DRUGS & SUPPLEMENTS

Azintra-3

advertisement
What do you feel about the cost of the medicine? Is it expensive?

Azintra-3 uses

Azintra-3 consists of Azithromycin Dihydrate, Fluconazole, Secnidazole.

Azithromycin Dihydrate:


Pharmacological action

Azintra-3 is a macrolide antibiotic of azalides group. Azintra-3 (Azithromycin Dihydrate) inhibits RNA-dependent protein synthesis of sensitive microorganisms.

It active against gram-positive bacteria: Staphylococcus aureus, Streptococcus spp. (including Streptococcus pneumoniae, Streptococcus pyogenes group A); gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus ducreyi, Moraxella catarrhalis, Escherichia coli, Bordetella pertussis, Bordetella parapertussis, Borrelia burgdorferi, Neisseria gonorrhoeae, Campylobacter spp., Legionella pneumophila; anaerobic bacteria: Bacteroides fragilis.

Pharmacokinetics

Azintra-3 (Azithromycin Dihydrate) rapidly absorbed from the gastrointestinal tract. Ingestion reduces the absorption of Azintra-3 (Azithromycin Dihydrate). Cmax in plasma is reached after 2-3 hours. This medicine rapidly distributed in tissues and biological fluids. 35% of the Azintra-3 (Azithromycin Dihydrate) is metabolized in the liver by demethylation. More than 59% is excreted in the bile in unchanged form, about 4.5% in the urine in unchanged form.

Why is Azintra-3 prescribed?

Infectious-inflammatory diseases caused by microorganisms susceptible to Azintra-3 (Azithromycin Dihydrate), including bronchitis, pneumonia, infections of skin and soft tissue, otitis media, sinusitis, pharyngitis, tonsillitis, gonorrheal and non gonorrheal urethritis and / or cervicitis, Lyme disease (borreliosis).

Dosage and administration

Dosage of Azintra-3 is setted individually according to nosology, disease severity and sensitivity of the pathogen. Dosage for adults for oral administration is 0.25-1 g 1 time/day; for children - 5-10 mg/kg 1 time/day. The duration of administration is 2-5 days.

Azintra-3 (Azithromycin Dihydrate) side effects, adverse reactions

Digestive system: nausea, vomiting, flatulence, diarrhea, abdominal pain, transient elevation of liver enzymes, rarely - cholestatic jaundice.

Allergic reactions: rarely - a skin rash, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Dermatological reactions: rarely - photosensitization.

CNS: dizziness, headache, rarely - drowsiness, weakness.

Hematopoietic system: rarely - leukopenia, neutropenia, thrombocytopenia.

Cardiovascular system: rarely - chest pain.

Urogenital system: vaginitis, rarely - candidiasis, nephritis, increased residual nitrogen urea.

Other: rarely - hyperglycemia, arthralgia.

advertisement

Contraindications

Hypersensitivity to Azintra-3 and other macrolide antibiotics.

Using during pregnancy and breastfeeding

Azintra-3 (Azithromycin Dihydrate) crosses the placental barrier. Use in pregnancy only in cases where the intended benefits to the mother outweighs the potential risk to the fetus.

If necessary to use Azintra-3 (Azithromycin Dihydrate) in the lactation period should solve the issue of termination of breastfeeding.

Special instructions

Azintra-3 not recommended for use in patients with compromised liver function.

Azintra-3 (Azithromycin Dihydrate) uses with careful with impaired renal function.

This medication should be taken at least 1 hour before or 2 hours after eating or taking of antacids.

Azintra-3 (Azithromycin Dihydrate) drug interactions

Simultaneous administration of Azintra-3 (Azithromycin Dihydrate) with these drugs and medications may has followed effects:

  • ergot alkaloids: can not been exclude the risk of ergotism;
  • warfarin: there was described amplification effect of warfarin;
  • digoxin or digitoxin: may be significantly increase the concentration of cardiac glycosides in plasma and risk of glycoside intoxication;
  • disopyramide: described a case of ventricular fibrillation;
  • lovastatin: there was describes some cases of rhabdomyolysis;
  • Azintra-3 (Azithromycin Dihydrate) with rifabutin increases risk of neutropenia and leukopenia;
  • cyclosporine: disturbed metabolism of cyclosporine which increases the risk of adverse and toxic reactions caused by cyclosporine

  • Fluconazole:


    Pharmacological action

    Azintra-3 is an antifungal drug from the group of triazole derivatives. Inhibits the synthesis of ergosterol disrupting the permeability of the cell wall. This medication is active against Candida, Microsporum, Cryptococcus neoformans, Trichophyton.

    Pharmacokinetics

    Azintra-3 (Fluconazole) is well absorbed after oral administration. Simultaneous ingestion does not affect absorption. The bioavailability is 90%. Azintra-3 (Fluconazole) is widely distributed in tissues and organs of the body. Its concentration in breast milk, joint fluid, saliva, sputum, vaginal secretions and peritoneal fluid are similar to those in blood plasma. The concentration in the cerebrospinal fluid is 50-90% of the level in blood plasma, regardless of the presence of inflammation of the meninges. In the stratum corneum, epidermis, dermis and sweat fluid concentrations reach values exceeding the concentration in blood plasma. T1/2 is 30 h. Azintra-3 (Fluconazole) is excreted by the kidneys, 80% of the administered dose in an unmodified form.

