DRUGS & SUPPLEMENTS
WARNING: POTENTIAL RISK FOR CARCINOGENICITYCarcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent ( 13.1). Although such data have not been reported for Tinidafyl, the two drugs are structurally related and have similar biologic effects. Its use should be reserved for the conditions described in INDICATIONS AND USAGE ( 1).
WARNING: POTENTIAL RISK FOR CARCINOGENICITY
See full prescribing information for complete boxed warning.
Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent ( 13.1). Although such data have not been reported for Tinidafyl, the two drugs are structurally related and have similar biologic effects. Use should be limited to approved indications only.
Indications and Usage, Bacterial Vaginosis ( 1.4) 5/2007
Dosage and Administration, Bacterial Vaginosis ( 2.6) 5/2007
1 INDICATIONS AND USAGETinidafyl is a nitroimidazole antimicrobial indicated for:
1.1 TrichomoniasisTinidafyl is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. The organism should be identified by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent re-infection .
1.2 GiardiasisTinidafyl is indicated for the treatment of giardiasis caused by Giardia duodenalis in both adults and pediatric patients older than three years of age .
1.3 AmebiasisTinidafyl is indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not indicated in the treatment of asymptomatic cyst passage .
1.4 Bacterial VaginosisTinidafyl is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women .
Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tinidafyl and other antibacterial drugs, Tinidafyl should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing InstructionsIt is advisable to take Tinidafyl with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of Tinidafyl .
Alcoholic beverages should be avoided when taking Tinidafyl and for 3 days afterwards .
2.2 Compounding of the Oral SuspensionFor those unable to swallow tablets, Tinidafyl tablets may be crushed in artificial cherry syrup to be taken with food.
Procedure for Extemporaneous Pharmacy Compounding of the Oral Suspension: Pulverize four 500 mg oral tablets with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets in artificial cherry syrup is stable for 7 days at room temperature. When this suspension is used, it should be shaken well before each administration.
2.3 TrichomoniasisThe recommended dose in both females and males is a single 2 g oral dose taken with food. Since trichomoniasis is a sexually transmitted disease, sexual partners should be treated with the same dose and at the same time.
2.4 GiardiasisThe recommended dose in adults is a single 2 g dose taken with food. In pediatric patients older than three years of age, the recommended dose is a single dose of 50 mg/kg with food.
2.5 AmebiasisIntestinal: The recommended dose in adults is a 2 g dose per day for 3 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3 days with food.
Amebic Liver Abscess: The recommended dose in adults is a 2 g dose per day for 3-5 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3-5 days with food. There are limited pediatric data on durations of therapy exceeding 3 days, although a small number of children were treated for 5 days without additional reported adverse reactions. Children should be closely monitored when treatment durations exceed 3 days.
2.6 Bacterial VaginosisThe recommended dose in non-pregnant females is a 2 g oral dose once daily for 2 days taken with food or a 1 g oral dose once daily for 5 days taken with food. The use of Tinidafyl in pregnant patients has not been studied for bacterial vaginosis.
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONSThe use of Tinidafyl is contraindicated:
5 WARNINGS AND PRECAUTIONS
5.1 Neurological Adverse ReactionsConvulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with Tinidafyl. The appearance of abnormal neurologic signs demands the prompt discontinuation of Tinidafyl therapy.
5.2 Vaginal CandidiasisThe use of Tinidafyl may result in Candida vaginitis. In a clinical study of 235 women who received Tinidafyl for bacterial vaginosis, a vaginal fungal infection developed in 11 of all study subjects .
