SAFETY

PROVEN SAFE AND WELL-TOLERATED ON ALREADY-SENSITIVE SKIN

MORE ON SAFETY

SYSTEMIC ABSORPTION

Zilxi delivers minocycline directly to the skin, and systemic absorption is very low

  • In a pharmacokinetic study, adults 18 years or older with inflammatory lesions of rosacea applied approximately 2 grams of Zilxi on the face once daily for 14 days. Steady state was reached by Day 1, and there was no accumulation of minocycline in the plasma concentration with continuous use over 14 days16

Zilxi 1.5% topically

(2 g/day)

Illustration of the skin and blood plasma, with orange dots on the top layer of skin and orange arrows pointing down

1.3 ng/mL

PLASMA CONCENTRATION

  • In a separate pharmacokinetic study, adults 18 years or older with acne vulgaris were administered 1 single dose of oral minocycline extended-release tablets dosed 1 mg/kg. After the single dose of minocycline, the geometric mean plasma concentration was 850 ng/mL4

Single-dose oral minocycline

(1 mg/kg)

Illustration of the skin and blood plasma, with blue dots coming up from the plasma and blue arrows pointing up

850 ng/mL

PLASMA CONCENTRATION

Zilxi was found to have low systemic exposure10*

*Clinical significance of lower systemic exposure with Zilxi is unknown.

ADVERSE EVENTS

In clinical trials, Zilxi was shown to have a low incidence of adverse events compared to vehicle12

SUMMARY OF TREATMENT-EMERGENT ADVERSE EVENTS (TEAEs) OF SUBJECTS15

Chart showing adverse events for patients treated with Zilxi 1.5% and for patients using MST-enabled vehicleChart showing adverse events for patients treated with Zilxi 1.5% and for patients using MST-enabled vehicle
ZOOM IN

In Zilxi clinical trials, there were no reported cases of minocycline-induced blue-gray skin hyperpigmentation.

Important Safety Considerations:

  • ZILXI is a topical foam. While systemic absorption of ZILXI is low, and serious adverse reactions were not seen in clinical studies, the following adverse reactions associated with oral minocycline should be considered: Clostridioides difficile associated diarrhea, hepatotoxicity, metabolic effects, central nervous system effects, intracranial hypertension, autoimmune syndromes, photosensitivity, hypersensitivity reactions and tissue hyperpigmentation. Discontinue ZILXI immediately if serious adverse reactions occur with ZILXI.
  • Patients should minimize or avoid exposure to natural or artificial sunlight while using ZILXI. Advise patients to discontinue treatment with ZILXI at the first evidence of sunburn.

TOLERABILITY

Zilxi was well-tolerated on already-sensitive skin in clinical trials10,17‡

FACIAL CUTANEOUS TOLERABILITY SIGNS AND SYMPTOMS§

Series of vertical bar graphs showing patients with mild, moderate, and severe symptoms of tolerability measures

FACIAL CUTANEOUS TOLERABILITY SIGNS AND SYMPTOMS§

Horizontal bar graph showing patients with mild, moderate, and severe erythema at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe burning/stinging at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe flushing/blushing at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe dryness/xerosis at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe itching at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe peeling/desquamation at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe hyperpigmentation at baseline and Weeks 4 and 12
Horizontal bar graph showing patients with mild, moderate, and severe telangiectasia at baseline and Weeks 4 and 12

All symptoms were evaluated on a 4-point scale consisting of 0=none, 1=mild, 2=moderate, and 3=severe, except for erythema, which was evaluated on a 5-point scale consisting of 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe.

§Of 1008 subjects, 897 had local tolerability assessments at Week 12.

Hyperpigmentation was most frequently assessed as characteristic of inflammatory and post-inflammatory changes associated with inflammatory lesions of rosacea.

