 11.76% (20/170) 11.31% (19/168) 1.0000 Reduced white blood cells 2.35% (4/170) 2.38% (4/168) 1.0000 TBIL abnormal 0% (0/170) 0.60% (1/168) 0.4970 In another phase III clinical trial study, the subject population was patients with septic or gangrenous appendicitis. Of the 437 cases enrolled, 66 subjects experienced adverse reactions, with an overall incidence of 15.1%. The major adverse reactions (incidence >2%) were: elevated transaminases. The details are shown in Table 2.
Table 2 Analysis of symptoms of adverse reactions occurring after drug administration in the two groups
Symptoms or signs Incidence of adverse reactions (%) P value Control drug morpholinizole sodium chloride injection Neurological dizziness/dizziness 1.37% (3/219) 0% (0/218) 0.2483 Digestive system Nausea 2.74% (6/219) 0.46% (1/218) 0.1220 Vomiting 2.28% (3/219) 0.46% (0/218) 0.2155 Dry mouth 0.46% (1/219) 0% (0/218) 1.0000 Loss of appetite 0% (0/219) 0.46% (1/218) 0.4989 Cardiovascular system ECG abnormalities 1.37% (3/219) 1.38% (3/218) 1.0000 Other symptoms Fever 0% (0/219) 0.46% (1/ (218) 0.4989 atopic dermatitis 0.46% (1/219) 0% (0/218) 1.0000 rash 0.46% (1/219) 0% (0/218) 1.0000 laboratory tests elevated transaminases 7.76% (17/219) 6.42% (14/218) 0.7100 decreased white blood cells 0.91% (2/219) 0.92% (2/218) 1.0000 Elevated platelets 2.74% (6/219) 1.38% (3/218) 0.3810 Increased uric acid 0.46% (1/219) 0% (0/218) 1.0000 Increased creatinine 0.46% (1/219) 0% (0/218) 1.0000 Elevated urine leukocytes 0% (0/218) 0.46%（1/218）0.4989
[Contraindications].
Contraindicated in patients with known hypersensitivity to this product and nitroimidazoles.
Contraindicated in patients with lesions of the brain and spinal cord, epilepsy, and various organ sclerosis.
Contraindicated in patients with hematopoietic hypoplasia and chronic alcoholism.
Precautions】
1.Warning
Transient peripheral neuropathy (main symptoms include numbness and abnormal sensation of limbs), convulsive seizures, encephalopathy and aseptic meningitis may occur with nitroimidazoles, including metronidazole and tinidazole, as reported in the literature. This is a nitroimidazole drug. Based on the current safety evaluation data for this drug, although no serious adverse reactions have been reported in patients treated with this drug and these adverse reactions have not been seen, they may occur and should be of concern during use, and the development of abnormal neurological signs and symptoms requires immediate evaluation of the risk/benefit ratio for continued treatment.
Nitroimidazoles cross the blood-brain barrier and are neurotoxic; therefore, attention should be paid to possible neurological adverse reactions during treatment. This product is a nitroimidazole, which has not been studied, but should also be of concern during use.
General Precautions
Lower daily doses and longer dosing intervals are recommended for patients with severe renal insufficiency.
In patients with mild to moderate hepatic insufficiency, no adjustment of dose or dosing interval is necessary if renal function is normal.
If renal function is normal, there is no need to adjust the dose and dosing interval. In case of combined abnormal renal function, it is recommended to extend the dosing interval.
(3) Discontinue immediately if abnormal neurological signs and symptoms occur during use, assess the risk/benefit ratio of continued treatment, and observe further.
This product is structurally similar to ornidazole and may have similar contraindications to dosing. This product is compatible with penicillin, cephalosporins
bacteriocins, or semi-synthetic antibiotics (including proprietary Chinese preparations, such as Yansuunin), care should be taken to observe any changes in the drug solution. If there is a contraindication, when the condition requires the use of these two drugs at the same time, the infusion tube should be flushed with saline or administered indirectly between the two groups of drugs to avoid chemical reactions in direct contact with the drugs, resulting in adverse consequences.
