Aspergillosis remains a major health threat despite decades of studies and the availability of a range of anti-fungal treatments (Bandres et al., 2021). The mortality rate among immunocompromised patients, such as stem organ transplant recipients, patients with inherited immunodeficiency or acquired immune deficiency syndrome, can exceed 50% (Beer et al., 2018). Aspergillus fumigatus is the most common cause of aspergillosis and can be found in soil, air, and carbon-rich substrates. People usually inhale hundreds of conidia of A. fumigatus each day, but only in immunocompromised patients can it cause diseases, indicating that the immune system could recognize inhaled mold and avoid germination.

(p2) Multiple cytokines/chemokines play important roles in the recruitment and activation of neutrophils.
The key protein that regulates neutrophil development, proliferation, differentiation, survival, and function is the granulocyte colony-stimulating factor (G-CSF), which is encoded by colony-stimulating factor (CSF) 3 gene (Panopoulos and Watowich, 2008). ...

(p4) Stromal cells are the first line of defense against invading pathogens in the mucosal tissue.
A. fumigatus infection-related lung diseases are usually caused by the colonization of inhaled conidia of A. fumigatus in the lower airways and germinate into hyphae which became invasive. ...

(p7) NETs released by neutrophils mainly contains DNA, histone proteins, fiber, etc., we analyzed the extracellular DNA via staining of propidium iodide (PI). As shown in Supplementary Figure 3, there were more extracellular DNAs in the CSF3 overexpression group and fewer extracellular DNAs in the CSF3 knockout group. In addition, the neutrophils seemed to be less clustered in co-culture with CSF3-/- HUVECs than WT HUVECs (Figure 6D). These results indicate that CSF3 is one of the crucial cytokines in regulating neutrophil function during anti-fungal immune responses. ...

Neutrophils are the first leukocyte type to arrive upon infection, and their proliferation, migration, and functions are tightly regulated by G-CSF (Martin et al., 2021). Neutrophils might be the most important immune cells in terms of the control of A. fumigatus infections in healthy subjects (Lehman and Segal, 2020). A healthy immune system has many negative regulatory mechanisms to constrain the activation and life-span of neutrophils (Azcutia et al., 2017; Silvestre-Roig et al., 2019). This is because the ROS, NETs, and other substance neutrophils released to eradicate pathogens could also cause damage to self-tissue (Mantovani et al., 2011; Papayannopoulos, 2018). In immunocompromised patients, the immune system also loses some of its abilities to self-regulate, and the dysfunctional immune responses and prolonged infections combined together may be the reason why they are actually more prone to autoimmune related diseases (Arason et al., 2010; Roe, 2021). ...

Neutrophils account for approximately 60% of nucleated cells in the bloodstream, and they play a pivotal role in immune responses against invading pathogens, such as bacteria and fungi. Patients with neutrophil disorders always suffer from recurrent or severe bacterial or fungal infections (Martin et al., 2021). One common example is pulmonary aspergillosis, which can only be seen in patients with immune system dysfunctions, such as patients with neutropenia and hematopoietic stem cell transplantation (HSCT) recipients. Neutrophils use several tools to combat invading fungi, such as phagocytosis via the activation of Fc?R, CR3, or PRRs; the release of reactive oxidants and non-oxidants, and generation of NETs with web-like structures (Lehman and Segal, 2020).

However, over-activated neutrophils can cause some non-specific damage to self-tissues, as observed in gout (Vedder et al., 2020), asthma (Ray and Kolls, 2017), pustular psoriasis (Marzano et al., 2019), and rheumatoid arthritis (Thieblemont et al., 2016); neutrophils also could mediate hyper-inflammation accompanied by infections, including SARS-CoV-2 (Cavalcante-Silva et al., 2021). Thus, the activation of neutrophils must be well calibrated and terminated quickly once the pathogens have been eradicated (Lehman and Segal, 2020). In the present study, our results showed that the conidia from A. fumigatus could stimulate stromal cells to secrete cytokines to activate neutrophils, leading to tissue damage after long-term exposure to fungi.

Article: Treatment and prevention of invasive aspergillosis. INDEX
https://www.uptodate.com/contents/treatment-and-prevention-of-invasive-aspergillosis
Author: Thomas F Patterson, MD, FACP, FIDSA
Section Editor: Carol A Kauffman, MD
Deputy Editor: Keri K Hall, MD, MS
This topic last updated: May 11, 2023.
(To continue reading this article, you must sign in with your personal, hospital, or group practice subscription.)

Invasive aspergillosis is the most common mold infection in immunocompromised hosts.
This infection is caused by Aspergillus, a hyaline mold that is ubiquitous. Exposure to Aspergillus conidia is frequent, ... The most common risk factors for infection include neutropenia and glucocorticoid use, but other risk factors include hematopoietic cell transplantation, solid organ transplantation (particularly lung transplantation), the use of biologic agents, pulmonary diseases, and critical illness.

The most common infecting species is Aspergillus fumigatus complex, but other species complexes that are common causes of disease include A. flavus, A. terreus, and A. niger. Less common species, such as A. nidulans, A. calidoustus, A. lentulus, and many others, have been reported to cause infection in highly immunosuppressed patients. Many of these unusual or "cryptic" species, which are often difficult to identify, are clinically important due to varying susceptibility to antifungal agents. The effective management of invasive aspergillosis includes strategies to optimize prevention, prompt diagnosis, early antifungal treatment, and, in some cases, immunomodulation and surgery. An increasing number of cases of invasive aspergillosis have also been reported as complications of coronavirus disease 2019 infection. ...

The most common clinical manifestation of invasive aspergillosis is pulmonary disease, but other manifestations include central nervous system infection, rhinosinusitis, endocarditis, gastrointestinal disease, and others. ...

Expert guidelines — Optimal management involves early and definitive diagnosis as well as early initiation of antifungal therapy. In addition to antifungal therapy, surgery should be considered for patients with certain manifestations. Reduction of immunosuppression, when feasible, is another important component of management. ...

