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Tinidazole Tablets Instructions
Please read the instruction manual carefully and use under the guidance of a physician
[Drug Name]
Generic Name: Tinidazole Tablets
English Name:Tinidazole Tablets
Hanyu Pinyin:Tixiaozuo Pian
[Cheng
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The active ingredient of this product is tinidazole.
Chemical name:2- Methyl-1-[2-(ethylsulfonyl)ethyl]-5-nitro-1HImidazole
Chemical structure formula:
Molecular Formula:C8H13N3O4S
Molecular weight:247.27
[Properties]
This product is a film-coated tablet, which appears off-white to light yellow after removing the coating.
[Indications]
To reduce the formation of resistant bacteria and to ensure the effectiveness of tinidazole and other antibacterial drugs, tinidazole should be used only for the treatment or prevention of infections caused by proven or suspected susceptible pathogens.
If information on culture and susceptibility testing is available, it should be consulted for selection or modification of antimicrobial therapy regimens. If this information is not available, local experience such as epidemiologic and bacterial susceptibility data may be helpful in selecting a treatment regimen.
1. This product is indicated for the treatment of the following diseases:
(1)Trichomoniasis
Tinidazole is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. The pathogenic organism should be validated by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, sexual partners of infected individuals should be treated concurrently to prevent recurrent infections.
(2)Jardiasis flagellosis
Roman”>patients older than 3 years of age in children.
(3) Amoebiasis
Tinidazole is indicated for the treatment of amebic enteropathy and amebic liver abscesses caused by amebas of dysentery in adults and3patients older than 3 years of age in children. However, it is not indicated for the treatment of asymptomatic cysts.
(4) Bacterial Vaginitis
Tinidazole is indicated for the treatment of bacterial vaginitis (previously known as Haemophilus vaginitis, Gardner’s vaginitis, nonspecific vaginitis, or anaerobic vaginitis) in nonpregnant women.
Other pathogens associated with vulvovaginitis should be excluded, such as Trichomonas vaginalis, Chlamydia trachomatis, gonococcus, Candida albicans, and herpes simplex virus.
(5) with antibiotics and antacids in combination for the eradication of H. pylori-associated duodenal ulcers
(6) anaerobic bacterial Infection
Intra-abdominal infections: peritonitis, abscesses;
Gynecologic infections: endometritis, myometritis, tubo-ovarian abscesses;
Sepsis;
Post-operative wound infection;
Skin soft tissue infection;
pneumonia, pulmonary abscess, and pus accumulation in the chest cavity;
Acute ulcerative gingivitis.
2. This product is used for the prevention of postoperative infections caused by anaerobic bacteria, such as post-surgical infections of the colon, gastrointestinal tract and genitourinary system.
[Specifications]
0.5g
[Dosage]
Use:
Orally. It is recommended to take tinidazole after meals thereby minimizing the incidence of gastrointestinal side effects such as upper abdominal discomfort. Food does not affect the oral bioavailability of tinidazole.
Dosage:
1. Treatment
(1)Trichomoniasis /span>
Single dose2gdone , taken with meals. Sexual partners should be treated at the same time with the same dose.
(2)Jardiasis flagellosis
Adults: Single dose2gTake with meals.
3Children over age: single dose50mg/kg(not to exceed2g) to be taken at mealtime.
(3) Amoebiasis
Amoebic enteropathy:
Recommended adult dose is 2g daily, taken with meals, for 3days.
The recommended dose for children 3years of age and older is50mg/kg/day (not to exceed2g/day), taken with meals, for 3days.
Amoebic liver abscess:
Recommended adult dose is 2g daily, taken with meals, taking 3 to 5days.
3Children over age: 50mg/kg/day (not to exceed2g/day) with meals and take 3to5days. Data regarding the duration of medication in children beyond 3days are limited, but there are a few children with sustained medication =”font-family:Times New Roman”>5days without reported adverse reactions. Children should be closely monitored during treatment for more than 3days.
(4) Bacterial Vaginitis
The recommended dose for non-pregnant adult women is2g dailywith meals for 2days, or daily1g with meals, take5day.
Tinidazole for bacterial vaginitis in pregnant patients has not been studied.