3.Notice to patients
Patients should be advised that antibacterial drugs, including morinidazole sodium chloride injection, should be used only to treat bacterial infections. These drugs should not be used to treat viral infections (e.g., the common cold).
When a patient is prescribed morpholinidazole sodium chloride injection for the treatment of bacterial infections, the patient should be advised that although he or she will often feel better early in the course of treatment, the drug should be administered exactly as directed. Skipping doses or not completing the entire course of treatment may: 1) reduce the effectiveness of treatment; and 2) increase the likelihood that the bacteria will become resistant and untreatable with morpholinidazole sodium chloride injection or other antibacterial agents in the future.
Pregnant and lactating women]
In preclinical reproductive toxicity studies, morpholinidazole sodium chloride injection was not significantly embryotoxic or teratogenic.
However, because animal reproduction tests are not fully predictive of human response, and there are no safety and efficacy data on the use of this product in women during pregnancy, morinidazole should not be used during pregnancy unless the physician believes that the benefits outweigh the risks.
There are no data on the safety and efficacy of this product in nursing mothers, and there is no information on whether this product can be secreted into breast milk; therefore, morinidazole should not be used during lactation unless the physician believes that the benefits outweigh the risks.
Pediatric Use
There is a lack of data on the safety and efficacy of this product in patients under 18 years of age.
Geriatric Use]
There is a lack of data on the safety and efficacy of this product in elderly patients over 65 years of age.
Drug Interactions
1. Based on the results of the current drug interaction studies for this product, it is known that
Warfarin: Morpholinidazole has no significant effect on the pharmacokinetics and pharmacodynamics of warfarin.
Rifampicin: Rifampicin has an inductive effect on the metabolism of this product, reducing the plasma exposure of morinidazole and its N-oxidized metabolites by approximately 28%.
Ketoconazole: Ketoconazole has no significant effect on the pharmacokinetics of morpholinidazole, resulting in reduced plasma exposure of glucuronide conjugates, but does not affect renal clearance.
No drug interactions were found when this product was combined with warfarin, rifampin, and ketoconazole, and no dose adjustment was required.
2. With reference to reports on nitroimidazoles that are chemically related to morpholine nitrozole (e.g., metronidazole, tinidazole, etc.), this product still requires attention for possible interactions with other drugs, including
Lithium: Metronidazole has been reported to increase serum lithium levels. Although it is not known whether morinidazole has the same properties, it is still recommended that patients on concomitant lithium and morinidazole should have their serum lithium and creatinine checked after several days of treatment to monitor the potential risk of lithium toxicity.
Phenytoin, fosphenytoin: It has been reported that concomitant intravenous phenytoin with oral metronidazole will result in a prolonged half-life and decreased clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of phenytoin administered orally.
Cyclosporine, Tacrolimus: Metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. Therefore, when morinidazole is co-administered with any of these drugs, care should be taken to monitor the toxic effects of immunosuppressive drugs in these patients.
Fluorouracil: Studies have shown that metronidazole decreases the clearance of fluorouracil, resulting in an increase in side effects rather than a therapeutic benefit. If coadministration of morinidazole with fluorouracil is unavoidable, patients should be monitored for fluorouracil-related toxic reactions.
Overdose]
No overdose studies have been conducted with this product.
In the phase I tolerability trial of this product, a single intravenous dose of 40 mg/kg of morinidazole (2-hour drip completion) in healthy subjects resulted in the occurrence of bitter and dry mouth with an incidence of 33% (2/6). In addition, in the 32-40 mg group, headache was found with some dose correlation (1/8 vs 4/6).
[Clinical Trials].
Gynecological pelvic inflammatory disease.
