RIGHT ON TARGET

THE ENHANCED TECHNOLOGY THAT EMPOWERS YOU

Tolsura with innovative SUBA® technology, has up to 90% bioavailability³ and nearly twice the absorption³ of conventional itraconazole capsules.

ABOUT TOLSURA

When C_trough was corrected for dose administration, the relative bioavailability of TOLSURA was nearly 2x that of conventional itraconazole capsules.

Parameter*	TOLSURA 130 mg twice daily (2 x 65 mg Capsules)	Itraconazole 200 mg twice daily (2 x 100 mg Capsules)
AUC_O-tau (hr•ng/ml)	15,600 ± 3,700	14,900 ± 3,800
C_through (ng/ml)	1,200 ± 400	1,000 ± 300
C_max (ng/ml)	1,600 ± 400	1,500 ± 400

Patients with a mean C_trough level of >1,034 ng/mL^6,†

TOLSURA 65 mg^‡
Itraconzole 100 mg^1,6

The bioavailability of TOLSURA at steady state, under fed conditions was determined by a comparative pharmacokinetic study with 100 mg itraconazole capsules. 16 healthy subjects were dosed orally immediately after a meal, twice-daily for 14.5 days.

^*Geometric mean ± standard deviation
†The mean C_trough level of the conventional itraconazole group
‡This difference represents the percentage of patients in a steady-state PK study above the geometric mean of the conventional itraconazole plasma trough level (1,034 ng/mL)

ADVANCED ANTIFUNGAL INNOVATION YOU CAN DEPEND ON

FOR ENDEMIC AND OPPORTUNISTIC FUNGAL INFECTIONS TOLSURA 65 mg capsules offer the efficacy of itraconazole capsules with improved absorption and less variability in plasma levels ¹

TOLSURA has up to 90% bioavailability

approximately twice that of conventional itraconazole, with improved absorption and reduced plasma variability².

BIOAVAILABILITY

TOLSURA's SUBA^® technology offers significantly improved solubility

in the higher pH of the upper small intestine, resulting in improved absorption³ which is not reduced with proton pump inhibitor use^1,4,5,*.

ABSORPTION

* Monitor for side effects as dosing with a proton pump inhibitor may increase peak and overall exposure of itraconazole

81% of subjects treated with TOLSURA achieved therapeutic blood levels^†

compared to 44% taking conventional itraconazole capsules.^1,6 With TOLSURA, therapeutic levels are achieved and maintained in both fed and fasted states (FDA dosing instructions require taking with food)^4,6,7.

THERAPEUTIC LEVELS

†mean trough level of conventional itraconazole, 1,034 ng/mL.

TOLSURA VS. CONVENTIONAL ITRACONAZOLE^3,8,9:

REDUCED DOSE
SIMILAR TOTAL AND PEAK ITRACONAZOLE EXPOSURE WITH LESS DRUG
~2X BIOAVAILABILITY
SIMILAR SAFETY PROFILE

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CAN TOLSURA HELP YOUR PATIENTS?

TOLSURA IS SUITABLE FOR ADULT PATIENTS who have been diagnosed with histoplasmosis, blastomycosis or aspergillosis^1,10,11, and

Oral antifungal therapy is the appropriate choice for treatment^{1,10,11,12,13,14}
Want a reliable treatment to deliver and maintain consistent therapeutic levels¹⁷
Patients who are immunocompromised and immunocompetent^15,16
Want the convenience of not having lifestyle and diet restraints^17,18,19
- E.g., no requirement for an acidic beverage or high-fat meal
Have gastrointestinal issues, or take a proton pump inhibitor^3,18,19,20
Want to take a lower dose of medication with a smaller capsule size without compromising on efficacy^3,5,6

CONVENIENT DOSING WITH TOLSURA

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Indications and Important
Safety Information

BOXED WARNING
WARNING: CONGESTIVE HEART FAILURE and DRUG INTERACTIONS

» CONGESTIVE HEART FAILURE

TOLSURA can cause or exacerbate congestive heart failure (CHF). When itraconazole was administered intravenously to healthy human volunteers and dogs, negative inotropic effects were seen. If signs or symptoms of congestive heart failure occur or worsen during administration of TOLSURA, reassess the benefit and risk of continuing treatment.