(5) with antibiotics and antacids in combination for the eradication of H. pylori-associated duodenal ulcers
Adults: 2times daily each time500mg,,7 days of coadministration.
The combination is omeprazole and clarithromycin at the following doses:
Omeprazole: daily2times, each time20mg.
Clarithromycin: 2 times per daytimes, each time250mg.
Clinically omeprazole is administered daily1times, each20 mgtime, had similar rates of H. pylori eradication to those prescribed above. For more information, see the omeprazole insert.
(6)Anaerobic Infection
Adults: Day1 The starting dose is2g, then daily1time, each time1g. Or2times per day, each time500mgtime. General course of treatment5 to 6days, but the course of treatment needs to be determined by clinical diagnosis, especially since some specific sites of infection may be more difficult to eradicate. Clinical trials have concluded that continuous treatment beyond 7days requires caution.
Children: No data are available for children12 Available data for children under age.
2. Prevention of post-surgical anaerobic infections: family:Times New Roman”>
Adults: before surgery12hourly single dose2g.
Children: Data not yet available12 Available data for children under age.
Older adults: not yet available.
Medication for renal insufficiency:
Dose adjustment is usually not required in renal insufficiency, but patients may require a dose increase due to the ease of clearance of tinidazole by hemodialysis.
[Adverse Reactions]
1. Experience with clinical studies
Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions observed in clinical trials for one drug cannot be directly compared to the incidence of adverse reactions for another drug and may not reflect the incidence of adverse reactions in practice.
In controlled and uncontrolled clinical trials for the treatment of trichomoniasis and giardia, it was reported that the administration of3669 patients with a single dose of2 g of tinidazole, the adverse reaction The incidence was11.0%. In controlled and uncontrolled clinical trials for the treatment of amebiasis given to 7165 patients on multiple days, the incidence of adverse reactions was 13.8%. Common (incidence of adverse reactions≥1%) body system adverse reactions are listed in the table below.
Table
Summary information of publicly reported adverse reactions
2gsingle doseMulti-day dosingGastrointestinal: metallic taste/Bitter3.7%6.3%Nauseous3.2%3.2%4.5%Anorexia nervosa1.5%2.5%Indigestion/Spasms/Upper abdominal discomfort1.8%1.4%Vomiting 1.5%0.9%Constipation0.4%1.4%Central nervous system: weakness/fatigue/Burnout2.1%1.1%Glare1.1%0.5%Other: headache1.3%0.7%Total number of patients with adverse reactions11.0%
(403/3669)13.8%
(244/1765)Other reported adverse effects of tinidazole include:
Central nervous system: Two serious adverse reactions included convulsions and transient peripheral neuropathy, the latter with numbness and abnormal sensation as the main symptoms. Other CNS adverse reactions include vertigo, ataxia, dizziness, insomnia, and lethargy.
Gastrointestinal: discoloration of the tongue, stomatitis, diarrhea.
Allergies: hives, scratching, rash, facial flushing, sweating, dry mouth, fever, burning sensation, thirst, salivation, angioedema.
Kidneys: dark urine.
Cardiovascular system: palpitations.
Hematologic system: transient leukopenia and neutropenia.
Other: Candida hyperplasia, increased vaginal discharge, oral candidiasis, abnormal liver function including increased transaminase levels, arthralgia, muscle pain, and arthritis.
Rare adverse reactions include:
Bronchospasm, dyspnea, coma, confusion, depression, tongue-tie, pharyngitis, and reversible thrombocytopenia.
Adverse effects in pediatric patients:
The nature and frequency of adverse reactions in clinical studies in pediatric patients were similar to those found in trials in adults, including nausea, vomiting, diarrhea, altered taste, loss of appetite, and abdominal pain.
Most common adverse reactions in patients with bacterial vaginitis in treated patients (incidence of adverse reactions≥2%) included gastrointestinal reactions (e.g., decreased appetite and flatulence), urinary tract infections, painful urination, and urinary abnormalities, and others including pelvic pain, vulvovaginal discomfort, vaginal odor, menorrhagia, and upper respiratory tract infections. These adverse effects were not found in studies of trichomoniasis, giardia and amoebiasis.
