text:
SIVEXTRO- tedizolid phosphate tablet, film coated
SIVEXTRO- tedizolid phosphate injection, powder, lyophilized, for solution
Nabriva Therapeutics US, Inc.
These highlights do not include all the information needed to use SIVEXTRO® safely and effectively. See full prescribing information for SIVEXTRO.
SIVEXTRO® (tedizolid phosphate) for injection, for intravenous use
SIVEXTRO® (tedizolid phosphate) tablet, for oral use
Initial U.S. Approval: 2014
SIVEXTRO is an oxazolidinone antibacterial indicated in adult and pediatric patients 12 years of age and older for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria. (1.1)
200 mg administered once daily orally or as an intravenous (IV) infusion over 1 hour for six (6) days in adult and pediatric patients 12 years of age and older. (2.1)
None (4)
The most common adverse reactions (≥2%) in adults are nausea, headache, diarrhea, infusion- or injection-related adverse reactions, vomiting, and dizziness. The most common adverse reactions (≥2%) in pediatric patients are phlebitis, and increased hepatic transaminases. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Pregnancy: Based on animal data, SIVEXTRO may cause fetal harm. Advise pregnant women of the potential risks to a fetus. (8.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 7/2022
1.1 Acute Bacterial Skin and Skin Structure Infections
1.2 Usage
2.1 Recommended Dosage
2.2 Preparation and Administration of Intravenous Solution
2.3 Compatible Intravenous Solutions
2.4 Incompatibilities
5.1 Patients with Neutropenia
5.2 Clostridioides difficile-Associated Diarrhea
5.3 Development of Drug-Resistant Bacteria
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.4 Microbiology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14.1 Acute Bacterial Skin and Skin Structure Infections
16.1 Tablets
16.2 For Injection
16.3 Storage and Handling
SIVEXTRO® is an oxazolidinone-class antibacterial indicated in adult and pediatric patients 12 years of age and older for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of SIVEXTRO and other antibacterial drugs, SIVEXTRO should be used only to treat ABSSSI 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.
The recommended dosage of SIVEXTRO is 200 mg administered once daily for six (6) days either orally (with or without food) or as an intravenous (IV) infusion in patients 12 years of age or older.
The recommended dosage and administration of SIVEXTRO are described in Table 1.
|Infusion Time
|Duration of Treatment
|Acute Bacterial Skin and Skin
Structure Infections
|200 mg
|Once daily
|1 hour
|6 days
|200 mg
|Once daily
|Not Applicable
No dose adjustment is necessary when changing from intravenous to oral SIVEXTRO.
If patients miss a dose, they should take it as soon as possible anytime up to 8 hours prior to their next scheduled dose. If less than 8 hours remain before the next dose, wait until their next scheduled dose.
SIVEXTRO is supplied as a sterile, lyophilized powder for injection in single-dose vials of 200 mg. Each 200 mg vial must be reconstituted with Sterile Water for Injection and subsequently diluted only with 0.9% Sodium Chloride Injection, USP.
SIVEXTRO vials contain no antimicrobial preservatives and are intended for single dose only. Discard any unused portion.
The contents of the vial should be reconstituted using aseptic technique as follows:
Note: To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
Administer as an intravenous infusion only.
Do not administer as an intravenous push or bolus. Do not mix SIVEXTRO with other drugs when administering. It is not intended for intra-arterial, intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.
The intravenous bag containing the reconstituted and diluted intravenous solution should be inspected visually for particulate matter prior to administration. Discard if visible particles are observed. The resulting solution is clear and colorless to pale-yellow in color.
After reconstitution and dilution, SIVEXTRO is to be administered via intravenous infusion using a total time of 1 hour.
The total time from reconstitution to administration should not exceed 24 hours at room temperature or under refrigeration at 2°C to 8°C (36°F to 46°F).
Discard unused portion.
SIVEXTRO is compatible with 0.9% Sodium Chloride Injection, USP.
SIVEXTRO for injection is incompatible with any solution containing divalent cations (e.g., Ca2+, Mg2+), including Lactated Ringer's Injection and Hartmann's Solution.
Limited data are available on the compatibility of SIVEXTRO for injection with other intravenous substances, additives or other medications and they should not be added to SIVEXTRO single-dose vials or infused simultaneously. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of SIVEXTRO with 0.9% Sodium Chloride Injection, USP.
SIVEXTRO 200 mg tablet is a yellow film-coated oval tablet; each tablet is debossed with "TZD" on one side and "200" on the other side.
SIVEXTRO for injection is a sterile, white to off-white lyophilized powder for injection in single-dose vials of 200 mg. Each 200 mg vial must be reconstituted with Sterile Water for Injection and subsequently diluted only with 0.9% Sodium Chloride Injection, USP.
The safety and efficacy of SIVEXTRO in patients with neutropenia (neutrophil counts <1000 cells/mm3) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes [see Clinical Pharmacology (12.2)]. Alternative therapies should be considered when treating patients with neutropenia and ABSSSI.
Clostridioides difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents including SIVEXTRO, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon and may permit overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible. Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice.
Adult Patients
Adverse reactions were evaluated for 1425 adult patients treated with SIVEXTRO in two Phase 2 and four Phase 3 clinical trials (three Phase 3 trials for 6 days of therapy and one Phase 3 trial for 7-21 days of therapy). The median age of adult patients treated with SIVEXTRO in the Phase 2 and Phase 3 trials was 44 years, ranging between 17 and 94 years old. The majority of adult patients treated with SIVEXTRO were male (66%) and White (67%).
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation in Adults
Serious adverse reactions occurred in 37/1425 (2.6%) of adult patients treated with SIVEXTRO and in 25/1000 (2.5%) of adult patients treated with the comparator. SIVEXTRO was discontinued due to an adverse reaction in 14/1425 (1%) of adult patients and the comparator was discontinued due to an adverse reaction in 13/1000 (1.3%) of adult patients.
Most Common Adverse Reactions in Adults
The most common adverse reactions in adult patients treated with SIVEXTRO were nausea (7.1%), headache (4.5%), diarrhea (3.6%), vomiting (2.7%), and dizziness (1.6%). The median time of onset of adverse reactions was 5 days for both SIVEXTRO and linezolid with 12% occurring on the second day of treatment in both treatment groups.
Table 2 lists selected adverse reactions occurring in at least 2% of adult patients treated with SIVEXTRO in clinical trials.
|Adverse Reactions
|Pooled Phase 3 ABSSSI Clinical Trials
(200 mg oral/intravenous once daily for 6 days)
(600 mg oral/intravenous twice daily for 10 days)
|Gastrointestinal Disorders
|Nervous System Disorder
|Infusion- or Injection-Related Adverse Reactions*
The following selected adverse reactions were reported in SIVEXTRO-treated adult patients at a rate of less than 2% in these clinical trials:
Blood and Lymphatic System Disorders: anemia
Cardiovascular: palpitations, tachycardia
Eye Disorders: asthenopia, vision blurred, visual impairment, vitreous floaters
Immune System Disorders: drug hypersensitivity
Infections and Infestations: Clostridioides difficile colitis, oral candidiasis, vulvovaginal mycotic infection
Investigations: hepatic transaminases increased (ALT increased, AST increased), gamma-glutamyltransferase (GGT) increased, white blood cell count decreased
Nervous System Disorders: hypoesthesia, paresthesia, VIIth nerve paralysis
Psychiatric Disorders: insomnia
Skin and Subcutaneous Tissue Disorders: pruritus, urticaria, dermatitis
Vascular Disorders: flushing, hypertension
Laboratory Parameters
Hematology laboratory abnormalities that were determined to be potentially clinically significant in the pooled Phase 3 ABSSSI clinical trials are provided in Table 3.
|Laboratory Assay
|Potentially Clinically Significant Values*,†
(200 mg oral/intravenous once daily for 6 days)
(600 mg oral/intravenous twice daily for 10 days)
|M = male; F = female
(<10.1 g/dL [M])
(<9 g/dL [F])
|Platelet count
(<112 × 103/mm3)
|Absolute neutrophil count
(<0.8 × 103/mm3)
Phase 1 studies conducted in healthy adults exposed to SIVEXTRO for 21 days showed a possible dose and duration effect on hematologic parameters beyond 6 days of treatment. In the Phase 3 trials, clinically significant changes in these parameters were generally similar for both treatment arms (see Table 3). In postmarketing experience, thrombocytopenia has been reported in patients treated with SIVEXTRO. In one postmarketing report, patients who experienced thrombocytopenia were treated with tedizolid for a median duration of 26.5 days. A duration of treatment beyond 6 days is not approved.
Peripheral and Optic Neuropathy
Peripheral and optic neuropathy have been described in patients treated with another member of the oxazolidinone class for longer than 28 days. In Phase 3 trials in adults, reported adverse reactions for peripheral neuropathy and optic nerve disorders were similar between both treatment arms (peripheral neuropathy 1.2% vs. 0.7% for tedizolid phosphate and linezolid, respectively; optic nerve disorders 0.3% vs. 0.1%, respectively).
Pediatric Patients
Adverse reactions were evaluated in 91 pediatric patients with ABSSSI ranging from 12 to <18 years of age treated with IV and/or oral SIVEXTRO 200 mg for 6 days and 29 patients treated with comparator agents for 10 days. The majority of pediatric patients treated with SIVEXTRO were male (64%) and white (88%).
Serious adverse reactions occurred in 1/91 (1%) of pediatric patients treated with SIVEXTRO and in none of the 29 patients treated with the comparator. Adverse reactions leading to discontinuation occurred in 1 (1%) pediatric patient in the SIVEXTRO arm and in none in the comparator arm.
The most common adverse reactions occurring in pediatric patients receiving SIVEXTRO in the ABSSSI clinical trial were phlebitis (3%), increased hepatic transaminases (alanine aminotransferase, aspartate aminotransferase) (3%), anemia, and vomiting (1%).
Safety has not been evaluated in pediatric patients under 12 years of age.
Laboratory Parameters
|Laboratory Assay
|Potentially Clinically Significant Values*,†
(200 mg oral/intravenous
once daily for 6 days)
(for 10 days)
|M = male; F = female
(<10.1 g/dL [M])
(<9 g/dL [F])
|Platelet count
(<112 × 103/mm3)
|Absolute neutrophil count
(<0.8 × 103/mm3)
The following adverse reactions have been identified during post approval use of SIVEXTRO. 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.
Blood and Lymphatic System Disorders: thrombocytopenia
Orally administered SIVEXTRO inhibits Breast Cancer Resistance Protein (BCRP) in the intestine, which can increase the plasma concentrations of orally administered BCRP substrates, and the potential for adverse reactions. If possible, an interruption in the treatment of the co-administered BCRP substrate medicinal product should be considered during treatment with SIVEXTRO, especially for BCRP substrates with a narrow therapeutic index (e.g., methotrexate or topotecan). If coadministration cannot be avoided, monitor for adverse reactions related to the concomitantly administered BCRP substrates, including rosuvastatin. [See Clinical Pharmacology (12.3).]
Risk Summary
Based on animal reproduction studies, SIVEXTRO may cause fetal harm when administered to pregnant women. The available data on the use of SIVEXTRO in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women of the potential risks to a fetus. Fetal developmental toxicities were observed in mice and rats treated with SIVEXTRO. In embryo-fetal studies in mice and rats, tedizolid phosphate was shown to produce fetal developmental toxicities in mice and maternal toxicity and fetal developmental toxicities in rats. Tedizolid phosphate administered orally during organogenesis to pregnant animals was associated with reduced fetal weights and an increased incidence of costal cartilage anomalies in the absence of maternal toxicity in mice; and maternal toxicity, decreased fetal weights, and increased skeletal variations in rats at plasma exposures approximately 4- and 6-times respectively, the human plasma exposure at the maximum recommended human dose (MRHD) of 200 mg/day. In female rats administered tedizolid phosphate during organogenesis through lactation, there was no evidence of fetal toxicity, developmental delays, or impaired reproduction in the offspring at plasma exposures approximately equivalent to the human plasma exposure at the MRHD (see Data).
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 miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Animal Data
In an embryo-fetal development study, tedizolid phosphate administered orally to pregnant mice at doses of 1, 5, and 25 mg/kg/day during organogenesis (Gestational Day [GD] 6 to GD15) was associated with fetal developmental effects occurring in the absence of maternal toxicity, including reduced fetal weights and an increased incidence of costal cartilage anomalies at the high dose (approximately 4-times the human plasma exposure at the MRHD based on plasma AUC comparison). Tedizolid phosphate administered orally at doses of 2.5, 5, and 15 mg/kg/day to pregnant rats during organogenesis (GD6 through GD17) was associated with maternal toxicity (reduced maternal body weights), decreased fetal weights, and increased skeletal variations including reduced ossification of the sternebrae, vertebrae, and skull at the high dose of 15 mg/kg/day (approximately 6-times the human plasma exposure at the MRHD based on plasma AUC comparison). The doses not associated with fetal toxicity in mice and maternal and fetal toxicity in rats were 5 and 2.5 mg/kg/day respectively (for both species approximately equivalent to the human plasma exposure at the MRHD based on plasma AUC comparison).
In a pre-postnatal study, oral tedizolid phosphate administered to female rats at doses of 1.25, 2.5, and 3.75 mg/kg/day during gestation and lactation (GD6 through Lactational Day 20) was not associated with maternal toxicity, fetal toxicity, developmental delays, or impaired reproduction at doses up to the high dose of 3.75 mg/kg/day (approximately equivalent to the human plasma exposure at the MRHD based on plasma AUC comparison).
Risk Summary
