- Intas Pharmaceuticals Limited on Tuesday announced the launch of an innovative antifungal drug.
- Intas Pharmaceuticals, based in India, has made a progressive breakthrough in the Antifungal Therapy domain with the launch of the world’s first Super Bioavailable Itraconazole-SB 100mg.
- The cost of this therapy for fungal infections will be reduced.
- The dosing of this antifungal drug will be reduced to halved.
- It has been recently approved by Indian Regulatory Authorities.
- It is on the World Health Organization’s List of Essential Medicines.
- Itraconazole was patented in 1978 and approved for medical use in the United States in 1992.
- Recent research works suggest itraconazole (ITZ) could also be used in the treatment of cancer by inhibiting the hedgehog pathway in a similar way to Sonidegib.
One of the world’s leading pharmaceutical companies, Intas Pharmaceuticals, has made a progressive breakthrough in the Antifungal Therapy domain with the launch of the world’s first Super Bioavailable Itraconazole-SB 100mg by the Brand Name of Itaspor-SB Forte/Subawin. It has been recently approved by Indian Regulatory Authorities.
Itaspor SB Forte/Subawin is expected to improve patient compliance and reduce the Doctor’s counseling time. It will reduce dosing to half. Furthermore, patients can take it with or without a meal with just water or as directed by the physician. The cost of the therapy is also reduced substantially.
“Intas’ newest formulation within the 25-year-old brand Itaspor is formulated with Super Bioavailable (SB) Technology that makes 1 Itaspor-SB Forte capsule equivalent to conventional 200mg Itraconazole,” said Dr. Alok Chaturvedi, Senior Vice-president & Head – Medical Affairs, Intas Pharmaceuticals.
“Given the benefits of Super Bioavailable (SB) Technology like half the drug, no inter-patient variability, freedom to prescribe with/without food, any beverage, even with Antacids, and that too with the reduction in overall treatment cost certainly seems to be a win-win proposition,” said Dr. R D Kharkar, Senior Consultant Dermatologist, Mumbai.
What is itraconazole?
Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. It belongs to a class of drugs known as azole antifungals. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth or intravenously.
Why do we use Itraconazole?
Itraconazole has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole). In particular, it is active against Aspergillus, which fluconazole is not. It is also licensed for use in blastomycosis, sporotrichosis, histoplasmosis, and onychomycosis. Itraconazole is over 99% protein-bound and has virtually no penetration into the cerebrospinal fluid. Therefore, it should not be used to treat meningitis or other central nervous system infections. According to the Johns Hopkins Abx Guide, it has “negligible CSF penetration, however, treatment has been successful for cryptococcal and coccidioidal meningitis”.
It is also prescribed for systemic infections, such as aspergillosis, candidiasis, and cryptococcosis, where other antifungal drugs are inappropriate or ineffective.
In the past decade, itraconazole has been explored as an anticancer agent for patients with basal cell carcinoma, non-small cell lung cancer, and prostate cancer. For example, in a phase II study involving men with advanced prostate cancer, high-dose itraconazole (600 mg/day) was associated with significant PSA responses and a delay in tumor progression. Itraconazole also showed activity in a phase II trial in men with non-small cell lung cancer when it was combined with the chemotherapy agent, pemetrexed. A recent review has also highlighted its use topically and orally in conjunction with other chemotherapeutic agents for advanced and metastatic basal cell carcinomas that cannot be treated surgically.
Itraconazole is produced as blue 22 mm (0.87 in) capsules with tiny 1.5 mm (0.059 in) blue pellets inside. Each capsule contains 100 mg and is usually taken twice a day at twelve-hour intervals. The Sporanox brand of itraconazole has been developed and marketed by Janssen Pharmaceutica, a subsidiary of Johnson & Johnson. The three-layer structure of these blue capsules is complex because itraconazole is insoluble and is sensitive to pH. The complicated procedure not only requires a specialized machine to create it but also the method used has manufacturing problems. Also, the pill is quite large, making it difficult for many patients to swallow. Parts of the processes of creating Sporanox were discovered by the Korean Patent Laid-open No. 10-2001-2590. The tiny blue pellets contained in the capsule are manufactured in Beerse, Belgium.
