Metvixia

Name: Metvixia

Warnings

Contraindications

Cutaneous photosensitivity

Sensitivity to porphyrin or other components (contains peanut and almond oil)

Cautions

Use within 2 hr of activation

Avoid light exposure between solution application and light treatment (wear hat, etc)

Should not be applied in or around the eyes or to mucous membranes

Avoid exposure to outdoor or bright light during time between drug application and light treatment, and for 2 days afterwards

Photosensitized skin may produce a stinging or burning sensation and become erythematous similarly to actinic keratoses; to ensure drug is only applied to actinic keratoses and not perilesional skin aminolevulinic acid should be applied by qualified professional

Therapy never tested in patients with inherited or acquired coagulation disorders

Therapy not tested for carcinogenic risk

Cream has demonstrated high rate of contact sensitization

Effects on therapy on fertility unknown

Metvixia Drug Class

Metvixia is part of the drug class:

  • Sensitizers used in photodynamic/radiation therapy

Side Effects of Metvixia

Serious side effects have been reported with Metvixia. See the "Metvixia" Precautions section.

Side effects were experienced following application of cream and exposure to red light (the illumination phase).

Common side effects of Metvixia with red light therapy include the following:

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

This is not a complete list of Metvixia side effects. Ask your doctor or pharmacist for more information.

Tell your doctor or pharmacist if you have any side effect that bothers you or does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Metvixia Dosage

Use this medication exactly as prescribed by your doctor. Your doctor will determine the correct amount of cream to apply in the doctor's office.

Not more than one gram (half a tube) of Metvixiae cream is to be applied per treatment session.

The dose your doctor recommends will depend on the size of the skin lesion.

Uses For Metvixia

Methyl aminolevulinate is used with photodynamic therapy (light treatment) to treat actinic keratosis (AK) on the face and scalp. Actinic keratoses are skin lesions or growths in areas where the skin has been exposed to the sun. AK normally occurs in older patients with light-colored skin. This medicine is only used for AK skin lesions that are thin and light in color.

This medicine is available only with your doctor's prescription.

Before Using Metvixia

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of methyl aminolevulinate in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of methyl aminolevulinate in the elderly.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Allergy to almond oil or
  • allergy to peanut oil or
  • allergy to porphyrins (e.g., porfimer [Photofrin®], verteporfin [Visudyne®]) or
  • photosensitivity (skin sensitive to sunlight), history of—Should not be used in patients with these conditions.
  • Bleeding problems or
  • Skin cancer or other skin lesions, history of—Use with caution. May cause side effects to become worse.

Proper Use of Metvixia

Methyl aminolevulinate will be applied to your skin in a clinic or doctor's office. You will receive two treatments with this medicine spaced 1 week apart.

Methyl aminolevulinate is for use on the skin only. Do not get it in your eyes, nose, or mouth. If it does get on these areas, tell your doctor right away.

Dosage Forms and Strengths

Cream, 16.8%.

Each gram of Metvixia Cream contains 168 mg of methyl aminolevulinate in an off-white to pale yellow cream base.

Drug Interactions

There have been no studies of the interaction of Metvixia Cream with 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 Metvixia Cream.

Metvixia - Clinical Pharmacology


Mechanism of Action

Photosensitization following application of Metvixia Cream occurs through the metabolic conversion of methyl aminolevulinate (prodrug) to photoactive porphyrins (PAPs), which accumulate in the skin lesions to which Metvixia Cream has been applied. When exposed to light of appropriate wavelength and energy, the accumulated photoactive porphyrins produce a photodynamic reaction, resulting in a cytotoxic process dependent upon the simultaneous presence of oxygen. The absorption of light results in an excited state of porphyrin molecules, and subsequent spin transfer from photoactive porphyrins to molecular oxygen generates singlet oxygen. Metvixia photodynamic therapy (PDT) of actinic (solar) keratosis lesions is the combination of photosensitization by topical application of Metvixia Cream to the lesions and subsequent illumination with red light of narrow spectrum using a light dose of 37 J/cm2 delivered by the Aktilite CL128 lamp.