There is no information on the presence of tedizolid in human milk. Tedizolid is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. There are no data on the effects of SIVEXTRO on the breastfed child or on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SIVEXTRO and any potential adverse effects on the breastfed child from SIVEXTRO or from the underlying maternal condition.
The safety and effectiveness of SIVEXTRO for the treatment of ABSSSI have been established in pediatric patients aged 12 years and older. Use of SIVEXTRO for the treatment of ABSSSI is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged 12 years and older [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)].
Safety and effectiveness of SIVEXTRO in pediatric patients below the age of 12 years have not been established.
In the event of overdosage, SIVEXTRO should be discontinued and general supportive treatment given. Hemodialysis does not result in meaningful removal of tedizolid from systemic circulation.
SIVEXTRO (tedizolid phosphate), a phosphate prodrug, is converted to tedizolid in the presence of phosphatases.
Tedizolid phosphate has the chemical name [(5R)-(3-{3-Fluoro-4-[6-(2-methyl-2H-tetrazol- 5-yl) pyridin-3-yl]phenyl}-2-oxooxazolidin- 5-yl]methyl hydrogen phosphate.
Its empirical formula is C17H16FN6O6P and its molecular weight is 450.32. Its structural formula is:
Tedizolid phosphate is a white to yellow solid and is administered orally or by intravenous infusion.
The pharmacologically active moiety, tedizolid, is an antibacterial agent of the oxazolidinone class.
SIVEXTRO tablets contain 200 mg of tedizolid phosphate, and the following inactive ingredients: crospovidone, magnesium stearate, mannitol, microcrystalline cellulose, and povidone. In addition, the film coating contains the following inactive ingredients: polyethylene glycol/macrogol, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide.
SIVEXTRO for injection is a sterile, white to off-white sterile lyophilized powder supplied in a clear glass single-dose vial. Each vial contains 200 mg of tedizolid phosphate and the inactive ingredient, mannitol (105 mg). Sodium hydroxide and hydrochloric acid are used as needed for pH adjustment. When reconstituted as directed with 4 mL of Sterile Water for Injection, each mL contains 50 mg of tedizolid phosphate. The pH of the reconstituted solution is 7.4 to 8.1.
Tedizolid is an antibacterial drug [see Microbiology (12.4)].
The AUC/minimum inhibitory concentration (MIC) was shown to best correlate with tedizolid activity in animal infection models.
In the mouse thigh infection model of S. aureus, antistaphylococcal killing activity was impacted by the presence of granulocytes. In granulocytopenic mice (neutrophil count <100 cells/mL), bacterial stasis was achieved at a human-equivalent dose of approximately 2000 mg/day; whereas, in non-granulocytopenic animals, stasis was achieved at a human-equivalent dose of approximately 100 mg/day. The safety and efficacy of SIVEXTRO for the treatment of neutropenic patients (neutrophil counts <1000 cells/mm3) have not been evaluated.
Cardiac Electrophysiology
In a randomized, positive- and placebo-controlled crossover thorough QTc study, 48 enrolled subjects were administered a single oral dose of SIVEXTRO at a therapeutic dose of 200 mg, SIVEXTRO at a supratherapeutic dose of 1200 mg, placebo, and a positive control; no significant effects of SIVEXTRO on heart rate, electrocardiogram morphology, PR, QRS, or QT interval were detected. Therefore, SIVEXTRO does not affect cardiac repolarization.
Tedizolid phosphate is a prodrug that is converted by phosphatases to tedizolid, the microbiologically active moiety, following oral and intravenous administration. Only the pharmacokinetic profile of tedizolid is discussed further due to negligible systemic exposure of tedizolid phosphate following oral and intravenous administration. Following multiple once-daily oral or intravenous administration, steady state concentrations are achieved within approximately three days with tedizolid accumulation of approximately 30% (tedizolid half-life of approximately 12 hours). Pharmacokinetic (PK) parameters of tedizolid following oral and intravenous administration of 200 mg once daily tedizolid phosphate are shown in Table 5.
|Pharmacokinetic Parameters of Tedizolid*
|Single Dose
|Steady State
|Single Dose
|Steady State
|Cmax (mcg/mL)
|2.0 (0.7)
|2.2 (0.6)
|2.3 (0.6)
|3.0 (0.7)
|Tmax (hr)†
|2.5 (1.0 - 8.0)
|3.5 (1.0 - 6.0)
|1.1 (0.9 - 1.5)
|1.2 (0.9 - 1.5)
|AUC (mcg∙hr/mL)‡
|23.8 (6.8)
|25.6 (8.5)
|26.6 (5.2)
|29.2 (6.2)
|CL or CL/F (L/hr)
|7.5 (2.3)
|6.9 (1.7)
|6.4 (1.2)
|5.9 (1.4)
Peak plasma tedizolid concentrations are achieved within approximately 3 hours following oral administration under fasting conditions or at the end of the 1 hour intravenous infusion of tedizolid phosphate. The absolute bioavailability is approximately 91% and no dosage adjustment is necessary between intravenous and oral administration.
Tedizolid phosphate (oral) may be administered with or without food as total systemic exposure (AUC0-∞) is unchanged between fasted and fed (high-fat, high-calorie) conditions.
Protein binding of tedizolid to human plasma proteins is approximately 70 to 90%. The mean steady state volume of distribution of tedizolid in healthy adults following a single intravenous dose of tedizolid phosphate 200 mg ranged from 67 to 80 L (approximately twice total body water). Tedizolid penetrates into the interstitial space fluid of adipose and skeletal muscle tissue with exposure similar to free drug exposure in plasma.
Other than tedizolid, which accounts for approximately 95% of the total radiocarbon AUC in plasma, there are no other significant circulating metabolites in humans.
There was no degradation of tedizolid in human liver microsomes indicating tedizolid is unlikely to be a substrate for hepatic CYP450 enzymes.
In vitro studies showed that conjugation of tedizolid is mediated via multiple sulfotransferase (SULT) isoforms (SULT1A1, SULT1A2, and SULT2A1).
Following single oral administration of 14C-labeled tedizolid phosphate under fasted conditions, the majority of elimination occurred via the liver, with 82% of the radioactive dose recovered in feces and 18% in urine, primarily as a non-circulating and microbiologically inactive sulfate conjugate. Most of the elimination of tedizolid (>85%) occurs within 96 hours. Less than 3% of the tedizolid phosphate-administered dose is excreted in feces and urine as unchanged tedizolid.
Specific Populations
Based on the population pharmacokinetic analysis, there are no clinically relevant demographic or clinical patient factors (including age, gender, race, ethnicity, weight, body mass index, and measures of renal or liver function) that impact the pharmacokinetics of tedizolid.
Patients with Hepatic Impairment
Following administration of a single 200 mg oral dose of SIVEXTRO, no clinically meaningful changes in mean tedizolid Cmax and AUC0-∞ were observed in adult patients with moderate (n=8) or severe (n=8) hepatic impairment (Child-Pugh Class B and C) compared to 8 matched healthy control subjects. No dose adjustment is necessary for patients with hepatic impairment.
Patients with Renal Impairment
Following administration of a single 200 mg intravenous dose of SIVEXTRO to 8 adult subjects with severe renal impairment defined as eGFR <30 mL/min/1.73 m2, the Cmax was essentially unchanged and AUC0-∞ was decreased by less than 10% compared to 8 matched healthy control adult subjects. Hemodialysis does not result in meaningful removal of tedizolid from systemic circulation, as assessed in subjects with end-stage renal disease (eGFR <15 mL/min/1.73 m2). No dosage adjustment is necessary in patients with renal impairment or patients on hemodialysis.
Geriatric Patients
The pharmacokinetics of tedizolid were evaluated in a Phase 1 study conducted in elderly healthy volunteers (age 65 years and older, with at least 5 subjects at least 75 years old; n=14) compared to younger control subjects (25 to 45 years old; n=14) following administration of a single oral dose of SIVEXTRO 200 mg. There were no clinically meaningful differences in tedizolid Cmax and AUC0-∞ between elderly subjects and younger control subjects. No dosage adjustment of SIVEXTRO is necessary in elderly patients.
Male and Female Patients
The impact of gender on the pharmacokinetics of SIVEXTRO was evaluated in clinical trials of adult healthy males and females and in a population pharmacokinetics analysis. The pharmacokinetics of tedizolid were similar in males and females. No dosage adjustment of SIVEXTRO is necessary based on gender.
Pediatric Patients
Compared to adult patients, tedizolid exposures are higher in pediatric patients 12 to <18 years of age following multiple dose administration of IV or oral SIVEXTRO (geometric mean Cmax 3.13 vs. 2.00 mcg/mL, AUC24h 28.6 vs. 21.0 mcg*h/mL); however, this increase in exposure is not considered clinically significant.
Drug Interaction Studies
Drug Metabolizing Enzymes
Transformation via Phase 1 hepatic oxidative metabolism is not a significant pathway for elimination of SIVEXTRO.
Neither SIVEXTRO nor tedizolid detectably inhibited or induced the metabolism of selected CYP enzyme substrates, suggesting that drug-drug interactions based on oxidative metabolism are unlikely.
Membrane Transporters
The potential for tedizolid or tedizolid phosphate to inhibit transport of probe substrates of important drug uptake (OAT1, OAT3, OATP1B1, OATP1B3, OCT1, and OCT2) and efflux transporters (P-gp and BCRP) was tested in vitro. No clinically relevant interactions are expected to occur with these transporters except BCRP.
Coadministration of multiple oral doses of SIVEXTRO (200 mg once daily) increased the Cmax and AUC of rosuvastatin (10 mg single oral dose), a known BCRP substrate, by approximately 55% and 70%, respectively, in healthy adult subjects [see Drug Interactions (7)].
Monoamine Oxidase Inhibition
Tedizolid is a reversible inhibitor of monoamine oxidase (MAO) in vitro. The interaction with MAO inhibitors could not be evaluated in Phase 2 and 3 trials, as subjects taking such medications were excluded from the trials.
Adrenergic Agents
Two placebo-controlled crossover studies were conducted to assess the potential of 200 mg oral SIVEXTRO at steady state to enhance pressor responses to pseudoephedrine and tyramine in healthy adults. No meaningful changes in blood pressure or heart rate were seen with pseudoephedrine. The median tyramine dose required to cause an increase in systolic blood pressure of ≥30 mmHg from pre-dose baseline was 325 mg with SIVEXTRO compared to 425 mg with placebo. Palpitations were reported in 21/29 (72.4%) adult subjects exposed to SIVEXTRO compared to 13/28 (46.4%) exposed to placebo in the tyramine challenge study.
Serotonergic Agents
Serotonergic effects at doses of tedizolid phosphate up to 30-fold above the human equivalent dose did not differ from vehicle control in a mouse model that predicts serotonergic activity. In Phase 3 trials, subjects taking serotonergic agents including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and serotonin 5-hydroxytryptamine (5-HT1) receptor agonists (triptans), meperidine, or buspirone were excluded.
Mechanism of Action
The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely. The results of in vitro time-kill studies show that tedizolid is bacteriostatic against enterococci, staphylococci, and streptococci.
Organisms resistant to oxazolidinones via mutations in chromosomal genes encoding 23S rRNA or ribosomal proteins (L3 and L4) are generally cross-resistant to tedizolid. In the limited number of Staphylococcus aureus strains tested, the presence of the chloramphenicol-florfenicol resistance (cfr) gene did not result in resistance to tedizolid in the absence of chromosomal mutations. Mutations in 23SrRNA (G2576T mutation) have been associated with tedizolid resistance in S. aureus isolates.
Spontaneous mutations conferring reduced susceptibility to tedizolid occur in vitro at a frequency rate of approximately 10-10.
Interaction with Other Antimicrobial Drugs
In vitro drug combination studies with tedizolid and aztreonam, ceftriaxone, ceftazidime, imipenem, rifampin, trimethoprim/sulfamethoxazole, minocycline, clindamycin, ciprofloxacin, daptomycin, vancomycin, gentamicin, amphotericin B, ketoconazole, and terbinafine demonstrate neither synergy nor antagonism.
Antimicrobial Activity
Tedizolid has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections, as described in Indications and Usage (1).
Aerobic bacteria
The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for tedizolid against isolates of similar genus or organism group. However, the efficacy of SIVEXTRO in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.
Aerobic bacteria
Gram-positive bacteria
Tedizolid phosphate was negative for genotoxicity in all in vitro assays (bacterial reverse mutation (Ames), Chinese hamster lung (CHL) cell chromosomal aberration) and in all in vivo tests (mouse bone marrow micronucleus, rat liver unscheduled DNA synthesis). Tedizolid, generated from tedizolid phosphate after metabolic activation (in vitro and in vivo), was also tested for genotoxicity. Tedizolid was positive in an in vitro CHL cell chromosomal aberration assay, but negative for genotoxicity in other in vitro assays (Ames, mouse lymphoma mutagenicity) and in vivo in a mouse bone marrow micronucleus assay.
Impairment of Fertility
In a fertility study, oral tedizolid phosphate administered in doses of 5, 15, and 50 mg/kg/day for 28 days before mating and during mating to male rats had no adverse effects on the fertility or reproductive performance, including spermatogenesis, at the maximum tested dose (50 mg/kg/day) with a plasma tedizolid AUC approximately 5-fold greater than the plasma AUC value in humans at the maximum recommended human dose (MRHD). Tedizolid phosphate administered in doses of 2.5, 5, and 15 mg/kg/day for 14 days before mating, during mating, and until Gestation Day (GD)7 to female rats also had no adverse effects on the fertility or reproductive performance at doses up to the maximum tested dose of 15 mg/kg/day (approximately 4-fold higher than exposures in humans at the MRHD based on plasma AUC comparison).
Repeated-oral and intravenous dosing of tedizolid phosphate in rats in 1-month and 3-month toxicology studies produced dose- and time-dependent bone marrow hypocellularity (myeloid, erythroid, and megakaryocyte), with associated reduction in circulating RBCs, WBCs, and platelets. These effects showed evidence of reversibility and occurred at plasma tedizolid exposure levels (AUC) ≥6-fold greater than the plasma exposure associated with the human therapeutic dose. In a 1-month immunotoxicology study in rats, repeated oral dosing of tedizolid phosphate was shown to significantly reduce splenic B cells and T cells and reduce plasma IgG titers. These effects occurred at plasma tedizolid exposure levels (AUC) ≥3-fold greater than the expected human plasma exposure associated with the therapeutic dose.
