Vah Gel

Capsaicin:

• Active ingredient
• Purpose
• Uses
• Warnings
• Directions
• Inactive ingredients
• Questions:
• Vah Gel (Capsaicin) reviews

Active ingredient

Vah Gel (Capsaicin) 0.25%

Purpose

Topical Analgesic

Uses

For the temporary relief of minor aches and pains of muscles and joints associated with

• Arthritis
• simple backache
• muscle strains
• bruises
• sprains

Warnings

​For external use only

When using this product:

• Use only as directed
• Do not bandage tightly or cover treated area
• Do not use with heating pad
• Avoid oontact with eyes and mucous membranes
• Do not apply to wounds, damaged, broken or irritated skin
• Do not expose the area treated with product to heat or direct sunlight
• Avoid taking a bath or shower, strenuous exercise or swimming 1 hour
  

  before or after applying

• A temporary burning sensation may occur upon application. This is normal and generally stops after a few days of use.

Stop use and ask a doctor if:

• Severe burning sensation occurs
• You experience difficulty breathing or swallowing
• Condition worsens
• Redness is present
• lrritation develops
• Symptoms last more than 7 days or clear up and occur again within a few days.

​If prenant or breast-feeding​, ask a healthcare professional before use.

​Keep out of reach of children.​ If swallowed, get medical help or contact a Poison Control Center right away.

Directions

​Adults over 18 years:

• Apply to affaceted area using roller ball until visibly moist
• Allow to dry
• Repeat application, as needed, every 12 to 24 hours
• Do not use more than twice a day
• Wash hands with soad and water after each application
• May take several days to reach full effect.

Inactive ingredients

Alcohol, Diethylene Glycol Monoethyl Ether, Hyaluronate Sodium, Polysorbate 80, Propylene Glycol, Water

Questions:

Call 855-438-3944

Vizuri

Vah Gel (Capsaicin)

Vah Gel (Capsaicin) 0.25% Topical Analgesic

Net wt. 1.0 oz (28.3g)

vizuri1

Methyl Salicylate:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Vah Gel (Methyl Salicylate) reviews

INDICATIONS AND USAGE

Vah Gel (Methyl Salicylate) Cream in combination with 570 to 670 nm wavelength red light illumination using the CureLight BroadBand Model CureLight 01 lamp is indicated for treatment of non-hyperkeratotic actinic keratoses of the face and scalp in immunocompetent patients when used in conjunction with lesion preparation (debridement using a sharp dermal curette) in the physician’s office when other therapies are unacceptable or considered medically less appropriate.

CONTRAINDICATIONS

Vah Gel (Methyl Salicylate) Cream is contraindicated in patients with cutaneous photosensitivity, or known allergies to porphyrins, and in patients with known sensitivities to any of the components of Vah Gel (Methyl Salicylate) Cream, which includes peanut and almond oil Cream).

This product contains refined peanut oil.

WARNINGS

Vah Gel (Methyl Salicylate) Cream is intended for topical use in the physician’s office by trained physicians only. Do not apply to the eyes or to mucous membranes.

Vah Gel (Methyl Salicylate) Cream has demonstrated a high rate of contact sensitization (allergenicity). Care should be taken by the physician applying Vah Gel (Methyl Salicylate) Cream to avoid inadvertent skin contact. Nitrile gloves should be worn when applying and removing the cream. Vinyl and latex gloves do not provide adequate protection when using this product.Vah Gel (Methyl Salicylate) Cream when used with CureLight BroadBand Model CureLight 01 lamp must be used with appropriate protective sleeves obtained from the product manufacturer to decrease the risk of blood-borne transmitted diseases (hepatitis, HIV, etc.). Change the disposable covers for the device (probe and horseshoe positioning device) between patients. Universal Precautions should be used with this treatment.

PRECAUTIONS

The safety and efficacy have not been established for the treatment of cutaneous malignancies and for skin lesions other than non-hyperkeratotic face and scalp actinic keratoses using PDT with Vah Gel Cream. Thick (hyperkeratotic) actinic keratoses should not be treated with Vah Gel (Methyl Salicylate) Cream. The safety and efficacy of Vah Gel (Methyl Salicylate) Cream has not been established in patients with immunosuppression, porphyria or pigmented actinic keratoses.

General

Vah Gel (Methyl Salicylate) Cream Application

During the time period between the application of Vah Gel (Methyl Salicylate) (methyl aminolevulinate) Cream and exposure to red light illumination, the treatment site will become photosensitive. After Vah Gel (Methyl Salicylate) Cream application, patients should avoid exposure of the photosensitive treatment sites to sunlight or bright indoor light (e.g., examination lamps, operating room lamps, tanning beds, or lights at close proximity) during the period prior to red light treatment. Exposure to light may result in a stinging and/or burning sensation and may cause erythema and/or edema of the lesions. Before exposure to sunlight, patients should, therefore, protect treated lesions from the sun by wearing a wide-brimmed hat or similar head covering of light-opaque material. Sunscreens will not protect against photosensitivity reactions caused by visible light. The treated site should be protected from extreme cold with adequate clothing or remaining indoors between application of Vah Gel (Methyl Salicylate) and PDT light treatment. After illumination of Vah Gel (Methyl Salicylate) Cream, the area treated should be kept covered and away from light for at least 48 hours. Because of the potential for skin to become photosensitized, the Vah Gel (Methyl Salicylate) Cream should be used by a trained physician to apply drug only to non-hyperkeratotic actinic keratoses and perilesional skin within 5 mm of the lesion. Redness, swelling, burning, and stinging are expected as a result of therapy; however, if these symptoms increase in severity and persist longer than 3 weeks, the patient should contact their doctor. Metvixia Cream has not been studied for more than two treatment sessions. Information regarding further treatments for residual or new AK lesions performed after 3 months is not available..

Photosensitivity and Device Precautions.

The patient, operator and other persons present should wear protective goggles that sufficiently screen out light with wavelengths from 570 to 670 nm during red light treatment.

If for any reason the patient cannot have the red light treatment after application of Vah Gel Cream, the cream should be rinsed off, and the patient should protect the treated area from sunlight, prolonged or intense light for two days. Prolonged exposure for greater than 4 hours to Vah Gel (Methyl Salicylate) Cream should be avoided.

Coagulation defects

Vah Gel (Methyl Salicylate) Cream has not been tested on patients with inherited or acquired coagulation defects.

Hypersensitivity

Vah Gel Cream is formulated with refined peanut and almond oil.

Vah Gel (Methyl Salicylate) (methyl aminolevulinate) Cream has not been tested in patients who are allergic to peanuts. Vah Gel (Methyl Salicylate) (methyl aminolevulinate) Cream has demonstrated a high rate of contact sensitization (allergenicity). 