Article: Novel Antifungal Agents and Their Activity against Aspergillus Species. INDEX
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711508/pdf/jof-06-00213.pdf
Roya Vahedi-Shahandashti and Cornelia Lass-Flörl
Institute of Hygiene and Medical Microbiology,
Medical University Innsbruck, 6020 Innsbruck, Austria;
Roya.Vahedi@i-med.ac.at
* Correspondence: cornelia.lass-floerl@i-med.ac.at Received: 8 September 2020;
Published: 9 October 2020
157 References --- pdf --- 21p

Abstract: There is a need for new antifungal agents, mainly due to increased incidence of invasive fungal infections (IFI), high frequency of associated morbidity and mortality and limitations of the current antifungal agents (e.g., toxicity, drug–drug interactions, and resistance). The clinically available antifungals for IFI are restricted to four main classes: polyenes, flucytosine, triazoles, and echinocandins. Several antifungals are hampered by multiple resistance mechanisms being present in fungi. Consequently, novel antifungal agents with new targets and modified chemical structures are required to combat fungal infections. ...

1. Introduction
Invasive fungal infections (IFI) are responsible for over one million deaths annually,...
This is mainly due to the increasing number of immunocompromised individuals with altered immune function including primary immune deficiency, cancer chemotherapy, HIV/AIDS, hematologic and solid organ transplantation, prematurity, and immune-modulatory medications. The number of at-risk patients and improved diagnostic techniques resulted in an alarming rise in the number of reported fungal infections. Invasive aspergillosis, an infection caused by fungi of the Aspergillus taxon, remains a significant threat, particularly in immunosuppressed patients. The most prevalent Aspergillus species are A. fumigatus, A. flavus, A. terreus, and A. niger. Aspergillus spp. have the capacity to cause a broad range of clinical diseases, from mild and superficial infections, to life-threatening and invasive illnesses with more than 80% mortality rate. Pulmonary aspergillosis is considered the most prevalent manifestation of invasive aspergillosis.

Antifungal drug discovery has been stagnant in the past. Hence, therapeutic possibilities for IFI are limited.
... These (current pharmaceuticals) antifungals have several limitations such as toxicity, drug–drug interactions, variable pharmacokinetics, and reduced bioavailability. The emergence of drug resistance has introduced further limitations. ... The rate of azole-resistant Aspergillus isolates has increased noticeably, contributing to therapeutic failures. The prevalence of azole-resistant clinical isolates of Aspergillus spp. has reached 30% in some regions in Europe ....

Figure 1. Target sites and potential pathways of the novel antifungals.
This diagram of a fungal cell indicates various molecules that can be tackled by antifungal agents (blue boxes), including cell wall, cell membrane, and also intracellular targets such as mitochondria and processes like metabolisms and stress responses.

(Drugs in pre-release trials)
2.1. CD101 (Cidara Therapeutics) (Biafungin) (Rezafungin), ...
2.2. SCY-078 (Formerly MK-3118) .. (Scynexis), a class of semisynthetic derivative of the natural product enfumafungin, ...
2.3. Amphotericin B (AMB) Renovated Structure .. AMB-deoxycholate has a potent wide-spectrum fungicidal activity ...

3. New Antifungal Compounds with Novel Targets in Aspergillus
3.1. T2307 .. or 4-{3-[1-(3-{4-[amino(imino)methyl] phenoxy} propyl) piperidin-4-yl] propoxy} benzamidine .. aromatic diamidines ..
3.2. Fosmanogepix (APX001) ... (formerly E1210, 2-amino-3-(3-{4-[(pyridine-2-yloxy) methylbenzyl}-1-2-isoxazol-5-yl) pyridinium-1-yl] methyl hydrogen phosphate) is a small cell wall-active antifungal ... active against a broad range of pathogenic yeast and molds, including Aspergillus spp., Fusarium spp., and black molds
3.3. ASP2397 (VL-2397) .. is a cyclic hexapeptide natural antifungal compound, cyclo{Asn-Leu-dPhe-[(N5-acetyl-N5-hydroxyOrn)3]- ..
3.4. F901318 (F2G) or Olorofim .. a representative member of .. the orotomides, ... exhibits exceptional potency against a broad range of dimorphic and filamentous fungi, particularly Aspergillus spp. ... F901318 demonstrates efficacy against Aspergillus spp., regardless of species and methods used, which is of significant importance given the increased prevalence of azole-resistant Aspergillus spp. ...

3.5. VT-1598 .. a selective fungal cytochrome P51 (CYP51) enzyme inhibiton ... An in vivo 12-day survival study in a disseminated mouse model of invasive aspergillosis showed 100% survival.

4. Potential Pathways as Targets against Aspergillus.
4.1. Calcium–Calcineurin Signaling Network ... crucial role in the survival and adaptation of fungi.
4.1.1. Tacrolimus (FK506) .. or Fujimycin), a macrolide lactone ... suppresses the phosphatase activity of the calmodulin–CnA–CnB complex, resulting in the inhibition of the transcription factor calcineurin-responsive zinc finger 1 (Crz1) ... may decrease the risk of serious Aspergillus infections ...
4.1.2. Cyclosporin A .. a family of lipophilic cyclic undecapeptides metabolites, ... is a calcineurin inhibitor ....
4.1.3. Geldanamycin .. is a member of the ansamycin antibiotic family with anti-tumor activity .... 4.1.4. Trichostatin A .. Hindering HDACs in pathogenic fungi .. synergistic activity between trichostatin A and caspofungin ...
4.1.5. MGCD290 ... is a.. selective HDAC inhibitor, ... a high MIC (8 to >32 µg/mL) against molds, including Aspergillus spp.

4.2. Ras and Sphingolipid Synthesis Pathways ...
... a lack of Ras signaling pathways in A. fumigatus ... results in decreased fungal growth, decreased cell wall integrity, and loss of virulence.
4.3. Trehalose Synthesis Pathway .. a non-reducing disaccharide, ..one of the pathways that exist in fungi, including C. albicans, C. neoformans, and A. fumigatus but not in humans, ... target for novel antifungal agents.

5. Natural Products as Anti-Aspergillus Agents.
... Rosemary essential oil (REO) ... in vitro activity against A. flavous, with an MIC and minimum fungicidal concentrations (MFC) ...
... Humidimycin, a bacterial ring peptide, ... antifungal activity of 82 essential oils against A. niger, C. albicans, and C. neoformans has been ... A. niger showed weak susceptibility, and 45% of essentialoils displayed activity against C. neoformans isolates.

Recently, an expanding insight into the fungal cellular structures and related processes has contributed to the development of promising antifungal drugs. ...

A Few of the References ...