The oral solution is better absorbed. The cyclodextrin contained in the oral solution can cause osmotic diarrhea, and if this is a problem, then half the dose can be given as an oral solution and half as a capsule to reduce the amount of cyclodextrin given. “Sporanox” itraconazole capsules should always be taken with food, as this improves absorption, however, the manufacturers of “Lozanoc” assert that it may be taken “without regard to meals”. Itraconazole oral solution should be taken an hour before food, or two hours after food (and likewise if a combination of capsules and oral solution are used). Itraconazole may be taken with orange juice or cola, as absorption is also improved by acid. Absorption of itraconazole is impaired when taken with an antacid, H2 blocker, or proton pump inhibitor.
The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal-mediated synthesis of ergosterol, via inhibition of lanosterol 14α-demethylase. Because of its ability to inhibit cytochrome P450 3A4 CC-3, caution should be used when considering interactions with other medications.
Itraconazole is pharmacologically distinct from other azole antifungal agents in that it is the only inhibitor in this class that has been shown to inhibit both the hedgehog signaling pathway and angiogenesis. These distinct activities are unrelated to inhibition of the cytochrome P450 lanosterol 14 alpha-demethylase and the exact molecular targets responsible remain unidentified. Functionally, the antiangiogenic activity of itraconazole has been shown to be linked to inhibition of glycosylation, VEGFR2 phosphorylation, trafficking, and cholesterol biosynthesis pathways. Evidence suggests the structural determinants for inhibition of hedgehog signaling by itraconazole are recognizably different from those associated with antiangiogenic activity.
Itraconazole, like cyclosporine, quinidine, and clarithromycin, can inhibit P-glycoprotein, causing drug interactions by reducing elimination and increasing absorption of organic cation drugs. With conventional itraconazole preparations, serum levels can vary greatly between patients, often resulting in serum concentrations lower than the therapeutic index. It has therefore been conventionally advised that patients take itraconazole after a fatty meal rather than prior to eating.
A product (Lozanoc) licensed through the European union decentralized procedure has increased bioavailability, decreased sensitivity to co-ingestion of food, and hence decreased variability of serum levels.
Common side effects include nausea, diarrhea, abdominal pain, rash, and headache. Severe side effects may include liver problems, heart failure, Stevens-Johnson syndrome, and allergic reactions including anaphylaxis. It is unclear if use during pregnancy or breastfeeding is safe. It is in the triazole family of medications. It stops fungal growth by affecting the cell membrane or affecting its metabolism.
Why do we need a low dose?
Conventional Itraconazole mainstay drug to fight fungal infection has high result variance and low patient compliance because of dosing dependence upon food, acidic beverage, antacids consumption, etc. and overall cost of treatment.
As per published literature and clinicians’ experience, the Itraconazole molecule has low blood drug concentration, affecting safety and efficacy when taken orally. These blood levels highly vary from patient to patient. Moreover, the recommendation to take it with a full fatty meal and an acidic beverage further reduces patient compliance and adds to the problem of desired blood drug concentration. Another factor is the cost of therapy for fungal infection patients, as treatment duration varies from 3 to 8 weeks.
Intas Pharmaceuticals Ltd. is a leading, vertically integrated pharmaceutical company based in Ahmedabad, India, having end-to-end capabilities of formulation development, manufacturing, and marketing along with backward integration of APIs. Intas has more than 18,000 employees, sells products in more than 85 countries, and has 14 manufacturing sites worldwide. The Intas group’s revenues amounted to USD 2.1 bn in FY 2020 and the compounded annual growth rate of Intas’ revenues has exceeded 25% in the past 10 years.
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