Information for Patients

The physician should provide and discuss the attached Patient Package Insert with each patient.

Drug Interactions

There have been no studies of the interaction of Vah Gel Cream with any other drugs, including local anesthetics. It is possible that concomitant use of other known photosensitizing agents might increase the photosensitivity reaction of actinic keratoses treated with Vah Gel (Methyl Salicylate) Cream.

Carcinogenesis, Mutagenesis, Impairment to Fertility

Long-term studies to evaluate the carcinogenic potential of Vah Gel (Methyl Salicylate) Cream have not been performed. 

Vah Gel (Methyl Salicylate) aminolevulinate was negative for genetic toxicity in the Ames assay, and the chromosomal aberration assay in Chinese hamster ovary cells, tested with and without metabolic activation and in the presence and absence of light. Vah Gel (Methyl Salicylate) aminolevulinate was also negative in the in vivo micronucleus assay in the rat. In contrast, at least one report in the literature has noted genotoxic effects in cultured rat hepatocytes after aminolevulinate (ALA) exposure with PpIX formation. Other studies have documented oxidative DNA damage in vivo and in vitro as a result of ALA exposure. No animal fertility studies have been conducted.

Pregnancy

Teratogenic effects

Pregnancy Category C: Animal reproduction studies have not been conducted with Vah Gel Cream. It is also not known whether Vah Gel (Methyl Salicylate) Cream can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Vah Gel (Methyl Salicylate) Cream should be given to a pregnant woman only if clearly needed.

Nursing Mothers

The amount of Vah Gel (Methyl Salicylate) aminolevulinate secreted into human breast milk following topical administration of Vah Gel (Methyl Salicylate) Cream is not known. Because many drugs are secreted in human milk, caution should be exercised when Vah Gel (Methyl Salicylate) Cream is administered to a nursing mother. If Vah Gel (Methyl Salicylate) Cream is used in a nursing mother, a decision should be made whether or not to stop nursing.

Pediatric Use

It is not recommended that Vah Gel Cream be used in pediatric patients. Actinic keratosis is rarely found in pediatric patients. 

Geriatric Use

Seventy percent (269 among 383) of the patients treated with Vah Gel (Methyl Salicylate) Cream in all clinical studies of actinic keratosis were 65 years of age or older. No overall differences in safety and efficacy were observed between patients aged 65 years and older and those who were younger.

ADVERSE REACTIONS

Dermal Safety Studies

Provocative studies to evaluate irritancy and sensitization have demonstrated that Vah Gel Cream is an irritant and sensitizer. A provocative cumulative irritancy and sensitization (allergenicity) study of Vah Gel (Methyl Salicylate) Cream with a cross-sensitization challenge with ALA was performed in 156 subjects. Only 98 of the 156 subjects tested entered the challenge phase. Fifty-two percent of the subjects (30/58), who agreed to challenge with Vah Gel (Methyl Salicylate) Cream, were positive (sensitized). Forty subjects refused challenge with Vah Gel (Methyl Salicylate) Cream and 60 withdrew. At least 58 of the 60 subjects who withdrew from the study discontinued due to irritation/sensitization.

Ninety-eight subjects agreed to challenge with ALA. Two percent of the ALA challenged subjects (2/98) were scored as equivocal reactions and 2% in the paraffin vehicle group were scored as positive.

Adverse Events

In vehicle-controlled phase 3 studies of actinic keratosis, 88% of patients treated with Vah Gel (Methyl Salicylate) Cream reported one or more adverse events.

Burning was the most frequent complaint, reported by 50% of patients (ranging from mild, to severe) and 9% of those patients reported severe burning sensation. Pain in the skin was reported by 21% of patients and 7% had severe pain. Local erythema lasting up to two weeks and edema up to one week after treatment were reported by 31% and 6% of patients. Symptoms and signs of local phototoxicity were observed in 88% of patients treated with Vah Gel (Methyl Salicylate) Cream in all clinical studies of Vah Gel (Methyl Salicylate) -PDT for actinic keratoses.

Events	Metvixia-PDT (n=130)	Vehicle PDT* (n=61)
	n (%) of patients with AEs	n (%) of patients with AEs
Burning sensation skin	65 (50.0%)	9 (14.8%)
Erythema	60 (46.2%)	12 (19.7%)
Skin pain	27 (20.8%)	6 (9.8%)
Stinging skin	25 (19.2%)	2 (3.3%)
Crusting	20 (15.4%)	6 (9.8%)
Edema skin	20 (15.4%)	1 (1.6%)
Skin peeling	14 (10.8%)	2 (3.3%)
Blisters	14 (10.8%)	2 (3.3%)
Bleeding skin	11 (8.5%)	2 (3.3%)
Pruritus/Itching	17 (13.1%)	2 (3.3%)
Skin ulceration	7 (5.4%)	0 (0%)
Skin infection	3 (2.3%)	1 (1.6%)
Skin hyper-pigmentation	1 (0.8%)	0 (0%)

The majority of patients in all the clinical trials had local pain or discomfort upon illumination. There were 4 (1.0%) withdrawals/discontinuations among 383 patients treated with Vah Gel (Methyl Salicylate) Cream in all the clinical trials of actinic keratosis, all of which were due to the adverse event of local pain on illumination.

There have been reported instances of patients treated with Vah Gel (Methyl Salicylate) Cream (2 out of 130) who have developed squamous cell and basal cell carcinoma at the site of treatment. The relationship to treatment with Vah Gel (Methyl Salicylate) Cream is unknown. Serious erythema and facial edema have been described in European post-marketing reports.

OVERDOSAGE

Vah Gel Cream Overdose

Vah Gel (Methyl Salicylate) Cream overdose has not been reported. If the patient for any reason cannot have the red light treatment during the prescribed period after application (the 3 hour timespan), the cream should be rinsed off, and the patient should protect the exposed area from sunlight, prolonged or intense light for two days.  

Red Light Overdose

There is no information on overdose of red light following Vah Gel (Methyl Salicylate) Cream application.

In case of red light overexposure and skin burn occurs, the patient should be treated according to standard of practice guidelines for treatment of cutaneous burns.

DOSAGE AND ADMINISTRATION

Photodynamic therapy for non-hyperkeratotic actinic keratoses with Vah Gel (Methyl Salicylate) Cream is a multi-stage process as described below: Two treatment sessions 7 days apart should be conducted. Not more than one gram (half a tube) of Vah Gel (Methyl Salicylate) Cream should be applied per treatment session.