• Brown, G.; Denning, D.; Gow, N.; Levitz, S.; Netea, M.; White, T.
  Hidden Killers: Human Fungal Infections.
  Sci. Transl. Med. 2012, 4, 165rv13. [CrossRef] [PubMed]

• Fisher, M.; Hawkins, N.; Sanglard, D.; Gurr, S.
  Worldwide emergence of resistance to antifungal drugs challenges human health and food security.
  Science 2018, 360, 739–742. [CrossRef] [PubMed]
  
  
• Lamoth, F.; Juvvadi, P.; Steinbach, W.
  Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.
  Front. Microbiol. 2015, 6, 96. [CrossRef]
  Histone deacetylases (HDACs) are enzymes responsible ... control ... the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance.

• Powers, C.; Satyal, P.; Mayo, J.; McFeeters, H.; McFeeters, R.
  Bigger data approach to analysis of essential oils and their antifungal activity against
  Aspergillus niger, Candida albicans, and Cryptococcus neoformans.
  Molecules 2019, 24, 2868. [CrossRef] [PubMed] {DOI}
  Overall, while essential oils remain a staple source for antimicrobial inhibitors, improving processes that efficiently identify lead candidates is of great benefit, expediting the next generation of drug discovery.

Product: Drugs, Antifungals for Aspergillus. INDEX
https://aspergillosis.org/antifungal-drugs/
Author: Elegant Themes
Author URL: http://www.elegantthemes.com

Antifungals:
Antifungal Availability:
Unfortunately not all antifungal drugs are available in every country around the world and, even if they are, the price can vary massively from country to country. Global Action Fund for Fungal Infections (GAFFI) has produced a set of maps showing the availability of the key antifungal drugs across the world.

Click here to view the GAFFI antifungal availability map
https://antifungalsavailability.org/

(PIL – Patient Information Leaflet) (BNF – British National Formulary)
The NICE British National Formulary (BNF) site is only available to users in the UK (England, Scotland, Wales and Northern Ireland).
• Amphotericin B, Neon Healthcare Ltd
  (Abelcet, Ambiosome, Fungizone)
  (BNF)
  https://bnf.nice.org.uk/drugs/amphotericin-b/#interactions
  emc: Blood and Lymphatic System, AND, Immune System , AND, Metabolism and Nutrition, AND, Nervous System Disorders.
  
  

• Anidulafungin, Pfizer Limited
  (ECALTA)
  (PIL)
  https://www.medicines.org.uk/emc/search?q=Anidulafungin&filters=...
  emc: rash, pruritus, dyspnoea, bronchospasm, hypotension (common events), flushing, hot flush, and urticaria (uncommon events)
  
  

• Caspofungin, Zentiva
  (CANCIDAS)
  (PIL)
  https://www.medicines.org.uk/emc/search?q=caspofungin&filters=...
  emc: https://www.medicines.org.uk/emc/product/2722/smpc
  Phlebitis was a commonly reported local injection-site adverse reaction in all patient populations.
  Other local reactions included erythema, pain/tenderness, itching, discharge, and a burning sensation.
  Hypersensitivity reactions (anaphylaxis and possibly histamine-mediated adverse reactions)
  Also reported in patients with invasive aspergillosis were pulmonary oedema, adult respiratory distress syndrome (ARDS), and radiographic infiltrates.
  
  

• Fluconazole, Pfizer Limited
  (Diflucan) (Canesten Thrush)
  (PIL)
  https://www.medicines.org.uk/emc/search?q=Fluconazole&filters=...
  emc: https://www.medicines.org.uk/emc/product/1065/smpc
  Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported
  in association with fluconazole treatment (see section 4.4).
  The most frequently ... reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting,
  alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased and rash.
  
  

• Flucytosine
  (Ancotil)
  (BNF)
  https://bnf.nice.org.uk/drugs/flucytosine/
  
  

• Micafungin
  (Mycamine)
  (PIL)
  https://www.medicines.org.uk/emc/search?q=micafungin&filters=...
  
  

• Itraconazole
  (Sporanox)
  (PIL) https://www.medicines.org.uk/emc/search?q=%22Itraconazole%22&filters=...
  (BNF)
  https://bnf.nice.org.uk/drugs/itraconazole/
  
  

• Posaconazole
  (>Noxafil)
  (PIL)
  https://www.medicines.org.uk/emc/search?q=%22posaconazole%22&offset=...
  
  

• Isavuconazole
  (BNF)
  https://bnf.nice.org.uk/drugs/isavuconazole/
  
  

• Voriconazole
  (VFEND)
  (PIL)
  https://www.medicines.org.uk/emc/search?q=voriconazole&filters=...

Polyenes
Amphotericin B is often used intravenously to treat systemic fungal infections.
It works by binding to a fungal cell wall component called ergosterol. Amphotericin B is probably the most broad spectrum intravenous antifungal available. It has activity against Aspergillus, Blastomyces, Candida (all species except some isolates of Candida krusei and Candida lusitania), Coccidioides, Cryptococcus, Histoplasma, Paracoccidiodes and most of the agents of zygomycosis (Mucorales), Fusarium and other rarer fungi.

It is not adequately active against Scedosporium apiospermum, Aspergillus terreus, Trichosporon spp., most of the species causing mycetoma and systemic infections due to Sporothrix schenkii. Acquired resistance to amphotericin B has been described in occasional isolates, usually after long term therapy in the context of endocarditis, but is rare.
Amphotericin B can cause many side effects which in some cases can be very severe.

Echinocandins
Echinocandins are often used to treat systemic fungal infections in immune deficient patients – these drugs inhibit the synthesis of glucan which is a specific component of the fungal cell wall. They include micafungin, caspofungin and anidulafungin.
Echinocandins are best administered by intravenous means because of poor absorption.

Caspofungin is very active against all Aspergillus species.
It does not kill Aspergillus completely in the test tube.
There is a very limited amount of activity against Coccidioides immitis, Blastomyces dermatitidis, Scedosporium species, Paecilomyces varioti and Histoplasma capsulata but it is likely that the activity is not sufficient for clinical use.

Triazoles
Itraconazole, fluconazole, voriconazole and posaconazole – the mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal cytochrome P450 oxidase-mediated synthesis of ergosterol.

Fluconazole is active against most Candida species, with the absolute exception of Candida krusei and partial exception of Candida glabrata, and a small number of isolates of Candida albicans, Candida tropicalis, Candida parapsilosis and other rare species. It is also active against the vast majority of Cryptococcus neoformans isolates. It is active against many other yeasts including Trichosporon beigelii, Rhodotorula rubra, and the dimorphic endemic fungi including Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatumand Paracoccidioides brasiliensis. It is less active than itraconazole against these dimorphic fungi. It is not active against Aspergillus or Mucorales. It is active against skin fungi such as Trichophyton. ...