AT WEEK 12>80%OF PATIENTS HAD
NO OR MILD

FLUSHING/BLUSHING, TELANGIECTASIA, OR ERYTHEMA17

AT WEEK 12>95% OF PATIENTS HAD
NO OR MILD

BURNING/STINGING, DRYNESS/XEROSIS, ITCHING, PEELING/DESQUAMATION, OR HYPERPIGMENTATION17

  • In an additional 40-week open-label extension, safety study (up to a total of 52 weeks of treatment), frequency and severity of local tolerability signs and symptoms, as well as adverse events, were comparable at Week 52 to those reported at Week 1210
IMPORTANT SAFETY INFORMATION

Contraindications

Persons who have shown hypersensitivity to any of the tetracyclines or any other ingredient in ZILXI.

Warnings and Precautions

Flammability: The propellant in ZILXI is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application.

ZILXI is a topical foam. While systemic absorption of ZILXI is low, and serious adverse reactions were not seen in clinical studies, the following adverse reactions associated with oral minocycline should be considered:

  • Teratogenic effects, inhibition of bone growth & permanent tooth discoloration: Use during the second and third trimesters of pregnancy, infancy and childhood up to the age of 8 years may cause permanent discoloration of the teeth (yellow-gray-brown) and reversible inhibition of bone growth.
  • Clostridioides difficile associated diarrhea (CDAD): If CDAD occurs, discontinue ZILXI.
  • Hepatotoxicity & metabolic effects: If renal impairment exists or if liver injury suspected, discontinue ZILXI.
  • Central nervous system effects: Patients experiencing light-headedness, dizziness or vertigo should be cautioned about driving vehicles or operating heavy machinery.
  • Intracranial hypertension: Clinical manifestations include headache, blurred vision, diplopia, and vision loss. Discontinue ZILXI immediately if symptoms occur.
  • Autoimmune syndromes: Symptoms may be manifested by fever, rash, arthralgia, and malaise. Discontinue ZILXI immediately if symptoms occur.
  • Photosensitivity: Patients should minimize or avoid exposure to natural or artificial sunlight while using ZILXI. Advise patients to discontinue treatment with ZILXI at the first evidence of sunburn.
  • Hypersensitivity reactions: Discontinue ZILXI immediately if symptoms of anaphylaxis, serious skin reactions, erythema multiforme, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome occur.
  • Tissue hyperpigmentation: Discoloration of organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves.
  • Superinfection: Overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue ZILXI and institute appropriate therapy.

Adverse Reactions

The most common adverse reaction reported during clinical trials of ZILXI was diarrhea.

Indications and Usage

ZILXI (minocycline) topical foam, 1.5% is a tetracycline-class drug indicated for the treatment of inflammatory lesions of rosacea in adults.

Limitations of Use: This formulation of minocycline has not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, ZILXI should be used only as indicated.

Please click to access full Prescribing Information.

IMPORTANT SAFETY INFORMATIONOrange arrow

Contraindications

Persons who have shown hypersensitivity to any of the tetracyclines or any other ingredient in ZILXI.

Warnings and Precautions

Flammability: The propellant in ZILXI is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application.

ZILXI is a topical foam. While systemic absorption of ZILXI is low, and serious adverse reactions were not seen in clinical studies, the following adverse reactions associated with oral minocycline should be considered:

  • Teratogenic effects, inhibition of bone growth & permanent tooth discoloration: Use during the second and third trimesters of pregnancy, infancy and childhood up to the age of 8 years may cause permanent discoloration of the teeth (yellow-gray-brown) and reversible inhibition of bone growth.
  • Clostridioides difficile associated diarrhea (CDAD): If CDAD occurs, discontinue ZILXI.
  • Hepatotoxicity & metabolic effects: If renal impairment exists or if liver injury suspected, discontinue ZILXI.
  • Central nervous system effects: Patients experiencing light-headedness, dizziness or vertigo should be cautioned about driving vehicles or operating heavy machinery.
  • Intracranial hypertension: Clinical manifestations include headache, blurred vision, diplopia, and vision loss. Discontinue ZILXI immediately if symptoms occur.
  • Autoimmune syndromes: Symptoms may be manifested by fever, rash, arthralgia, and malaise. Discontinue ZILXI immediately if symptoms occur.
  • Photosensitivity: Patients should minimize or avoid exposure to natural or artificial sunlight while using ZILXI. Advise patients to discontinue treatment with ZILXI at the first evidence of sunburn.
  • Hypersensitivity reactions: Discontinue ZILXI immediately if symptoms of anaphylaxis, serious skin reactions, erythema multiforme, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome occur.
  • Tissue hyperpigmentation: Discoloration of organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves.
  • Superinfection: Overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue ZILXI and institute appropriate therapy.