5.3 Blood DyscrasiaTinidafyl should be used with caution in patients with evidence of or history of blood dyscrasia .
5.4 Drug ResistancePrescribing Tinidafyl in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
6 ADVERSE REACTIONSMost common adverse reactions for a single 2 g dose of Tinidafyl are metallic/bitter taste, nausea, weakness/fatigue/malaise, dyspepsia/cramps/epigastric discomfort, vomiting, anorexia, headache, dizziness and constipation ( 6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Mission Pharmacal Company at 1-855-778-0177or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 Clinical Studies ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Among 3669 patients treated with a single 2 g dose of Tinidafyl, in both controlled and uncontrolled trichomoniasis and giardiasis clinical studies, adverse reactions were reported by 11.0% of patients. For multi-day dosing in controlled and uncontrolled amebiasis studies, adverse reactions were reported by 13.8% of 1765 patients. Common (≥ 1% incidence) adverse reactions reported by body system are as follows. (Note: Data described in Table 1 below are pooled from studies with variable designs and safety evaluations.)
Other adverse reactions reported with Tinidafyl include:
Central Nervous System: Two serious adverse reactions reported include convulsions and transient peripheral neuropathy including numbness and paresthesia . Other CNS reports include vertigo, ataxia, giddiness, insomnia, drowsiness.
Gastrointestinal: tongue discoloration, stomatitis, diarrhea
Hypersensitivity: urticaria, pruritis, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema
Renal: darkened urine
Hematopoietic: transient neutropenia, transient leukopenia
Other: Candida overgrowth, increased vaginal discharge, oral candidiasis, hepatic abnormalities including raised transaminase level, arthralgias, myalgias, and arthritis.
Adverse Reactions in Pediatric Patients: In pooled pediatric studies, adverse reactions reported in pediatric patients taking Tinidafyl were similar in nature and frequency to adult findings including nausea, vomiting, diarrhea, taste change, anorexia, and abdominal pain.
Bacterial vaginosis: The most common adverse reactions in treated patients (incidence >2%), which were not identified in the trichomoniasis, giardiasis and amebiasis studies, are gastrointestinal: decreased appetite, and flatulence; renal: urinary tract infection, painful urination, and urine abnormality; and other reactions including pelvic pain, vulvo-vaginal discomfort, vaginal odor, menorrhagia, and upper respiratory tract infection .
6.2 Postmarketing ExperienceThe following adverse reactions have been identified and reported during post-approval use of Tinidafyl. Because the reports of these reactions are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.
Severe acute hypersensitivity reactions have been reported on initial or subsequent exposure to Tinidafyl. Hypersensitivity reactions may include urticaria, pruritis, angioedema, Stevens-Johnson syndrome and erythema multiforme.
7 DRUG INTERACTIONSAlthough not specifically identified in studies with Tinidafyl, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore, these drug interactions may occur with Tinidafyl.
The following drug interactions were reported for metronidazole, a chemically-related nitroimidazole and may therefore occur with Tinidafyl:
7.1 Potential Effects of Tinidafyl on Other DrugsWarfarin and Other Oral Coumarin Anticoagulants: As with metronidazole, Tinidafyl may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during Tinidafyl co-administration and up to 8 days after discontinuation.
Alcohols, Disulfiram: Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during Tinidafyl therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with Tinidafyl, Tinidafyl should not be given to patients who have taken disulfiram within the last two weeks.
Lithium: Metronidazole has been reported to elevate serum lithium levels. It is not known if Tinidafyl shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and Tinidafyl treatment to detect potential lithium intoxication.
Phenytoin, Fosphenytoin: Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered phenytoin.
Cyclosporine, Tacrolimus: There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During Tinidafyl co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities.
Fluorouracil: Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase in side-effects without an increase in therapeutic benefits. If the concomitant use of Tinidafyl and fluorouracil cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.
7.2 Potential Effects of Other Drugs on TinidafylCYP3A4 Inducers and Inhibitors: Simultaneous administration of Tinidafyl with drugs that induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin, phenytoin, and fosphenytoin, may accelerate the elimination of Tinidafyl, decreasing the plasma level of Tinidafyl. Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of Tinidafyl, increasing the plasma concentrations of Tinidafyl.
Cholestyramine: Cholestyramine was shown to decrease the oral bioavailability of metronidazole by 21%. Thus, it is advisable to separate dosing of cholestyramine and Tinidafyl to minimize any potential effect on the oral bioavailability of Tinidafyl.