A total of 1333 adults with acute bacterial skin and skin structure infections (ABSSSI) were randomized in two multicenter, multinational, double-blind, non-inferiority trials. Both trials compared SIVEXTRO 200 mg once daily for 6 days versus linezolid 600 mg every 12 hours for 10 days. In Trial 1, patients were treated with oral therapy, while in Trial 2, patients could receive oral therapy after a minimum of one day of intravenous therapy. Patients with cellulitis/erysipelas, major cutaneous abscess, or wound infection were enrolled in the trials. Patients with wound infections could have received aztreonam and/or metronidazole as adjunctive therapy for gram-negative bacterial coverage, if needed. The intent-to-treat (ITT) patient population included all randomized patients.
In Trial 1, 332 patients with ABSSSI were randomized to SIVEXTRO and 335 patients were randomized to linezolid. The majority (91%) of patients treated with SIVEXTRO in Trial 1 were less than 65 years old with a median age of 43 years (range: 18 to 86 years). Patients treated with SIVEXTRO were predominantly male (61%) and White (84%); 13% had BMI ≥35 kg/m2, 8% had diabetes mellitus, 35% were current or recent intravenous drug users, and 2% had moderate to severe renal impairment. The overall median surface area of infection was 188 cm2. The types of ABSSSI included were cellulitis/erysipelas (41%), wound infection (29%), and major cutaneous abscess (30%). In addition to local signs and symptoms of infection, patients were also required to have at least one regional or systemic sign of infection at baseline, defined as lymphadenopathy (87% of patients), temperature 38°C or higher (16% of patients), white blood cell count greater than 10,000 cells/mm3 or less than 4000 cells/mm3 (42%), or 10% or more band forms on white blood cell differential (4%).
The primary endpoint in Trial 1 was early clinical response defined as no increase from baseline lesion area at 48-72 hours after the first dose and oral temperature of ≤37.6°C, confirmed by a second temperature measurement within 24 hours in the ITT population.
In Trial 2, 332 patients with ABSSSI were randomized to SIVEXTRO and 334 patients were randomized to linezolid. The majority (87%) of patients treated with SIVEXTRO in Trial 2 were less than 65 years old with a median age of 46 years (range: 17 to 86 years). Patients treated with SIVEXTRO were predominantly male (68%) and White (86%); 16% had BMI ≥35 kg/m2, 10% had diabetes mellitus, 20% were current or recent intravenous drug users, and 4% had moderate to severe renal impairment. The overall median surface area of infection was 231 cm2. The types of ABSSSI included were cellulitis/erysipelas (50%), wound infection (30%), and major cutaneous abscess (20%). In addition to local signs and symptoms of infection, patients were also required to have at least one regional or systemic sign of infection at baseline, defined as lymphadenopathy (71% of patients), temperature 38°C or higher (31% of patients), white blood cell count greater than 10,000 cells/mm3 or less than 4000 cells/mm3 (53%), or 10% or more band forms on white blood cell differential (16%).
The primary endpoint in Trial 2 was early clinical response defined as at least a 20% decrease from baseline lesion area at 48-72 hours after the first dose in the ITT population (Table 6).
(200 mg)
(1200 mg)
|Treatment Difference
(2-sided 95% CI)
|CI=confidence interval
|No increase in lesion surface area from baseline and oral temperature of ≤37.6°C, confirmed by a second temperature measurement within 24 hours at 48-72 hours*
|Trial 1, N
|Responder, n (%)
|264 (79.5)
|266 (79.4)
|0.1 (-6.1, 6.2)
|Trial 2, N
|Responder, n (%)
|286 (86.1)
|281 (84.1)
|2.0 (-3.5, 7.3)
|At least a 20% decrease from baseline in lesion area at 48-72 hours†
|Trial 1, N
|Responder, n (%)
|259 (78.0)
|255 (76.1)
|1.9 (-4.5, 8.3)
|Trial 2, N
|Responder, n (%)
|283 (85.2)
|276 (82.6)
|2.6 (-3.0, 8.2)
An investigator assessment of clinical response was made at the post-therapy evaluation (PTE) (7 - 14 days after the end of therapy) in the ITT and CE (Clinically Evaluable) populations. Clinical success was defined as resolution or near resolution of most disease-specific signs and symptoms, absence or near resolution of systemic signs of infection if present at baseline (lymphadenopathy, fever, >10% immature neutrophils, abnormal WBC count), and no new signs, symptoms, or complications attributable to the ABSSSI requiring further treatment of the primary lesion (Table 7).
(200 mg)
n/N (%)
(1200 mg)
n/N (%)
|Treatment Difference
(2-sided 95% CI)
|CI=confidence interval; ITT=intent-to-treat; CE=clinically evaluable
|Trial 1
|284/332 (85.5)
|288/335 (86.0)
|-0.5 (-5.8, 4.9)
|264/279 (94.6)
|267/280 (95.4)
|-0.8 (-4.6, 3.0)
|Trial 2
|292/332 (88.0)
|293/334 (87.7)
|0.3 (-4.8, 5.3)
|268/290 (92.4)
|269/280 (96.1)
|-3.7 (-7.7, 0.2)
Clinical success by baseline pathogens from the primary infection site or blood cultures for the microbiological intent-to-treat (MITT) patient population for two integrated Phase 3 ABSSSI studies are presented in Table 8 and Table 9.
|No increase in lesion surface area from baseline and oral temperature of ≤37.6°C*
|At least a 20% decrease from baseline in lesion area†
(200 mg)
n/N (%)
(1200 mg)
n/N (%)
(200 mg)
n/N (%)
(1200 mg)
n/N (%)
|Pooled analysis; n=number of patients in the specific category; N=Number of patients with the specific pathogen isolated from the ABSSSI
|Staphylococcus aureus
|276/329 (83.9)
|278/342 (81.3)
|280/329 (85.1)
|276/342 (80.7)
|Methicillin-resistant S. aureus
|112/141 (79.4)
|113/146 (77.4)
|114/141 (80.9)
|111/146 (76.0)
|Methicillin-susceptible S. aureus
|164/188 (87.2)
|167/198 (84.3)
|166/188 (88.3)
|167/198 (84.3)
|Streptococcus pyogenes
|27/33 (81.8)
|18/20 (90.0)
|25/33 (75.8)
|16/20 (80.0)
|Streptococcus anginosus Group
|22/30 (73.3)
|26/28 (92.9)
|22/30 (73.3)
|25/28 (89.3)
|Streptococcus agalactiae
|6/9 (66.7)
|8/10 (80.0)
|6/9 (66.7)
|7/10 (70.0)
|Enterococcus faecalis
|7/10 (70.0)
|3/4 (75.0)
|6/10 (60.0)
|1/4 (25.0)
Baseline bacteremia in the tedizolid arm with relevant pathogens included two subjects with MRSA, four subjects with MSSA, two subjects with S. pyogenes, one subject with S. agalactiae, and one subject with S. constellatus. All of these subjects were Responders at the 48-72 hour evaluation. At the Post-therapy Evaluation (PTE), 8 of 10 subjects were considered clinical successes.
|Clinical Response at PTE
(200 mg)
n/N (%)
(1200 mg)
n/N (%)
|Pooled analysis; n=number of patients in the specific category; N=Number of patients with the specific pathogen isolated from the ABSSSI
|Staphylococcus aureus
|291/329 (88.5)
|303/342 (88.6)
|Methicillin-resistant S. aureus
|118/141 (83.7)
|119/146 (81.5)
|Methicillin-susceptible S. aureus
|173/188 (92.0)
|186/198 (93.9)
|Streptococcus pyogenes
|30/33 (90.9)
|19/20 (95.0)
|Streptococcus anginosus Group
|21/30 (70.0)
|25/28 (89.3)
|Streptococcus agalactiae
|8/9 (88.9)
|8/10 (80.0)
|Enterococcus faecalis
|7/10 (70.0)
|4/4 (100.0)
Baseline bacteremia in the tedizolid arm with relevant pathogens included two subjects with MRSA, four subjects with MSSA, two subjects with S. pyogenes, one subject with S. agalactiae, and one subject with S. constellatus. All of these subjects were Responders at the 48-72 hour evaluation. At the Post-therapy Evaluation (PTE) 8 of 10 subjects were considered clinical successes.
Pediatric Patients
The safety and efficacy of SIVEXTRO in pediatric patients 12 to < 18 years of age were investigated in a randomized, single blind, active-controlled trial of 120 patients with clinically documented ABSSSI (91 receiving tedizolid, 29 receiving comparator). Patients were randomized in a 3:1 ratio with stratification by geographic region to receive SIVEXTRO IV and/or oral therapy, dosed 200 mg once daily for 6 days, or comparator IV and/or oral therapy, dosed over 10 days. Comparator therapy was selected by the investigator from a list of 5 IV and 4 oral comparators per local standard of care. The most frequently used comparators were cefazolin (11 patients) and vancomycin (8 patients).
The primary objective was to evaluate the safety and tolerability of SIVEXTRO. The trial was not powered for comparative inferential efficacy analysis. Clinical response at the test of cure visit (Day 18-25) was assessed by a blinded investigator in the ITT population (all randomized patients). Clinical successes were required to have resolution or near resolution of all related signs and symptoms such that no further antibacterial therapy was needed. Early clinical response, defined as at least a 20% reduction in lesion size at 48-72 hours after start of treatment, was also assessed in the ITT population.
Clinical success at test of cure was 96.7% (88/91) in the tedizolid group and 93.1% (27/29) in the comparator group (difference 3.6%, 95% CI: -6.3, 13.5). Early clinical response at 48-72 hours was 92.3% (84/91) in the tedizolid group and 96.6% (28/29) in the comparator group (difference -4.2%, 95% CI: -12.9, 4.4).
SIVEXTRO tablets are yellow film-coated oval tablets containing 200 mg of tedizolid phosphate; each tablet is debossed with "TZD" on one side and "200" on the other side.
They are supplied as follows:
HDPE bottles of 30 tablets with child-resistant closure (NDC 72000-310-30)
Unit dose blister packs of 6 tablets (NDC 72000-310-06)
SIVEXTRO is supplied as a sterile, lyophilized powder for injection in single-dose vials of 200 mg. Each 200 mg vial must be reconstituted with Sterile Water for Injection and subsequently diluted only with 0.9% Sodium Chloride Injection, USP.
They are supplied as follows:
Package of ten 200 mg single-dose vials (NDC 72000-320-10)
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Administration with Food
Patients should be informed that SIVEXTRO tablets may be taken with or without food and without any dietary restrictions [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
Usage Safeguards
Patients should be advised that antibacterial drugs including SIVEXTRO should only be used to treat bacterial infections. SIVEXTRO does not treat viral infections (e.g., the common cold). When SIVEXTRO 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 SIVEXTRO or other antibacterial drugs in the future [see Indications and Usage (1.2)].
Patients should be informed that if they miss a dose, they should take the dose as soon as possible anytime up to 8 hours prior to their next scheduled dose. If less than 8 hours remains before the next dose, then they should wait until their next scheduled dose. Patients should take the prescribed number of doses [see Dosage and Administration (2.1)].
Keep SIVEXTRO and all medications out of reach of children.
Potentially Serious Adverse Reactions
Patients should be advised that diarrhea is a common problem caused by antibacterial drugs including SIVEXTRO and usually resolves when the drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop frequent watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug and may be a sign of a more serious intestinal infection [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]. If this occurs, patients should contact their healthcare provider as soon as possible.
Embryo-Fetal Toxicity
Based on animal data, advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].
Manuf. for: Nabriva Therapeutics US, Inc.
Nabriva THERAPEUTICS, Fort Washington, PA 19034
Sivextro tablets
Manufactured by: Patheon Inc.
Whitby, Ontario, L1N 5Z5 Canada
Sivextro for injection
Manufactured by: Patheon Italia S.p.A.
03013, Ferentino, FR Italy
For patent information: www.msd.com/research/patent
Copyright © 2015-2022 Merck & Co., Inc., Rahway, NJ, USA, and its affiliates.
All rights reserved.
|Patient Information
(tedizolid phosphate)
What you need to know about SIVEXTRO
|What is SIVEXTRO?
SIVEXTRO is a tablet for people 12 years of age and older who have a skin infection or an infection in the tissue below the skin. SIVEXTRO is an antibiotic that works by stopping the growth of certain bacteria.
SIVEXTRO should not be used for people under 12 years old. It is not known if SIVEXTRO works or is safe for people under age 12.
|What should I tell my doctor before taking SIVEXTRO?
Medical Conditions
Tell your doctor if you:
|Are you taking other medicines?
|How do I take SIVEXTRO?
|What if I forget to take SIVEXTRO?
If you do not finish your medicine, SIVEXTRO may not work.
You may get sick again and the remaining bacteria may be harder to treat.
|What are the possible side effects of SIVEXTRO?
SIVEXTRO may cause serious side effects, including diarrhea from C-diff (Clostridioides difficile) infection. Call your healthcare provider right away if you get stomach cramps, fever, watery diarrhea, diarrhea that does not go away, or bloody stools. C-diff infection can happen 2 or more months after you have finished your antibacterial medicine.
C-diff is an infection of your intestines (bowels) that can happen with many antibiotics like SIVEXTRO and may cause mild diarrhea to life-threatening swelling of your intestines (colitis).
Common side effects of SIVEXTRO include:
Some less common side effects are:
Problems with your skin
Problems with your sleep
Problems with your body
Problems with infections
Problems with your eyes
Problems with your heart
Problems with your vascular system
Problems with your blood work
Your doctor may tell you that you have the following while taking SIVEXTRO:
Side effects where the frequency is not known:
If you have any side effect that bothers you or does not go away, tell your doctor.
These are not all the possible side effects of SIVEXTRO. For information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
|How should I store SIVEXTRO?
|General information about SIVEXTRO.
|What if I have questions?
|What are the ingredients in SIVEXTRO?
Manuf. for: Nabriva Therapeutics US, Inc.
Nabriva THERAPEUTICS, Fort Washington, PA 19034
Sivextro tablets Manufactured by: Patheon Inc., Whitby, Ontario, L1N 5Z5 Canada
Sivextro for injection Manufactured by: Patheon Italia S.p.A., 03013, Ferentino, FR Italy
For patent information: www.msd.com/research/patent. The trademarks depicted herein are owned by their respective companies.
Copyright © 2017-2022 Merck & Co., Inc., Rahway, NJ, USA, and its affiliates. All rights reserved.
This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 07/2022
30 tablets
(tedizolid phosphate) tablets
200 mg per tablet
Rx only
6 tablets
(tedizolid phosphate) tablets
200 mg per tablet
Rx only
tedizolid phosphate tablet, film coated
tedizolid phosphate injection, powder, lyophilized, for solution
|Labeler - Nabriva Therapeutics US, Inc. (072863844)
|Registrant - Merck Sharp & Dohme LLC (118446553)