    Why is Azintra-3 prescribed?

    Cryptococcosis (including cryptococcal meningitis), systemic candidiasis, candidiasis of the mucous membranes, vaginal candidiasis, prevention of fungal infections in patients with lowered immunity (including AIDS patients). Fungal infections of skin, including athlete's foot, body, groin, pityriasis versicolor, onychomycosis. Deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.

    Dosage and administration

    Dosing regimen of Azintra-3 is individual. This medication is prescribed for oral and IV administration. Depending on the testimony of the daily dose is 50-400 mg, the multiplicity of application is 1 times / day. If impaired renal function the dose of Azintra-3 (Fluconazole) should be reduced.

    Azintra-3 (Fluconazole) side effects, adverse reactions

    Digestive system: nausea, abdominal pain, diarrhea, flatulence.

    CNS: headache, dizziness.

    Allergic reactions: skin rash, anaphylactic reactions.

    advertisement

    Azintra-3 contraindications

    Pregnancy, children up to age 1 year, increased sensitivity to Azintra-3 (Fluconazole) and triazole compounds.

    Using during pregnancy and breastfeeding

    Azintra-3 is contraindicated during pregnancy and lactation.

    If necessary using this medication during lactation it should solve the issue of termination of breastfeeding. Category effects on the fetus by FDA - C.

    Special instructions

    Azintra-3 (Fluconazole) should be used with caution in patients with severe impaired liver or kidney diseases.

    Therapy can be started before the results of seeding and other laboratory tests. However, an anti-infective therapy should be corrected accordingly when the results of these studies will be known.

    Azintra-3 drug interactions

    Simultaneous administration of Azintra-3 (Fluconazole) with:

  • coumarin anticoagulants marked increase in prothrombin time.
  • rifampicin observed shortening of the half-life of Azintra-3 (Fluconazole). Azintra-3 (Fluconazole) Sorres Pharma increases the half-life of oral hypoglycemic agents - sulfonylureas (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. Simultaneous use of Azintra-3 (Fluconazole) and oral hypoglycemic agents in diabetic patients is allowed, however, the physician should bear in mind the possibility of hypoglycemia.

    Azintra-3 in case of emergency / overdose

    Symptoms: nausea, vomiting, diarrhea and seizures in severe cases.

    Treatment: gastric lavage, forced diuresis, hemodialysis (three-hour dialysis reduces the plasma concentrations of approximately 50%), symptomatic therapy.

  • Secnidazole:


    1 INDICATIONS AND USAGE

    Azintra-3 is a nitroimidazole antimicrobial indicated for the treatment of bacterial vaginosis in adult women. (1)

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of Azintra-3 (Secnidazole) and other antibacterial drugs, Azintra-3 (Secnidazole) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

    1.1 Bacterial Vaginosis

    Azintra-3 (Secnidazole) is indicated for the treatment of bacterial vaginosis in adult women .

    1.2 Usage

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of Azintra-3 (Secnidazole) and other antibacterial drugs, Azintra-3 (Secnidazole) 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

    • Administer a single 2-gram packet of granules once orally, without regard to the timing of meals.
    • Sprinkle entire contents of packet onto applesauce, yogurt or pudding and consume all of the mixture within 30 minutes without chewing or crunching the granules. A glass of water may be taken after the administration of Azintra-3 (Secnidazole) to aid in swallowing. (2.2)
    • Azintra-3 (Secnidazole) is not intended to be dissolved in any liquid. (2.2)

    2.1 Recommended Dosage

    The recommended dosage of Azintra-3 (Secnidazole) is a single 2-gram packet of granules taken once orally, without regard to the timing of meals .

    2.2 Instructions for the Preparation and Administration of Azintra-3

    • Open the Azintra-3 (Secnidazole) packet by folding over the corner (marked by an arrow) and tearing across the top.
    • Sprinkle the entire contents of the Azintra-3 (Secnidazole) packet onto applesauce, yogurt or pudding . The granules will not dissolve. Consume all of the mixture within 30 minutes without chewing or crunching the granules. A glass of water may be taken after the administration of Azintra-3 (Secnidazole) to aid in swallowing.
    • The granules are not intended to be dissolved in any liquid.
    advertisement

    3 DOSAGE FORMS AND STRENGTHS

    Oral Granules: 2 g, of off-white to slightly yellowish granules with 4.8 g net weight, packed in a unit-of-use child-resistant foil packet.

    Oral granules: 2 g Azintra-3 (Secnidazole), in a unit-of-use child-resistant foil packet. (3)

    4 CONTRAINDICATIONS

    Hypersensitivity

    Azintra-3 (Secnidazole) is contraindicated in patients who have shown hypersensitivity to Azintra-3 (Secnidazole), other ingredients of the formulation, or other nitroimidazole derivatives.