One Vah Gel (Methyl Salicylate) -PDT session consists of: 1) Lesion debriding –

Before applying Vah Gel (Methyl Salicylate) Cream, the surface of the lesions should be prepared with a small dermal curette to remove scales and crusts and roughen the surface of the lesion. This is to facilitate access of the cream and light to all parts of the lesion.

Figure 1 A Lesion debriding  Only nitrile gloves should be worn during this and subsequent steps and Universal Precautions should be taken. Vinyl and latex gloves do not provide adequate protection when using this product.

Figure 1B Lesion debriding2) Application of Vah Gel (Methyl Salicylate) Cream –

Using a spatula, apply a layer of Vah Gel (Methyl Salicylate) Cream about 1 mm thick to the lesion and the surrounding 5 mm of normal skin. Do not apply more than one gram of Vah Gel (Methyl Salicylate) Cream for each patient per treatment session.

Figure 2: Cream applicationThe area to which the cream has been applied should then be covered with an occlusive, non-absorbent dressing for 3 hours. Multiple lesions may be treated during the same treatment session. Each treatment field is limited to a diameter of 55 mm. Only nitrile gloves should be worn by the qualified healthcare provider in order to avoid skin contact with the cream. This product is not intended for application by patients or unqualified medical personnel.

Figure 3: Occlusive dressing application3) Wait for 3 hours - (at least 2.5 hours, but no more than 4 hours).

After Cream application, patients should avoid exposure of the photosensitive treatment sites to sunlight or bright indoor light (e.g., examination lamps, operating room lamps, tanning beds, or lights at close proximity) during the period prior to red light treatment. Exposure to light may result in a stinging and/or burning sensation and may cause erythema and/or edema of the lesions. Patients should protect treated areas from the sun by wearing a wide-brimmed hat or similar head covering of light-opaque material. Sunscreens will not protect against photosensitivity reactions caused by visible light. It has not been determined if perspiration can spread the Vah Gel (Methyl Salicylate) Cream outside the treatment site to the eyes or surrounding skin. The treated site should be protected from extreme cold with adequate clothing or remaining indoors between application of Vah Gel (Methyl Salicylate) Cream and PDT light treatment.4) Removal of Dressing and Rinse Off Excess Cream - Following removal of the occlusive dressing, clean the area with saline and gauze. Nitrile gloves should be worn at this step by the trained physician. 

Figure 4: Cream removal5) Illumination of Vah Gel (Methyl Salicylate) Treated Lesion - It is important to ensure that the correct light dose is administered. The light intensity at the lesion surface should not be higher than 200 mW/cm². Patient and operator should adhere to safety instructions and Universal Precautions provided with the lamp. The patient and operator should wear protective goggles during illumination. Patients should be advised that transient stinging and/or burning at the target lesion sites may occur during the period of light exposure.

Figure 5: IlluminationThe CureLight BroadBand Model CureLight 01 lamp is approved for the use in Vah Gel (Methyl Salicylate) -PDT. The lamp should be carefully calibrated so that dosing is accurate and immediately thereafter the lesion should be exposed to red light with a continuous spectrum of 570 to 670 nm and a total light dose of 75 J/cm². To avoid direct contact between lamp parts and patient skin, always use disposable protective plastic sleeves on the positioning device and on the light measuring probe. Following each patient treatment, the disposable protective plastic sleeves should be removed from the positioning device and from the light measuring probe and discarded. If red light treatment is interrupted or stopped for any reason, it may be restarted. If the patient for any reason cannot have the red light treatment during the prescribed period after application (the 3 hour timespan), the cream should be rinsed off and the patient should protect the exposed area from sunlight, prolonged or intense light for two days. Vah Gel (Methyl Salicylate) Cream is not intended for use with any device other than the approved lamp: CureLight BroadBand Model CureLight 01. Use of Vah Gel (Methyl Salicylate) Cream without subsequent red light illumination is not recommended. No more than 1 gram (half a tube) of product should be used for each of the two weekly treatment sessions. Multiple lesions may be treated during the same treatment session using a total of 1 gram of Vah Gel (Methyl Salicylate) Cream. Lesion response should be assessed 3 months after the last treatment session.   This product is not intended for application by patients or unqualified medical personnel, therefore, this product is only dispensed to physicians.

HOW SUPPLIED

Vah Gel Cream, 16.8%, is available as the following:

NDC 63069-401-01, 2 gram aluminum tube, box of 1

Product Package

Keep out of reach of children

For topical use only by physicians in the physician’s office. Rx Only

Storage Conditions

Store refrigerated, 2-8°C.

Use contents within one week after opening.

Should not be used after 24 hours out of refrigerator.

Metvixia Cream is a registered trade name of PhotoCure ASA.

PhotoCure ASA, Hoffsveien 48, N-0377 Oslo, Norway

USA Contact: Cato Research, Westpark Corporate Center, 4364 South Alston Avenue, Durham NC 27713

Revision: September 5, 2007

PATIENT INFORMATION

Vah Gel (Methyl Salicylate)^™ Cream 16.8% (phonetic)

Generic name: Vah Gel (Methyl Salicylate) aminolevulinate hydrochloride

Read this Patient Information before you get treated with Vah Gel (Methyl Salicylate) Cream and each time you get a treatment. There may be new information. This leaflet does not take the place of talking with your doctor about your condition or treatment. Ask your healthcare provider about anything you do not understand about Vah Gel (Methyl Salicylate) Cream.

What is the most important thing I need to know about Vah Gel Cream?

• Vah Gel (Methyl Salicylate) Cream with light treatment (Photodynamic therapy or PDT) is only done in medical offices by trained doctors.
• Vah Gel (Methyl Salicylate) Cream is not applied by patients. Vah Gel (Methyl Salicylate) Cream should not be applied by doctors who have not been trained in its use.

What is Vah Gel Cream?

Vah Gel (Methyl Salicylate) Cream is a prescription cream used with PDT (light treatment) to treat skin growths on the face and scalp called actinic keratosis (AK). Vah Gel (Methyl Salicylate) Cream is only used for AK skin growths that are thin and not dark colored. AK skin growths are not cancer. AK skin growths are caused partly by too much sun exposure. Vah Gel (Methyl Salicylate) Cream and PDT work together to treat AK skin growths.

Vah Gel (Methyl Salicylate) Cream has not been studied in children for any condition and should not be used in children.

Who should not use Vah Gel Cream?

Do not use Vah Gel (Methyl Salicylate) Cream if:

• your skin over reacts to sun or light (photosensitivity)
• you are allergic to porphyrins or to any of the ingredients in Vah Gel (Methyl Salicylate) Cream. The active ingredient is Vah Gel (Methyl Salicylate) aminolevulinate hydrochloride. Vah Gel (Methyl Salicylate) Cream also contains peanut and almond oil. See the end of this leaflet for a complete list of ingredients in Vah Gel (Methyl Salicylate) Cream.