2. Post-marketing experience
The following adverse reactions were reported and identified after tinidazole was approved for use. Because the reporting of these reactions was voluntary and the population size was uncertain, the incidence of adverse reactions cannot be reliably estimated from these data, nor can a necessary causal relationship with the drug be established from them.
Severe acute allergic reactions have been reported in the initial and late stages of tinidazole use. Allergic reactions include: urticaria, itching, angioedema,Stevens – Johnson syndrome, and erythema multiforme. Stevens – Johnson syndrome and erythema multiforme.
[Contraindicated]
It is contraindicated in patients with hypersensitivity to tinidazole or pyrroles, hypersensitivity to other ingredients in this product, and in patients with organic central nervous system disease.
As with other structurally similar drugs, it is contraindicated in patients with a history of blood dyscrasias or cachexia. Although no examples of long-term hematologic disorders have been identified in current animal and clinical studies.
Early pregnancy (first3months) is contraindicated in pregnant women.
Contraindicated in nursing mothers. Breastfeeding is suspended except during tinidazole treatment and for 3days after discontinuation of the drug.
[Caution]
1. Information for patients
Patients should be advised that this product should be taken with food in order to minimize upper abdominal discomfort and gastrointestinal adverse effects. Food does not affect the oral bioavailability of tinidazole.
Patients should be informed that during and after the treatment period3days, alcoholic beverages and preparations containing ethanol or propylene glycol are prohibited to avoid possible disulfiram-like reactions such as facial flushing, abdominal cramps, nausea, vomiting, headache, and rapid heartbeat.
Patients should take this product regularly. Missing a dose or not completing the entire course of treatment can directly reduce the effectiveness of treatment and may lead to bacterial resistance.
2. Antibacterial drugs including tinidazole are used only for bacterial infections; this product is not used for viral infections.
3. Drugs with similar chemical structures, including tinidazole, are thought to be associated with various neurological symptoms, such as dizziness, lightheadedness , ataxia, peripheral neuropathy, and, less commonly, convulsions. If any psychiatric symptoms develop during the application of this product, discontinue the medication immediately.
4. Adverse reactions of spastic seizures and peripheral neuropathy have been reported in some patients treated with tinidazole, the latter mainly characterized is numbness or abnormal sensation in the extremities.
5. Tinidazole use may lead to Candida vaginitis. In clinical studies,235 women used tinidazole for bacterial vaginitis, of whom11 (4.7%) style=”font-family:equinox”>) developed vaginal mycobacterial infections.
6. Impact on motor vehicle driving and machine operation
No special attention is needed. However, as previously mentioned, a class of drugs with similar chemical structures, including tinidazole, are thought to be associated with a range of neurological symptoms such as dizziness, lightheadedness, ataxia, peripheral neurological symptoms (abnormal sensation, confusion, hyperalgesia), and less frequently, convulsions. If any neurological symptoms occur during the application of this product, it should be discontinued immediately.
[For pregnant and lactating women]
There are no data on the safety and efficacy studies of tinidazole in pregnant patients. Because it crosses the placenta and rapidly enters the fetal circulation, it should be contraindicated during the 3months of pregnancy.
Animal studies have found a maximum dose of 2500mg/kg in rat litters. =”font-family:isoline”> (converted to body surface area, approximately 6.3times the maximum human therapeutic dose) without placental toxicity and teratogenic effects. In one study, maternal administration of 500 mg/kg (converted to body surface area, approximately) in pregnant rats was shown to have no placental toxicity or teratogenic effects. =”font-family:Times New Roman”>2.5times the maximum human therapeutic dose) has a high fetal mortality rate. Maternal administration of 600 mg/kg (converted by body surface area, approximately3 times the maximum human therapeutic dose) had no biological relevance to the development of newborn pups. Although it is true that potential mutagenicity and effects on animal regeneration in animal studies do not necessarily anticipate drug reactions in humans, the administration of tinidazole during the first trimester of pregnancy is potentially dangerous to both mother and fetus.
This product is administered72 It is excreted in breast milk after 72 hours and the concentration in breast milk is similar to that in blood, so it should be contraindicated in nursing women. If the drug must be used, breastfeeding should be suspended and lactation should not be allowed until 3 days after discontinuation of the drug.