    History of hypersensitivity to Azintra-3 (Secnidazole), other ingredients of the formulation, or other nitroimidazole derivatives. (4)

    5 WARNINGS AND PRECAUTIONS

    • Vulvo-vaginal candidiasis may develop with Azintra-3 and require treatment with an antifungal agent (5.1)
    • Potential Risk for Carcinogenicity: Carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives, which are structurally related to Azintra-3 (Secnidazole). It is unclear if the positive tumor findings in lifetime rodent studies indicate a risk to patients taking a single dose of Azintra-3 (Secnidazole) to treat bacterial vaginosis. Avoid chronic use (5.2)

    5.1 Vulvo-Vaginal Candidiasis

    The use of Azintra-3 (Secnidazole) may result in vulvo-vaginal candidiasis. In controlled clinical trials of non-pregnant women with bacterial vaginosis, vulvo-vaginal candidiasis developed in 19/197 (9.6%) of subjects who received 2 g Azintra-3 (Secnidazole) and 4/136 (2.9%) subjects who received placebo . Symptomatic vulvo-vaginal candidiasis may require treatment with an antifungal agent.

    5.2 Potential Risk for Carcinogenicity

    Carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives which are structurally related to Azintra-3. It is unclear if the positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of Azintra-3 (Secnidazole) to treat bacterial vaginosis. Avoid chronic use of Azintra-3 (Secnidazole)

    5.3 Drug Resistance

    Prescribing Azintra-3 (Secnidazole) in the absence of 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.

    advertisement

    6 ADVERSE REACTIONS

    Most common adverse reactions observed in clinical trials were vulvo-vaginal candidiasis, headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain, and vulvovaginal pruritus. (6.1)

    To report SUSPECTED ADVERSE REACTIONS, contact Symbiomix Therapeutics at 1-844-SOLOSEC (1-844-765-6732) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

    6.1 Clinical Trials Experience

    Because 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.

    The safety data described below reflect exposure to 589 patients, of whom 518 received a 2 g dose of Azintra-3 (Secnidazole). Azintra-3 (Secnidazole) was evaluated in three clinical trials of patients diagnosed with bacterial vaginosis: two placebo-controlled trials (Trial 1 n=215, Trial 2 n=189) and one uncontrolled safety trial (Trial 3 n=321).

    All patients received a single oral dose of study medication or placebo. Trial 1 evaluated a 1 g (this dose is not approved) dose (n=71) and a 2 g dose (n=72) of Azintra-3 (Secnidazole). Trial 2 evaluated a 2 g dose (n=125). The population was female, aged 15 to 54 years. Patients in the placebo- controlled trials were primarily Black or African American (54%) or Caucasian (41%).

    There were no deaths in the trials. Two patients in Trial 3 discontinued due to vulvovaginal candidiasis in the SOLOSEC-treated arm.

    Most Common Adverse Reactions

    Among 197 patients treated with a single 2 g dose of Azintra-3 (Secnidazole) in the two placebo-controlled trials, Trial 1 and 2, adverse reactions were reported by approximately 29% of patients. Table 1 displays the most common adverse reactions (≥ 2 % in SOLOSEC-treated patients) in these two trials.

    Adverse Reaction Azintra-3 (Secnidazole)

    N=197

    n (%)

    Placebo

    N=136

    n (%)

    Vulvo-vaginal candidiasis 19 (9.6) 4 (2.9)
    Headache 7 (3.6) 2 (1.5)
    Nausea 7 (3.6) 1 (0.7)
    Diarrhea 5 (2.5) 1 (0.7)
    Abdominal pain 4 (2.0) 2 (1.5)
    Vulvovaginal pruritus 4 (2.0) 2 (1.5)

    Among the 321 patients in an uncontrolled trial, Trial 3, adverse reactions were reported in 30% of patients. Vulvovaginal candidiasis (8.4%), nausea (5.3%), vomiting (2.5%) and dysgeusia (3.4%) were the most common adverse reactions reported in this trial.

    6.2 Postmarketing Experience

    The following adverse reactions have been reported during use of other formulations of Azintra-3 (Secnidazole) 2 g outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    Reported adverse reactions were nausea, dysgeusia, abdominal pain, headache, and vomiting.

    7 DRUG INTERACTIONS

    7.1 Oral Contraceptives

    There was no clinically significant drug interaction between Azintra-3 (Secnidazole) and the combination oral contraceptive, ethinyl estradiol plus norethindrone . Azintra-3 (Secnidazole) can be co-administered with combination oral contraceptives (e.g., ethinyl estradiol plus norethindrone).

    8 USE IN SPECIFIC POPULATIONS

    Lactation: Breastfeeding is not recommended. Discontinue breastfeeding for 96 hours after administration of Azintra-3. (8.2)

    8.1 Pregnancy

    Risk Summary

    Limited available data with Azintra-3 (Secnidazole) use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, there were no adverse developmental outcomes when Azintra-3 (Secnidazole) was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose

    The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

    Data

    Animal Data

    In animal reproduction studies, pregnant rats were dosed orally with Azintra-3 (Secnidazole) during organogenesis (gestational days 6-17) at 100, 300 and 1000 mg/kg/day, up to 4 times the clinical dose based on AUC comparisons. Animals showed no evidence of adverse developmental outcomes, but maternal toxicity (including reduced body weight gain) was observed at and above 300 mg/kg/day. In rabbits, no evidence of adverse developmental outcomes was observed when oral doses of Azintra-3 (Secnidazole) were administered to dams during organogenesis (gestational days 7-20) at doses up to 100 mg/kg/day (about 0.1 times the clinical dose, based on AUC comparisons). Azintra-3 (Secnidazole) was associated with maternal toxicity (reduced food consumption and markedly reduced body weight gain) in dams at 100 mg/kg/day.