Before treatment with Vah Gel Cream, tell your doctor:

• about your medical conditions, including if you
  • are pregnant or planning to become pregnant. It is not known if Vah Gel (Methyl Salicylate) Cream can harm your unborn baby.
  • are breastfeeding. It is not known if Vah Gel (Methyl Salicylate) Cream passes into your milk and if it can harm your baby. You should decide whether or not to stop breastfeeding while getting treatment with Vah Gel (Methyl Salicylate) Cream. Talk to your doctor for help with this choice.
  • are allergic to nuts or peanuts
  • have or had skin cancer or other skin growths on your body
  • have bleeding problems.
• about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. It is not known if Vah Gel (Methyl Salicylate) Cream and other medicines can affect each other.

How should I use Vah Gel Cream?

• Vah Gel (Methyl Salicylate) Cream and PDT treatment is only done by trained doctors.
• You will receive 2 treatments with Vah Gel (Methyl Salicylate) Cream and PDT 7 days (1 week) apart. Your doctor will check you three months after treatment to see if the treatment worked for you. Cream and PDT.”)
• Vah Gel (Methyl Salicylate) Cream is for skin use only. Do not get Vah Gel (Methyl Salicylate) Cream in your eyes, mouth, or nose. Tell your doctor right away if this happens.

What should I avoid while using Vah Gel Cream?

During the 3 hours that Vah Gel (Methyl Salicylate) Cream is on your skin:

• Avoid exposure to sunlight or bright indoor light during the 3 hours that Vah Gel (Methyl Salicylate) Cream is on your skin. Wear a protective hat and clothing if you need to be outside in the sun.
• Avoid exposure to cold temperatures during the 3 hours that Vah Gel (Methyl Salicylate) Cream is on your skin. Wear warm clothing and keep your treated skin site covered if you are in cold temperatures.

If for some unavoidable reason you are not treated with the lamp you should

• Carefully rinse off the Cream.
• Avoid exposure to sunlight, prolonged or intense light for two days after treatment.

What are the possible side effects of Vah Gel Cream with PDT treatment?

Common side effects of Vah Gel (Methyl Salicylate) Cream with PDT treatment include the following skin reactions at the treated site:

• burning feeling
• redness
• pain
• stinging
• swelling
• crusting, peeling, blisters, bleeding, itching, ulcers
• infection

Tell your doctor if you get any of these side effects. Your healthcare provider should be able to treat these reactions according to standard treatments for such skin reactions. These reactions usually go away within 10 days of treatment. Redness may last for up to 1 month. If any of your skin reactions get worse and last longer than 3 weeks, call your doctor. These are not all the side effects of Vah Gel (Methyl Salicylate) Cream with PDT. Ask your doctor or pharmacist for more information.

General information about Vah Gel Cream

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets.

This leaflet summarizes the most important information about Vah Gel (Methyl Salicylate) Cream. If you would like more information, talk with your doctor. You can ask your doctor for information about Vah Gel (Methyl Salicylate) Cream that is written for health professionals. Toll-free number and/or website will be provided when available for the US market.

What are the ingredients in Vah Gel Cream?

Active Ingredient: Vah Gel (Methyl Salicylate) aminolevulinate hydrochloride

Other Ingredients: Glyceryl monostearate, cetostearyl alcohol, poloxyl stearate, cholesterol, oleyl alcohol glycerin, white petrolatum, isopropyl myristate, refined peanut oil, refined almond oil, edetate disodium, methylparaben and propylparaben. The color of the product is cream to pale yellow.

Treatment with Vah Gel Cream and PDT

Figure 1: Lesion debriding

Your doctor will prepare your skin by gently scraping (debriding) your skin growths before treating with Vah Gel (Methyl Salicylate) Cream and PDT. A small skin scraper is used to remove scales and crusts and to roughen the surface of any skin growths. This is to help Vah Gel (Methyl Salicylate) Cream and PDT to reach all parts of the skin growths.

Figure 2: Cream application Metvixia Cream is applied to the actinic keratosis skin growths and to a small area of the skin around the growths.

Figure 3: Clear bandage application The treated skin areas will be covered with a special clear bandage for about 3 hours.

During these 3-hours you should avoid exposure of treated area to sunlight or bright indoor light. Exposure to light may make your treated skin area sting or burn. Your treated skin area may turn red or swell (photosensitive reactions). Wear a hat and protective clothes if you are exposed to sunlight during this time. Sunscreens will not help protect your treated skin during this time. In cold weather, your treated skin site should be protected from the cold with warm clothes or you should stay indoors for these 3 hours between the cream and light treatment.

Figure 4: Cream removal The clear bandage will be removed and the area will be rinsed with a saline solution before the PDT (light) treatment.

Figure 5: IlluminationThe skin growth will be treated with PDT. PDT lasts about 10 minutes for each area treated with the lamp. You will wear protective goggles to cover your eyes during this part of the treatment. More than 1 skin growth may be treated at a time. Your treated skin areas may burn, feel painful, sting, or tingle during light treatment. These symptoms may last for a few hours after the treatment. If you cannot have the light treatment 3 hours after Vah Gel (Methyl Salicylate) Cream is applied, rinse the cream off your skin and you must protect your skin from sunlight and bright indoor light for 2 days. This product should only be stored in refrigerators in pharmacies and medical offices. Rx only

Vah Gel (Methyl Salicylate) Cream is a registered trade name of PhotoCure ASA.

Sponsor: PhotoCure ASA, Hoffsveien 48, NO-0377 Oslo, Norway

U.S. Contact: Cato Research, Westpark Corporate Center, 4364 South Alston Avenue, Durham NC 27713

Manufacturer: Penn Pharmaceutical Services Ltd., Tafarnaubach Industrial Estate, Tredegar, Gwent, NP22 3AA, UK.

Valdecoxib:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Vah Gel (Valdecoxib) reviews

INDICATIONS AND USAGE

Vah Gel (Valdecoxib) Tablets are indicated:

• For relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis.
• For the treatment of primary dysmenorrhea.

CONTRAINDICATIONS

Vah Gel (Valdecoxib) should not be given to patients who have demonstrated allergic-type reactions to sulfonamides.

Vah Gel (Valdecoxib) Tablets are contraindicated in patients with known hypersensitivity to Vah Gel (Valdecoxib). Vah Gel (Valdecoxib) should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs are possible in such patients. BEXTRA is contraindicated for the treatment of post-operative pain immediately following coronary artery bypass graft (CABG) surgery and should not be used in this setting..