Itraconazole is one of the most broad spectrum antifungals available and includes activity against Aspergillus, Blastomyces Candida (all species including many fluconazole resistant isolates) Coccidioides, Cryptoccocus, Histoplasma, Paracoccidioides, Scedosporium apiospermum and Sporothrix schenkii. It is also active against all skin fungi. It is not active against Mucorales or Fusarium and a few other rare fungi. It is the best agent against black moulds, including Bipolaris, Exserohilum etc. Resistance to itraconazole is described in Candida, although less often than with fluconazole and also in Aspergillus.

Voriconazole has an extremely broad spectum.
It is active against the vast majority of Candida species, Cryptococcus neoformans, all Aspergillus species, Scedosporium agiospermum, some isolates of Fusarium and a multitude of rather rare pathogens. It is not active against Mucorales species such as Mucor spp, Rhizopus spp, Rhizomucor spp, Absidia spp and others. Voriconazole has become invaluable in the treatment of invasive aspergillosis.

Posaconazole has an extremely wide spectrum of action.
The fungi whose growth are inhibited by posaconazole include Aspergillus, Candida, Coccidioides, Histoplasma, Paracoccidioides, Blastomyces, Cryptococcus, Sporothrix, various species of Mucorales (causing Zygomyetes) and numerous other black moulds such as Bipolaris and Exserohilum. The majority of Aspergillus isolates are killed by posaconazole at clinically relevant concentrations. Acquired resistance to posaconazole does occur in Aspergillus fumigatus and Candida albicans but is otherwise rare.

The side effects of azole drugs are well characterized and there are also some important drug-drug interactions which exclude the use of prescribing certain drugs at the same time.

Absorption
Some of the antifungal drugs (e.g. itraconazole) are taken orally and can be difficult to absorb, particularly if you are on antacid medication (medicine used to treat indigestion, stomach ulcers or heartburn). This is because some acid in the stomach is needed to dissolve the capsules and allow absorption.

In the case of itraconazole the standard advice is to ensure that there is plenty of acid in the stomach by taking a fizzy drink such as cola with the medication (the carbon dioxide that causes the fizz also makes the drink quite acidic). Some people dislike fizzy drinks so substitute a fruit juice e.g.. orange juice.

Itraconazole capsules are taken after a meal and 2 hours before taking antacids.
Itraconazole solution is taken one hour before a meal as it is more easily absorbed.

Product: 10 Best Antifungal Herbs. INDEX
https://botanicalinstitute.org/antifungal-herbs/
Written by: Siobhan Mendicino
Medical Review by: Daniel Powers, MS
Published on: September 13, 2022

1. Garlic
2. Turmeric
3. Cinnamon
4. Ginger
5. Olive Leaf
6. Echinacea
7. Black Walnut
8. Goldenseal
9. Yellow Dock
10. Osha Root

Product: Herbal Teas, London Drugs. INDEX
(Making a combo tea of 3 or more of the following, 1 to 3 bags of each, with 5 cups of water / each day)

L2725273 --- Stash -- Pomegranate Raspberry Green Tea w/ Matcha - 18s
https://www.londondrugs.com/stash-pomegranate-raspberry-green-tea-with-matcha---18s/L2725273.html
Ingredients: Green Tea

• Green tea
• Hibiscus
• Orange peel
• Chamomile
• natural Pomegranate flavor
• natural Raspberry flavor
• Matcha

L6321608 --- Stash Tea - Cinnamon Apple Chamomile - 20s
https://www.londondrugs.com/stash-tea---cinnamon-apple-chamomile---20s/L6321608.html
Ingredients:

• Cinnamon
• Hibiscus
• Chamomile
• natural apple flavor

L7754088 --- Stash Tea - Spice Dragon Red Chai - 18s
https://www.londondrugs.com/stash-tea---spice-dragon-red-chai---18s/L7754088.html
Ingredients:

• South African Rooibus
• Ginger Root
• Clove Bud oil
• Cinnamon

L1315134 --- Stash Tea - Double Spice Chai - 18s
https://www.londondrugs.com/stash-tea---spice-dragon-red-chai---18s/L7754088.html
Ingredients: Black tea

• Blended Black teas
• Cinnamon
• Ginger Root
• Clove Bud oil
• Allspice
• natural Cinnamon flavor
• Cardamon oil

Product: Essential Oils (EOs). INDEX

Possibilities:
• Basil
• Carvacrol Oil.
• Cinnamon.
• Echinacea.
• Garlic.
• Ginger.
• Ginkgo.
• Ginseng.
• Hot Peppers.
• Magnolia.
• Olive Leaf.
• Onions.
• Osha Root.
• Parsley, Chinese.
• Saw Palmetto.
• Tea Tree.
• Turmeric.
• Walnut, Black.
• Yellow Dock.
• ======
• Caspofungin, drug.

Product: Carvacrol-Oregano capsules. INDEX
https://www.amazon.com/130-Carvacrol-Concentration-Essential-Softgels/dp/B09N6FC9ZD
130 mg Carvacrol - 150 mg Oregano Oil per Softgel.
World Highest Concentration Oregano Oil Capsule. Zane Hellas Oregano Oil.
Softgel Contains 30% Greek Essential Oil of Oregano. 60 Softgels.
Date First Available ? : ? December 6, 2021
Manufacturer: Zane Hellas
Country of Origin: Greece
Retail: $19.49
60 softgels
No Import Charges & $7.55 Shipping to Canada

FEATURES:

• From the Best Well Known Variety and Indigenous to the Greece Region.
  - Zane Hellas Oregano Softgels contain - 30% Oregano Oil - 70% Extra Virgin Greek Olive Oil
  We Provide CoA with every Order -
  
  

• Effectiveness, Carvacrol is the Main Compound in Oregano Oil.
  Superior Carvacrol Rating of 130 mg per Softgel.
  The Higher Content of Carvacrol In Oregano Oil, Resulting in Higher Effectiveness.
  
  

• Good Source of Polyphenols - High in Antioxidants
  - Rich in Phenolic Compounds - Free of Alcohol and Additives

Dosage: Take 1 daily, preferably after a meal.