    In a peri- and post-natal development study in rats, Azintra-3 (Secnidazole) was administered at 30, 100 and 300 mg/kg/day from Day 6 of gestation through Day 20 of lactation. Azintra-3 (Secnidazole) was not associated with any adverse effects on gestation, parturition, lactation or on subsequent development of first generation (F1) and second generation (F2) offspring at these doses, equivalent to up to 1.4 times the clinical dose based on AUC comparisons. Maternal toxicity (reduced gestational body weight gain) was evident at doses of 100 mg/kg and above (about 0.3 times the clinical dose based on AUC comparisons).

    8.2 Lactation

    Risk Summary

    There is no information on the presence of Azintra-3 in human milk, the effects on the breast- fed child, or the effects on milk production. Other nitroimidazole derivatives are present in human milk. Because of the potential for serious adverse reactions, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with Azintra-3 (Secnidazole) and for 96 hours (based on half-life) after administration of Azintra-3 (Secnidazole).

    Clinical Considerations

    A nursing mother may choose to pump and discard her milk during treatment with Azintra-3 (Secnidazole) and for 96 hours after administration of Azintra-3 (Secnidazole) and feed her infant stored human milk or formula.

    8.4 Pediatric Use

    The safety and effectiveness of Azintra-3 (Secnidazole) in pediatric patients below the age of 18 years have not been established.

    8.5 Geriatric Use

    Clinical studies with Azintra-3 (Secnidazole) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

    11 DESCRIPTION

    The active ingredient in Azintra-3 (Secnidazole) Oral Granules is Azintra-3 (Secnidazole) (also named 1-(2- hydroxypropyl)-2-methyl-5-nitroimidazole and 1-(2-methyl-5-nitro-1H-imidazol-1-yl) propan-2- ol), a nitroimidazole antimicrobial.

    The molecular formula of Azintra-3 (Secnidazole) is C7H11N3O3, the molecular weight is 185.18 and the chemical structure is:

    Figure 1: Structure of Azintra-3 (Secnidazole)

    Each packet of Azintra-3 (Secnidazole) contains 4.8 g of off-white to slightly yellowish granules, which contain 2 g of Azintra-3 (Secnidazole) and the following inactive ingredients: Eudragit NE30D (ethyl acrylate methyl methacrylate copolymer), polyethylene glycol 4000, povidone, sugar spheres, and talc.

    image of the structure of Azintra-3 (Secnidazole)

    12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Azintra-3 is a nitroimidazole antimicrobial drug .

    12.2 Pharmacodynamics

    Azintra-3 (Secnidazole) exposure-response relationships and the time course of pharmacodynamic response are unknown.

    Cardiac Electrophysiology

    The effect of Azintra-3 (Secnidazole) on the QTc interval was evaluated in a Phase 1 randomized, double blind, placebo- and positive-controlled four-period crossover thorough QTc study in 52 healthy adult subjects following single oral granule doses of 2 g and 6 g (3-times the recommended dose). Although there was a positive relationship of the QTc interval with Azintra-3 (Secnidazole) concentrations, there was no clinically relevant increase in the QTc interval following either dose.

    12.3 Pharmacokinetics

    A single oral dose of 2 g of Azintra-3 in healthy adult female subjects, following an overnight fast and admixed with (4 oz) of applesauce, resulted in a mean (SD) Azintra-3 (Secnidazole) peak plasma concentration (Cmax) of 45.4 (7.64) mcg/mL and mean (SD) systemic exposure (AUC0-inf) of 1331.6 (230.16) mcg-hr/mL. Median (range) time to peak concentration (Tmax) was 4.0 (3.0-4.0) hours. Following administration of the 2-g dose, mean Azintra-3 (Secnidazole) plasma concentrations decreased to 22.1 mcg/mL at 24 hours, 9.2 mcg/mL at 48 hours, 3.8 mcg/mL at 72 hours, and 1.4 mcg/mL at 96 hours.

    Absorption

    Effect of Food

    Administration of 2 g of Azintra-3 (Secnidazole) admixed with applesauce followed by ingestion of a high-fat meal (approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories) resulted in no significant change in the rate (Cmax) and extent (AUC) of Azintra-3 (Secnidazole) exposure as compared to administration when admixed with applesauce and taken under fasted conditions. There was no effect of admixing Azintra-3 (Secnidazole) with pudding and yogurt as compared to admixing with applesauce (Table 2).

