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These highlights do not include all the information needed to use Veregen safely and effectively. See full prescribing information for Veregen. Veregen (sinecatechins) Ointment, 15% For topical dermatologic use only Initial U.S. Appro | Veregen

13:15 EDT 24th July 2014 | BioPortfolio

Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

1 INDICATIONS AND USAGE

1.1 Indication

Veregen is indicated for the topical treatment of external genital and perianal warts (Condylomata acuminata) in immunocompetent patients 18 years and older.

1.2 Limitations of Use

The safety and effectiveness of Veregen have not been established for treatment beyond 16-weeks or for multiple treatment courses.

The safety and effectiveness of Veregen in immunosuppressed patients have not been established.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

Veregen is to be applied three times per day to all external genital and perianal warts.

Apply about an 0.5 cm strand of the Veregen to each wart using the finger(s), dabbing it on to ensure complete coverage and leaving a thin layer of the ointment on the warts. Patients should wash their hands before and after application of Veregen.

It is not necessary to wash off the ointment from the treated area prior to the next application.

Veregen is not for ophthalmic, oral, intravaginal, or intra-anal use.

2.2 Treatment Period

Treatment with Veregen should be continued until complete clearance of all warts, however no longer than 16 weeks.

Local skin reactions (e.g. erythema) at the treatment site are frequent. Nevertheless, treatment should be continued when the severity of the local skin reaction is acceptable.

3 DOSAGE FORMS AND STRENGTHS

Veregen is a brown ointment and is supplied in an aluminum tube containing 15 grams (NDC # 10337-450-15) of ointment per tube.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

Veregen has not been evaluated for the treatment of urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease and should not be used for the treatment of these conditions.

Use of Veregen on open wounds should be avoided.

Patients should be advised to avoid exposure of the genital and perianal area to sun/UV-light as Veregen has not been tested under these circumstances.

6 ADVERSE REACTIONS

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.

In Phase 3 clinical trials, a total of 397 subjects received Veregen three times per day topical application for the treatment of external genital and perianal warts for up to 16 weeks.

Serious local adverse events of pain and inflammation were reported in two subjects (0.5%), both women.

In clinical trials, the incidence of patients with local adverse events leading to discontinuation or dose interruption (reduction) was 5% (19/397). These included the following events: application site reactions (local pain, erythema, vesicles, skin erosion/ulceration), phimosis, inguinal lymphadenitis, urethral meatal stenosis, dysuria, genital herpes simplex, vulvitis, hypersensitivity, pruritus, pyodermitis, skin ulcer, erosions in the urethral meatus, and superinfection of warts and ulcers.

Local and regional reactions (including adenopathy) occurring at >1% in the treated groups are presented in Table 1.

A total of 266/397 (67%) of subjects in the Veregen group had either a moderate or a severe reaction that was considered probably related to the drug, of which 120 (30%) subjects had a severe reaction. Severe reactions occurred in 37% (71/192) of women and in 24% (49/205) of men. The percentage of subjects with at least one severe, related adverse event was 26% (86/328) for subjects with genital warts only, 42% (19/45) in subjects with both genital and perianal warts and 48% (11/23) of subjects with perianal warts only.

Phimosis occurred in 3% of uncircumcised male subjects (5/174) treated with Veregen and in 1% (1/99) in vehicle.

The maximum mean severity of erythema, erosion, edema, and induration was observed by week 2 of treatment.

Less common local adverse events included urethritis, perianal infection, pigmentation changes, dryness, eczema, hyperesthesia, necrosis, papules, and discoloration. Other less common adverse events included cervical dysplasia, pelvic pain, cutaneous facial rash, and staphylococcemia.

In a dermal sensitization study of Veregen in healthy volunteers, hypersensitivity (type IV) was observed in 5 out of 209 subjects (2.4%) under occlusive conditions.