Product: Cinnamon Leaf EO. INDEX
https://www.amazon.com/dp/B0B4PPC5DD/ref=pe_386300_440135490_TE_simp_item_image
HBNO Store: https://www.amazon.com/stores/HBNO/
page/5FB3AD09-E710-41F5-9CC0-93BA27B56185?
ref_=ast_bln&store_ref=bl_ast_dp_brandLogo_sto
Date First Available : June 21, 2022
From: SRI LANKA: Obtained by steam distilling the leaves of Cinnamomum Verum
and packaged in an amber glass bottle with a side glass dropper.
Size: 4 Fl Oz
Retail: USD $9.99 ---
No Import Charges & $7.48 Shipping to Canada

FEATURES:

• PREMIUM QUALITY CINNAMON LEAF ESSENTIAL OIL FROM SRI LANKA
  - Obtained by steam distilling the leaves of Cinnamomum Verum and packaged in an amber glass bottle with a side glass dropper.

• REDISCOVER WARMTH AND COMFORT
  Cinnamon Oil has a warm, spicy, and comforting scent ...

• Cinnamon oil is a versatile gem
  - perfect for soaps, shampoos, homemade cleaning solutions, ....

• BOTTLED IN THE USA
  Strategically located in Northern California, ... in our vast 100,000 sq foot facility.

Product: Ginger EO. INDEX
https://www.amazon.com/gp/product/B08FVHG7X9/ref=ppx_od_dt_b_asin_title_s00?ie=UTF8&psc=1
Handcraft Blends Store: https://www.amazon.com/stores/HandcraftBlends/
page/B34DF280-3214-4A3D-A72B-9D78982F0941?ref_=ast_bln&store_ref=bl_ast_dp_brandLogo_sto
Date First Available : August 14, 2020 Retail: USD $17.95
No Import Charges

FEATURES:

• 100% PURE & NATURAL GINGER OIL
  - Each essential oil is tested by an independent lab which is why every bottle comes with a Quality Guaranty.

• PREMIUM GRADE & QUALITY
  – All Handcraft Blends Essential Oils are tested by an independent lab to test the efficacy of each oil.
  Each oil is tested for its constituents as well as to have no fillers, additives and to be undiluted.

• HIGH QUALITY GLASS BOTTLE AND DROPPER – Our essential oil comes in an amber glass bottle to keep out UV rays and protect the oil against sunlight.
  We also provide a glass dropper, so you get the exact amount of oil without any waste.

• GINGER OIL BLENDS WELL WITH
  – Bergamot, Cedarwood, Cassia, Eucalyptus, Frankincense, Lemon, Orange, and Rosemary.

• BOTTLED IN THE USA
  Our oils are sourced from the best regions all over the world to bring you the best and finest.

Product: Magnolia EO. INDEX
https://kiaromashop.ca/products/champaca-red-absolute-oil-magnolia
Champaca Red Absolute Oil (Michelia champaca)
Origin: India
Extraction Method: Hexane free solvent extraction of flowers
Main Constituents: methyl benzoate (30.3%), 1,8-cineole (22.8%), indole (16.6% and B-elemene (10.4%)
Appearance and Consistency: Reddish amber, slightly thick transparent liquid
We are currently offering FREE SHIPPING* within Canada on all orders with subtotals over $99.00
Ki Aroma, PO Box 16, Sooke, BC V9Z 0E4 --- 1-800-683-6739

LINK 2: Magnolia Michelia alba.
https://www.doterra.com/CA/en/p/doterra-magnolia-touch-oil
Magnolia oil primarily contains linalool, combined with Fractionated Coconut Oil,
Roll Magnolia Touch essential oil blend on the bottoms of the feet to create a calming, relaxing atmosphere.
PIP (Product Information Page) - https://media.doterra.com/ca-otg/en/pips/doterra-touch-magnolia-oil.pdf
800.411.8151 --- Press 1 for English, then 4 for Canada Market --- CONTACT
Phone lines: Monday-Friday 8:00 am - 6:00 pm (MST)

LINK 3: Michelia Alba, Magnolia Alba
White Champaca, White Jade Orchid, White sandalwood
https://www.lovingessentialoils.com/blogs/essential-oil-tips/
magnolia-essential-oil-uses-benefits-recipes
... distilled from the petals of the magnolia tree. ...
is costly due to the difficulty growing and harvesting the flower blossoms.
1043 Garland Ave Unit C #760, San Jose, CA 95126
Jennifer Lane - Certified Aromatherapist on 11/21/2023
jen @ lovingessentialoils.com
(Many Recipes, free manual)

LINK 4: Complete Guide to Magnolia Essential Oil.
https://volantaroma.com/blogs/guides/magnolia-essential-oil-guide
By Saga Vigre Bohinen
Oct 23, 2023
Sågverksgatan 15, 652 21 Karlstad, Sverige
support@volantaroma.com
(NO stores in Canada)

LINK 5: Magnolia Essential Oil: Potential Benefits & Uses.
https://naturallydaily.com/magnolia-essential-oil/
by Editorial Team --- naturallydaily@gmail.com
May 11, 2022

The magnolia was named by the famous Swedish botanist Carl Linneaus in 1737 in honor of the French botanist, Pierre Magnol (1638-1715). Magnolias are, however, one of the most primitive plants in evolutionary history, and fossil records show that magnolias were present in Europe, North America and Asia over 100 million years ago.

Today, magnolias are indigenous only to southern China, Malaysia, Thailand, and the southern US

The earliest western record of Magnolias in cultivation is found in Aztec history where there are illustrations of what we now know are the rare Magnolia dealbata. This plant survives only in a few places in the wild, and, although climate change is largely to blame, the Aztecs cut the flowers for festivals, and this prevented the plants from seeding. The plant was found by a Spanish explorer called Hernandez in 1651.

There are about 80 species of Magnolia, of which about half are tropical.
In their native countries, magnolia trees can grow up to 80 feet tall and 40 feet wide.
They bloom in spring, with the flowers reaching their peak in summer.

The petals are traditionally hand-picked, and harvesters have to use ladders or scaffolds to reach the prized flowers.

Champaca Red Absolute Oil (Magnolia) has a complex, enticing, exotic, sublime floral aroma layered beneath nuances of apricot, honey and mango. When used in Aromatherapy Champaca Red Absolute is calming, soothing, relaxing, sense enhancing, and is both spiritually uplifting and euphoric. This enticing aroma has traditionally been used in luxury perfumes, decadent soaps, lotions, skin care products and fine incense.

doTERRA Magnolia essential oil comes from Michelia x alba, a variety of magnolia plant that flourishes in Southeast Asia. Magnolia trees can grow nearly 30.5 meters tall and bear fragrant white or light pink flowers twice per year. The harvesting process became easier when magnolia farmers started growing the trees in giant wooden or cement containers, causing the trees to grow outward rather than up. Magnolia blossoms are harvested in the summer and then again in late fall or early winter and go through a steam distillation process to produce the ... Magnolia oil.