[Children’s medication]
For the treatment of protozoal disease, use in children is limited to3Giardia and amebiasis in children older than 3 years of age. The safety and efficacy of this product in the treatment of giardia and amebiasis in children 3 years of age and younger is not known.
For the treatment of anaerobic infections and prevention of post-surgical anaerobic infections, this product is not available12Available data for children under the age of .
Clinical studies have not provided sufficient65data on tinidazole in elderly patients older than 65 years of age, so it is not possible to determine whether they are different from younger patients. In general, dosing in older patients needs to be determined carefully, taking into account minimizing liver, kidney, and heart damage, and some complications and interactions with other therapeutic agents.
[Drug Interactions]
The following drug interactions have been reported for metronidazole, a nitroimidazole analog that is chemically related to tinidazole, so the following reports may also occur with tinidazole.
1. Potential effects of tinidazole on other drugs
Warfarin and other oral coumarin anticoagulants: In light of reports of metronidazole, tinidazole can potentiate the efficacy of warfarin and other coumarin anticoagulants, resulting in prolonged prothrombin time. The anticoagulant dosage may need to be adjusted during tinidazole therapy and for 8days after its discontinuation.
Alcohol, disulfiram: during and after discontinuation of tinidazole therapy3 family:Arial”>drinks and any preparations containing alcohol or propylene glycol should be avoided for 3 days, otherwise reactions of abdominal cramps, nausea, vomiting, headache, and flushing may occur. Psychotic reactions have been reported in alcoholic patients taking both metronidazole and disulfiram. Although similar reports have not been seen with tinidazole, tinidazole should still not be given to patients who have taken disulfiram within the last 2 weeks.
Lithium: Metronidazole has been reported to raise serum lithium levels. It is not known whether tinidazole has the same properties, but patients on concomitant lithium and tinidazole are advised to have serum lithium and creatinine tests a few days after treatment to monitor the potential risk of lithium toxicity.
Phenytoin, fosphenytoin: Intravenous phenytoin administered concomitantly with oral metronidazole has been reported to result in a prolongation of the half-life and a decrease in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of phenytoin administered orally.
Cyclosporine, Tacrolimus: According to some reports, metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. Toxic reactions to immunosuppressive drugs should be monitored in these patients when tinidazole is co-administered with either of these.
Fluorouracil: Studies have shown that metronidazole decreases the clearance of fluorouracil resulting in increased side effects without therapeutic benefit, and if the combination of tinidazole and fluorouracil is unavoidable, patients should be monitored for fluorouracil-related toxic reactions.
2. Potential effects of other drugs on tinidazole
CYP3A4Inducer/inhibitors: Tinidazole is administered in combination with drugs that induce hepatic microsomal enzymes, namely CYP3A4 inducers, such as phenobarbital, rifampin, phenytoin, and fosphenytoin (a precursor drug to phenytoin), may accelerate the elimination of tinidazole and decrease plasma levels of tinidazole. Co-administration of tinidazole with drugs that inhibit hepatic microsomal enzyme activity, i.e.CYP3A4inhibitors such as cimetidine and ketoconazole, may prolong the the half-life of tinidazole and decrease its plasma clearance, thereby increasing tinidazole concentrations in plasma.
Deglutethimide: Deglutethimide has been reported to reduce metronidazole by 21%. family:Arial”>of oral bioavailability. Therefore, it is recommended that abciximide and tinidazole be administered separately to reduce the potential impact on the oral bioavailability of tinidazole.
Oxytetracycline: oxytetracycline has been reported to antagonize the therapeutic effect of metronidazole.
3. Drug interactions in laboratory trials
Similar to metronidazole, tinidazole may interfere with the determination of certain specific serum biochemical markers, such as glutamate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglycerides, and glucose hexokinase. Zero values may be observed. All content determination tests with reported interference phenomena involved the redox reaction of nicotinamide adenine dinucleotide during (NAD +NADH)coupling of the enzyme. The potential interference is due to the similarity of the absorption peaks of NADH and tinidazole.
Similar to metronidazole, tinidazole may produce transient leukocytopenia and neutropenia, however, no persistent hematologic abnormalities caused by tinidazole have been observed in clinical trials. If repeat therapy is necessary, total leukocyte and sorting counts are recommended.