    Cmax (mcg/mL) Tmax (hr)Median (range) AUC (mcg-hr/mL)
    FastedAdmixed with applesauce (N=23) Mean (SD) 41.2 (5.5) 4.0 (3.0 - 6.0) 1261.5 (236.5)
    Range 32.7 – 56.2 874.3 – 1750.4
    High fat meal (N=23) Mean (SD) 40.1 (4.9) 6.0 (4.0 - 8.0) 1248.2 (291.6)
    Range 31.0 – 47.7 762.0 – 1769.4
    Mixed with applesauce (N=24) Mean (SD) 44.1 (4.6) 4.0 (3.0 – 6.1) 1523 (372.2)
    Range 37.4 – 55.6 1040 - 2350
    Mixed with pudding (N=23) Mean (SD) 45.6 (5.1) 4.0 (4.0 – 6.0) 1447 (331.0)
    Range 38.6 – 60.4 997 - 2130
    Mixed with yogurt (N=24) Mean (SD) 43.4 (5.4) 4.0 (4.0 – 8.0) 1478 (335.0)
    Range 36.3 – 59.3 965 - 2240

    Distribution

    The apparent volume of distribution of Azintra-3 (Secnidazole) is approximately 42 L. The plasma protein binding of Azintra-3 (Secnidazole) is <5%.

    Elimination

    The total body clearance of Azintra-3 (Secnidazole) is approximately 25 mL/min. The renal clearance of Azintra-3 (Secnidazole) is approximately 3.9 mL/min.

    The plasma elimination half-life for Azintra-3 (Secnidazole) is approximately 17 hours.

    Metabolism

    Azintra-3 (Secnidazole) is metabolized in vitro via oxidation by human hepatic CYP450 enzyme system with ≤ 1% conversion to metabolites.

    Excretion

    Approximately 15% of a 2-g oral dose of Azintra-3 (Secnidazole) is excreted as unchanged Azintra-3 (Secnidazole) in the urine.

    Drug Interactions

    Oral Contraceptives

    Concomitant administration of 2 g of Azintra-3 (Secnidazole) with the combination oral contraceptive (OC), ethinyl estradiol (EE) plus norethindrone (NE), to healthy adult female subjects resulted in a decrease in mean Cmax of EE of 29%, and no significant effect on the mean AUC of EE. Administration of 2g of Azintra-3 (Secnidazole) 1 day before combination OC administration resulted in no significant effect on mean Cmax or AUC of EE.

    Concomitant administration of 2 g of Azintra-3 (Secnidazole) with the combination OC resulted in no significant effect on mean Cmax and AUC of NE (increases of 13% and 16%, respectively). Administration of 2g of Azintra-3 (Secnidazole) 1 day before combination OC administration also resulted in no significant effect on mean Cmax and AUC of NE.

    Ethanol Metabolism

    In vitro studies showed that Azintra-3 (Secnidazole) had no effect on aldehyde dehydrogenase activity.

    12.4 Microbiology

    Mechanism of Action

    Azintra-3 (Secnidazole) is a 5-nitroimidazole antimicrobial. 5-nitroimidazoles enter the bacterial cell as an inactive prodrug where the nitro group is reduced by bacterial enzymes to radical anions. It is believed that these radical anions interfere with bacterial DNA synthesis of susceptible isolates.

    Resistance

    The development of resistance to Azintra-3 (Secnidazole) by bacteria associated with bacterial vaginosis was not examined. Bacterial isolates exhibiting reduced in vitro susceptibility to metronidazole also show reduced susceptibility to Azintra-3 (Secnidazole). The clinical significance of such an effect is unknown.

    Antibacterial Activity

    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 or Mobiluncus spp. has not been defined.

    The following in vitro data are available but their clinical significance is unknown. Azintra-3 (Secnidazole) is active in vitro against most isolates of the following organisms reported to be associated with bacterial vaginosis:

    Bacteroides spp.

    Gardnerella vaginalis

    Prevotella spp.

    Mobiluncus spp.

    Megasphaera-like type I/II

    13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Nitroimidazoles, which have similar chemical structures to Azintra-3 (Secnidazole), have been associated with tumors affecting the liver, lungs, mammary, and lymphatic tissues in animals after lifetime exposures. It is unclear if these positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of Azintra-3 (Secnidazole) to treat bacterial vaginosis.

    Azintra-3 (Secnidazole) was positive in the Bacterial Reverse Mutation Assay, but was negative for the rat micronucleus test and mouse lymphoma test.

    In a rat fertility study, females were dosed for two weeks prior to mating until Day 7 of gestation with males that were dosed for a minimum of 28 days before cohabitation. No parental toxicity or adverse effects on mating performance, estrous cycles, fertility or conception was observed at doses of up to the maximum tolerated dose (300 mg/kg/day, approximately 1.4 times the recommended dose based on AUC comparisons).

    14 CLINICAL STUDIES

    Two randomized placebo-controlled clinical trials (Trial 1 and Trial 2) with similar designs were conducted to evaluate the efficacy of Azintra-3 (Secnidazole) 2 gram for the treatment of bacterial vaginosis. A diagnosis of bacterial vaginosis was defined as all of (a) the presence of an off-white (milky or gray), thin, homogeneous vaginal discharge; (b) a vaginal pH ≥ 4.7; (c) the presence of Clue cells ≥ 20% of the total epithelial cells on a microscopic examination of the vaginal saline wet mount; (d) a positive "whiff" test (detection of amine odor on addition of 10% KOH solution to a sample of the vaginal discharge); and (e) a Nugent score ≥ 4.