Table 1: Local and Regional Adverse Reactions During Treatment (% Subjects)
Veregen®
(N = 397)
Vehicle
(N = 207)
Erythema 70 32
Pruritus 69 45
Burning 67 31
Pain/discomfort 56 14
Erosion/Ulceration 49 10
Edema 45 11
Induration 35 11
Rash vesicular 20 6
Regional Lymphadenitis 3 1
Desquamation 5 <1
Discharge 3 <1
Bleeding 2 <1
Reaction 2 0
Scar 1 0
Irritation 1 0
Rash 1 0

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. Veregen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The Maximum Recommended Human Dose (MRHD) of Veregen was set at three times daily topical administration of 250 mg, 750 mg total, containing 112.5 mg sinecatechins for the animal multiple of human exposure calculations presented in this labelling. Dose multiples were calculated based on the human equivalent dose (HED).

Embryo-fetal development studies were conducted in rats and rabbits using intravaginal and systemic routes of administration, respectively. Oral administration of sinecatechins during the period of organogenesis (gestational Days 6 to 15 in rats or 6 to 18 in rabbits) did not cause treatment related effects on embryo-fetal development or teratogenicity at doses of up to 1,000 mg/kg/day (86-fold MRHD in rats; 173-fold MRHD in rabbits).

In the presence of maternal toxicity (characterized by marked local irritation at the administration sites and decreased body weight and food consumption) in pregnant female rabbits, subcutaneous doses of 12 and 36 mg/kg/day of sinecatechins during the period of organogenesis (gestational Days 6 to 19) resulted in corresponding influences on fetal development including reduced fetal body weights and delays in skeletal ossification. No treatment related effects on embryo-fetal development were noted at 4 mg/kg/day (0.7-fold MRHD). There was no evidence of teratogenic effects at any of the doses evaluated in this study.

A combined fertility / embryo-fetal development study using daily vaginal administration of Veregen to rats from Day 4 before mating and throughout mating until Day 17 of gestation did not show treatment-related effects on embryo-fetal development or teratogenicity at doses up to 0.15 mL/rat/day (8-fold MRHD).

A pre- and post-natal development study was conducted in rats using vaginal administration of Veregen at doses of 0.05, 0.10 and 0.15 mL/rat/day from Day 6 of gestation through parturition and lactation. The high and intermediate dose levels of 0.15 (8-fold MRHD) and 0.10 mL/rat/day resulted in an increased mortality of the F dams, associated with indications of parturition complications. The high dose level of 0.15 mL/rat/day also resulted in an increased incidence of stillbirths. There were no other treatment-related effects on pre- and post-natal development, growth, reproduction and fertility at any dose tested.

8.3 Nursing Mothers

It is not known whether topically applied Veregen is excreted in breast milk.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Seven patients (1.4%), older than 65 years of age were treated with Veregen in clinical studies. This, however, is an insufficient number of subjects to determine whether they respond differently from younger subjects.

11 DESCRIPTION

Veregen (sinecatechins) Ointment, 15% is a botanical drug product for topical use. The drug substance in Veregen is sinecatechins, which is a partially purified fraction of the water extract of green tea leaves from Camellia sinensis (L.) O Kuntze, and is a mixture of catechins and other green tea components. Catechins constitute 85 to 95% (by weight) of the total drug substance which includes more than 55% of Epigallocatechin gallate (EGCg), other catechin derivatives such as Epicatechin (EC), Epigallocatechin (EGC), Epicatechin gallate (ECg), and some additional minor catechin derivatives i.e. Gallocatechin gallate (GCg), Gallocatechin (GC), Catechin gallate (Cg), and Catechin (C). In addition to the known catechin components, it also contains gallic acid, caffeine, and theobromine which together constitute about 2.5% of the drug substance. The remaining amount of the drug substance contains undefined botanical constituents derived from green tea leaves.

The structural formulae of catechins are shown below.

General Structure of Catechins

Each gram of the ointment contains 150 mg of sinecatechins in a water free ointment base consisting of isopropyl myristate, white petrolatum, cera alba (white wax), propylene glycol palmitostearate, and oleyl alcohol.

IMAGE veregen-figure-1.jpg

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mode of action of Veregen involved in the clearance of genital and perianal warts is unknown. In vitro, sinecatechins had anti-oxidative activity; the clinical significance of this finding is unknown.