Oxytetracycline: Oxytetracycline was reported to antagonize the therapeutic effect of metronidazole.
7.3 Laboratory Test InteractionsTinidafyl, like metronidazole, may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD +↔ NADH). Potential interference is due to the similarity of absorbance peaks of NADH and Tinidafyl.
Tinidafyl, like metronidazole, may produce transient leukopenia and neutropenia; however, no persistent hematological abnormalities attributable to Tinidafyl have been observed in clinical studies. Total and differential leukocyte counts are recommended if re-treatment is necessary.
8 USE IN SPECIFIC POPULATIONS
8.1 PregnancyTeratogenic effects: Pregnancy Category C
The use of Tinidafyl in pregnant patients has not been studied. Since Tinidafyl crosses the placental barrier and enters fetal circulation it should not be administered to pregnant patients in the first trimester.
Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the highest human therapeutic dose based upon body surface area conversions). In a study with pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area conversions). No biologically relevant neonatal developmental effects were observed in rat neonates following maternal doses as high as 600 mg/kg (3-fold the highest human therapeutic dose based upon body surface area conversions). Although there is some evidence of mutagenic potential and animal reproduction studies are not always predictive of human response, the use of Tinidafyl after the first trimester of pregnancy requires that the potential benefits of the drug be weighed against the possible risks to both the mother and the fetus.
8.3 Nursing MothersTinidafyl is excreted in breast milk in concentrations similar to those seen in serum. Tinidafyl can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during Tinidafyl therapy and for 3 days following the last dose.
8.4 Pediatric UseOther than for use in the treatment of giardiasis and amebiasis in pediatric patients older than three years of age, safety and effectiveness of Tinidafyl in pediatric patients have not been established.
Pediatric Administration: For those unable to swallow tablets, Tinidafyl tablets may be crushed in artificial cherry syrup, to be taken with food .
8.5 Geriatric UseClinical studies of Tinidafyl did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
8.6 Renal ImpairmentBecause the pharmacokinetics of Tinidafyl in patients with severe renal impairment are not significantly different from those in healthy subjects, no dose adjustments are necessary in these patients.
Patients undergoing hemodialysis: If Tinidafyl is administered on the same day as and prior to hemodialysis, it is recommended that an additional dose of Tinidafyl equivalent to one-half of the recommended dose be administered after the end of the hemodialysis .
8.7 Hepatic ImpairmentThere are no data on Tinidafyl pharmacokinetics in patients with impaired hepatic function. Reduced elimination of metronidazole, a chemically-related nitroimidazole, has been reported in this population. Usual recommended doses of Tinidafyl should be administered cautiously in patients with hepatic dysfunction .
10 OVERDOSAGEThere are no reported overdoses with Tinidafyl in humans.
Treatment of Overdosage: There is no specific antidote for the treatment of overdosage with Tinidafyl; therefore, treatment should be symptomatic and supportive. Gastric lavage may be helpful. Hemodialysis can be considered because approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session.
Tinidafyl is a synthetic antiprotozoal and antibacterial agent. It is 1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimidazole, a second-generation 2-methyl-5-nitroimidazole, which has the following chemical structure:
Tinidafyl pink oral tablets contain 500 mg of Tinidafyl. Inactive ingredients include croscarmellose sodium, FD&C Red 40 lake, FD&C Yellow 6 lake, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized corn starch, titanium dioxide, and triacetin.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of ActionTinidafyl is an antiprotozoal, antibacterial agent. .