In a multicenter, randomized, blinded, positive drug-parallel controlled phase III clinical trial study, the efficacy and safety of morinidazole sodium chloride injection in the treatment of gynecological pelvic inflammatory disease were investigated. A total of 339 patients with gynecological pelvic inflammatory diseases were entered into the study, including 170 patients in the ornidazole sodium chloride injection group (control group) and 169 patients in the morinidazole sodium chloride injection group. The administration method of both groups was intravenous drip, 500 mg/dose, twice a day, for 14 days. The main efficacy evaluation index was the clinical cure rate from 7 to 30 days after the end of treatment. The results showed that the clinical cure rate of morinidazole was 94.29%, compared with 80.65% in the control group, and morinidazole was non-inferior to the control group (the non-inferiority median was 10%), indicating that the efficacy of morinidazole sodium chloride injection in the treatment of gynecological pelvic inflammatory diseases was comparable to that of the control group. The incidence of morinidazole adverse reactions was lower than that of the control group (24.40%v.s. 39.41%, P < 0.05). In addition, for the bacteriological observations of the efficacy and safety study of pelvic inflammatory diseases, the main pathogenic anaerobic bacteria were Streptococcus alginolyticus (23 strains), Bacteroides fragilis (7 strains), Veronococcus (5 strains), Bacteroides gigantica (5 strains), and Bifidobacterium (4 strains). The geometric mean of the MIC of morinidazole was 0.51, which was lower than that of ornidazole (0.66) and metronidazole (0.88). The cumulative percent inhibition curves of morinidazole against Streptococcus digestiveis, Bacteroides fragilis and 62 anaerobic strains were to the left of the curves for both ornidazole and metronidazole.
Septic appendicitis, gangrenous appendicitis.
A multicenter, randomized, blinded, positive drug-parallel controlled phase III clinical trial study compared the efficacy and safety of morinidazole with ornidazole (both administered intravenously at 500 mg/dose twice a day for 5-7 days) for the treatment of purulent and gangrenous appendicitis disease. A total of 437 patients with suppurative and gangrenous appendicitis were enrolled in this study. Among them, 219 cases were in the ornidazole sodium chloride injection group (control group) and 218 cases were in the morinidazole sodium chloride injection group (test group). The main efficacy evaluation index was the clinical cure rate from 5 to 10 days after the end of treatment. The results showed that the clinical cure rate was 91.59% for morinidazole and 91.55% for ornidazole, and morinidazole was non-inferior to the control group (non-inferiority median of 10%), indicating that the efficacy of morinidazole sodium chloride injection combined with surgical treatment of pyogenic or gangrenous appendicitis was comparable to that of the control group. Safety results showed a lower incidence of morpholinidazole adverse reactions compared with the control group (11.47% v.s. 18.72%, P<0.05). In addition, for the bacteriological observation of the effectiveness and safety study of septic or gangrenous appendicitis, 69 anaerobic strains and 33 dead strains were obtained in this study. The results of the group leader unit review and identification were in general agreement with the sub-center results. Among them, the main pathogenic anaerobic bacteria were: 39 strains of the genus Aspergillus, including: Aspergillus fragilis (17 strains), Aspergillus ovoid/polytype (14 strains), Aspergillus monomorphicus (6 strains), Aspergillus commonus (1 strain) and Aspergillus spp. (1 strain); Bifidobacterium spp. (3 strains); 2 strains of Clostridium spp. including Clostridium perfringens (1 strain) and Clostridium perfringens (1 strain); 7 strains of anaerobic cocci: Streptococcus digestiveis (4 strains) and C. virens (3 strains); 4 strains of other anaerobic bacteria including Actinomyces maltophiliae (2 strains), Escherichia retardans (1 strain), and Peptostreptophilus insoluble in sugar (1 strain). The MIC of 69 surviving clinical isolates of anaerobic bacteria was determined, and the results showed that morpholinidazole was slightly more effective than ornidazole and significantly better than metronidazole for the anaerobic bacteria isolated in this clinical trial. The results of the preclinical in vivo and in vitro pharmacodynamic tests initially suggest that the antibacterial activity of this product is stronger than or equivalent to that of metronidazole, tinidazole and ornidazole against clinical isolates of pathogenic anaerobic bacteria. The bacteriological results of the clinical test isolates of this product are basically consistent with the results of preclinical pharmacodynamic study.