Magnolia essential oil can be applied topically or diffused for stress relief or aromatherapy benefits.
Magnolia has a sweet floral scent that promotes feelings of relaxation and peace while reducing symptoms of anxiety and depression when inhaled. When applied topically, it helps improve skin's elasticity, tone, texture, brightness and appearance by moisturizing dry patches.

Like lavender and bergamot essential oil, magnolia primarily contains linalool.
Linalool rich oils have powerful soothing and relaxing benefits to the emotions and skin.

Magnolia flower essential oil contains about 73% linalool and small amounts of a-terpineol, ß-pinene and geraniol.

As a perfume, it can be used on the pulse points, wrists, throat, behind the ears and inside your elbows.

... roll doTERRA Touch Magnolia into your palms and inhale the scent by cupping your hands over your nose and delight in the fresh, relaxed aromatic atmosphere as you wind down ....

Blends with: Bergamot, Black Pepper, Cardamom, Cedarwood, Cinnamon, Frangipani, Frankincense, Helichrysum,
Jasmine, Neroli, Orange, Patchouli, Petitgrain, Rose, Sandalwood, Vanilla, Vetiver and Ylang Ylang.

Therapeutic Uses:
Scars, wounds, muscular aches, abdominal cramp, intestinal spasm, fear-induced anxiety,
insomnia, inability to communicate, stress-related tension, depression
(from The Complete Book of Essential Oils and Aromatherapy by Valerie Ann Wormwood, page 601).

Magnolia Essential Oil Benefits
• Ease anxiety
• Increase appetite
• Increase confidence
• Relaxes the mind and body
• Improve memory and focus
• Relieve feelings of depression
• Calm worry, tension, and feelings of stress
• Acts as a natural sedative (great for bedtime!)
• Creates a calm and serene atmosphere
• Encourage better communication
• Uplifts when feeling down and grounding when anxious
• Insect deterrent: Applying a product scented with magnolia oil can protect your skin from insect bites.

• has antifungal properties
• Soothe cough
• Ease inflammation
• Heal dry skin
• Reduce scars
• Help heal minor wounds
• Soothes and moisturizes the skin
• Alleviate rashes, hives, eczema, and psoriasis
• Stimulates the generation of new cells, beneficial for skin
• Stimulate the lymphatic system
• Soothes aches and pains - has analgesic properties
• Promotes circulation and relieves congestion
• Eases discomfort from abdominal or menstrual cramps (antispasmodic properties)
• Has anti-aging properties.

Magnolia oil is claimed to prevent certain cancers, such as colon cancer and liver cancer.
It’s because the oil contains magnolol that can prevent the spread of certain cancer cells. [2]
The oil is also great for preventing certain cancers such as leukemia, colon cancer, and prostate cancer.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.10059

Magnolia oil can help treat Alzheimer’s disease.
The magnolol component helps with cognitive ability by stimulating the acetylcholine level in the brain. [4]
https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.3178

Besides, the oil contains another component named Honokiol.
It helps in improving brain activity, especially memory.
Honokiol ... has certain anxiolytic qualities to keep the hormonal balance in your body. [8]
https://www.sciencedirect.com/science/article/abs/pii/S0278584607004101

Magnolia essential oil contains the naturally occurring corticosteroids in it.
Thus, it can treat respiratory conditions like asthma. [5]
https://pubs.acs.org/doi/abs/10.1021/np800494e

This oil can decrease the build-up of fat around the liver.

Antifungal effects of magnolia essential oil - 2017, 2021
In one study ( https://www.sciencedirect.com/science/article/abs/pii/S0956713516305503?via%3Dihub),
magnolia essential oil was found to have antifungal effects against various species of fungus and mold including Aspergillus niger, Aspergillus flavus, Penicillium, Rhizopus, Fusarium and Cladosporium.

Another study (https://pubmed.ncbi.nlm.nih.gov/32836380/)
looked at the effects of magnolia oil vapor on both mold growth and human brain activity. ...
found that magnolia oil vapor reduced mold growth and also enhanced alpha brain waves in human subjects, enhancing pleasant feelings of relaxation.

Product: Tea Tree EO. INDEX
https://www.rockymountainsoap.com/pages/tea-tree-oil-naturalpedia
Author: Rocky Mountain Soap

LINK 2: 14 Everyday Uses for Tea Tree Oil
https://www.healthline.com/nutrition/tea-tree-oil
Written by The Healthline Editorial Team
Medically reviewed by Debra Rose Wilson, Ph.D., MSN, R.N., IBCLC, AHN-BC, CHT
Updated on February 6, 2023

LINK 3: Terpinen-4-ol from tea tree oil prevents Aspergillus flavus growth in postharvest wheat grain.
https://www.sciencedirect.com/science/article/abs/pii/S0168160524001855
International Journal of Food Microbiology
-- School of Biological Engineering, Henan University of Technology,
Zhengzhou 450001, People's Republic of China
-- School of International Education, Henan University of Technology,
Zhengzhou 450001, People's Republic of China
Available online 9 May 2024
Volume 418, 16 June 2024,
83 References

LINK 4: The significance of essential oils and their antifungal properties
in the food industry: A systematic review.
https://www.sciencedirect.com/science/article/pii/S2405844023085948
Zohreh Abdi-Moghadam, Yeganeh Mazaheri, Alieh Rezagholizade-shirvan, Maryam Mahmoudzadeh,
Mansour Sarafraz, Mahnaz Mohtashami, Samira Shokri, Ahmad Ghasemi, Farshid Nickfar,
Majid Darroudi, Hedayat Hossieni Zahra Hadian, Ehsan Shamloo, Zeinab Rezaei
Available online 29 October 2023 -- 22p

Extracted from the leaves of the Melaleuca Alternifolia tree, native to Australia.
Main Constituents: Terpinen-4-ol, terpinene, a-terpinene
Terpinen-4-ol increases the activity of your white blood cells, which help fight germs.
Works against Bacteria, fungus, inflammation, and viruses.

