Birch Triterpenes
FDA Drug Information • Also known as: Filsuvez
- Brand Names
- Filsuvez
- Dosage Form
- GEL
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION FILSUVEZ (birch triterpenes) topical gel is a sterile botanical drug product for topical use and contains birch triterpenes in an oil base. FILSUVEZ is a colorless to slightly yellowish, opalescent, non-aqueous gel. Birch triterpenes is a botanical drug substance composed of a mixture of pentacyclic triterpenes. The botanical drug substance is a dry extract, refined, from birch bark from Betula pendula Roth , Betula pubescens Ehrh., as well as hybrids of both species, quantified to 72-88% (w/w) betulin, 2.4-5.7% (w/w) lupeol, 2.6-4.2% (w/w) betulinic acid, 0.5-1.2% (w/w) erythrodiol, 0.3-0.8% (w/w) oleanolic acid. The structural formulae of the main triterpene constituents are shown in Figure 1. Figure 1: Structure of Triterpene Constituents Betulin Erythrodiol Betulinic acid Oleanolic acid Lupeol Each gram of FILSUVEZ topical gel 10% (w/w) contains 100 mg of birch triterpenes in an oil base of refined sunflower oil. FILSUVEZ contains no additional excipients. Chemical Structure - Betulin Chemical Structure - Erythrodiol Chemical Structure - Betulinic acid Chemical Structure - Oleanolic acid Chemical Structure - Lupeol
What Is Birch Triterpenes Used For?
1 INDICATIONS AND USAGE FILSUVEZ is indicated for the treatment of wounds associated with dystrophic and junctional epidermolysis bullosa (EB) in adult and pediatric patients 6 months of age and older. FILSUVEZ topical gel is indicated for the treatment of wounds associated with dystrophic and junctional epidermolysis bullosa in adult and pediatric patients 6 months of age and older. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Wash hands before and after applying FILSUVEZ or wear gloves for application. Apply a 1 mm layer of FILSUVEZ to the affected wound surface only. Do not rub in the gel. Cover the wound with a sterile non-adhesive wound dressing. Alternatively, apply FILSUVEZ directly to the dressing so that the topical gel is in direct contact with the wound. Apply FILSUVEZ to cleansed wounds with wound dressing changes until the wound is healed. If a FILSUVEZ-treated wound becomes infected, discontinue treatment to that wound until the infection has resolved. Each tube of FILSUVEZ is for one-time use only. Once the tube is opened, use the product immediately. Discard the tube after use in household trash or through a drug take back site, if available. Avoid contact of FILSUVEZ with eyes and mucous membranes (e.g., mouth, vagina, anus). In case of accidental contact, irrigate the area with water. FILSUVEZ is for topical use only. Not for use on mucous membranes (oral, intravaginal, or intra-anal). Not for ophthalmic use. Apply a 1 mm layer of FILSUVEZ to the affected wound surface and cover with wound dressing or apply FILSUVEZ directly to dressing so that the topical gel is in direct contact with the wound. Do not rub in the topical gel. ( 2 ) Apply FILSUVEZ at wound dressing changes until the wound is healed. ( 2 ) Each tube of FILSUVEZ is for one-time use only. ( 2 ) For topical use; not for oral, intravaginal, intra-anal, or ophthalmic use. ( 2 )
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] The most common (incidence ≥2%) adverse reactions are application site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of FILSUVEZ was evaluated in EASE, a randomized, double-blind, multicenter, placebo-controlled trial in 223 adult and pediatric subjects with inherited EB. During the double-blind phase of EASE, subjects received topical treatment with either FILSUVEZ or a placebo gel on partial-thickness wounds every 1 to 4 days for a total of 90 days. Treated wounds were covered with non-adhesive dressings. Following completion of the double-blind phase, all subjects received FILSUVEZ for a total of 24 months during the open-label phase [see Clinical Studies (14) ] . Table 1 presents adverse reactions that occurred in at least 2% of subjects treated with FILSUVEZ during the 90-day double-blind phase of EASE and at a greater frequency than in the placebo gel group. Table 1: Number (%) of Subjects with Adverse Reactions Occurring in ≥ 2% Adverse Reaction FILSUVEZ (N=109) n (%) Placebo Gel (N=114) n (%) Application site reaction Includes: application site pruritus, administration site pain, administration site pruritus. 8 (7.3) 7 (6.1) Squamous cell carcinoma of the skin (SCC) was reported as an adverse event in the double-blind and open-label periods of EASE. Four subjects with recessive dystrophic EB each reported one SCC: a 20-year-old male on day 1 of the double-blind period; three female subjects ages 22, 46, and 49 years during the open-label period. Two of the four subjects had applied FILSUVEZ to the area which developed the SCC.
Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data with use of FILSUVEZ in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In an animal reproduction study, oral administration of birch triterpenes to pregnant rats during the period of organogenesis had no effects on reproductive or fetal parameters (see Data ) . Systemic absorption of FILSUVEZ in humans is low following topical administration of FILSUVEZ, and maternal use is not expected to result in fetal exposure to the drug [see Pharmacokinetics (12.3) ] . The background risk of major birth defects and miscarriage for the indicated population is unknown . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study, birch triterpenes were orally administered to pregnant rats at doses of 10, 30, or 100 mg/kg/day during the period of organogenesis. Birch triterpenes did not cause maternal toxicity or fetal malformations at doses up to 100 mg/kg/day. In a prenatal and postnatal development study, birch triterpenes were orally administered to pregnant rats at doses of 10, 30, or 100 mg/kg/day from gestation day 5 through lactation day 20. Birch triterpenes did not affect development at doses up to 100 mg/kg/day. The available data do not support relevant comparisons of systemic birch triterpenes exposures achieved in the animal studies to exposures observed in humans after topical use of FILSUVEZ.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING FILSUVEZ (birch triterpenes) topical gel, 10% (w/w) is a colorless to slightly yellowish, opalescent, non-aqueous gel and is supplied in 25 mL white aluminum tubes containing 23.4 grams of gel per tube (NDC 10122-310-01). Each sterile tube is for one-time use only. Once opened, the product should be used immediately and discarded after use. Store at 20°C to 25°C (68° F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]). Do not freeze. Do not use beyond the expiration date.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.