Inongan

Methyl Salicylate:

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

INDICATIONS AND USAGE

Inongan (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

Inongan (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 Inongan (Methyl Salicylate) Cream, which includes peanut and almond oil Cream).

This product contains refined peanut oil.

WARNINGS

Inongan (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.

Inongan (Methyl Salicylate) Cream has demonstrated a high rate of contact sensitization (allergenicity). Care should be taken by the physician applying Inongan (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.Inongan (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 Inongan Cream. Thick (hyperkeratotic) actinic keratoses should not be treated with Inongan (Methyl Salicylate) Cream. The safety and efficacy of Inongan (Methyl Salicylate) Cream has not been established in patients with immunosuppression, porphyria or pigmented actinic keratoses.

General

Inongan (Methyl Salicylate) Cream Application

During the time period between the application of Inongan (Methyl Salicylate) (methyl aminolevulinate) Cream and exposure to red light illumination, the treatment site will become photosensitive. After Inongan (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 Inongan (Methyl Salicylate) and PDT light treatment. After illumination of Inongan (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 Inongan (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 Inongan 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 Inongan (Methyl Salicylate) Cream should be avoided.

Coagulation defects

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

Hypersensitivity

Inongan Cream is formulated with refined peanut and almond oil.

Inongan (Methyl Salicylate) (methyl aminolevulinate) Cream has not been tested in patients who are allergic to peanuts. Inongan (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 Inongan 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 Inongan (Methyl Salicylate) Cream.

Carcinogenesis, Mutagenesis, Impairment to Fertility

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

Inongan (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. Inongan (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 Inongan Cream. It is also not known whether Inongan (Methyl Salicylate) Cream can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

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

Nursing Mothers

The amount of Inongan (Methyl Salicylate) aminolevulinate secreted into human breast milk following topical administration of Inongan (Methyl Salicylate) Cream is not known. Because many drugs are secreted in human milk, caution should be exercised when Inongan (Methyl Salicylate) Cream is administered to a nursing mother. If Inongan (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 Inongan 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 Inongan (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 Inongan Cream is an irritant and sensitizer. A provocative cumulative irritancy and sensitization (allergenicity) study of Inongan (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 Inongan (Methyl Salicylate) Cream, were positive (sensitized). Forty subjects refused challenge with Inongan (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 Inongan (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 Inongan (Methyl Salicylate) Cream in all clinical studies of Inongan (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 Inongan (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 Inongan (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 Inongan (Methyl Salicylate) Cream is unknown. Serious erythema and facial edema have been described in European post-marketing reports.

OVERDOSAGE

Inongan Cream Overdose

Inongan (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 Inongan (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 Inongan (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 Inongan (Methyl Salicylate) Cream should be applied per treatment session.

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

Before applying Inongan (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 Inongan (Methyl Salicylate) Cream –

Using a spatula, apply a layer of Inongan (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 Inongan (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 Inongan (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 Inongan (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 Inongan (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 Inongan (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. Inongan (Methyl Salicylate) Cream is not intended for use with any device other than the approved lamp: CureLight BroadBand Model CureLight 01. Use of Inongan (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 Inongan (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

Inongan 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

Inongan (Methyl Salicylate)^™ Cream 16.8% (phonetic)

Generic name: Inongan (Methyl Salicylate) aminolevulinate hydrochloride

Read this Patient Information before you get treated with Inongan (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 Inongan (Methyl Salicylate) Cream.

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

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

What is Inongan Cream?

Inongan (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). Inongan (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. Inongan (Methyl Salicylate) Cream and PDT work together to treat AK skin growths.

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

Who should not use Inongan Cream?

Do not use Inongan (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 Inongan (Methyl Salicylate) Cream. The active ingredient is Inongan (Methyl Salicylate) aminolevulinate hydrochloride. Inongan (Methyl Salicylate) Cream also contains peanut and almond oil. See the end of this leaflet for a complete list of ingredients in Inongan (Methyl Salicylate) Cream.

Before treatment with Inongan Cream, tell your doctor:

• about your medical conditions, including if you
  • are pregnant or planning to become pregnant. It is not known if Inongan (Methyl Salicylate) Cream can harm your unborn baby.
  • are breastfeeding. It is not known if Inongan (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 Inongan (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 Inongan (Methyl Salicylate) Cream and other medicines can affect each other.

How should I use Inongan Cream?

• Inongan (Methyl Salicylate) Cream and PDT treatment is only done by trained doctors.
• You will receive 2 treatments with Inongan (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.”)
• Inongan (Methyl Salicylate) Cream is for skin use only. Do not get Inongan (Methyl Salicylate) Cream in your eyes, mouth, or nose. Tell your doctor right away if this happens.

What should I avoid while using Inongan Cream?

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

• Avoid exposure to sunlight or bright indoor light during the 3 hours that Inongan (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 Inongan (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 Inongan Cream with PDT treatment?

Common side effects of Inongan (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 Inongan (Methyl Salicylate) Cream with PDT. Ask your doctor or pharmacist for more information.

General information about Inongan Cream

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

This leaflet summarizes the most important information about Inongan (Methyl Salicylate) Cream. If you would like more information, talk with your doctor. You can ask your doctor for information about Inongan (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 Inongan Cream?

Active Ingredient: Inongan (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 Inongan Cream and PDT

Figure 1: Lesion debriding

Your doctor will prepare your skin by gently scraping (debriding) your skin growths before treating with Inongan (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 Inongan (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 Inongan (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

Inongan (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.