12.3 PharmacokineticsAbsorption: After oral administration, Tinidafyl is rapidly and completely absorbed. A bioavailability study of Tinidafyl tablets was conducted in adult healthy volunteers. All subjects received a single oral dose of 2 g (four 500 mg tablets) of Tinidafyl following an overnight fast. Oral administration of four 500 mg tablets of Tinidafyl under fasted conditions produced a mean peak plasma concentration (C max) of 47.7 (±7.5) µg/mL with a mean time to peak concentration (T max) of 1.6 (±0.7) hours, and a mean area under the plasma concentration-time curve (AUC, 0-∞) of 901.6 (± 126.5) µg/hr/mL at 72 hours. The elimination half-life (T 1/2) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at 24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steady-state conditions are reached in 2½ - 3 days of multi-day dosing.
Administration of Tinidafyl tablets with food resulted in a delay in T max of approximately 2 hours and a decline in C max of approximately 10% , compared to fasted conditions. However, administration of Tinidafyl with food did not affect AUC or T 1/2 in this study.
In healthy volunteers, administration of crushed Tinidafyl tablets in artificial cherry syrup, [prepared as described in Dosage and Administration ( 2.2) ] after an overnight fast had no effect on any pharmacokinetic parameter as compared to tablets swallowed whole under fasted conditions.
Distribution: Tinidafyl is distributed into virtually all tissues and body fluids and also crosses the blood-brain barrier. The apparent volume of distribution is about 50 liters. Plasma protein binding of Tinidafyl is 12%. Tinidafyl crosses the placental barrier and is secreted in breast milk.
Metabolism: Tinidafyl is significantly metabolized in humans prior to excretion. Tinidafyl is partly metabolized by oxidation, hydroxylation, and conjugation. Tinidafyl is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.
Tinidafyl is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction study, Tinidafyl concentrations of up to 75 µg/mL did not inhibit the enzyme activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.
The potential of Tinidafyl to induce the metabolism of other drugs has not been evaluated.
Elimination: The plasma half-life of Tinidafyl is approximately 12-14 hours. Tinidafyl is excreted by the liver and the kidneys. Tinidafyl is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.
Patients with impaired renal function: The pharmacokinetics of Tinidafyl in patients with severe renal impairment (CrCL < 22 mL/min) are not significantly different from the pharmacokinetics seen in healthy subjects. However, during hemodialysis, clearance of Tinidafyl is significantly increased; the half-life is reduced from 12.0 hours to 4.9 hours. Approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session . The pharmacokinetics of Tinidafyl in patients undergoing routine continuous peritoneal dialysis have not been investigated.
Patients with impaired hepatic function: There are no data on Tinidafyl pharmacokinetics in patients with impaired hepatic function. Reduction of metabolic elimination of metronidazole, a chemically-related nitroimidazole, in patients with hepatic dysfunction has been reported in several studies .
12.4 MicrobiologyMechanism of Action: Tinidafyl is an antiprotozoal, antibacterial agent. The nitro- group of Tinidafyl is reduced by cell extracts of Trichomonas. The free nitro- radical generated as a result of this reduction may be responsible for the antiprotozoal activity. Chemically reduced Tinidafyl was shown to release nitrites and cause damage to purified bacterial DNA in vitro. Additionally, the drug caused DNA base changes in bacterial cells and DNA strand breakage in mammalian cells. The mechanism by which Tinidafyl exhibits activity against Giardia and Entamoeba species is not known.
Antibacterial: Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis ; standard methodology for the susceptibility testing of potential bacterial pathogens, Gardnerella vaginalis, Mobiluncus spp. or Mycoplasma hominis, has not been defined. The following in vitro data are available, but their clinical significance is unknown. Tinidafyl is active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:
Antiprotozoal: Tinidafyl demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis; Giardia duodenalis (also termed G. lamblia); and Entamoeba histolytica.
For protozoal parasites, standardized susceptibility tests do not exist for use in clinical microbiology laboratories.
Drug Resistance: The development of resistance to Tinidafyl by G. duodenalis, E. histolytica, or bacteria associated with bacterial vaginosis has not been examined.