12.2 Pharmacodynamics

The pharmacodynamics of Veregen is unknown.

12.3 Pharmacokinetics

The pharmacokinetics of topically applied Veregen has not been sufficiently characterized at this time. However, data suggest that systemic exposure to catechins after repeated topical application of Veregen is likely to be less than observed after a single oral intake of 400 mL green tea.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In an oral (gavage) carcinogenicity study, sinecatechins was administered daily for 26 weeks to p53 transgenic mice at doses up to 500 mg/kg/day (22-fold MRHD; [see Use in Specific Populations (8.1)]). Treatment with sinecatechins was not associated with an increased incidence of either neoplastic or non-neoplastic lesions in the organs and tissues examined. Veregen has not been evaluated in a dermal carcinogenicity study.

Sinecatechins was negative in the Ames test, in vivo rat micronucleus assay, UDS test, and transgenic mouse mutation assay, but positive in the mouse lymphoma mutation assay.

Daily vaginal administration of Veregen to rats from Day 4 before mating and throughout mating until Day 17 of gestation did not cause adverse effects on mating performance and fertility at doses up to 0.15 mL/rat/day. This dose corresponds to approximately 150 mg/rat/day (8-fold MRHD).

14 CLINICAL STUDIES

Two randomized, double-blind, vehicle-controlled studies were performed to investigate the safety and efficacy of Veregen in the treatment of immunocompetent patients 18 years of age and older with external genital and perianal warts. The subjects applied the ointment 3 times daily for up to 16 weeks or until complete clearance of all warts (baseline and new warts occurring during treatment).

Over both studies the median baseline wart area was 51 mm (range 12 to 585 mm), and the median baseline number of warts was 6 (range 2 to 30).

The primary efficacy outcome measure was the response rate defined as the proportion of patients with complete clinical (visual) clearance of all external genital and perianal warts (baseline and new) by week 16, presented in Tables 2 and 3 for all randomized subjects dispensed medication.

Median time to complete wart clearance was 16 weeks and 10 weeks, respectively, in the two phase 3 clinical trials.

The rate of recurrence of external genital and perianal warts 12 weeks after completion of treatment in subjects with complete clearance is 6.8% (14/206) for those treated with Veregen and 5.8% (4/69) for those treated with vehicle.

Table 2: Efficacy by Region
Complete Clearance
All Countries
 (includes the United States)
    Veregen® 15% (N = 397) 213 (53.6%)
    Vehicle (N = 207) 73 (35.3%)
United States
    Veregen® 15% (N = 21) 5 (23.8%)
    Vehicle (N = 9) 0 (0.0%)
Table 3: Efficacy by Gender
Complete Clearance
Males
    Veregen® 15% (N = 205) 97 (47.3%)
    Vehicle (N = 118) 34 (28.8%)
Females
    Veregen® 15% (N = 192) 116 (60.4%)
    Vehicle (N = 89) 39 (43.8%)

16 HOW SUPPLIED/STORAGE AND HANDLING

Veregen is a brown ointment and is supplied in an aluminum tube containing 15 grams (NDC # 10337-450-15) of ointment per tube.

Prior to dispensing to the patient, store refrigerated 2℃ to 8℃ (36℉ to 46℉). After dispensing, store refrigerated or up to 25℃ (77℉). Do not freeze.

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

See FDA-approved Patient Labeling (17.2)

17.1 Instructions for Use

Patients using Veregen should receive the following information and instructions:

17.2 FDA-Approved Patient Labeling

PATIENT INFORMATION

Veregen (sinecatechins) Ointment, 15%Rx Only

Read this leaflet carefully before you start using Veregen Ointment, 15% and each time you refill your prescription. There may be new information. This information does not take the place of your doctor’s advice. If you have any questions about Veregen Ointment, 15% or your condition ask your doctor or pharmacist. Only your doctor can prescribe Veregen and determine if it is right for you.