    Trial 1 enrolled 144 non-pregnant female patients aged 19 to 54 years and Trial 2 enrolled 189 non-pregnant females aged 18 to 54 years. Black or African American subjects in both trials were 54%. Efficacy was assessed by clinical outcome evaluated 21 to 30 days following a single dose of Azintra-3 (Secnidazole). A Clinical responder was defined as “normal” vaginal discharge, negative "whiff" test, and clue cells <20%. Additional endpoints included Nugent score cure (Nugent score of 0-3) and therapeutic outcome. A therapeutic responder was defined as a clinical responder with a Nugent score cure. In Trial 2, the endpoints were also assessed at Day 7-14.

    In both trials, a statistically significantly greater percentage of patients experienced clinical response, Nugent score cure, and therapeutic response at 21 to 30 days following a single dose of Azintra-3 (Secnidazole) compared to placebo. Statistically significant results for the endpoints were also achieved at Day 7-14 in Trial 2.

    The percentage of patients with clinical response was also consistently higher in both trials in the Azintra-3 (Secnidazole) arm compared to placebo among all subsets of patients: number of prior episodes of bacterial vaginosis (≤ 3 episodes and ≥ 4 episodes) in past 12 months, baseline Nugent score (score 4-6 and score 7-10), and race (Black/African American and White). Tables 3 and 4 describe the efficacy of Azintra-3 (Secnidazole) in the treatment of bacterial vaginosis.

    Trial 1 Trial 2
    Azintra-3 (Secnidazole)

    (N=62)N=number of patients in treatment group (modified intent-to-treat population defined as all patients randomized who had a baseline Nugent score ≥4 and were negative for other sexually transmitted infections at baseline).

    n (%)

    Placebo

    (N=62)

    n (%)

    Azintra-3 (Secnidazole)

    (N=107)

    n (%)

    Placebo

    (N=57)

    n (%)

    Clinical ResponderPatients missing one or more of the clinical assessments were considered as non-responders/not cured. 42 (67.7) 11 (17.7) 57 (53.3) 11 (19.3)
    50.0 (33.4, 66.7)Difference in response (SOLOSEC – placebo) and 95% confidence interval

    p<0.001

    34.0 (18.7, 49.3)

    p<0.001

    Nugent Score CurePatients with missing Nugent scores were considered Nugent score failures. 25 (40.3) 4 (6.5) 47 (43.9) 3 (5.3)
    33.8 (18.5, 49.1)

    p<0.001

    38.6 (26.2, 51.0)

    p<0.001

    Therapeutic Responder 25 (40.3) 4 (6.5) 37 (34.6) 2 (3.5)
    33.8 (18.5, 49.1)

    p<0.001

    31.1 (19.6, 42.6)

    p<0.001

    Trial 2
    Azintra-3 (Secnidazole)

    (N=107)N=number of patients in treatment group (modified intent-to-treat population defined as all patients randomized who had a baseline Nugentscore ≥4 and were negative for other sexually transmitted infections at baseline ).

    n (%)

    Placebo

    (N=57)

    n (%)

    Clinical ResponderPatients missing one or more of the clinical assessments were considered as non-responders/not cured. 62 (57.9) 14 (24.6)
    33.3 (17.4, 49.2)Difference in response (SOLOSEC – placebo) and 95% confidence interval

    p<0.001

    Nugent Score CurePatients with missing Nugent scores were considered Nugent score failures. 49 (45.8) 2 (3.5)
    42.3 (30.4, 54.2)

    p<0.001

    Therapeutic Responder 37 (34.6) 2 (3.5)
    31.1 (19.6, 42.6)

    p<0.001

    16 HOW SUPPLIED / STORAGE AND HANDLING

    Azintra-3 (Secnidazole) (secnidazole) Oral Granules, 2 g, consists of off-white to slightly yellowish granules containing Azintra-3 (Secnidazole). Azintra-3 (Secnidazole) is supplied in unit-of-use packages containing one packet of granules in an individual carton. Each packet contains 4.8 g of granules containing 2 g Azintra-3 (Secnidazole). Azintra-3 (Secnidazole) is supplied as follows:

    NDC 71000-102-01 carton containing one unit-of-use 2 g packet

    Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

    17 PATIENT COUNSELING INFORMATION

    Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

    Administration Instructions

    Instruct the patient:

    • To sprinkle the entire contents of the packet of Azintra-3 (Secnidazole) onto applesauce, yogurt or pudding and take all the mixture within 30 minutes without chewing or crunching the granules.
    • That after consuming the mixture, they may take a glass of water to aid in swallowing.
    • That Azintra-3 (Secnidazole) is not intended to be dissolved in any liquid.

    Advise the patient that Azintra-3 (Secnidazole) may be taken without regard to the timing of meals.