Scientifically proven to be an effective acne, athlete's foot, and Cold sores treatment

USES include:
1. Hand sanitizer against E. coli, S. pneumoniae, H. influenzae, others.
2. Insect repellent against flies, ants, mosquitoes, ....
3. Deodorant against sweat bacterial odors.
4. Minor cuts and scrapes cleansed against S. aureus and other bacteria.
5. Wound healing increased by reducing inflammation and stimulating the activity of white blood cells.
6. Acne benefit by helping reduce the amount and overall severity of acne.
7. Nail fungus cure in up tp 60% within 6 months.
8. Mouthwash to reduce the inflammation of gingivitis and plaque-causing bacteria.
9. All-purpose surface cleanser without chemical residues.
10. Reduce the severity of contact dermatitis, rosacea, bug bites, blepharitis symptoms.
11. Dandruff (Candida albicans (yeast)) reduction when added to shampoo.
12. Athlete’s foot (tinea pedis) improved recovery when combined with other treatments.
13. Eliminating mold on fruits and vegetables with a 5–10 drops rinse.
14. Psoriasis symptoms can be eased by combining 10–15 drops of tea tree oil with 2 tablespoons of melted coconut oil.

Certain EOs, including tea tree, thyme, coriander, peppermint, and clove oils, have the capacity to bind to ergosterol and inhibit yeast growth.

According to the Food and Agriculture Organization of the United Nations (FAO), foodborne molds and their toxic byproducts are responsible for approximately 25% of agricultural food losses worldwide. Certain fungal genera, including Fusarium, Penicillium, Aspergillus, and Alternaria, are capable of producing secondary metabolites known as mycotoxins. Some of these mycotoxins can be lethal and exhibit carcinogenic, mutagenic, teratogenic, and immunosuppressive properties in both humans and animal. ... Various toxins have been identified in food products, including aflatoxin and ochratoxin.

Ochratoxins can be produced by Aspergillus ochraceus in corn, wheat, barley, flour, rice, oats, rye, beans, peas, green coffee beans, pancake mix, and mixed feeds. ... Marjoram, mint, basil, coriander, thyme, dill, and rosemary EOs reduced aflatoxin production by A. flavus by 96 %. ... oregano EOs have shown significant reductions in spores of Aspergillus terreus and Penicillium expansum, while lavender EOs have similarly reduced spores of Fusarium oxysporum and P. expansum.

Terpinen-4-ol was identified as the main volatile antifungal constituent of TTO, demonstrating promising application in preventing AAspergillus flavus spoilage in postharvest grains. Metabolomics and biochemical analyses showed that terpinen-4-ol exerts its antifungal activity against Aspergillus flavus through several mechanisms. It disrupts the integrity of the cell wall and cytoplasmic membrane, interferes with multiple metabolic pathways, induces mitochondrial dysfunction, and causes DNA damage.

Product: Drug - Caspofungin (Monograph). INDEX
https://www.drugs.com/monograph/caspofungin.html
Written by ASHP
-- .American Society of Health-System Pharmacists (ASHP)
Aug 25, 2023.
2001 - January 26 -- Type 1 - New Molecular Entity
2016 - Decemb 30 -- Type 5 - New Formulation or New Manufacturer

Alternatives: https://www.drugs.com/compare/caspofungin

LINK 2: Caspofungin injection.
https://my.clevelandclinic.org/health/drugs/21421-caspofungin-injection
... will give you this injection in a hospital or clinic setting.
This medicine may cause serious skin reactions.
2024

LINK 3: Caspofungin (from Wikipedia)
https://reference.medscape.com/drug/cancidas-caspofungin-342584#5
for injection was initially approved by both the US Food and Drug Administration (FDA),
and the European Medicines Agency (EMA) in 2001
The mean duration of therapy in previous studies was 34 days.
Some people were even healed by a one-day treatment.
However, a few people were treated for as long as 162 days

LINK 4: caspofungin (Rx)
https://reference.medscape.com/drug/cancidas-caspofungin-342584

LINK: Interactions - Serious - Use Alternative (6), Monitor Closely (20), Minor (9)
LINK: Adverse Effects - (Very Many), Postmarketing Reports
LINK: Warnings & Cautions:

Brand name: Cancidas
Drug class: Echinocandins
VA class: AM700
Chemical name:
1-[(4R,5S)-5-[(2-Aminoethyl)amino]-N2-(10,12-dimethyl-1-oxotetradecyl)-4-hydroxy-l-ornithine]-5-[(3R)-3-hydroxy-l-ornithine]pneumocandin B0 diacetate (salt)
CAS number: 179463-17-3

Aspergillosis
Treatment of invasive aspergillosis in adults, adolescents, and children = 3 months of age whose disease is refractory to, or who are intolerant of, other antifungals. Has not been evaluated for initial therapy of invasive aspergillosis.

IDSA and other clinicians consider IV voriconazole the drug of choice for primary treatment of invasive aspergillosis in adult and pediatric patients, including HIV-infected patients; IV amphotericin B or isavuconazonium (prodrug of isavuconazole) usually recommended as alternatives for primary treatment.

For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B, an IV echinocandin (caspofungin, micafungin), oral or IV posaconazole, or itraconazole oral suspension. IDSA states that echinocandins (either alone or in conjunction with other antifungals) may be effective for salvage therapy of invasive aspergillosis; however, routine use of echinocandin monotherapy not recommended for primary treatment of invasive aspergillosis.

Consult current IDSA clinical practice guidelines available at [http://www.idsociety.org/] and current CDC, NIH, and IDSA clinical practice guidelines for prevention and treatment of opportunistic infections in HIV-infected individuals available at [http://www.aidsinfo.nih.gov/] for additional information on management of aspergillosis.

Candidemia and Other Invasive Candida Infections
Treatment of candidemia and certain other invasive Candida infections (intra-abdominal abscess, peritonitis, pleural space infections) in adults, adolescents, and children =3 months of age. A drug of choice.

Has been effective in C. albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis infections, principally in nonneutropenic patients.

Manufacturer states safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients in intensive care units (ICUs), IDSA recommends

an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial therapy;
IV or oral fluconazole is an acceptable alternative for initial therapy in selected patients,
----- including those who are not critically ill and unlikely to have infections caused by fluconazole-resistant Candida.

...

Candida auris Infections
Treatment of infections caused by C. auris, an emerging pathogen associated with potentially fatal candidemia or other invasive infections.