Pharmacology and Toxicology
Pharmacological effects
Morinidazole is a third-generation nitroimidazole derivative. The mechanism of its anti-microbial effect may be through the reduction of nitro in its molecule to amino or the formation of free radicals in the anaerobic environment, which interacts with cellular components, thus leading to the death of microorganisms.
The results of in vitro antibacterial tests showed that morpholinidazole had strong antibacterial effects against both clinically isolated anaerobic Gram-negative non-spore-forming bacilli and Gram-positive cocci. The MIC50 and MIC90 values of morpholinidazole against B. fragilis, B. gigas, B. ovalis, B. vulgaris, B. niger, B. polysporum, C. nucleatum, and B. polymorpha were 0.06~0.125mg/L and 0.125~0.5mg/L, respectively. The MIC50 and MIC90 values of morpholinidazole against B. aerogenes were 0.03mg/L and 0.03mg/L and 0.5mg/L, respectively. The MIC50 and MIC90 values of morinidazole against Gram-positive anaerobic bacteria, such as Streptococcus virens, Streptococcus intermedius and Streptococcus pepticus, were 0.125 ~ 0.5 mg/L and 0.5 mg/L, respectively. The MIC50 and MIC90 values of morinidazole against Porphyromonas gingivalis were 0.125 mg/L and 0.5 mg/L, respectively. Morpholinidazole has a strong bactericidal effect, and its MBC value is basically equal to its MIC value or 2~4 times of its MIC value. There was no significant effect of serum concentration change on the antibacterial activity of morpholinidazole.
Toxicological studies
Repeated dosing toxicity.
In dogs given morinidazole 30 ~ 180 mg/kg/day intravenously for 60 consecutive days, it was seen that animals in the high dose group were quieter, salivated and had reduced body weight gain compared to other groups, with the main toxic target organs being the central nervous system and the gastrointestinal tract, with a non-toxic response dose of 90 mg/kg.
Genotoxicity.
The results of Ames test, mammalian culture cell chromosome aberration test and mouse micronucleus test for morpholinidazole were all negative.
Reproductive toxicity.
In a toxicity test on fertility and early embryonic development in SD rats, morpholinidazole was administered intravenously at 300, 150 and 75 mg/kg. The results showed some toxicity to both male and female rats at the doses indicated, as evidenced by reduced body weight and food intake, but no significant effects on fertility and early embryonic development.
In a rabbit embryo and fetus effect test, 150, 75 and 37.5 mg/kg of morpholinidazole were administered intravenously to pregnant rabbits during the teratogenic sensitive period, which showed no significant maternal toxicity but some embryotoxicity and possible fetotoxicity, including reduced live fetus rate, increased stillbirth rate and resorption rate, reduced fetal parietal and rump length, reduced mean placental weight and placental lysis. One fetus in the mid-dose group had cranial hypoplasia.
In a perinatal toxicity test in SD rats, rats were injected intravenously with 300, 150 and 75 mg/kg of morinidazole, and the postnatal weights (D4, D14 and D21) of mothers in the mid-dose group were lighter than those in the solvent control group, with a significant difference (P < 0.05). (P < 0.01), and there was also a highly significant difference in vaginal opening time of female pups in the high-dose group compared with the solvent control group (P < 0.01). Morpholinidazole may have some maternal toxicity, but no significant effects were observed on the growth and reproductive function of rats during pregnancy, lactation and offspring.
[Pharmacokinetics].
Pharmacokinetics.
Absorption.
Single intravenous doses of 10, 16 and 24 mg/kg dosed for 2 h in healthy volunteers showed a positive correlation between the Cmax and AUC0-t of single administration and the dose administered (r 0.979). The AUC and Cmax were (123,388±18,269) ng*h/mL and (16,588±2854) ng/mL, respectively, for morpholinidazole 16 mg/kg IV drip for 2 h.
The duration of intravenous drip had no significant effect on the PK parameter AUC of morinidazole, while Cmax decreased with increasing drip time. 500 mg, AUC0-t for 45 min, 60 min and 120 min of intravenous drip were (72.1±14.5), (72.6±12.0) and (73±12.2) h*μg/ml, respectively, and Cmax were ( 10.8±1.88), (9.91±1. 59) and (8.94±1.26) μg/ml, respectively.