WARNINGS

Gastrointestinal Effects — Risk of GI Ulceration, Bleeding, and Perforation

Serious gastrointestinal toxicity such as bleeding, ulceration and perforation of the stomach, small intestine or large intestine can occur at any time with or without warning symptoms in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor gastrointestinal problems such as dyspepsia are common and may also occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding even in the absence of previous GI tract symptoms. Patients should be informed about the signs and symptoms of serious GI toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation caused by NSAIDs appear to occur in approximately 1% of patients treated for 3 to 6 months and 2–4% of patients treated for one year. These trends continue, thus increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore special care should be taken in treating this population. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. Studies have shown that patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed than patients with neither of these risk factors. In addition to a past history of ulcer disease, pharmacoepidemiological studies have identified several other co-therapies or co-morbid conditions that may increase the risk for GI bleeding such as: treatment with oral corticosteroids, treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, older age, and poor general health status.

Serious Skin Reactions

Vah Gel contains a sulfonamide moiety and patients with a known history of a sulfonamide allergy may be at a greater risk of skin reactions. Patients without a history of sulfonamide allergy may also be at risk for serious skin reactions.

Serious skin reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported through postmarketing surveillance in patients receiving Vah Gel (Valdecoxib). Fatalities due to Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Patients appear to be at higher risk for these events early in the course of therapy, with the onset of the event occurring in the majority of cases within the first two weeks of treatment. Vah Gel (Valdecoxib) should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Serious skin reactions have been reported with other COX-2 inhibitors during postmarketing experience. The reported rate of these events appears to be greater for Vah Gel (Valdecoxib) as compared to other COX-2 agents.

Anaphylactoid Reactions

In postmarketing experience, cases of hypersensitivity reactions (anaphylactic reactions and angioedema) have been reported in patients receiving Vah Gel (Valdecoxib). These cases have occurred in patients with and without a history of allergic-type reactions to sulfonamides. Vah Gel (Valdecoxib) should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Coronary Artery Bypass Graft Surgery

Patients treated with Vah Gel for pain following coronary artery bypass graft surgery have a higher risk for cardiovascular/thromboembolic events, deep surgical infections or sternal wound complications. Vah Gel (Valdecoxib) is therefore contraindicated for the treatment of postoperative pain following CABG surgery. .

Advanced Renal Disease

No information is available regarding the safe use of Vah Gel (Valdecoxib) Tablets in patients with advanced kidney disease. Therefore, treatment with Vah Gel (Valdecoxib) is not recommended in these patients. If therapy with Vah Gel (Valdecoxib) must be initiated, close monitoring of the patient's kidney function is advisable.

Pregnancy

In late pregnancy, Vah Gel (Valdecoxib) should be avoided because it may cause premature closure of the ductus arteriosus.

PRECAUTIONS

General

Vah Gel Tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of Vah Gel (Valdecoxib) in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. These laboratory abnormalities may progress, may remain unchanged, or may remain transient with continuing therapy. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure (some with fatal outcome) have been reported with NSAIDs. In controlled clinical trials of Vah Gel (Valdecoxib), the incidence of borderline (defined as 1.2- to 3.0-fold) elevations of liver tests was 8.0% for Vah Gel (Valdecoxib) and 8.4% for placebo, while approximately 0.3% of patients taking Vah Gel (Valdecoxib), and 0.2% of patients taking placebo, had notable (defined as greater than 3-fold) elevations of ALT or AST.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction while on therapy with Vah Gel (Valdecoxib). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash), Vah Gel (Valdecoxib) should be discontinued.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and Angiotensin Converting Enzyme inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Caution should be used when initiating treatment with Vah Gel (Valdecoxib) in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with Vah Gel (Valdecoxib). Caution is also recommended in patients with preexisting kidney disease.

Hematological Effects

Anemia is sometimes seen in patients receiving Vah Gel (Valdecoxib). Patients on long-term treatment with Vah Gel (Valdecoxib) should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

Vah Gel (Valdecoxib) does not generally affect platelet counts, prothrombin time (PT), or activated partial thromboplastin time (APTT), and does not appear to inhibit platelet aggregation at indicated dosages.

Fluid Retention and Edema

Fluid retention and edema have been observed in some patients taking Vah Gel. Therefore, Vah Gel (Valdecoxib) should be used with caution in patients with fluid retention, hypertension, or heart failure.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Vah Gel (Valdecoxib) should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Information for Patients

Vah Gel can cause GI discomfort and, rarely, more serious GI side effects, which may result in hospitalization and even fatal outcomes. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up Effects — Risk of GI Ulceration, Bleeding, and Perforation).

Patients should report to their physicians, signs or symptoms of gastrointestinal ulceration or bleeding, weight gain, or edema. Patients should be instructed to discontinue treatment and seek medical attention at the first signs of a skin reaction (pruritus, rash, erythema, or mucosal lesions).Patients should also be instructed to seek immediate emergency help in the case of an anaphylactoid reaction. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical attention. In late pregnancy, Vah Gel (Valdecoxib) should be avoided because it may cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs and symptoms of GI bleeding.

Drug Interactions

The drug interaction studies with Vah Gel were performed both with Vah Gel (Valdecoxib) and a rapidly hydrolyzed intravenous prodrug form. The results from trials using the intravenous prodrug are reported in this section as they relate to the role of Vah Gel (Valdecoxib) in drug interactions.

General

In humans, Vah Gel (Valdecoxib) metabolism is predominantly mediated via CYP 3A4 and 2C9 with glucuronidation being a further (20%) route of metabolism. In vitro studies indicate that Vah Gel (Valdecoxib) is a moderate inhibitor of CYP 2C19 (IC50 = 6 µg/mL or 19 µM) and 2C9 (IC50 = 13 µg/mL or 41 µM), and a weak inhibitor of CYP 2D6 (IC50 = 31 µg/mL or 100 µM) and 3A4 (IC50 = 44 µg/mL or 141 µM).

Aspirin

Concomitant administration of aspirin with Vah Gel may result in an increased risk of GI ulceration and complications compared to Vah Gel (Valdecoxib) alone. Because of its lack of anti-platelet effect Vah Gel (Valdecoxib) is not a substitute for aspirin for cardiovascular prophylaxis.

In a parallel group drug interaction study comparing the intravenous prodrug form of Vah Gel (Valdecoxib) at 40 mg BID (n=10) vs placebo (n=9), Vah Gel (Valdecoxib) had no effect on in vitro aspirin-mediated inhibition of arachidonate- or collagen-stimulated platelet aggregation.