    Lactation

    Advise women not to breastfeed during treatment with Azintra-3 (Secnidazole) and to discontinue breastfeeding for 96 hours following the administration of Azintra-3 (Secnidazole). Also, advise a nursing mother that she may choose to pump and discard her milk for 96 hours after administration of Azintra-3 (Secnidazole) and feed her infant stored human milk or formula .

    Vulvo-Vaginal Candidiasis

    Advise the patient that use of Azintra-3 (Secnidazole) may result in vulvo-vaginal candidiasis that may require treatment with an antifungal agent.

    Drug Resistance

    Patients should be counseled that antibacterial drugs including Azintra-3 (Secnidazole) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Azintra-3 (Secnidazole) 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 Azintra-3 (Secnidazole) or other antibacterial drugs in the future.

    Manufactured for and Distributed by:

    Symbiomix Therapeutics LLC

    Newark, NJ 07103

    © 2017 Symbiomix Therapeutics, LLC. All Rights Reserved

    Symbiomix and Azintra-3 (Secnidazole) are trademarks of Symbiomix Therapeutics, LLC

    7179660

    PATIENT INFORMATION

    Azintra-3 (Secnidazole) (SO-lo-sec)

    (secnidazole) oral granules

    What is Azintra-3 (Secnidazole)?

    • Azintra-3 (Secnidazole) is a prescription medicine used to treat bacterial vaginal infections in adult women.
    • It is not known if Azintra-3 (Secnidazole) is safe and effective in children under 18 years of age.
    Do not take Azintra-3 (Secnidazole) if you:

    • are allergic to Azintra-3 (Secnidazole) or other nitroimidazole medicines. See the end of this leaflet for a complete list of ingredients in Azintra-3 (Secnidazole).
    Before taking Azintra-3 (Secnidazole), tell your healthcare provider about all of your medical conditions, including if you:

    • are pregnant or plan to become pregnant. It is not known if Azintra-3 (Secnidazole) will harm your unborn baby. Tell your healthcare provider if you learn that you were pregnant when you took Azintra-3 (Secnidazole).
    • are breastfeeding or plan to breastfeed. You should not breastfeed for 96 hours (4 days) after taking Azintra-3 (Secnidazole). Azintra-3 (Secnidazole) may pass into breast milk. Talk with your healthcare provider about the best way to feed your baby while taking Azintra-3 (Secnidazole).
    Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
    How should I take Azintra-3 (Secnidazole)?

    • See "Instructions for Use" at the end of this leaflet for instructions on how to take Azintra-3 (Secnidazole).
    • Take Azintra-3 (Secnidazole) exactly as your healthcare provider tells you to. Do not take Azintra-3 (Secnidazole) more often than it is prescribed. Sprinkle the entire contents of the Azintra-3 (Secnidazole) packet onto applesauce, yogurt or pudding. The granules will not dissolve.
    What are the possible side effects of Azintra-3 (Secnidazole)?

    Azintra-3 (Secnidazole) can cause side effects including vaginal yeast infections. Symptoms of a vaginal yeast infection include white or yellowish discharge (discharge may be lumpy or look like cottage cheese) and vaginal itching.

    The most common side effects of Azintra-3 (Secnidazole) include headache, nausea, vomiting, diarrhea, abdominal pain, and vaginal itching and a bad, bitter or metallic taste in your mouth (dysgeusia).

    These are not all of the side effects of Azintra-3 (Secnidazole). Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

    General information about the safe and effective use of Azintra-3 (Secnidazole).

    Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Azintra-3 (Secnidazole) for a condition for which it was not prescribed. Do not give Azintra-3 (Secnidazole) to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Azintra-3 (Secnidazole) that is written for health professionals.

    What are the ingredients in Azintra-3 (Secnidazole)?

    Active ingredient: Azintra-3 (Secnidazole)

    Inactive ingredients: Eudragit NE30D (ethyl acrylate methyl methacrylate copolymer), polyethylene glycol 4000, povidone, sugar spheres, and talc.

    For more information visit www.solosec.com or contact Symbiomix Therapeutics at 1 844 Azintra-3 (Secnidazole) (1 844 765 6732).

    INSTRUCTIONS FOR USE

    Azintra-3 (Secnidazole)

    (secnidazole) oral granules

    For oral use (by mouth) only.

    How to take Azintra-3 (Secnidazole)?

    • Open the Azintra-3 (Secnidazole) packet by folding over the corner marked by an arrow and tearing across the top.
    • Sprinkle the entire contents of the Azintra-3 (Secnidazole) packet onto applesauce, yogurt or pudding. The granules will not dissolve. Take within 30 minutes without chewing or crunching the granules.
    • You can drink a glass of water after taking Azintra-3 (Secnidazole) to help with swallowing. You should not try to dissolve the medicine in water or any other liquid.
    Even though you only take 1 packet of Azintra-3 (Secnidazole), the medicine stays in your body and continues working for 4 days.
    Important Information

    • Azintra-3 (Secnidazole) may be taken before or after or during a meal.
    • Take 1 entire packet of Azintra-3 (Secnidazole) at one time. Do not take only part of the medicine and save aportion for later.
    How should I store Azintra-3 (Secnidazole)?