text:
[vc_row][vc_column width="3/4″ el_class="colPostMain"][vc_column_text css=".vc_custom_1551376388898{padding-top: 15px !important;padding-bottom: 40px !important;}" el_class="amp-wp-content"]
We love Lauv. Today, March 6, marks the release of his studio debut album ~how I'm feeling~ via AWAL Recordings. The album is a long time coming for Lauv, who has been producing and writing for other stars (cough*Celine Dion*cough) striking out on his own. His personal songs are just that. They hit on relationships and mental health and the things that affect anyone in everyday life.
Lauv came by the Music Choice studios and we had a long chat all about how he's gotten to this point in his career, performing live, his super cute dog, and everything in between. Read the conversation below and then head to the Music Choice webplayer to catch some of Lauv's music videos!
Interview by Tegan Alexander
MC: The first singles from the album "f*ck, i'm lonely" and "Sad Forever" were more somber but more recent songs like "Feelings" and "Sims" are a little more lighthearted. Was that the strategy?
L: Honestly, I didn't even think of it that way. I just started releasing songs as I finished them. That's what I do. Release stuff as I finish it.
MC: "Sims" is my jam. Can you take us behind the concept for the video?
L: I wanted to make this thing with identity where I was like "am I this type or person?" Or "am I this type of guy?" How am I going to present myself on the Internet? I created these six different characters that are like Positive Lauv, Existential Lauv, Hopeless Romantic Lauv (with my old hair), F*ckboy Lauv, Spicy Lauv, and Goofy Lauv. I wanted to represent all aspects of my personality. It's a one-man boy band.
MC: You're obviously not afraid to put your feelings in the mix. Is there anywhere you wouldn't go in a song?
LM: I've never really thought about that. I don't think so. This album has songs about mental health and where we're at with that. I have a song about my favorite bar and a song about my dog. I write about anything.
MC: What kind of dog do you have?
L: A Pomeranian! He's super cute and his name is Billy.
MC: Speaking of mental health, you have this website called My Blue Thoughts where people can just unload whatever is on their mind. Have you read through these things? Have people given you feedback on the project?
L: I've seen footage of people talking about it. I've been doing the project for a few years now. It started as a physical box that people could put pieces of paper into. After that I saw that people were reacting well to it and used it for real things. Also, some people would write "I like chicken tenders" [laughs].
L: Then there are people who use it to open up about crazy sh*t in their life. Some very personal stuff. That takes a lot of courage and vulnerability which I respect. I think the website will make it easier to connect with other people who are experiencing similar things.
MC: So, you're a songwriter and you wrote a song for Celine Dion!
L: I was not expecting that to happen. It's crazy!
MC: How did it all happen?
L: It was a song I started with some friends about two years ago. As happens with tons of songs they sit around, and I feel strongly about them but I don't know what to do with them. Celine heard the idea and loved it. It became her song!
MC: When you write a song do you know right then if you want to use it or if it's going to someone else?
L: Sometimes I have artists in mind. Sometimes I just love the song, but I don't really know what should happen to it because I don't feel like I need to sing it. If I keep it I feel that I need to sing the song.
MC: When a song you wrote blows up, like Cheat Codes "No Promises" do you feel like you should have kept it for yourself?
L: I don't because I never really felt like that song was meant for me. I loved it but I never felt it was mine. If I had let go of a song like "I Like Me Better" I definitely would've been bummed.
One of my friends, before I released it was like "what if Justin Bieber wanted to cut it?" I was like, "NOPE!"
MC: Good for you!
L: Can you imagine how big that song would be if he had? It would be the biggest song in the world. I would've written the biggest song in the world if Justin Bieber recorded it. I'm gonna say that.
MC: That song was pretty big with you! Are there any songs that you wish you would have written?
L: I really love Ed Sheeran and Khalid's "Beautiful People." The first time Ed played that for me I freaked out.
MC: You toured with Ed Sheeran. What was that experience like?
L: Crazy, crazy, crazy, crazy! I was out for a run at 7 am and my manager called me and I told him to call me back. Then he quickly asked if I wanted to go on tour with Ed Sheeran in arenas throughout Asia. I obviously said no.
That was such a big, surreal moment for me. I got to call my parents and tell them. I look up to him as a human, as a songwriter, as an artist, as a performer. Just on every level.
MC: Was your aim to be a songwriter or an artist when starting out?
L: I started writing songs when I was 13. I always wanted to be an artist. I didn't even know you could be a writer or producer for other artists. My bands and the MySpace era didn't really work out so I thought maybe I'd become a songwriter and producer for other artists. I did for a few years then made my first song as Lauv by accident. It was just supposed to be a side project.
MC: Wow. So, a natural progression. Outside of music do you have a hidden talent?
L: I like to skateboard, but I haven't had time recently. Other than that, I barely do anything besides making music.
MC: You're currently touring, what's one song crowds are really responding to?
L: "f*ck, i'm lonely" goes crazy! The first few times I performed it I didn't know what was going on. I didn't even have to sing "f*ck." They just scream!
MC: How is touring different than songwriting to you?
L: That's a good question. It's a different energy and a different high. The high of writing an amazing song you love is so cool because it came out of nothing. Then being on stage you're totally in the moment and so many unexpected things, flaws, happen and you have to roll with it. It's the most human part of music. In the studio things can be redone and edited. Live, it is what it is.
[/vc_column_text][vc_column_text css=".vc_custom_1554313675198{padding-top: 15px !important;}" el_class="news-cta-lg"]
Back to news
[/vc_column_text][/vc_column][vc_column width="1/4″ el_class="colPostLg"][vc_column_text]
Related Articles
[/vc_column_text][vcex_blog_grid columns="1″ title="false" excerpt_length="" read_more="false" img_width="800″ img_height="400″ overlay_style="title-center" img_hover_style="opacity" date_font_size="10″ offset="1″][/vc_column][/vc_row][vc_row][vc_column el_class="colPostSm"][vc_column_text]
Related Articles
[/vc_column_text][vc_row_inner][vc_column_inner][vcex_blog_grid columns="2″ title="false" excerpt_length="" read_more="false" img_width="800″ img_height="400″ overlay_style="title-center" img_hover_style="opacity" date_font_size="10″ offset="1″][/vc_column_inner][/vc_row_inner][vc_column_text css=".vc_custom_1543269474731{padding-top: 15px !important;}"]
Back to news