First identified in 2009, C. auris has now been reported as the cause of serious invasive infections (including fatalities) in multiple countries worldwide (e.g., Japan, South Korea, India, Kuwait, South Africa, Pakistan, United Kingdom, Venezuela, Colombia, US). As of May 2017, a total of 77 clinical cases of C. auris had been reported to CDC from 7 different states. May be difficult to identify using standard in vitro methods. Large percentage of C. auris clinical isolates are resistant to fluconazole; multidrug-resistant isolates with reduced susceptibility or resistance to all 3 major classes of antifungal agents (azoles, polyenes, echinocandins) reported.

CDC issued interim recommendations regarding laboratory diagnosis, treatment, and infection control measures for suspected or known C. auris infections. Based on limited data available to date, CDC recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial treatment of invasive C. auris infections (e.g., bloodstream or intra-abdominal infections) in adults. CDC states a switch to IV amphotericin B (lipid formulation) could be considered if patient is clinically unresponsive to the echinocandin or if fungemia persists >5 days. Consultation with an infectious disease specialist highly recommended.

CDC recommends that infection control measures be observed for all patients with cultures yielding C. auris, including those with positive cultures only from noninvasive body sites.

If C. auris infection is suspected, immediately contact state or local public health authorities and the CDC (candidaauris@cdc.gov) for guidance. Consult interim recommendations and most recent information from CDC available at [Web] for additional information on diagnosis and management of C. auris infections.

Administration
Administer by slow IV infusion. Do not administer by rapid IV injection.
Do not admix or infuse concomitantly with other drugs.
Must be reconstituted and diluted prior to administration.
Use strict aseptic technique since the drug contains no preservatives.
Do not use diluents containing dextrose (e.g., 5% dextrose injection).

Reconstitution
Prior to reconstitution, allow vial of lyophilized caspofungin to reach room temperature.
Reconstitute 50- or 70-mg vials by adding 10.8 mL of 0.9% sodium chloride injection, sterile water for injection, bacteriostatic water for injection (with methylparaben and propylparaben or 0.9% benzyl alcohol) to provide solutions containing 5 or 7 mg/mL, respectively. Mix gently until drug dissolves completely and a clear solution obtained.

The 50- and 70-mg reconstituted vials are formulated to provide a slight overfill, yielding 54.6 and 75.6 mg, respectively, of caspofungin. The vials are for single-use only; discard any unused reconstituted solution.

Rate of Administration
Administer by IV infusion over approximately 1 hour.

DOSAGE: Aspergillosis, Adults. A single 70-mg loading dose on day 1, followed by 50 mg once daily.
Efficacy of dosages >50 mg once daily not evaluated.

Duration of treatment is based on severity of patient's underlying disease, recovery from immunosuppression, and clinical response. IDSA recommends that treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks.

Geriatric Patients
Adults: 65 years of age: Dosage adjustments not necessary.
LINK: Detailed Caspofungin dosage information
https://www.drugs.com/dosage/caspofungin.html

Usual Adult Dose for Aspergillosis - Invasive
Loading dose: 70 mg IV on Day 1
Maintenance dose: 50 mg IV once a day thereafter
Comments:
Treatment duration should be based on the severity of the patient's underlying disease,
recovery from immunosuppression, and clinical response.

Patient advice:
Report signs/symptoms of hypersensitivity reaction (including rash, facial swelling, angioedema, pruritus, sensation of warmth, bronchospasm) ...

Product: Opdivo + Yervoy, Herbal Combo. INDEX
https://www.opdivo.com/advanced-kidney-cancer/opdivo-yervoy-combination

LINK 2: Side Effects Booklet.
https://www.opdivo.com/assets/commercial/us/
opdivodtc/en/pdf/lung/Side_Effect_Tracker.pdf
Separate indications for a variety of diseases.
17 pages --- Bristol-Myers Squibb Company.
Daily Check-In Table, 2 weeks
7356-US-2300118 03/23

LINK 3: Full Prescribing Information.
https://packageinserts.bms.com/pi/pi_opdivo.pdf
54 pages --- Revised: March 2024

LINK 4: Why Would Opdivo and Yervoy Be Used Together?
https://www.healthline.com/health/drugs/opdivo-and-yervoy
Written by Jill Seladi-Schulman, Ph.D
Medically reviewed by Patricia Weiser, PharmD
2024-04-18

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.

personal Care Counselor, visit www.OPDIVOwithYou.com or call 1-855-OPDIVO-1 (1-855-673-4861) to request a registration form.

Opdivo is not known to interact with other medications, herbs, supplements, or foods.

Opdivo and Yervoy are immunotherapy drugs that are used to treat certain types of advanced cancer.
Immunotherapy drugs help your immune system detect and destroy cancer cells.
More specifically, Opdivo and Yervoy are immune checkpoint inhibitors (ICIs).
ICIs work by blocking checkpoint proteins on immune cells.
Normally, checkpoint proteins prevent your immune cells from attacking healthy cells.
But cancer cells can use them to avoid detection.

About 50%Trusted Source of cancers don’t respond to immune checkpoint inhibitor therapy with just one drug, which is called monotherapy. Because Opdivo and Yervoy have different targets, they can be used together to help improve treatment outcomes.

Opdivo and Yervoy target two different checkpoint proteins.
Opdivo targets PD-1, while Yervoy targets CTLA-4.
By blocking these checkpoint proteins, Opdivo and Yervoy help your immune cells find and destroy cancer cells.

OPDIVO and YERVOY are medicines that may treat certain cancers by working with your immune system.
OPDIVO and YERVOY can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. Some of these problems may happen more often when OPDIVO is used in combination with another therapy.

OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) as a first treatment for adults with a type of advanced stage lung cancer (called non-small cell lung cancer) when your lung cancer has spread to other parts of your body (metastatic) and your tumors are positive for PD-L1, but do not have an abnormal EGFR or ALK gene.

OPDIVO and YERVOY can cause problems that can sometimes become serious or life-threatening and can lead to death.
Serious side effects may include lung problems; intestinal problems; liver problems; hormone gland problems; kidney problems; skin problems; eye problems; problems in other organs and tissues; severe infusion reactions; and complications of stem cell transplant, including graft-versus-host disease (GVHD), that uses donor stem cells (allogeneic).
Call or see your healthcare provider right away for any new or worsening signs or symptoms.

Clinical Trial Results

In the primary analysis at 2 years (25.2 months) 67% of patients on OPDIVO + YERVOY
were alive compared to 56% of patients being alive on SUTENT.

OPDIVO + YERVOY was proven to lower the risk of dying
by 37% compared to SUTENT.

Half of the patients on SUTENT were alive at 25.9 months
compared to more than half being alive on OPDIVO + YERVOY.

Product: INDEX