What is Veregen Ointment, 15%? Veregen Ointment, 15% is a medicine for skin use only (topical) for the treatment of warts on the outside of the genitals and around the outside of the anus. It is not a treatment for warts in the vagina, cervix, or inside the anus. Your doctor may recommend examination and screening tests (such as a Pap smear) to evaluate these areas.

Who should not use Veregen Ointment, 15%? Do not use Veregen Ointment, 15% if you are allergic to an ingredient in Veregen Ointment, 15%. The list of ingredients is at the end of this leaflet.

What should I tell my doctor before using Veregen Ointment, 15%? Tell your doctor about all your health conditions and all the medicines you take including prescription, over-the-counter medicine, vitamins, supplements, and herbals. Be sure to tell your doctor if you are:

How should I use Veregen Ointment, 15%?

What should I avoid while using Veregen Ointment, 15%?

What are the possible side effects of Veregen Ointment, 15%?

The most common side effects with Veregen Ointment, 15% are local skin and application site reactions including:

Many patients experience itching, reddening or swelling on or around the application site during the course of treatment. Some of these side effects could be a sign of an allergic reaction. If you experience open sores or other severe reactions at the locations you applied Veregen Ointment, 15%, stop treatment and call your doctor right away.

You may experience other side effects of Veregen Ointment, 15%, which are not mentioned here. Ask your doctor or pharmacist for more information.

Patients should be aware that new warts may develop during treatment as Veregen Ointment, 15% is not a cure.

How should I store Veregen Ointment, 15%?

Keep Veregen Ointment, 15% and all medicines out of the reach of children.

General advice about prescription medicines Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Veregen Ointment, 15% for a condition for which it was not prescribed. Do not give Veregen Ointment, 15% to other people, even if they have the same symptoms you have. It may harm them. Do not use Veregen Ointment, 15% after the expiration date on the tube.

This leaflet summarizes the most important information about Veregen Ointment, 15%. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Veregen Ointment, 15% that is written for the doctor.

What are the ingredients in Veregen Ointment, 15%?

Active ingredient: A defined green tea extract named sinecatechins.

Inactive ingredients: Isopropyl myristate, white petrolatum, cera alba (white wax), propylene glycol palmitostearate, and oleyl alcohol.

Veregen is a registered trademark of MediGene AG, D-82152 Planegg/Martinsried, Germany.

Manufactured for: PharmaDerm A division of Fougera Pharmaceuticals Inc. Melville, New York 11747 www.pharmaderm.com

Manufactured by: C.P.M. Contract Pharma GmbH & Co. KGFrühlingstrasse 7D-83620 Feldkirchen-WesterhamGermany

U.S. Patent Nos. 5795911 and 5968973

Package Label - Principal Display Panel – 15g Tube Label

Package Label - Principal Display Panel – 15g Tube Carton

Manufacturer

Fougera Pharmaceuticals Inc.

Active Ingredients

Source

Drugs and Medications [0 Results]

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Clinical Trials [4 Associated Clinical Trials listed on BioPortfolio]

Investigating Veregen ™ 15% Ointment Treatment For Non-facial Verrucae in Pediatric Patients: A Pilot Study

The purpose of this study is to investigate topical treatment with Veregen™ 15% ointment as a single therapeutic agent and compare it to combination therapy with Veregen ™ 15% ointment ...

Pharmacokinetic Study of Topically Applied Veregen 15% Compared With Oral Intake of Green Tea Beverage

This open, monocentric study is designed to investigate plasma concentrations of certain catechins after topical application of Veregen 15% ointment to genital or perianal warts in compari...

Treatment of the Recessive Nonbullous Congenital Ichthyosis by the Epigallocatechine Cutaneous

Lamellar ichthyosis (IL) is a rare autosomal recessive genodermatosis with a defect of keratinization of the skin which results in a severe generalized cutaneous xerosis with dark brown bi...

Topical Treatment for Vestibulodynia, Vulvar Pain, in Postmenopausal Women Not Taking Hormones

This study will evaluate the use of topical 5% sinecatechins,(diluted Veregen) a botanical drug derived from green tea for the alleviation of pain in the vulvar vestibule that is a cause o...

PubMed Articles [0 Results]

None

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