subset: commoncrawl


text:
Whether you are going layered, lucite, heart-shaped or even rocking
retro cowrie shells
, this summer is going to be all about the bling. But how can you keep your jewelry sparkling clean and free from product buildup?
You don't need to rush off to the local jewelry store and shell out cash to have your jewelry cleaned for you. Here are easy ways you can DIY some jewelry cleaners at
Baking Soda And Dish Detergent
You probably already have
everything you need
in your
to keep your favorite rings shining bright like a diamond. Simply gather up some dish detergent, baking soda, salt, aluminum foil and a bowl. After lining the bowl with the aluminum foil, pile in the baking soda, salt and dish detergent, followed by some hot water. Drop in your jewelry for 10 minutes and then remove from the cleaner and scrub with an old toothbrush.
White Vinegar
Gold (or gold-tone) jewelry
is trending
right now, whether
we are talking
minimalist bar necklaces or extravagant gold hoops. Keeping your gold jewelry clean is as simple as reaching into your kitchen pantry.
Good old
white vinegar
is an easy way to make gold shine. Let your gold jewelry sit in white vinegar for up to 15 minutes, making sure to move it around every now and then. Then use a soft toothbrush to clean and rinse the jewelry. It's as easy as that!
a bottle of antacids
from the
cabinet. No, really. Antacids are wonderful at cleaning away built-up debris from your favorite jewelry. Just put a tablet in a bowl of warm water and then drop in your jewelry. Let it sit, then remove and rinse with gentle scrubbing from a soft toothbrush.
Your favorite bottle of
ketchup can keep your jewelry
sparkling and shining, thanks to the acidic tomatoes used in ketchup. This is a good option for silver jewelry that has become tarnished over time. Just let the item sit in the condiment for 5-10 minutes, then gently scrub and rinse.
Glass Cleaner
You know the blue stuff you use to make your mirrors gleam? Just reach for that same bottle when you want your jewelry to be as sparkly as a freshly cleaned mirror. You can use Windex on its own, or make
a concoction
with one part glass cleaner and one part hydrogen peroxide. The result will make your jewels shine — including your diamonds.
This story originally appeared on
. Checkout
for other great tips and ideas to make the most out of life.
Related stories
window.fbAsyncInit = function() { FB.init({
appId : '471244696370916',
xfbml : true, version : 'v2.9' }); };
(function(d, s, id){
var js, fjs = d.getElementsByTagName(s)[0];
if (d.getElementById(id)) {return;}
js = d.createElement(s); js.id = id;
js.src = "http://connect.facebook.net/en_US/sdk.js";
fjs.parentNode.insertBefore(js, fjs);
}(document, 'script', 'facebook-jssdk'));


text:
project-leader: Klaus Listmann
Deutsche Version dieser Seite
On saturday, July 5th 1997, project UNION was launched under the management of Klaus Listmann. Aim of the project was to create a formation in a field of crop under practicable realistic "hoaxing"-conditions. On that occasion the possibilities to create a previously planned pictogram with several people in the dark should be examined. More important, the circle should be the basis for further examinations, already carried out in supposed "genuine" formations or plannedto be carried out in these. Therefore project UNION was subdivided in several subprojects that were carried out on the field or are stll in realization:
Fotos: Harald Hoos / Aerial shot of the formation: Wolfgang
Discussion with the farmer Mr. Öttermann
at the project-field near Zierenberg/Burghasungen
Aerial shot of the formation created during the project
Inner views to the formation
The morning after...
project-participants and spectators at the project-field, from which both of the
labyrinth-formations in that area could be seen (see also CropCicles
in Germany '97 and the reportKornkreise bei Kassel 1997 (German)).


