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DRUGS & SUPPLEMENTS
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Zimac Plus
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Zimac Plus uses
Zimac Plus consists of Azithromycin, Fluconazole, Secnidazole.Azithromycin:
Pharmacological action
Zimac Plus is a macrolide antibiotic of azalides group. Zimac Plus (Azithromycin) 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
Zimac Plus (Azithromycin) rapidly absorbed from the gastrointestinal tract. Ingestion reduces the absorption of Zimac Plus (Azithromycin). Cmax in plasma is reached after 2-3 hours. This medicine rapidly distributed in tissues and biological fluids. 35% of the Zimac Plus (Azithromycin) 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 Zimac Plus prescribed?
Infectious-inflammatory diseases caused by microorganisms susceptible to Zimac Plus (Azithromycin), 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 Zimac Plus 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.
Zimac Plus (Azithromycin) 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.
Contraindications
Hypersensitivity to Zimac Plus and other macrolide antibiotics.
Using during pregnancy and breastfeeding
Zimac Plus (Azithromycin) 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 Zimac Plus (Azithromycin) in the lactation period should solve the issue of termination of breastfeeding.
Special instructions
Zimac Plus not recommended for use in patients with compromised liver function.
Zimac Plus (Azithromycin) 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.
Zimac Plus (Azithromycin) drug interactions
Simultaneous administration of Zimac Plus (Azithromycin) with these drugs and medications may has followed effects:
Fluconazole:
Pharmacological action
Zimac Plus 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
Zimac Plus (Fluconazole) is well absorbed after oral administration. Simultaneous ingestion does not affect absorption. The bioavailability is 90%. Zimac Plus (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. Zimac Plus (Fluconazole) is excreted by the kidneys, 80% of the administered dose in an unmodified form.
Why is Zimac Plus 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 Zimac Plus 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 Zimac Plus (Fluconazole) should be reduced.
Zimac Plus (Fluconazole) side effects, adverse reactions
Digestive system: nausea, abdominal pain, diarrhea, flatulence.
CNS: headache, dizziness.
Allergic reactions: skin rash, anaphylactic reactions.
Zimac Plus contraindications
Pregnancy, children up to age 1 year, increased sensitivity to Zimac Plus (Fluconazole) and triazole compounds.
Using during pregnancy and breastfeeding
Zimac Plus 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
Zimac Plus (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.
Zimac Plus drug interactions
Simultaneous administration of Zimac Plus (Fluconazole) with:
Zimac Plus 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:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied / storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Zimac Plus 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 Zimac Plus (Secnidazole) and other antibacterial drugs, Zimac Plus (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
Zimac Plus (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 Zimac Plus (Secnidazole) and other antibacterial drugs, Zimac Plus (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 Zimac Plus (Secnidazole) to aid in swallowing. (2.2)
- Zimac Plus (Secnidazole) is not intended to be dissolved in any liquid. (2.2)
2.1 Recommended Dosage
The recommended dosage of Zimac Plus (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 Zimac Plus
- Open the Zimac Plus (Secnidazole) packet by folding over the corner (marked by an arrow) and tearing across the top.
- Sprinkle the entire contents of the Zimac Plus (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 Zimac Plus (Secnidazole) to aid in swallowing.
- The granules are not intended to be dissolved in any liquid.
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 Zimac Plus (Secnidazole), in a unit-of-use child-resistant foil packet. (3)
4 CONTRAINDICATIONS
Hypersensitivity
Zimac Plus (Secnidazole) is contraindicated in patients who have shown hypersensitivity to Zimac Plus (Secnidazole), other ingredients of the formulation, or other nitroimidazole derivatives.
History of hypersensitivity to Zimac Plus (Secnidazole), other ingredients of the formulation, or other nitroimidazole derivatives. (4)
5 WARNINGS AND PRECAUTIONS
- Vulvo-vaginal candidiasis may develop with Zimac Plus 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 Zimac Plus (Secnidazole). It is unclear if the positive tumor findings in lifetime rodent studies indicate a risk to patients taking a single dose of Zimac Plus (Secnidazole) to treat bacterial vaginosis. Avoid chronic use (5.2)
5.1 Vulvo-Vaginal Candidiasis
The use of Zimac Plus (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 Zimac Plus (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 Zimac Plus. 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 Zimac Plus (Secnidazole) to treat bacterial vaginosis. Avoid chronic use of Zimac Plus (Secnidazole)
5.3 Drug Resistance
Prescribing Zimac Plus (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.