[Drug overdose]
Tinidazole overdose has not been reported in humans.
Treatment of drug overdose: There is no specific antidote for tinidazole overdose, therefore, treatment should be symptomatic. Gastric lavage may be effective. Hemodialysis may also be considered, as approximately 43% of the drugs in the body can be administered on hemodialysis6hours to eliminate.
[Pharmacology and Toxicology]
Pharmacological effects
Mechanism: Tinidazole is an antiprotozoal and antibacterial agent. The nitro group of tinidazole can be reduced by cell extracts of Trichuris trichiura, and the free nitro group produced by the reduction has antiprotozoal activity. In in vitro assays, chemically reduced tinidazole released nitrite and caused damage to purified bacterialDNA. In addition, the drug can cause base changes in bacterial cellDNAand mammalian cellDNAstrand breaks. The mechanism of action of tinidazole against Giardia and Amoeba protozoa is unclear.
Antimicrobial activity: Bacterial culture and drug sensitivity testing are not yet routinely used as diagnostic methods for bacterial vaginitis. Standard methods for drug sensitivity testing for potential bacterial pathogens, Gardnerella vaginalis, active Campylobacter spp. or mycoplasma have not been established. The following in vitro data have been obtained, but their clinical significance is unclear Tinidazole has in vitro activity against most of the following pathogens associated with bacterial vaginosis: Bacteroidetes spp, Gardnerella vaginalis, Prevotella spp. Tinidazole did not show antibacterial activity against most vaginal lactobacilli.
Antiprotozoal activity: Tinidazole has been shown to be active in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis, Giardia lamblia (also known as Pear-shaped flagellates), and Amoeba protozoa. There is no standard drug sensitivity test method for protozoan parasites that can be used in clinical microbiology laboratories.
Resistance: resistance of tinidazole to Giardia, amoeba or bacteria associated with bacterial vaginitis has not been examined.
Cross-resistance: in vitro, approximately 38%trichomonas vaginalis with decreased sensitivity to metronidazole also exhibited decreased sensitivity to tinidazole. The clinical significance of this is unclear.
Toxicological studies
Repeated dosing toxicity:BeagleDogs were given tinidazole via mouth for 28 consecutivedays100,300and1000mg/kg/day on day18day high dose was reduced to600mg/kg due to severe clinical symptoms Roman”>600 mg/kg/day. The reactions associated with the administration were manifested as thymic atrophy in male and female animals in the medium and high dose groups and prostate atrophy in male animals in all dose groups. The no apparent toxic response dose (NOAEL) for female animals was 100mg/kg/day; males were found to be at a low level of 100mg/ kg/day (approximately 0.9of the highest human therapeutic dose in terms of body surface areafold) dose produced mild prostate atrophy without definitiveNOAEL.
Genotoxicity: In theAmesIn the test, tinidazole was mutagenic against Salmonella typhimuriumTA100strain,TA98strain was negative,TA1535, 1537 and and span>1538strain positive and negative results were seen with positive results for Klebsiella pneumoniae. Negative results were seen for TinidazoleCHL/CHOchromosome aberration test and positive results for mouse micronucleus test.
Reproductive toxicity: in a 60day administration of tinidazole in a fertility toxicity test at 600 mg/kg/day dose (approximately the highest human therapeutic dose in terms of body surface area) 3fold) reduced fertility and caused testicular tissue damage in male rats. 300and600 mg/kg Roman”>600 mg/kg/day dose can affect sperm formation. 100mg/kg/day (approximately the highest human therapeutic dose in terms of body surface area) “font-family:Times New Roman”>0.5fold) as the no significant effect dose for testicular and sperm formation. The above effects are characteristic of 5-nitroimidazoles.
Gestational Mouse Embryos- The results of the fetal developmental toxicity test showed that tinidazole at the highest dose2500 mg/kg (approximately the highest therapeutic dose in humans in terms of body surface area) 6.3fold) of the highest human therapeutic dose, no embryos were seen-fetal toxicity or teratogenic effects. In pregnant rats at 500 mg/kg (approximately the highest human therapeutic dose in terms of body surface area2.5times the highest human therapeutic dose), a slight increase in fetal mortality was observed.