text:
Search for atmospheres
Ambient categories
Singing Well
- 1h
- 10m
- 1m
New sound
Current sound
Singing Well
A dilapidated old well--mostly just a circle of old stones piled on top of each other that eventually lead to water. There is a shallow gouge in the earth at the foot of an old tree and the largest of the roots produces a perfect natural bench. In a hollow in the old tree is a pile of old coins, green with patina, their inscriptions lost to time and the insides of many pockets.
Toss in a coin. See what the well will sing to you today.
Comments for "Singing Well"
License details for "Singing Well"
This atmosphere sound has been released under the
Creative Commons Sampling Plus 1.0 License.
Creative Commons Sampling Plus 1.0 License.
List of audio files used:
- Humming by AlucardsBride from http://freesound.org +)
- paper boats by Darren Korb feat Ashley Barett +)
- Page Turning by DrMaysta from http://freesound.org +)
- Coin Flip by https://freesound.org/s/198877/ +)
- Little stream underwater by ingeos from http://freesound.org +)
- Distant Church Bells by Ivopla +)
- Summer Open Field by kvgarlic from http://www.freesound.org +)
- Quiet college campus (outside) by louismay1 from http://freesound.org +)
+) Creative Commons Sampling Plus 1.0 License


text:
Are you currently overweight, feeling tired and/or suffering from a chronic illness? Are you worried that your child weighs too much for their current size and age? Are you looking for a class to help you through the changes your body goes through while pregnant or for what to expect after you arrive home with the baby? Are you 40+ and looking to prevent common aging ailments and looking to increase your longevity? Do you suffer from chronic conditions and want to learn how the body can repair itself? If you answered "YES!" to any of these questions, you could benefit from attending one of Healthy & Fit for Life's workshops or individual coaching sessions. Why should you have a health coach on your side? BECAUSE ILLNESS COSTS MORE THAN WELLNESS! Click here to register for the next workshop in your area.
For more information on group and individual coaching, including an available on-line workshop, please contact us at (678) 719-2283 or email firstname.lastname@example.com


text:
For the third consecutive season, the Saints will close out the regular season with a trip to Bank of America Stadium to play the Panthers (12:00 p.m. CST). In the offseason, the Panthers signed QB Teddy Bridgewater, who played for New Orleans from 2018-19 and went 5-0 as a starter last season during a five-game stretch when Brees was sidelined with a right thumb injury. Bridgewater will face off against the Saints for the third time in his career. Bridgewater saw his first NFL action against the Saints in the Mercedes-Benz Superdome in Week Three of 2014 when he came on in relief of Matt Cassel.
Saints at Panthers Tickets and History for Week 17 on January 3, 2021
New Orleans Saints 12-4
Carolina Panthers 5-11
History: New Orleans Saints vs. Carolina Panthers
The regular season series is tied 25-25 with the Saints capturing the only playoff meeting between the two clubs. In 2019, New Orleans swept Carolina for the second time in three seasons, as 34-31 win at the Mercedes-Benz Superdome on November 24 and a 42-10 victory to close out the regular season on December 29. The Saints are 13-12 all-time on the road against the Panthers. This will be the third consecutive year the Saints and Panthers close out the regular season and the eleventh time since Carolina entered the NFL as an expansion franchise in 1995.
Players and Coaches to Know
Carolina Panthers
Head Coach: Matt Rhule
Quarterback: Teddy Bridgewater
Key Position Players: RB Christian McCaffrey, WR Robby Anderson, WR D.J. Moore
New Orleans Saints
Head Coach: Sean Payton
Quarterback: Drew Brees
Key Position Players: RB Alvin Kamara, WR Michael Thomas, TE Jared Cook
Latest News on Saints at Panthers
Ty Montgomery, Grant Haley come up big for New Orleans Saints in win over Carolina
Montgomery ran for 105 yards, Haley had first NFL interception
New Orleans Saints again prove adaptability in victory over Carolina to close out regular season
Offense went four of five in red zone, defense had five interceptions and three sacks
Postgame notes from New Orleans Saints' 33-7 win over Carolina Panthers
Saints clinch No. 2 seed in NFC playoffs, host Chicago Bears in Wild Card round
Transcript - New Orleans Saints Coach Sean Payton postgame quotes | Saints-Panthers 2020 Week 17
Get postgame reactions from New Orleans Saints head coach Sean Payton
Transcript - New Orleans Saints quarterback Drew Brees and Saints players postgame quotes | Saints-Panthers 2020 Week 17
Get postgame reactions from New Orleans Saints quarterback Drew Brees and Saints players.
Halftime update - New Orleans Saints 16, Carolina Panthers 7
Saints trying to secure a top playoff seed
5 things to know about the New Orleans Saints on Sunday, Jan. 3
Saints will play at the Carolina Panthers at 3:25 p.m. Sunday on Fox
Tony Chachere's Key Ingredients to a Saints victory vs. Carolina Panthers
Saints need to keep running the football effectively
Saints Gameday Guide 2020: Week 17 at Panthers
Helpful tips and information for the Saints Week 17 matchup against the Panthers
Week 17 2020 Ways to Watch: Saints at Panthers
How to watch, listen and live stream New Orleans Saints at Carolina Panthers on January 3, 2021
Saints at Panthers 2020 Week 17 Preview
Taking a look at the New Orleans Saints at Carolina Panthers Week 17 matchup
2020 New Orleans Saints opponent profile: Minnesota Vikings
Vikings travel to New Orleans on Christmas Day to take on the Saints
2020 New Orleans Saints opponent profile: Carolina Panthers
Saints will face off against Teddy Bridgewater and the Panthers in Week 7 and Week 17
Take a detailed look at the New Orleans Saints' 2020 opponents
Tom Brady and Bucs will visit Saints in season opener
Marquee matchups line New Orleans Saints schedule in 2020
Saints play both Super Bowl LIV participants, and face Vikings on Christmas Day


text:
According to the Ministry of Earth Sciences' air quality monitor, SAFAR, the share of stubble burning in Delhi's pollution rose to 40 percent on Sunday, the maximum so far this season.
New Delhi: Pollution levels in the national capital dipped on Monday with high wind speed aiding dispersion of pollutants, even as farm fires continued to rage in neighbouring states.
The city recorded an air quality index (AQI) of 286, which falls in the "poor" category.
The 24-hour average AQI was 364 on Sunday, with stubble burning contributing 40 percent to Delhi's pollution and negating the effect of better ventilation.
It was 367 on Saturday, 374 on Friday, 395 on Thursday, 297 on Wednesday, 312 on Tuesday, and 353 on Monday.
An AQI between 0 and 50 is considered 'good', 51 and 100 'satisfactory', 101 and 200 'moderate',201 and 300 'poor', 301 and 400 'very poor', and 401 and 500 'severe'.
The Air Quality Early Warning System for Delhi said a "significantly" large number of fires were observed over Punjab, Haryana, Uttar Pradesh and Madhya Pradesh on Sunday which is likely to impact the air quality in Delhi-NCR and northwest India.
Higher wind speed and better ventilation index will be favourable for dispersion of pollutants on Monday, it said.
According to the Ministry of Earth Sciences' air quality monitor, SAFAR, the share of stubble burning in Delhi's pollution rose to 40 percent on Sunday, the maximum so far this season.
It was 32 percent on Saturday, 19 percent on Friday and 36 percent on Thursday, the second highest this season so far.
Last year, the stubble contribution to Delhi's pollution had peaked to 44 percent on November 1, according to SAFAR data.
NASA's satellite imagery showed a large, dense cluster of fire dots covering Punjab and parts of Haryana and Uttar Pradesh. According to the India Meteorological Department, the predominant wind direction was westerly-northwesterly and the maximum wind speed was 18 kilometers per hour on Monday. The city recorded a minimum temperature of 10.8 degrees Celsius, the lowest in the season so far.
Calm winds and low temperatures trap pollutants close to the ground, while favourable wind speed helps in their dispersion.
According to the central government's Air Quality Early Warning System for Delhi, the city's ventilation index – a product of mixing depth and average wind speed – was around 12,000 meter square per second on Monday – favourable for dispersion of pollutants.
Mixing depth is the vertical height in which pollutants are suspended in the air. It reduces on cold days with calm wind speed.
A ventilation index lower than 6,000 sqm/second, with the average wind speed less than 10 kmph, is unfavourable for dispersal of pollutants.


text:
Recommend Jeanne's obituary to your friends
Return to Thorne Funeral Home
Obituary of Jeanne Victoria Marie Bryan
Please share a memory of Jeanne to include in a keepsake book for family and friends.
(May 27th, 1934 to August 18th, 2020) Jeanne Bryan (nee Pearson) was born and raised on a farm north of Uxbridge where she fostered her appreciation and affiliation with animals of all varieties. While attending Uxbridge High School she excelled academically, athletically and musically. It was her love of music that would prove to be a lifelong passion. Following the completion of her formal education, Jeanne remained a dedicated and highly motivated member of Junior Farmers. It was this perseverance that would lead Jeanne to be chosen to represent Canada as a member of a Junior Farmer delegation that was sent to tour the United Kingdom in 1959. Upon her return, Jeanne married Paul Bryan and was instrumental in aiding him in growing his milk trucking business while also finding time to dedicate to the Sunderland United Church as its organist and choir leader for many decades. Jeanne always appreciated, and exhibited, a dry wit coupled with an impressive vocabulary and a perpetual thirst for knowledge. She is survived by her husband of 55 years Paul, her three "supercilious" children John, Scott and Elizabeth, and five grandchildren Colin, Jack, Claire, Owen and Henry. A Service to celebrate her life was held at the Thorne Funeral Home, 98 River Street in Sunderland (705-432-2672), on Tuesday, August 25th, 2020. Interment Sunderland Cemetery. Memories, photos and condolences may be shared at www.thornefuneralhome.ca
Final Resting Place
Sunderland Cemetery
Highway 12
Sunderland, Ontario, Canada
Need Directions?
Online Memory & Photo Sharing Event
Online Event
About this Event
In Loving Memory
Jeanne Bryan
1934 - 2020
Look inside to read what others have shared
Family and friends are coming together online to create a special keepsake. Every memory left on the online obituary will be automatically included in this book.


text:
Verticillium lecanii as a control agent of Bemisia tabaci on mist propagated Euphorbia pulcherima
AuthorMeade, Donna Lee, 1958-
Issue Date1991
AdvisorByrne, David N.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractThe fungus Verticillium lecanii was assessed for entomopathogenicity against nymphal Bemisia tabaci in an environmental chamber and in a greenhouse mist chamber on the host Euphorbia pulcherima. Proportional mortality of Bemisia nymphs due to fungal exposure were; in the environmental chamber 89-96%, and in the mist chamber 61-89%. Two fungal characteristics, hyphae growth and sporulation, were used as parameters for augmentation experiments. Response to particular honeydew constituents, glutamine, glutamic acid, serine and sucrose in concentrations ranging 500-40,000 ppm were measured. Hyphae growth, in comparison to water agar (1.26-1.52 mm/24 h), was inhibited by all substrates at all concentrations (0.82-1.47 mm/24 h). Sporulation was enhanced at higher concentrations, 17.0-117.0 (x10⁴) spores produced, in comparison with water agar, 10.2-15.5 (x10⁴) spores produced.
Thesis-Reproduction (electronic)


text:
Get images that make Supersized seem small. Tailor your auctions with Auctiva's. The item "Antique African Tribal Hand-carved Crown & Elephant Wooden Walking Stick 88cm" is in sale since Monday, August 6, 2018. This item is in the category "Antiques\Woodenware\Walking Sticks/Canes".
thefisherman" and is located in Pontyclun. This item can be shipped worldwide.