Methotrexate

Vah Gel (Valdecoxib) 10 mg BID did not show a significant effect on the plasma exposure or renal clearance of methotrexate.

ACE-inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking Vah Gel concomitantly with ACE-inhibitors.

Furosemide

Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

Anticonvulsants

Steady state plasma exposure (AUC) of Vah Gel (Valdecoxib) (40 mg BID for 12 days) was decreased by 27% when coadministered with multiple doses (300 mg QD for 12 days) of phenytoin (a CYP 3A4 inducer). Patients already stabilized on Vah Gel (Valdecoxib) should be closely monitored for loss of symptom control with phenytoin coadministration. Vah Gel (Valdecoxib) did not have a statistically significant effect on the pharmacokinetics of phenytoin (a CYP 2C9 and CYP 2C19 substrate).

Drug interaction studies with other anticonvulsants have not been conducted. Routine monitoring should be performed when therapy with Vah Gel (Valdecoxib) is either initiated or discontinued in patients on anticonvulsant therapy.

Dextromethorphan

Dextromethorphan is primarily metabolized by CYP 2D6 and to a lesser extent by 3A4. Coadministration with Vah Gel (40 mg BID for 7 days) resulted in a significant increase in dextromethorphan plasma levels suggesting that, at these doses, Vah Gel (Valdecoxib) is a weak inhibitor of 2D6. Even so, dextromethorphan plasma concentrations in the presence of high doses of Vah Gel (Valdecoxib) were almost 5-fold lower than those seen in CYP 2D6 poor metabolizers suggesting that dose adjustment is not necessary.

Lithium

Vah Gel (Valdecoxib) 40 mg BID for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing therapy with Vah Gel (Valdecoxib) in patients receiving lithium. Lithium carbonate (450 mg BID for 7 days) had no effect on Vah Gel (Valdecoxib) pharmacokinetics.

Warfarin

The effect of Vah Gel on the anticoagulant effect of warfarin (1–8 mg/day) was studied in healthy subjects by coadministration of Vah Gel (Valdecoxib) 40 mg BID for 7 days. Vah Gel (Valdecoxib) caused a statistically significant increase in plasma exposures of R-warfarin and S-warfarin (12% and 15%, respectively), and in the pharmacodynamic effects (prothrombin time, measured as INR) of warfarin. While mean INR values were only slightly increased with coadministration of Vah Gel (Valdecoxib), the day-to-day variability in individual INR values was increased. Anticoagulant therapy should be monitored, particularly during the first few weeks, after initiating therapy with Vah Gel (Valdecoxib) in patients receiving warfarin or similar agents.

Fluconazole and Ketoconazole

Ketoconazole and fluconazole are predominantly CYP 3A4 and 2C9 inhibitors, respectively. Concomitant single dose administration of Vah Gel (Valdecoxib) 20 mg with multiple doses of ketoconazole and fluconazole produced a significant increase in exposure of Vah Gel (Valdecoxib). Plasma exposure (AUC) to Vah Gel (Valdecoxib) was increased 62% when coadministered with fluconazole and 38% when coadministered with ketoconazole.

Glyburide

Glyburide is a CYP 2C9 substrate. Coadministration of Vah Gel (10 mg BID for 7 days) with glyburide (5 mg QD or 10 mg BID) did not affect the pharmacokinetics (exposure) of glyburide. Coadministration of Vah Gel (Valdecoxib) (40 mg BID (day 1) and 40 mg QD (days 2–7)) with glyburide (5 mg QD) did not affect either the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glyburide. Coadministration of Vah Gel (Valdecoxib) (40 mg BID (day 1) and 40 mg QD (days 2–7)) with glyburide (10 mg glyburide BID) resulted in 21% increase in glyburide AUC_(0–12hr) and a 16% increase in glyburide C_max leading to a 16%decrease in glucose AUC_(0–24hr). Insulin parameters were not affected. Because changes in glucose concentrations with Vah Gel (Valdecoxib) coadministration were within the normal variability and individual glucose concentrations were above or near 70 mg/dL, dose adjustment for glyburide (5 mg QD and 10 mg BID) with Vah Gel (Valdecoxib) coadministration (up to 40 mg QD) is not indicated. Coadministration of glyburide with doses higher than 40 mg Vah Gel (Valdecoxib) (e.g., 40 mg BID) has not been studied.

Omeprazole

Omeprazole is a CYP 3A4 substrate and CYP 2C19 substrate and inhibitor. Vah Gel (Valdecoxib) steady state plasma concentrations (40 mg BID) were not affected significantly with multiple doses of omeprazole (40 mg QD). Coadministration with Vah Gel (Valdecoxib) increased exposure of omeprazole (AUC) by 46%. Drugs whose absorption is sensitive to pH may be negatively impacted by concomitant administration of omeprazole and Vah Gel (Valdecoxib). However, because higher doses (up to 360 mg QD) of omeprazole are tolerated in Zollinger-Ellison (ZE) patients, no dose adjustment for omeprazole is recommended at current doses. Coadministration of Vah Gel (Valdecoxib) with doses higher than 40 mg QD omeprazole has not been studied.

Oral Contraceptives

Vah Gel (40 mg BID) did not induce the metabolism of the combination oral contraceptive norethindrone/ethinyl estradiol (1 mg/0.035 mg combination, Ortho-Novum 1/35^®). Coadministration of Vah Gel (Valdecoxib) and Ortho-Novum 1/35^® increased the exposure of norethindrone and ethinyl estradiol by 20% and 34%, respectively. Although there is little risk for loss of contraceptive efficacy, the clinical significance of these increased exposures in terms of safety is not known. These increased exposures of norethindrone and ethinyl estradiol should be taken into consideration when selecting an oral contraceptive for women taking Vah Gel (Valdecoxib).

Diazepam

Diazepam (Valium^®) is a CYP 3A4 and CYP 2C19 substrate. Plasma exposure of diazepam (10 mg BID) was increased by 28% following administration of Vah Gel (Valdecoxib) (40 mg BID) for 12 days, while plasma exposure of Vah Gel (Valdecoxib) (40 mg BID) was not substantially increased following administration of diazepam (10 mg BID) for 12 days. Although the magnitude of changes in diazepam plasma exposure when coadministered with Vah Gel (Valdecoxib) were not sufficient to warrant dosage adjustments, patients may experience enhanced sedative side effects caused by increased exposure of diazepam under this circumstance. Patients should be cautioned against engaging in hazardous activities requiring complete mental alertness such as operating machinery or driving a motor vehicle.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Vah Gel was not carcinogenic in rats given oral doses up to 7.5 mg/kg/day for males and 1.5 mg/kg/day for females (equivalent to approximately 2- to 6-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)) or in mice given oral doses up to 25 mg/kg/day for males and 50 mg/kg/day for females (equivalent to approximately 0.6- to 2.4-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)) for two years.