Adverse Reactions

The most common adverse reaction reported during clinical trials of ZILXI was diarrhea.

Indications and Usage

ZILXI (minocycline) topical foam, 1.5% is a tetracycline-class drug indicated for the treatment of inflammatory lesions of rosacea in adults.

Limitations of Use: This formulation of minocycline has not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, ZILXI should be used only as indicated.

Please click to access full Prescribing Information.

REFERENCES

  1. Sapadin AN, et al. J Am Acad Dermatol. 2006;54(2):258-265.
  2. Mrowietz U, et al. Am J Clin Dermatol. 2018;19(3):427-436. doi: 10.1007/s40257-017-0339-0.
  3. Rivero AL, Whitfeld M. Aust Prescr. 2018;41(1):20‐24. doi: 10.18773/austprescr.2018.004.
  4. Jones TM, et al. J Drugs Dermatol. 2017;16(10):1022-1028.
  5. Hazot Y, et al. J Anal Pharm Res. 2017;4(5):00117.
  6. Tamarkin D. Foam: a unique delivery vehicle for topically applied formulations. In: Dayan N, ed. Handbook of Formulating Dermal Applications: A Definitive Practical Guide. Beverly, MA: Scrivener Publishing LLC; 2017:233-260.
  7. Moribe K, et al. Chem Pharm Bull. 2010;58(8):1096-1099.
  8. Yokota J, et al. J Chin Med Assoc. 2018;81(6):511-519.
  9. Tamarkin D, et al. Expert Opin Drug Deliv. 2006;3(6):799-807.
  10. ZILXI™ (minocycline) topical foam, 1.5% Prescribing Information. Bridgewater, NJ: Foamix Pharmaceuticals Inc; 2020.
  11. Lin TK, et al. J Mol Sci. 2017;19(1):70. doi: 10.3390/ijms19010070.
  12. Stein Gold L, et al. J Am Acad Dermatol. 2020;82(5):1166-1173. doi: 10.1016/j.jaad.2020.01.043.
  13. Stein Gold L, et al. Open-label extension study evaluating the long-term safety, efficacy, and tolerability of FMX103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea. Poster presented at: 39th Annual Fall Clinical Dermatology Conference®; October 17-20, 2019; Las Vegas, Nevada.
  14. Del Rosso JQ, et al. Integrated summary of efficacy of FMX103 1.5% topical minocycline foam for the treatment of moderate-to-severe papulopustular rosacea: results from two Phase 3 studies. Poster presented at: 17th Annual South Beach Symposium in Dermatology; February 6-9, 2020; Miami, Florida.
  15. Data on file. Foamix Pharmaceuticals Inc.
  16. Jones TM, et al. SKIN J Cutan Med. 2019;3(2). doi: 10.25251/skin.3.2.2.
  17. Stein Gold L, et al. Integrated safety analysis of FMX103 1.5% topical minocycline foam for the treatment of moderate-to-severe papulopustular rosacea (PPR): results from two Phase 3 studies. Poster presented at: American Academy of Dermatology Annual Meeting; March 20-24, 2020; Denver, CO. Poster No. 13509.

Foamix Pharmaceuticals is a wholly owned subsidiary of VYNE Therapeutics Inc.

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