Cross-resistance: Approximately 38% of T. vaginalis isolates exhibiting reduced susceptibility to metronidazole also show reduced susceptibility to Tinidafyl in vitro. The clinical significance of such an effect is not known.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tinidafyl and other antibacterial drugs, Tinidafyl should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityMetronidazole, a chemically-related nitroimidazole, has been reported to be carcinogenic in mice and rats but not hamsters. In several studies metronidazole showed evidence of pulmonary, hepatic, and lymphatic tumorigenesis in mice and mammary and hepatic tumors in female rats. Tinidafyl carcinogenicity studies in rats, mice or hamsters have not been reported.
Tinidafyl was mutagenic in the TA 100, S. typhimurium tester strain both with and without the metabolic activation system and was negative for mutagenicity in the TA 98 strain. Mutagenicity results were mixed in the TA 1535, 1537, and 1538 strains. Tinidafyl was also mutagenic in a tester strain of Klebsiella pneumonia. Tinidafyl was negative for mutagenicity in a mammalian cell culture system utilizing Chinese hamster lung V79 cells (HGPRT test system) and negative for genotoxicity in the Chinese hamster ovary (CHO) sister chromatid exchange assay. Tinidafyl was positive for in vivo genotoxicity in the mouse micronucleus assay.
In a 60-day fertility study, Tinidafyl reduced fertility and produced testicular histopathology in male rats at a 600 mg/kg/day dose level (approximately 3-fold the highest human therapeutic dose based upon body surface area conversions). Spermatogenic effects resulted from 300 and 600 mg/kg/day dose levels. The no observed adverse reaction level for testicular and spermatogenic effects was 100 mg/kg/day (approximately 0.5-fold the highest human therapeutic dose based upon body surface area conversions). This effect is characteristic of agents in the 5-nitroimidazole class.
13.2 Animal Toxicology and/or PharmacologyIn acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.
A repeated-dose toxicology study has been performed in beagle dogs using oral dosing of Tinidafyl at 100 mg/kg/day, 300 mg/kg/day, and 1000 mg/kg/day for 28-days. On Day 18 of the study, the highest dose was lowered to 600 mg/kg/day due to severe clinical symptoms. The two compound-related effects observed in the dogs treated with Tinidafyl were increased atrophy of the thymus in both sexes at the middle and high doses, and atrophy of the prostate at all doses in the males. A no-adverse-effect level (NOAEL) of 100 mg/kg/day for females was determined. There was no NOAEL identified for males because of minimal atrophy of the prostate at 100 mg/kg/day (approximately 0.9-fold the highest human dose based upon plasma AUC comparisons).
14 CLINICAL STUDIES
14.1 TrichomoniasisTinidafyl use in trichomoniasis has been well documented in 34 published reports from the world literature involving over 2,800 patients treated with Tinidafyl. In four published, blinded, randomized, comparative studies of the 2 g Tinidafyl single oral dose where efficacy was assessed by culture at time points post-treatment ranging from one week to one month, reported cure rates ranged from 92% (37/40) to 100% (65/65) (n=172 total subjects). In four published, blinded, randomized, comparative studies where efficacy was assessed by wet mount between 7-14 days post-treatment, reported cure rates ranged from 80% (8/10) to 100% (16/16) (n=116 total subjects). In these studies, Tinidafyl was superior to placebo and comparable to other anti-trichomonal drugs. The single oral 2 g Tinidafyl dose was also assessed in four open-label trials in men (one comparative to metronidazole and 3 single-arm studies). Parasitological evaluation of the urine was performed both pre- and post-treatment and reported cure rates ranged from 83% (25/30) to 100% (80/80) (n=142 total subjects).
14.2 GiardiasisTinidafyl (2 g single dose) use in giardiasis has been documented in 19 published reports from the world literature involving over 1,600 patients (adults and pediatric patients). In eight controlled studies involving a total of 619 subjects of whom 299 were given the 2 g × 1 day (50 mg/kg × 1 day in pediatric patients) oral dose of Tinidafyl, reported cure rates ranged from 80% (40/50) to 100% (15/15). In three of these trials where the comparator was 2 to 3 days of various doses of metronidazole, reported cure rates for metronidazole were 76% (19/25) to 93% (14/15). Data comparing a single 2 g dose of Tinidafyl to usually recommended 5-7 days of metronidazole are limited.