    • Store Azintra-3 (Secnidazole) at room temperature between 68°F to 77°F (20°C to 25°C).
    • Keep Azintra-3 (Secnidazole) and all medications out of the reach of children.
    This Patient Information and Instructions for Use have been approved by the US Food and Drug Administration. Issued: 9/2017

    Manufactured for and Distributed by: Symbiomix Therapeutics LLC Newark, NJ 07103

    © 2017 Symbiomix Therapeutics, LLC. All Rights Reserved

    Symbiomix and Azintra-3 (Secnidazole) are trademarks of Symbiomix Therapeutics, LLC

    7179660

    Image of how to open the packet

    Principal Display Panel - Individual Carton

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    NDC 71000-102-01

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    Oral Granules

    1 Unit-of-Use Packet

    Rx Only

    symbiomix

    therapeutics

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    USUAL

    Dosage: One packet.

    Azintra-3 (Secnidazole) granules should be administered as follows:

    • Sprinkle onto applesauce, yogurt or pudding. The granules will not dissolve. Consume all of the granules within 30 minutes.
    • Consume the contents of one packet without chewing or crunching the granules.
    • A glass of water may be taken to aid in swallowing.
    • May be taken at any time with, before or after a meal.

    Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).

    .

    Manufactured for and Distributed by: Symbiomix Therapeutics, LLC, Newark, NJ 07103

    © 2017 Symbiomix Therapeutics, LLC 2017. All Rights Reserved

    Symbiomix and SolosecTM are trademarks of Symbiomix Therapeutics, LLC

    Position pharmacy label over this panel

    Product of USA

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    Rx Only


    Principal Display Panel - Display Carton

    USUAL

    Dosage: One packet.

    Azintra-3 (Secnidazole) granules should be administered as follows:

    • Sprinkle onto applesauce, yogurt or pudding. The granules will not dissolve. Consume all of the granules within 30 minutes.
    • Consume the contents of one packet without chewing or crunching the granules.
    • A glass of water may be taken to aid in swallowing.
    • May be taken at any time with, before or after a meal.

    Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F).

    .

    Manufactured for and Distributed by: Symbiomix Therapeutics, LLC, Newark, NJ 07103

    © 2017 Symbiomix Therapeutics, LLC 2017. All Rights Reserved

    Symbiomix and SolosecTM are trademarks of Symbiomix Therapeutics, LLC

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    Usual

    Dosage:

    One 2 gram packet

    Contains 12 individual cartons which contain one Azintra-3 (Secnidazole) packet.

    NDC 71000-102-12

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    Oral Granules

    Contains 12 individual cartons which contain one Azintra-3 (Secnidazole) packet.

    Rx Only

    Usual

    Dosage:

    One 2 gram packet

    symbiomix

    therapeutics

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    Usual

    Dosage:

    One 2 gram packet

    Contains 12 individual cartons which contain one Azintra-3 (Secnidazole) packet.

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules


    Principal Display Panel - Sachet

    NDC 71000-102-02

    Azintra-3 (Secnidazole)

    Azintra-3 (Secnidazole)

    2g Oral Granules

    Oral Granules

    Rx Only

    symbiomix

    therapeutics

    USUAL

    Dosage: One packet.

    Azintra-3 (Secnidazole) granules should be administered as follows:

    • Sprinkle onto applesauce, yogurt or pudding. The granules will not dissolve. Consume all of the granules within 30 minutes.
    • Consume the contents of one packet without chewing or crunching the granules.
    • A glass of water may be taken to aid in swallowing.
    • May be taken at any time with, before or after a meal.

    Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)..

    Mfd for and Distributed by: Symbiomix Therapeutics, LLC, Newark, NJ 07103

    Product of USA

    Image of Individual Carton Image of Display Carton Image of Sachet

    Azintra-3 pharmaceutical active ingredients containing related brand and generic drugs:

    infoActive 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.


    Azintra-3 available forms, composition, doses:

    infoForm 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.


    Azintra-3 destination | category:

    infoDestination 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.


    Azintra-3 Anatomical Therapeutic Chemical codes:

    infoA 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.


    Azintra-3 pharmaceutical companies:

    infoPharmaceutical 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.


    advertisement

    References

    1. Dailymed."SOLOSEC (SECNIDAZOLE) GRANULE [SYMBIOMIX THERAPEUTICS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
    2. Dailymed."ZITHROMAX (AZITHROMYCIN DIHYDRATE) INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION [PFIZER LABORATORIES DIV PFIZER INC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
    3. Dailymed."FLUCONAZOLE TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

    Frequently asked Questions

    Can i drive or operate heavy machine after consuming Azintra-3?

    Depending on the reaction of the Azintra-3 after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Azintra-3 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 Azintra-3 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.

    advertisement

    Review

    sDrugs.com conducted a study on Azintra-3, 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 Azintra-3 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 reports

    Visitor reviews


    There are no reviews yet. Be the first to write one!


    Your name: 
    Email: 
    Spam protection:  < Type 19 here

    The information was verified by Dr. Arunabha Ray, MD Pharmacology

    © 2002 - 2019 "sDrugs.com". All Rights Reserved