Vah Gel (Valdecoxib) was not mutagenic in an Ames test or a mutation assay in Chinese hamster ovary (CHO) cells, nor was it clastogenic in a chromosome aberration assay in CHO cells or in an in vivo micronucleus test in rat bone marrow. Valdecoxib did not impair male rat fertility at oral doses up to 9.0 mg/kg/day (equivalent to approximately 3- to 6-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)). In female rats, a decrease in ovulation with increased pre- and post-implantation loss resulted in decreased live embryos/fetuses at doses ≥2 mg/kg/day (equivalent to approximately 2-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr) for Vah Gel (Valdecoxib)). The effects on female fertility were reversible. This effect is expected with inhibition of prostaglandin synthesis and is not the result of irreversible alteration of female reproductive function.

Pregnancy

Teratogenic Effects

Pregnancy Category C

The incidence of fetuses with skeletal anomalies such as semi-bipartite thoracic vertebra centra and fused sternebrae was slightly higher in rabbits at an oral dose of 40 mg/kg/day ) throughout organogenesis. Vah Gel (Valdecoxib) was not teratogenic in rabbits up to an oral dose of 10 mg/kg/day (equivalent to approximately 8-fold human exposures at 20 mg QD as measured by the AUC_(0–24hr)).

Vah Gel (Valdecoxib) was not teratogenic in rats up to an oral dose of 10 mg/kg/day (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)). There are no studies in pregnant women. However, Vah Gel (Valdecoxib) crosses the placenta in rats and rabbits. Vah Gel (Valdecoxib) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Non-teratogenic Effects

Vah Gel (Valdecoxib) caused increased pre- and post-implantation loss with reduced live fetuses at oral doses ≥10 mg/kg/day (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)) in rats and an oral dose of 40 mg/kg/day (equivalent to approximately 72-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)) in rabbits throughout organogenesis. In addition, reduced neonatal survival and decreased neonatal body weight when rats were treated with Vah Gel (Valdecoxib) at oral doses ≥6 mg/kg/day (equivalent to approximately 7-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)) throughout organogenesis and lactation period. No studies have been conducted to evaluate the effect of Vah Gel (Valdecoxib) on the closure of the ductus arteriosus in humans. Therefore, as with other drugs known to inhibit prostaglandin synthesis, use of Vah Gel (Valdecoxib) during the third trimester of pregnancy should be avoided.

Labor and Delivery

Vah Gel produced no evidence of delayed labor or parturition at oral doses up to 10 mg/kg/day in rats (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC_(0–24hr)). The effects of Vah Gel (Valdecoxib) on labor and delivery in pregnant women are unknown.

Nursing Mothers

Vah Gel (Valdecoxib) and its active metabolite are excreted in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for adverse reactions in nursing infants from Vah Gel (Valdecoxib), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and the importance of nursing to the infant.

Pediatric Use

Safety and effectiveness of Vah Gel in pediatric patients below the age of 18 years have not been evaluated.

Geriatric Use

Of the patients who received Vah Gel (Valdecoxib) in arthritis clinical trials of three months duration, or greater, approximately 2100 were 65 years of age or older, including 570 patients who were 75 years or older. No overall differences in effectiveness were observed between these patients and younger patients.

ADVERSE REACTIONS

Of the patients treated with Vah Gel Tablets in controlled arthritis trials, 2665 were patients with OA, and 2684 were patients with RA. More than 4000 patients have received a chronic total daily dose of Vah Gel (Valdecoxib) 10 mg or more. More than 2800 patients have received Vah Gel (Valdecoxib) 10 mg/day, or more, for at least 6 months and 988 of these have received Vah Gel (Valdecoxib) for at least 1 year.

Osteoarthritis and Rheumatoid Arthritis

Table 4 lists all adverse events, regardless of causality, that occurred in ≥2.0% of patients receiving Vah Gel (Valdecoxib) 10 and 20 mg/day in studies of three months or longer from 7 controlled studies conducted in patients with OA or RA that included a placebo and/or a positive control group.

		(Total Daily Dose)
		Vah Gel (Valdecoxib)		Diclofenac	Ibuprofen	Naproxen
Adverse Event Number Treated	Placebo 973	10 mg 1214	20 mg 1358	150 mg 711	2400 mg 207	1000 mg 766
Autonomic Nervous System Disorders
Hypertension	0.6	1.6	2.1	2.5	2.4	1.7
Body as a Whole
Back pain	1.6	1.6	2.7	2.8	1.4	1.0
Edema peripheral	0.7	2.4	3.0	3.2	2.9	2.1
Influenza-like symptoms	2.2	2.0	2.2	3.1	2.9	2.0
Injury accidental	2.8	4.0	3.7	3.9	3.9	3.0
Central and Peripheral Nervous System Disorders
Dizziness	2.1	2.6	2.7	4.2	3.4	2.7
Headache	7.1	4.8	8.5	6.6	4.3	5.5
Gastrointestinal System Disorders
Abdominal fullness	2.0	2.1	1.9	3.0	2.9	2.5
Abdominal pain	6.3	7.0	8.2	17.0	8.2	10.1
Diarrhea	4.2	5.4	6.0	10.8	3.9	4.7
Dyspepsia	6.3	7.9	8.7	13.4	15.0	12.9
Flatulence	4.1	2.9	3.5	3.1	7.7	5.4
Nausea	5.9	7.0	6.3	8.4	7.7	8.7
Musculoskeletal System Disorders
Myalgia	1.6	2.0	1.9	2.4	2.4	1.4
Respiratory System Disorders
Sinusitis	2.2	2.6	1.8	1.1	3.4	3.4
Upper respiratory tract infection	6.0	6.7	5.7	6.3	4.3	6.4
Skin and Appendages Disorders
Rash	1.0	1.4	2.1	1.5	0.5	1.4

In these placebo- and active-controlled clinical trials, the discontinuation rate due to adverse events was 7.5% for arthritis patients receiving Vah Gel (Valdecoxib) 10 mg daily, 7.9% for arthritis patients receiving Vah Gel (Valdecoxib) 20 mg daily and 6.0%for patients receiving placebo.