Tinidazole can cross the placental barrier into the fetal circulation. Tinidazole is excreted in breast milk at concentrations similar to serum drug concentrations.
Carcinogenicity: Metronidazole (a nitroimidazole with a related chemical structure) has been reported to be carcinogenic in mice and rats, and has not been shown to be carcinogenic in hamsters. Several tests with metronidazole have shown evidence of carcinogenicity in mice with lung, liver, and lymphoma and in female rats with breast and liver. No tests of carcinogenicity of tinidazole in rats, mice, or hamsters have been reported.
[Pharmacokinetics]
Absorption:
This product is rapidly and completely absorbed after oral administration. In a study of oral administration of 2g tinidazole in healthy volunteers,2hours to reach40-51µg/ml peak serum levels and decreases to 24hours11-19µg/ml. At 72hours after oral administration, plasma concentrations slowly decreased and tinidazole was still detectable in plasma at concentrations up to1µg/ml. The plasma elimination half-life of tinidazole is 12-14hours.
The concomitant administration of this product with food compared to fasting administration resulted inTmaxdelay2hours,Cmaxis reduced by approximately10% , but for AUC andT1/2have no effect.
Distribution:
It is absorbed rapidly into the tissues and body fluids, crosses the blood-brain barrier, and is widely distributed throughout the body. The volume of distribution is approximately50liters, and 12%Tinidazole is bound to plasma proteins. Tinidazole crosses the placental barrier and is excreted through breast milk.
Metabolism:
Tinidazole is mostly metabolized in vivo, mainly by oxidation, hydrolysis, and conjugate binding. It is mostly present in plasma in its native form, with a small amount metabolized to 2-hydroxymethyl metabolites. Tinidazole completes biotransformation via CYP3A4, and in vitro metabolism studies have shown that tinidazole concentrations at 75 μg/mL and does not inhibitCYP1A2 ,CYP2B6, CYP2C9, CYP2D6,CYP2E1and CYP3A4 and other enzymes activity.
Metabolic interactions of tinidazole with other drugs are not known at this time.
Elimination:
The plasma half-life of tinidazole is approximately12 ~14hours. The drug is excreted via the liver and kidneys. Tinidazole is excreted in the urine as a prototype (approximately 20%to of the administered dose. family:Times New Roman”>25%) discharged, about 12%of the drug is excreted in the feces.
Patients with renal insufficiency:
Tinidazole in healthy subjects and in subjects with impaired renal function(CrCL ≤ 22 mL/min)no significant differences in pharmacokinetics were observed in patients. However, renal elimination of tinidazole was significantly enhanced by hemodialysis; the half-life was reduced from 12.0hours to4.9hours.
About 43% of in vivo tinidazole on hemodialysis eliminated in 6hours of dialysis.
No data are available from pharmacokinetic studies in patients on conventional peritoneal dialysis.
Patients with hepatic insufficiency:
There are no data on the pharmacokinetics of tinidazole in patients with impaired hepatic function. Metronidazole, a similar drug that also contains a nitroimidazole-like structure, has been reported in several reports to show reduced metabolic elimination in patients with impaired hepatic function.
[Storage]Store under shade, sealed, at room temperature.
Polyvinyl chloride/polyvinylidene chloride solid pharmaceutical laminated rigid tablets and aluminum foil for pharmaceutical packaging,4tablets/Plate×1 span style=”font-family:isoline”>board/box,box,8pieces//pieces “font-family:isoline”>plate×1plateplate/box,10pieces/board×1board/boardbox.
[Expiration date]24months.
[Executive Standard]
[Approval number]国药准字 H10950320
[Marketing Authorization Holder]
Unit Name:Lizhu Group Lizhu Pharmaceutical Factory
Registered Address: Venture North Road, Jinwan District, Zhuhai38No.[Manufacturer
Enterprise Name:Lizhu Group Lizhu Pharmaceutical FactoryManufacturing Address: Venture North Road, Jinwan District, Zhuhai38No.
Postal Code:519045
Phone Number:4008031238Fax Number:0756- 8870128
Net
Address:www.livzon.com.cn