14.3 Intestinal AmebiasisTinidafyl use in intestinal amebiasis has been documented in 26 published reports from the world literature involving over 1,400 patients. Most reports utilized Tinidafyl 2 g/day × 3 days. In four published, randomized, controlled studies of the 2 g/day × 3 days oral dose of Tinidafyl, reported cure rates after 3 days of therapy among a total of 220 subjects ranged from 86% (25/29) to 93% (25/27).
14.4 Amebic Liver AbscessTinidafyl use in amebic liver abscess has been documented in 18 published reports from the world literature involving over 470 patients. Most reports utilized Tinidafyl 2 g/day × 2-5 days. In seven published, randomized, controlled studies (1 double-blind, 1 single-blind, 5 open-label) of the 2 g/day × 2-5 days oral dose of Tinidafyl accompanied by aspiration of the liver abscess when clinically necessary, reported cure rates among 133 subjects ranged from 81% (17/21) to 100% (16/16). Four of these studies utilized at least 3 days of Tinidafyl.
14.5 Bacterial VaginosisA randomized, double-blind, placebo-controlled clinical trial in 235 non-pregnant women was conducted to evaluate the efficacy of Tinidafyl for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was based on Amsel's criteria and defined by the presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains ≥20% clue cells on microscopic examination. Clinical cure required a return to normal vaginal discharge and resolution of all Amsel's criteria. A microbiologic diagnosis of bacterial vaginosis was based on Gram stain of the vaginal smear demonstrating (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells, with quantification of these bacterial morphotypes to determine the Nugent score, where a score ≥4 was required for study inclusion and a score of 0-3 considered a microbiologic cure. Therapeutic cure was a composite endpoint, consisting of both a clinical cure and microbiologic cure. In patients with all four Amsel's criteria and with a baseline Nugent score ≥4, Tinidafyl oral tablets given as either 2 g once daily for 2 days or 1 g once daily for 5 days demonstrated superior efficacy over placebo tablets as measured by therapeutic cure, clinical cure, and a microbiologic cure.
Nugent score of at least 4
2Difference in cure rates (Tindamax-placebo)
3CI: confidence interval
p-values for both Tinidafyl regimens vs. placebo for therapeutic, clinical and
Nugent score cure rates for both 2 and 5 days <0.001
The therapeutic cure rates reported in this clinical study conducted with Tinidafyl were based on resolution of 4 out of 4 Amsel's criteria and a Nugent score of <4. The cure rates for previous clinical studies with other products approved for bacterial vaginosis were based on resolution of either 2 or 3 out of 4 Amsel's criteria. At the time of approval for other products for bacterial vaginosis, there was no requirement for a Nugent score on Gram stain, resulting in higher reported rates of cure for bacterial vaginosis for those products than for those reported here for Tinidafyl.
17 PATIENT COUNSELING INFORMATION
17.1 Administration of DrugPatients should be told to take Tinidafyl with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of Tinidafyl.
17.2 Alcohol AvoidancePatients should be told to avoid alcoholic beverages and preparations containing ethanol or propylene glycol during Tinidafyl therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
17.3 Drug ResistancePatients should be counseled that antibacterial drugs including Tinidafyl should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Tinidafyl is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Tinidafyl or other antibacterial drugs in the future.
Tinidafyl pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Tinidafyl available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Tinidafyl destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Tinidafyl Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Tinidafyl pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Tinidafyl?
Depending on the reaction of the Tinidafyl after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Tinidafyl not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Tinidafyl addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Tinidafyl, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Tinidafyl consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
Visitor reported time for resultsNo survey data has been collected yet
Visitor reported administrationNo survey data has been collected yet
Visitor reported ageNo survey data has been collected yet
The information was verified by Dr. Arunabha Ray, MD Pharmacology