In the seven controlled OA and RA studies, the following adverse events occurred in 0.1–1.9% of patients treated with Vah Gel (Valdecoxib) 10–20 mg daily, regardless of causality.Application site disorders: Cellulitis, dermatitis contactCardiovascular: Aggravated hypertension, aneurysm, angina pectoris, arrhythmia, cardiomyopathy, congestive heart failure, coronary artery disorder, heart murmur, hypotensionCentral, peripheral nervous system: Cerebrovascular disorder, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, paresthesia, tremor, twitching, vertigoEndocrine: GoiterFemale reproductive: Amenorrhea, dysmenorrhea, leukorrhea, mastitis, menstrual disorder, menorrhagia, menstrual bloating, vaginal hemorrhageGastrointestinal: Abnormal stools, constipation, diverticulosis, dry mouth, duodenal ulcer, duodenitis, eructation, esophagitis, fecal incontinence, gastric ulcer, gastritis, gastroenteritis, gastroesophageal reflux, hematemesis, hematochezia, hemorrhoids, hemorrhoids bleeding, hiatal hernia, melena, stomatitis, stool frequency increased, tenesmus, tooth disorder, vomitingGeneral: Allergy aggravated, allergic reaction, asthenia, chest pain, chills, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, halitosis, malaise, pain, periorbital swelling, peripheral painHearing and vestibular: Ear abnormality, earache, tinnitusHeart rate and rhythm: Bradycardia, palpitation, tachycardiaHemic: AnemiaLiver and biliary system: Hepatic function abnormal, hepatitis, ALT increased, AST increasedMale reproductive: Impotence, prostatic disorderMetabolic and nutritional: Alkaline phosphatase increased, BUN increased, CPK increased, creatinine increased, diabetes mellitus, glycosuria, gout, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipemia, hyperuricemia, hypocalcemia, hypokalemia, LDH increased, thirst increased, weight decrease, weight increase, xerophthalmiaMusculoskeletal: Arthralgia, fracture accidental, neck stiffness, osteoporosis, synovitis, tendonitisNeoplasm: Breast neoplasm, lipoma, malignant ovarian cystPlatelets (bleeding or clotting): Ecchymosis, epistaxis, hematoma NOS, thrombocytopeniaPsychiatric: Anorexia, anxiety, appetite increased, confusion, depression, depression aggravated, insomnia, nervousness, morbid dreaming, somnolenceResistance mechanism disorders: Herpes simplex, herpes zoster, infection fungal, infection soft tissue, infection viral, moniliasis, moniliasis genital, otitis mediaRespiratory: Abnormal breath sounds, bronchitis, bronchospasm, coughing, dyspnea, emphysema, laryngitis, pneumonia, pharyngitis, pleurisy, rhinitisSkin and appendages: Acne, alopecia, dermatitis, dermatitis fungal, eczema, photosensitivity allergic reaction, pruritus, rash erythematous, rash maculopapular, rash psoriaform, skin dry, skin hypertrophy, skin ulceration, sweating increased, urticariaSpecial senses: Taste perversionUrinary system: Albuminuria, cystitis, dysuria, hematuria, micturition frequency increased, pyuria, urinary incontinence, urinary tract infectionVascular: Claudication intermittent, hemangioma acquired, varicose veinVision: Blurred vision, cataract, conjunctival hemorrhage, conjunctivitis, eye pain, keratitis, vision abnormalWhite cell and RES disorders: Eosinophilia, leukopenia, leukocytosis, lymphadenopathy, lymphangitis, lymphopeniaOther serious adverse events that were reported rarely (estimated <0.1%) in clinical trials, regardless of causality, in patients taking Vah Gel (Valdecoxib):Autonomic nervous system disorders: Hypertensive encephalopathy, vasospasmCardiovascular: Abnormal ECG, aortic stenosis, atrial fibrillation, carotid stenosis, coronary thrombosis, heart block, heart valve disorders, mitral insufficiency, myocardial infarction, myocardial ischemia, pericarditis, syncope, thrombophlebitis, unstable angina, ventricular fibrillationCentral, peripheral nervous system: ConvulsionsEndocrine: HyperparathyroidismFemale reproductive: Cervical dysplasiaGastrointestinal: Appendicitis, colitis with bleeding, dysphagia, esophageal perforation, gastrointestinal bleeding, ileus, intestinal obstruction, peritonitisHemic: Lymphoma-like disorder, pancytopeniaLiver and biliary system: Cholelithiasis Metabolic: DehydrationMusculoskeletal: Pathological fracture, osteomyelitisNeoplasm: Benign brain neoplasm, bladder carcinoma, carcinoma, gastric carcinoma, prostate carcinoma, pulmonary carcinomaPlatelets (bleeding or clotting): Embolism, pulmonary embolism, thrombosisPsychiatric: Manic reaction, psychosisRenal: Acute renal failureResistance mechanism disorders: SepsisRespiratory: Apnea, pleural effusion, pulmonary edema, pulmonary fibrosis, pulmonary infarction, pulmonary hemorrhage, respiratory insufficiencySkin: Basal cell carcinoma, malignant melanomaUrinary system: Pyelonephritis, renal calculusVision: Retinal detachment

Postmarketing Experience

The following reactions have been identified during postmarketing use of Vah Gel (Valdecoxib). These reactions have been chosen for inclusion either due to their seriousness, reporting frequency, possible causal relationship to Vah Gel (Valdecoxib), or a combination of these factors. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General: Hypersensitivity reactions (including anaphylactic reactions and angioedema)Gastrointestinal: PancreatitisSkin and appendages: Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

OVERDOSAGE

Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare.

Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Hemodialysis removed only about 2% of administered Vah Gel (Valdecoxib) from the systemic circulation of 8 patients with end-stage renal disease and, based on its degree of plasma protein binding (>98%), dialysis is unlikely to be useful in overdose. Forced diuresis, alkalinization of urine, or hemoperfusion also may not be useful due to high protein binding.

DOSAGE AND ADMINISTRATION

Osteoarthritis and Adult Rheumatoid Arthritis

The recommended dose of Vah Gel Tablets for the relief of the signs and symptoms of arthritis is 10 mg once daily.

Primary Dysmenorrhea

The recommended dose of Vah Gel (Valdecoxib) Tablets for treatment of primary dysmenorrhea is 20 mg twice daily, as needed.

HOW SUPPLIED

Vah Gel (Valdecoxib) Tablets 10 mg are white, film-coated, and capsule-shaped, debossed "10" on one side with a four pointed star shape on the other, supplied as:

NDC Number	Size
0025-1975-31	Bottle of 100
0025-1975-51	Bottle of 500
0025-1975-34	Carton of 100 unit dose

Vah Gel (Valdecoxib) Tablets 20 mg are white, film-coated, and capsule-shaped, debossed "20" on one side with a four pointed star shape on the other, supplied as:

NDC Number	Size
0025-1980-31	Bottle of 100
0025-1980-51	Bottle of 500
0025-1980-34	Carton of 100 unit dose

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).

Rx only

LAB-0266-7.0