The pharmacokinetic parameters of a single intravenous dose of 500 mg of this product titrated for 45 minutes in healthy volunteers are shown in the following table.
Pharmacokinetic parameters after a single intravenous dose in healthy volunteers
Parameter Unit MeanSDCV%t1/2z(h)5.750.65811.4Tmax(h)0.7280.091012.5Cmax(ug/ml)10.81.8817.5AUC0-t(h*ug/ml)72.114.520.1AUC0-∞(h*ug/ml)72.514. 520.0MRT0-∞(h)7.440.84911.4Vz(L)59.113.222.3Cl(L/h)7.181.6122.4
Distribution.
The Vss was (1209±158) mL/kg when morpholinidazole 16 mg/kg was administered intravenously for 2 h. The binding rate of morpholinidazole to human plasma proteins was 22.1-27.2%, suggesting that morpholinidazole can be widely distributed in various tissues and body fluids.
Metabolism.
The main metabolic pathways of morpholinidazole in humans are glucuronide binding and sulfate binding of the prodrug. The glucuronide-binding process is mainly mediated by the UGT1A9 enzyme. In vitro studies have shown that morinidazole has almost no inhibitory effect on the major CYP450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4; it has no induction effect on CYP1A2 and CYP3A4. The main metabolic pathway of morinidazole is not CYP450 enzyme-mediated, suggesting that drug-drug interactions between morinidazole and inducers, inhibitors or substrates of CYP450 enzymes are less likely to occur when used in clinical combination. In vivo tests have also demonstrated that the CYP3A4 inhibitor ketoconazole and the CYP3A4 inducer rifampicin do not affect the pharmacokinetics and renal clearance of morinidazole; nor does morinidazole affect the pharmacokinetics and efficacy of warfarin. No UGT1A9 enzyme inducers or inhibitors are known to be in clinical use; therefore, morinidazole and UGT enzyme inducers or inhibitors drug-drug interactions have not been studied.
Excretion.
The half-life of morinidazole is 5.6 to 6.4 h. After the intravenous infusion of morinidazole into the body, approximately 70% of the drug is excreted via the kidneys as pro- and phase II metabolites after an average of 36 h of metabolism in healthy subjects.
Patients with hepatic insufficiency
There were no significant differences in pharmacokinetics in patients with moderate hepatic insufficiency compared with healthy subjects. The total urinary elimination of morinidazole (amount of metabolites converted to morinidazole) in moderate hepatic insufficiency was 71.9% of total entry, which was not significantly different from 72.1% in healthy subjects. Exposure (AUC) in those with moderate hepatic decompensation with renal decompensation was 2.2 times higher than in the healthy group and clearance of the drug was slower, suggesting a cumulative effect on morinidazole PK in hepatic insufficiency with concomitant renal insufficiency.
Patients with renal insufficiency
Significant differences in pharmacokinetics were observed in patients with severe renal insufficiency compared to healthy subjects. In the severe renal insufficiency group t1/2 and MRT were prolonged by 35.7% and 39.9%, respectively, and both AUC0-t and AUC0-∞ were 1.4 times higher than those in the healthy group, with a clearance of 72.3% of the normal state. In patients with severe renal insufficiency about 5.95±2.22% of the morinidazole prototype was excreted via the kidneys, while in healthy volunteers about 15.46±4.59% of the prototype was excreted via the kidneys.
Storage
Store in a cool place (not more than 20℃) under shade and airtight.
Package】
Filled in soda lime glass infusion bottle with chlorinated butyl rubber stopper and sealed with aluminum cap.
Expiration date
24 months.
Execution Standard
Approval number】
【Manufacturer】
Enterprise name: Jiangsu Haosen Pharmaceutical Co.
Production Address: Lianyungang Economic and Technological Development Zone, Jiangsu Province
Postal Code: 222047
Customer service telephone: 800-828-5227 800-828-5117 (free, only for landline calls)
0518-82343315
Website: http://www.hansoh.cn