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 Zimac Plus (Secnidazole). Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 | Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) and the combination oral contraceptive, ethinyl estradiol plus norethindrone . Zimac Plus (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 Zimac Plus. (8.2)
8.1 Pregnancy
Risk Summary
Limited available data with Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (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). Zimac Plus (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, Zimac Plus (Secnidazole) was administered at 30, 100 and 300 mg/kg/day from Day 6 of gestation through Day 20 of lactation. Zimac Plus (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 Zimac Plus 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 Zimac Plus (Secnidazole) and for 96 hours (based on half-life) after administration of Zimac Plus (Secnidazole).
Clinical Considerations
A nursing mother may choose to pump and discard her milk during treatment with Zimac Plus (Secnidazole) and for 96 hours after administration of Zimac Plus (Secnidazole) and feed her infant stored human milk or formula.
8.4 Pediatric Use
The safety and effectiveness of Zimac Plus (Secnidazole) in pediatric patients below the age of 18 years have not been established.
8.5 Geriatric Use
Clinical studies with Zimac Plus (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 Zimac Plus (Secnidazole) Oral Granules is Zimac Plus (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 Zimac Plus (Secnidazole) is C7H11N3O3, the molecular weight is 185.18 and the chemical structure is:
Figure 1: Structure of Zimac Plus (Secnidazole)
Each packet of Zimac Plus (Secnidazole) contains 4.8 g of off-white to slightly yellowish granules, which contain 2 g of Zimac Plus (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 Zimac Plus (Secnidazole)
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Zimac Plus is a nitroimidazole antimicrobial drug .
12.2 Pharmacodynamics
Zimac Plus (Secnidazole) exposure-response relationships and the time course of pharmacodynamic response are unknown.
Cardiac Electrophysiology
The effect of Zimac Plus (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 Zimac Plus (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 Zimac Plus in healthy adult female subjects, following an overnight fast and admixed with (4 oz) of applesauce, resulted in a mean (SD) Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) exposure as compared to administration when admixed with applesauce and taken under fasted conditions. There was no effect of admixing Zimac Plus (Secnidazole) with pudding and yogurt as compared to admixing with applesauce (Table 2).
| Cmax (mcg/mL) | Tmax (hr) | AUC (mcg-hr/mL) | ||
|---|---|---|---|---|
| Fasted | 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 | 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 Zimac Plus (Secnidazole) is approximately 42 L. The plasma protein binding of Zimac Plus (Secnidazole) is <5%.
Elimination
The total body clearance of Zimac Plus (Secnidazole) is approximately 25 mL/min. The renal clearance of Zimac Plus (Secnidazole) is approximately 3.9 mL/min.
The plasma elimination half-life for Zimac Plus (Secnidazole) is approximately 17 hours.
Metabolism
Zimac Plus (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 Zimac Plus (Secnidazole) is excreted as unchanged Zimac Plus (Secnidazole) in the urine.
Drug Interactions
Oral Contraceptives
Concomitant administration of 2 g of Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) had no effect on aldehyde dehydrogenase activity.
12.4 Microbiology
Mechanism of Action
Zimac Plus (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 Zimac Plus (Secnidazole) by bacteria associated with bacterial vaginosis was not examined. Bacterial isolates exhibiting reduced in vitro susceptibility to metronidazole also show reduced susceptibility to Zimac Plus (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. Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) to treat bacterial vaginosis.
Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) in the treatment of bacterial vaginosis.
| Trial 1 | Trial 2 | |||
|---|---|---|---|---|
| Zimac Plus (Secnidazole) (N=62) n (%) | Placebo (N=62) n (%) | Zimac Plus (Secnidazole) (N=107) n (%) | Placebo (N=57) n (%) | |
| Clinical Responder | 42 (67.7) | 11 (17.7) | 57 (53.3) | 11 (19.3) |
| 50.0 (33.4, 66.7) p<0.001 | 34.0 (18.7, 49.3) p<0.001 | |||
| Nugent Score Cure | 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 | ||
|---|---|---|
| Zimac Plus (Secnidazole) (N=107) n (%) | Placebo (N=57) n (%) | |
| Clinical Responder | 62 (57.9) | 14 (24.6) |
| 33.3 (17.4, 49.2) p<0.001 | ||
| Nugent Score Cure | 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
Zimac Plus (Secnidazole) (secnidazole) Oral Granules, 2 g, consists of off-white to slightly yellowish granules containing Zimac Plus (Secnidazole). Zimac Plus (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 Zimac Plus (Secnidazole). Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) is not intended to be dissolved in any liquid.
Advise the patient that Zimac Plus (Secnidazole) may be taken without regard to the timing of meals.
Lactation
Advise women not to breastfeed during treatment with Zimac Plus (Secnidazole) and to discontinue breastfeeding for 96 hours following the administration of Zimac Plus (Secnidazole). Also, advise a nursing mother that she may choose to pump and discard her milk for 96 hours after administration of Zimac Plus (Secnidazole) and feed her infant stored human milk or formula .
Vulvo-Vaginal Candidiasis
Advise the patient that use of Zimac Plus (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 Zimac Plus (Secnidazole) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole) are trademarks of Symbiomix Therapeutics, LLC
7179660
| PATIENT INFORMATION Zimac Plus (Secnidazole) (SO-lo-sec) (secnidazole) oral granules |
What is Zimac Plus (Secnidazole)?
|
Do not take Zimac Plus (Secnidazole) if you:
|
Before taking Zimac Plus (Secnidazole), tell your healthcare provider about all of your medical conditions, including if you:
|
How should I take Zimac Plus (Secnidazole)?
|
| What are the possible side effects of Zimac Plus (Secnidazole)? Zimac Plus (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 Zimac Plus (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 Zimac Plus (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 Zimac Plus (Secnidazole). Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Zimac Plus (Secnidazole) for a condition for which it was not prescribed. Do not give Zimac Plus (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 Zimac Plus (Secnidazole) that is written for health professionals. |
| What are the ingredients in Zimac Plus (Secnidazole)? Active ingredient: Zimac Plus (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 Zimac Plus (Secnidazole) (1 844 765 6732). |
| INSTRUCTIONS FOR USE Zimac Plus (Secnidazole) (secnidazole) oral granules |
|---|
| For oral use (by mouth) only. How to take Zimac Plus (Secnidazole)? |
|
Important Information
|
How should I store Zimac Plus (Secnidazole)?
Manufactured for and Distributed by: Symbiomix Therapeutics LLC Newark, NJ 07103 © 2017 Symbiomix Therapeutics, LLC. All Rights Reserved Symbiomix and Zimac Plus (Secnidazole) are trademarks of Symbiomix Therapeutics, LLC 7179660 |
Principal Display Panel - Individual Carton
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
NDC 71000-102-01
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Oral Granules
1 Unit-of-Use Packet
Rx Only
symbiomix
therapeutics
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
USUAL
Dosage: One packet.
Zimac Plus (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
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Rx Only
Principal Display Panel - Display Carton
USUAL
Dosage: One packet.
Zimac Plus (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
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Usual
Dosage:
One 2 gram packet
Contains 12 individual cartons which contain one Zimac Plus (Secnidazole) packet.
NDC 71000-102-12
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Oral Granules
Contains 12 individual cartons which contain one Zimac Plus (Secnidazole) packet.
Rx Only
Usual
Dosage:
One 2 gram packet
symbiomix
therapeutics
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Usual
Dosage:
One 2 gram packet
Contains 12 individual cartons which contain one Zimac Plus (Secnidazole) packet.
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Principal Display Panel - Sachet
NDC 71000-102-02
Zimac Plus (Secnidazole)
Zimac Plus (Secnidazole)
2g Oral Granules
Oral Granules
Rx Only
symbiomix
therapeutics
USUAL
Dosage: One packet.
Zimac Plus (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
Zimac Plus pharmaceutical active ingredients containing related brand and generic drugs:
Zimac Plus available forms, composition, doses:
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.