» DRUG INTERACTIONS

Co-administration of certain drugs that are metabolized by human CYP3A4 enzymes are contraindicated with TOLSURA because plasma concentrations of such drugs are increased, which may also increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs.
Co-administration with colchicine, fesoterodine and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and
Co-administration with eligustat is contraindicated in subjects taking strong or moderate CYP2D6 inhibitors.
Increased plasma concentrations of some of these drugs caused by co-administration with TOLSURA can lead to QT prolongation and/or ventricular tachyarrhythmias, including occurrences of torsades de pointes, a potentially fatal arrhythmia.

Indications and Usage

TOLSURA is an azole antifungal indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised adult patients:

Blastomycosis, pulmonary and extrapulmonary
Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and
Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy

Limitations of Use:

TOLSURA is not indicated for the treatment of onychomycosis.

TOLSURA is NOT interchangeable or substitutable with other itraconazole products.

Contraindications

Co-administration with certain drugs that either affect metabolism of itraconazole or whose metabolism is affected by itraconazole Hypersensitivity to itraconazole

Warnings and Precautions

Hepatotoxicity: Serious hepatotoxicity, including liver failure and death, were reported with the use of itraconazole. Discontinue treatment if signs of liver dysfunction occur
Cardiac Dysrhythmias: Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using certain drugs that are metabolized by human CYP450 enzymes concomitantly with oral itraconazole and/or other CYP3A4 inhibitors.
Peripheral Neuropathy: This has been reported in patients on long-term therapy with itraconazole. Monitor and promptly evaluate neurologic symptoms
Hearing loss: Reversible or permanent hearing loss has been reported in patients. Discontinue treatment if hearing loss occurs

Adverse Reactions

Most common adverse reactions (incidence ≥ 1%) are nausea, rash, vomiting, edema, headache, diarrhea, fatigue, fever, pruritus, hypertension, abnormal hepatic function, abdominal pain, dizziness, hypokalemia, anorexia, malaise, decreased libido, somnolence, albuminuria, and impotence.

To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For more information, please see full Prescribing Information and Patient Information Leaflet.

REFERENCES:

TOLSURA® Product Information. Mayne Pharma. Greenville, NC. 12/2018.
Abuhelwa AY, Foster DJ, Mudge S, Hayes D, Upton RN. Population pharmacokinetic modeling of itraconazole and hydroxyitraconazole for oral SUBA-itraconazole and sporanox capsule formulations in healthy subjects in fed and fasted states. Antimicrob Agents Chemother. 2015;59(9):5681-5696. doi:10.1128/AAC.00973-15.
Data on File. Mayne Pharma, Inc. 2017.
Lindsay J, Mudge S, Thompson GR 3rd. Effects of food and omeprazole on a novel formulation of super bioavailability itraconazole in healthy subjects. Antimicrob Agents Chemother. 2018; 62(12).
Data on File. Clinical study report MPG 016.
Mudge S, Burnett BP. Pharmacokinetic Analysis of SUBATM-itraconazole Capsules Compared to Conventional Itraconazole Capsules for a 3-Day Loading Dose Regimen and Afer 15 Days of Administration. Poster presented (#L0043) at 29th European Congress of Clinical Microbiology & Infectious Diseases, Amsterdam, Netherlands. April 13-16, 2019.
Data on File. Clinical study report MPG 017.
Thompson GR, et al. Antimicrob Agents Chemother. 2020;64(8):e00400-20.
Data on file. Mayne Pharma, Inc. Clinical study report MPG015.
Patterson TF, et al. Clin Infect Dis. 2016;63(4):433-442.
Limper AH, et al. Am J Respir Crit Care Med. 2011;183:96-128.
Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12)1801-1812.
Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007;45(7)807-825.
Denning DW, et al. Eur Respir J. 2016;47(1):45-68.
Badiee P, Hashemizadeh Z. Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res. 2014;132(2):195-204.
Cornely OA. Aspergillus to Zygomycetes: causes, risk factors, prevention, and treatment of invasive fungal infections. Infection. 2008;36(4)296-313.
Lindsay J, et al. Antimicrob Agents Chemother. 2018;62(12)e01723-18.
Sporanox® Product Information. Janssen Pharmaceuticals, Inc. Titusville, NJ. May 2018.
Sporanox® oral solution Product Information. Janssen Pharmaceuticals, Inc. Titusville, NJ. Apr 2019.
Poirier JM, et al. Therapie. 1996;51(2):163-167.