Pharmacokinetics

The time-course of Protoporphyrin IX in actinic keratosis lesions and surrounding skin after application of Metvixia Cream has been monitored by means of fluorescence. The optimum concentration of methyl aminolevulinate cream (16.8 %) and duration of application (3 h) were derived from such studies of pharmacokinetics in skin using a range of concentrations (1.6%, 8% and 16.8%) and cream application times (up to 28 h). Three hours after the application of Metvixia Cream fluorescence in the treated lesions was significantly greater than that seen in both treated and untreated normal skin, and after application of vehicle cream (not containing methyl aminolevulinate) to normal skin. In a fluorescence study of 8 patients with actinic keratoses using Metvixia Cream 16.8% applied for 3 h and illumination with the Aktilite CL128 lamp, 88% photodegradation of Protoporphyrin IX was observed immediately after illumination, followed by a transient small secondary increase in fluorescence 2 hours after illumination. At 24 and 48 hours, 94% and 96% degradation of Protoporphyrin IX, respectively from baseline, was observed.

Clinical Studies

Metvixia Cream 16.8 % for photodynamic therapy (PDT) by illumination using the Aktilite CL128 lamp was studied in 211 randomized subjects with a total of 1555 non-hyperkeratotic actinic keratoses in two multicenter, randomized, double-blind vehicle-controlled clinical trials. One trial was conducted in the USA and the other in the USA and Germany.

Each subject had 4 to 10 previously untreated, nonpigmented, grade 1 (thin) or 2 (moderate) actinic keratoses on the face and or scalp. Grade 3 (very thick and obvious) actinic keratoses were not treated in the trials. Two sessions of PDT were administered at an interval of one week with patients randomized 1:1 to receive Metvixia-PDT or Vehicle-PDT on both occasions. Each session comprised lesion preparation (debridement with sharp curette) to roughen the surface, application of cream with subsequent maintenance for 3 hours under occlusion using an adhesive, non-absorbent dressing, removal of residual cream followed immediately by light activation. Red light illumination (630 nm) was provided by the Aktilite CL128 lamp and the light dose was 37 J/cm2.

The subject complete response rate was assessed 3 months after the last treatment. Lesion clinical complete response was defined as complete disappearance of a lesion upon visual inspection and palpation. If all treated lesions within a subject were in clinical complete response 3 months after treatment, the subject was assessed as a complete responder. The subject complete response rates are shown in Table 2 for each of the two studies.The overall lesion complete response rates and the response rates by lesion grade and location are shown in Table 3 for the two studies.

Table 2: Subject Complete Response after Lesion Debridement followed by Aktilite PDT with Metvixia Cream vs. Vehicle Studies 1 and 2
Study 1 Study 2

Metvixia

n=49

Vehicle

n=47

Metvixia

n=57

Vehicle

n=58

Subjects with Complete Response 29 7 39 4
59.2% 14.9% 68.4% 6.9%
Table 3: Lesion Complete Response Rate by Grade and Location Studies 1 and 2 conducted with Aktilite photodynamic therapy
Study 1 Study 2
Metvixia
N=363
Vehicle
n=360
Metvixia
n=418
Vehicle
n=414
Lesions with Complete response
Grade 1 259 267 182 161
Face Total 191 201 99 88
Face CR 167 (87%) 121 (60%) 90 (91%) 33 (38%)
Scalp Total 68 66 76 73
Scalp CR 63 (93%) 29 (44%) 66 (87%) 31 (42%)

Grade 2

104 93 236 253
Face Total 76 68 119 157
Face CR 65 (86%) 29 (43%) 103 (87%) 35 (22%)
Scalp Total 28 25 115 96
Scalp CR 18 (64%) 9 (36%) 89 (77%) 20 (21%)

There was no difference between response rates to Metvixia Aktilite PDT for Grade 1 lesions on the face and scalp (CR rates of 89 % and 90 % respectively). For Grade 2 lesions, the corresponding CR rates to Metvixia Aktilite PDT were 86 % and 75 % respectively. Metvixia Cream has not been studied for more than one course which consists of two treatment sessions one week apart. There is no information regarding the recurrence rate for lesions treated with this therapy. Clinical studies did not follow patients beyond 3 months, and the recurrence rate of treated lesions is unknown.

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