text:
Fast Mail Order 7 Days A Week 24 Hours A Day All Year Round
Unisex Clothing
Old website news New website news
Bunnywear website News
|Hello again ! I am happy to say that the white box pleated sports skirts in 8 inch and 14 inch lengths will be back in stock in about 2 weeks time plus a selection of new style skirts also I have just recently added the excellent 2 striped Gymphlex gym shorts in 2 fantastic bright colours over the coming weeks I will be adding more sizes to these shorts .
Bunnywear website News
|Back in stock .. Hi I am pleased to say the the Latex Mini Skirts are now back in stock in all 3 sizes small medium and large and now in a choice of 2 colours black and red . Plus I now have the Latex Corselettes back in stock in 3 sizes small medium and large .
Bunnywear website News
|Hello to you ! just a short note from me to let you know I have back in stock the white 8 inch and 14 inch sports skirts ... for all you people that have been wanting them .... plus the blue and black box pleated 12 inch mini skirts are also back in I do apologise for being out of stock of the plain mini skirts this is very rare ... but they are back in now !
Bunnywear website News
|Hi everybody I hope you are all enjoying yourselves I am pleased to say I have now back in stock the 10 inch Hamilton Red tartan mini skirt ... my apologize to all of you who were wanting one .... also I have the 22 inch box pleated bottle green school skirt back in stock plus a new length of 14 inches in the grey box pleated school skirt and yet another tartan has just arrived a Grey Granite Traditional Tartan skirt in 4 lengths 8 inch 10 inch 12 inch and 14 inch which will be available on the site in the next couple of days .
Bunnywear website News
|Well talk about rain ! hasn't it been just terrible and what with the postal strike I have been stuck this week and not been able to get on very well . Anyway another week is here so now for some good news I have just added an 8 inch Aqua summer mini skirt plus a 14 inch knife pleated Royal Stuart mini skirt to my site so many people wanted a shorter Aqua and a longer Royal Stuart well now you've got them . Also I now have back in stock the 8 inch St Edmunds so all is well .
Bunnywear website News
|Due to Trutex no longer manufacturing gym knickers and because I only have very limited stock left I have decided to concentrate on Gymphlex cotton gym knickers and I will continue to add new colours and for those who like the Trutex cotton knickers I am sure you will find the Gymphlex cotton just as comfortable and appealing .
Bunnywear website News
|Back in stock ... Hi everyone I am pleased to say that the Latex Pants in all 3 sizes are now back in stock and the full pleated 22 inch school skirts plus I have added some lovely new knickers and body stockings plus new skirts .... more items on the way soon
Bunnywear website News
|More items .... due to massive requests I am now pleased to say that I have shoes on my site in a full range of sizes plus more socks you love your socks so I approached a sock manufacturer and had made a supply of lovely baby pink ribbed over the knee socks and more stripy over the knee socks . A lot of people have asked for larger picture size so I am starting to replace existing pictures with much larger ones . On a last note I would like to say a big big thank you to the wonderful person who made my day by having sent to me a beautiful bunch of roses and chocolates ... what a surprise I had .
Bunnywear website News
|New Skirts ... fantastic news .... I have 2 fabulous wrap over tartan skirts coming very very soon to my site that will be just amazing for tartan lovers plus some new exciting very stylish wigs . I am always here with an open ear for anyone that needs me and ready to help all I can with your questions so don't be shy to ask because there is always an answer to a question and a solution to any problem .
Bunnywear website News
|More new goodies ... I have more fabulous new items on my site included 5 yes 5 fantastic new styled wigs a new cheeky school girl outfit and a sensational new suspender belt ... so there is something new there for everyone . Plus this coming week I will be adding an brand new wooli bunny skirt that will be sure to turn some heads .
Bunnywear website News
|More more more new exciting goodies coming to my site soon .... look out for the the Regulation White Cuff Leg Airtex school knickers they are a must have item and sure to please all of you who have been asking for them ... plus I will be adding very shortly a brand new tartan wrap over skirt and an existing tartan will be styled and made into a wrap over skirt . Recently I have been out of stock of a few items and I do apologise for this but I am now happy to say that these items are now coming back in .
Bunnywear website News
|A superb new tartan has just been added to my tartan collection and it is fabulous .... it is bright and bold and classy it is in 2 lengths 8 inch and 12 inch and I love it .... also I will shortly be adding some startling new clubbing hot pants in gorgeous gold and sizzling silver .... and a new pvc bra and pants set with cheeky slits
Bunnywear website News
|Items back in stock ... there have been a few items out of stock recently namely the Black Latex minis ... Shortie Knickers ... Zip Knickers ... Black Leotards of which I am adding NEW larger sizes and colours ... all these items are now back in stock . And I have coming in very soon a fantastic NEW Bunnywear tartan mini skirt which is just amazing .
|Items now back in stock are the Royal Stuart Gym Skirt size 40-14 and the 14 inch Black Knife Pleated Mini Skirt . And more welcome news is that the ever so popular Tartan Anderson Skirt is coming back in 14 inch Box Pleated .
Bunnywear Home of Just For You www.sisterfunbunny.com
|Tartan mini skirts More minis
|Wrap over mini skirts Stretch mini skirts
|Plain mini skirts Sports mini skirts
|snippet about me and this website
|Site news What's going on
|Email Need help just ask
|View basket shopping basket
|Your emails your emails
This is a crossdresser and tv friendly shop


text:
This hi-vis parka can handle the cold weather from any region of the Great White North. A perfect parka for those on a road crew or a construction site. The quick release hood can accommodate a hard hat.
Fabric: 100% polyester fleece3M™ Scotchlite™ Reflective Material with 4″ contrast backingFull front zipperQuick-release hoodRib-knit cuffs and waistLower pouch pocketsMachine washable FLUORESCENT CSA-Z96-15 COMPLIANT-CLASS 2 LEVEL...View full product details
300D Poly Oxford shell. Our best-selling hi-vis jacket with reflective tape is extremely versatile and functional. It's unequaled when it comes to quality and is...View full product details
300D waterproof/breathable Ripstop. A midweight jacket that addresses the need for transitional outerwear gives you warmth without being too heavy. This hi-vis jacket provides lots...View full product details
Premium cotton duck. Some people say this jacket is tough as hell. It's warm, sturdy and can handle anything you put it through. It has...View full product details


text: Categories Sports & Entertainment 10 Best Comic Creator Apps for Students and Professionals June 20, 2022June 20, 2022 6 mins read Comic books are a great way to tell a story. They can be used for entertainment, education, or marketing purposes. With the popularity of comic books and graphic novels at… Read more


text:
Cook your favorite dishes from the comfort of your dining room table with the Lux Japanese BBQ™! A revolutionary and simple grill that will allow you to enjoy interactive dinners with family and friends like never before!
**Not available in stores
✔ Barbeque On The Go: Enjoy cooking your favorite veggies, meats, fish, and more wherever you like!
✔ Grill Fresh - Eat Healthy:Eliminate those radiation-filled microwaves for good and cool naturally anywhere, anytime!
✔ Easy To Use:Simply place an alcohol stove below and enjoy your healthy, environmentally friendly meal.
✔ Interactive Dining: cook amazing meals together with family and friends while at home, camping, tailgating, etc.
✔ Easy to Clean: The detachable non-stick structure makes it easy for you to deep clean after every use.
✔ Picnics
✔ Alcohol Stove Recommended and Not Included
Package Includes:
1x Lux Japanese BBQ™
Delivery Time:
US, Canada, Europe, Australia: 7-15 days
Other countries: 10-20 days
Handling time: Ships within 1 to 3 business days


text:
National Geography Awareness Week is November 13-19 and was created by National Geographic to raise awareness about how we all rely on geographical information on a daily basis, and to get the public excited about all things geography!
The week-long event known as GeoWeek was also created to highlight the lack of geography education in the American education system. Many students do not understand basics about geography, cannot name places around the globe, and do not recognize their roles as global citizens. National Geographic views this as a "dangerous deficiency in American education."
GeoWeek was established by a presidential proclamation over 25 years ago, and is organized annually by NatGeo's Education Programs (NGEP), and supported by institutions and corporations worldwide. Over 100,000 students, families and community members participated in 2015. The initiative reminds all citizens about the "significance of place" and the relationships between environment and the people that live there.
As an educator, you can use lessons, games and classroom challenges to focus on geography or your school can host an event. This is a great week to schedule meetings with lawmakers and business leaders to understand their perspectives on geography. If you're lucky enough to live near a city, state or national park, use this week to take students on a field trip to learn spatial thinking through maps, a great and useful skill that will help students develop simultaneously with their curricula in geography, Earth sciences and environmental sciences.
The perceived decreased in the importance of teaching social sciences that has occurred over the last decade means that geography is no longer widely taught in American schools, and if it is taught, there is too much importance placed on teaching dates and events. The United States is in last place worldwide regarding quality and quantity in every facet of geography education.
By sponsoring GeoWeek, National Geographic hopes to raise awareness about this educational morass in hopes of turning the trend around. The material emphasizes human-environment systems and geographic reasoning. They use the week to promote much-needed educational policies on geographic literacy, better state standards, and federal funding for teacher training.


text:
Credit Department has been opened in the Public Bank!
Published on 04-13-2015 by THE REIGN OF THE HEAVENS SOCIETY POST
International Public Notice
The assembly for the Government of The United States of America (assembly) opened a Credit Department in the Public Bank governed by the Committee of the Government of The United States of America. The Credit Department was opened last week headed by American National-Paul Pieczynski that has 20 years experience in the field.
The Credit Department will be issuing credit in the form of Continental Dollars. The assembly is aware that the Continental Dollar is not widely accepted at the moment. Hopefully, with the recent videos released, it is possible it will wake some people up that will have the capability of assisting the Government with those issues.
However, if many started opening accounts at https://www.continentaldollar.co the acceptance issues would be resolved right away.
Many markets and products that have been shunned are welcome at the Public Bank. This does not include terrorist or child pornography activity of course. The Committee is talking about alternative energy, clean water devices, alternative energy for automobiles etc….
The counties and states are welcome to open a letter of credit account without fear of losing territory or creating a split title situation that places those body politics in a slave-master relationship aka Trustee relationship with a foreign entity.
The credit accounts are without interest, tax free and can revolve continually in circulars to maintain a condition of stability. It also resolves the constant taxation issues through the local police departments in the form of traffic tickets.
The Continental Dollar site linked above does have a core bank account where the currency does not go outside of the main core credit account so nothing is lost. All that is needed are gateways and people that have a little ambition to change their current condition to something positive.
The following videos prove that the assembly is real, the Government is real, and the Continental Dollar is real. The next move is up to you. The core bank account has been filled with 10 billion Continental Dollars to start. The total amount available will not be disclosed at this time. However, the country can be sustained indefinitely with the Public Bank system in its design and applications. The request forms for letters of credit accounts will be available as soon as possible. Welcome to a Brand New Market!
Link to the Official Assembly Record: Official Assembly Record
Links to videos:
The Failed Mandate: A 240 Year Old Lie
OZ on Manhattan Island, Part One
No Longer in OZ, Manhattan Island, Part Two


text:
Work With Me
Healing is deciding YOU deserve better and once you have that awareness, you can no longer run from it.
I've helped 100's of Soul clients decide that they are worthy and if your heart and soul have led you here… It must be our time to work together.
My gift is being able to see the underlying patterns, core belief systems, lineage patterns, wounds, traumas, discordance, and imbalance that hinder your highest potential. I help you transform fear and self-doubt by setting a new foundation for all of your life that is rooted in radical truth and peace.
But you have to be ready and not tip toe around the hard stuff.
If you're really ready to evolve with clear boundaries, clarity and an open heart willing to receive.
Let me guide you and support you with ways that you can rewrite your story by re-framing your focus. I will help reflect your own power back to you.
Because you are so strong in your capabilities, your awareness and belief in yourself need to catch up!
Anyone who has known me for 5 minutes knows that I go deep straight away, full-length mirrors and all – leaving no stone unturned.
None of my offerings are for the faint-hearted…. Are you ready?
Uncaged – Sacred Life Accelerator
You Must Have
- Beginners Mindset
- Open Heart
- Willingness to be Heard, Seen & Held
You will get my unconditional support and guidance throughout your journey. This is your Radical awakening, remembrance and embodiment. This is not for the faint-hearted.
- You & Me Deep Diving
- 2 Private Sessions per Month
- Weekly Check-Ins
- Resources & Exercises
- Spirit Bonsuses
A Private Mentorship that follows no curriculum; join me on a sacred journey of deep discovery.
(minimum of three months with six and nine-month options available)
Some of what we uncover will be inner alchemy, remembering the truth of who you are and enriching your energetic relationship with the many avenues of your life, identifying the rooted fear to allow for liberation.
Mentorship is a dance between you and me that covers all ranges of business, mothering, relationships, history, the mystical and all of your glorious complexities.
Designed specifically for those that are ready to honour their limitations, this intimate container is luxe, bespoke, private, immersive, and expansive by nature.
This is a space to experience the healing that you didn't know you needed, this is where you'll give yourself permission to be held, heard and seen.
As I only take on a few clients at any given time, entry into this Private Mentorship will be considered on a case-by-case basis.
A lot will happen on this journey so I want to ensure you're anchored well into the truth of who that is, moving forward.
We go free-range, roaming around the inner dimensions of your being to alchemize the gold living in there and shaping it into tangible and clear expression to deepen your relationship with yourself and the world around you.
Sacred Sensuality
Train in the mysteries of sensuality and the evocative power of the sacred courtesan. Have fun, and connection, in an uplifting community where we explore edgy topics safely and openly.
Discover the inherent magic that resides in living life where pleasure is considered very sacred and activate untapped beauty within, through simple, yet effective practices.
The Hidden Secrets Of Pleasure: 5-week Immersive Challenge.
In this journey together, Lisa invites and supports women to explore more fully their own cultivation of pleasure for the purpose of vitality, joy, wellbeing, and magnetic influence.
Understand how embodied magnetism actually works and watch the conscience of beauty in action, transform the shadow of seduction into a sacred offering of inspiration that ignites change and creativity.
This challenge will guide you to embrace the power of connection, alchemizing competitive and comparison behaviours into ones that connect, uplift and celebrate others. This is an opportunity to experience the power of opening your heart and self-generating bliss and pleasure, and discover how pleasure is a sacred offering.
By the end of the five weeks, you will have been so fully immersed in pleasure, your wisdom so expanded, that you will be a magnet to all you desire.
This immersion is for you if you are ready to; Exude Confidence, Sensuality, Beauty, and a Mastery of Feminine Magnetism.
Pillars of Content
- Understanding Our True Desires & Transforming Hijacked Desires
- Beauty Of Our Gift
- Embodiment Of Integrated Pleasure
- Sexual Sovereignty
- Reclamation Of Our Power
- Transforming Our Over-Mothering/People Pleaser
Inclusions & Elements;
- 5 x Weekly Calls
- Pleasure Flows
- Sensual Meditations
- Sound Bath
- Private Playlist
Soul Shaker
Soul Shaker Pillars
- Self Realization
- Generational Linerage
- Boundaries
- Receiving
We will explore the challenges, blocks and limitations holding you back from accessing your own inner wisdom. While exploring all areas of your life to help move stuck and stagnant energies back into flow and abundance.
- 6 x Private 1:1 Session
- Monthly Group Coaching Calls
- Private Group Space
- Resources & Exercises
- Bonuses
Would you like to delve into your inner spirit and shake up your soul with me for six months?
Are you ready to shine? Are you ready to be seen? Are you ready to receive? Are you ready to invest in yourself… energetically and financially?
Are you ready to be heard? Are you ready to set boundaries where you give yourself permission to rise?
I will be your guide as we navigate your soul and you uncover your core truths. I will be reminding you of your why, and most importantly, your purpose. We will uncover and transform fears that are holding you back while honouring your gifts and connecting to guidance that is within you.
Although you'll receive weekly modules to help you, I will customize our sessions together so that you experience what you will need to emerge from your comfortable, yet chaotic, cocoon.
Comfort and Sacredness will be at the centre as you dig through insecurities replacing them with ease and compassion. We will be uncovering your strengths and weaknesses, healing, restoring and aligning you with your core strengths.
You are worthy. You are whole. You are love.
Whatever you want to achieve in your life, love, wellness, business, confidence, soul purpose, or all of the above, I'm here to be your wing-woman. Together we'll develop a customized plan to determine where you want to go and get you there gracefully, and I'll be by your side every step of the way.
Private Session
Share with me what's present in your current reality, and let me show you what energy patterns are hindering your highest potential and holding you back.
I can give YOU ways to help rewrite your reality by re-framing your focus and sharing with you self-empowerment tools and greater understanding as to why you are the way you are or why your life has been the way it's been for you thus far.
Join a community of Souls leading themselves with love and purpose. This is a safe place where you uncage yourself and create change through self-awareness and service.
Join us for monthly ceremonies, rituals, masterclasses and more. Everyone in this community is here to reclaim their sovereignty. They are here to heal, remember, and create a life that feels sacredly grounded and aligned.
Fire Starter Business Session
Does your passion project need some fire? If you're looking for a single zap or some serious inferno-style heat, this one-off business session is for you.
For the business souls who are feeling lost and desiring a creative brainstorming, clarity, and soul-shaking session where we will celebrate the shit of your business. This session will help you draw out more of YOUR essence.
Lovely Words


text:
LOS ANGELES -- Josh Beckett has made a remarkable recovery thus far in 2014, and is making a push for an All-Star Game berth. But the long road back has been full of bumps and bruises, leaving the Dodgers concerned about the 34-year-old right-hander.
The Dodgers over the weekend had Triple-A Albuquerque skip the scheduled start on Sunday of Red Patterson, just in case the team needed him to replace Beckett, who is scheduled to start for the Dodgers against the Indians on Tuesday.
Despite the initial concern, the Dodgers expect Beckett to make his start on Tuesday.
"Josh is always a guy that, in between starts, we worry about," manager Don Mattingly said before Monday's game at Dodger Stadium. "He battles every time to get ready for the next one. We just wanted to be sure we were lined up."
Beckett has been a revelation this season, at 5-4 with a 2.11 ERA that currently ranks third in the National League. He has 88 strikeouts against 28 walks in 93⅔ innings, threw a no-hitter on May 25, and has an active string of 14 consecutive scoreless innings.
In eight of his 15 starts this season, Beckett has allowed zero or one run.
Not bad for a pitcher who had surgery in 2013 to relieve nerve pressure caused by Thoracic Outlet Syndrome. The procedure involved removing one of Beckett's ribs. But the 14-year veteran isn't suffering any ill effects from the surgery nor is he having any arm problems.
Mattingly chalked it up to Beckett's odometer having over 2,000 innings (he's at 2,029 career innings and counting).
"There are times he doesn't throw his bullpen," Mattingly said. "He's got hip stuff that he deals with. It's just been general stuff, nothing in particular. Nothing about surgery or his arm. Just general soreness."


text:
During the pandemic, the Northwest Tri-County Intermediate Unit and the Children's Charity Variety teamed up to provide life changing equipment to kids with disabilities.
Here is more on the adaptive bikes and strollers that were donated and how they are changing lives.
Over 400 pieces of equipment have been donated to kids with disabilities across Erie, Crawford and Warren Counties.
In a year that has been difficult for everyone, it's nice to see smiles in the faces of children.
The mother of one child said that her son Giovanni Coletta out grew his first adaptive bike, so they've returned to Northwest Tri-County Intermediate Unit for a brand new bike.
"It's helped facilitate his speech. It's helped him meet all of our neighbors, greet and be social and just have you know something to enjoy day in and day out," said Haley Coletta, Mother of Giovanni Coletta.
The executive director of Northwest Tri County Intermediate Unit 5 said that children with disabilities can sometimes feel limited.
"Game changer in many cases. These families often see other children outside riding bikes or going for walks and they often wonder how can I do this with my children," said Brad Whitman, Executive Director of Northwest Tri County Intermediate Unit 5.
Haley Coletta said that her son's adaptive bike makes her son Giovanni feel included.
"He also has a brother who he can ride side by side with and get exercise from it," said Coletta.
These pieces of equipment are one of the many ways variety helps to improve children's lives.
The CEO of Variety the Children's Charity Show, shows another piece of equipment, a communication device that helps give kids a voice who have a communication disorder or are non-verbal.
The CEO said that one child made strides using this device.
"But then over this 18 month period he went from two words to communication devices to his own voice. How do you convey what it's like when you hear your child talk for the first time and communicate, I think that's probably beyond words," said Charlie LaVallee, CEO of Variety the Children's Charity.
Families can apply for these devices if their child is eligible. To apply click here.


text:
Agriculture Minister Narendra Singh Tomar has been given the additional charge of Food Processing Industries Ministry. He has been given the additional charge as President Ram Nath Kovind has accepted the resignation of Smt. Harsimrat Kaur Badal from the Union Council of Ministers, with immediate effect, under clause (2) of Article 75 of the Constitution.
Boost your Banking Awareness Knowledge with Adda247 Live Batch: TARGET GA BATCH | Banking Awareness Batch for SBI, RRB, RBI and IBPS Exams