Metvixia

Pregnancy Category: C

Lactation: unknown whether distributed in milk; use caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Before using Metvixia, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• Are allergic to Metvixia or any of its ingredients
• Have had an allergic reaction to any topical (applied to the skin) products in the past
• Are allergic to peanuts or almonds (their oils are used to make the cream)
• Are allergic to porphyrins (Metvixia belongs to a class of medications called porphyrins)
• Are pregnant or breastfeeding

Tell your doctor about all the medicine you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

• Store under refrigeration.
• Use contents within one week after opening.
• Should not be used after 24 hours out of refrigerator.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Breakdown of the skin
• irritation and redness of the skin
• scabbing
• swelling of the eyelid
• swelling of the skin

• Discharge at the site of application
• sores on the skin that do not heal

• Blistering, burning, crusting, dryness, or flaking of the skin
• blurred vision or other change in vision
• eye redness, irritation, or pain
• hives or welts
• itching, scaling, or severe redness of the skin
• persistent non-healing sore
• pink growth on the skin
• reddish patch or irritated area on the skin
• seeing flashes or sparks of light
• seeing floating spots before the eyes, or a veil or curtain appearing across part of the vision
• shiny bump on the skin
• skin rash, encrusted, scaly and oozing
• white, yellow, or waxy scar-like area on the skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Darkening of the skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

• It is used to treat a precancerous skin problem called actinic keratosis.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Do not take Metvixia by mouth. Use on your skin only. Keep out of your mouth, nose, and eyes (may burn).
• This medicine is used with light therapy.
• Your doctor will put on the skin.
• If you cannot have the light therapy after this medicine has been put on, talk with your doctor. Avoid bright light for as long as you have been told by your doctor.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Metvixia or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Metvixia. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Metvixia Cream in combination with Aktilite CL128 lamp red light illumination is indicated for treatment of thin and moderately thick, non-hyperkeratotic, non-pigmented actinic keratoses of the face and scalp in immunocompetent patients. This photodynamic therapy should be used in conjunction with appropriate lesion preparation in the physician’s office when other therapies are considered medically less appropriate.

Limitations of Use:

The safety and efficacy have not been established for the treatment of cutaneous malignancies or for skin lesions other than non-hyperkeratotic face and scalp actinic keratoses using PDT with Metvixia Cream.

The safety and efficacy of Metvixia Cream have not been established in patients with immunosuppression, porphyria or pigmented actinic keratoses.

Metvixia Cream has not been tested on patients with inherited or aquired coagulation defects.

Use of Metvixia Cream without subsequent red light illumination is not recommended.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Long-term studies to evaluate the carcinogenic potential of Metvixia Cream have not been performed. Methyl 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. Methyl 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.

A fertility study was performed in male and female rats with intravenous doses of methyl aminolevulinate hydrochloride up to 500 mg/kg/day (3000 mg/m2, 1158 times the MTHD based on mg/m2 comparisons and an estimated maximum systemic uptake of 1%). Males were treated for 4 weeks prior to mating and for 5 additional weeks after mating. The females were treated for 2 weeks prior to mating and then until Day 6 of gestation. There were no treatment-related effects on fertility and mating performance seen in this study.

Reproductive Toxicology

Development toxicity studies have been performed in pregnant rats with intravenous doses of methyl aminolevulinate hydrochloride up to 700 mg/kg/day on Days 6 to 16 of gestation. There were no treatment-related effects on fetal body weight, sex ratio, external malformations and variations, and skeletal abnormalities and ossification extent. Only a slight non-significant increase in early embryonic death was noted in the 700 mg/kg/day group, compared to the control group. The fetal NOAEL (No Adverse Effect Level) was 350 mg/kg/day methyl aminolevulinate hydrochloride in pregnant rats (2100 mg/m2, 811 times the MTHD based on mg/m2 comparisons and an estimated maximum systemic uptake of 1%).

Development toxicity studies have also been performed in pregnant rabbits with intravenous doses of methyl aminolevulinate hydrochloride up to 200 mg/kg/day on Days 6 to 18 of gestation. Slightly lower fetal body weights and increased incidences of fetuses with jugals connected/fused to maxilla, supernumerary ribs, incompletely ossified cranial bones and other ossification irregularities were noted in the high dose (200 mg/kg/day) group, compared to the control group. The fetal NOAEL was 100 mg/kg/day methyl aminolevulinate hydrochloride in pregnant rabbits (1200 mg/m2, 463 times the MTHD based on mg/m2 comparisons and an estimated maximum systemic uptake of 1%).

In the prenatal and postnatal development toxicity study in rats treated with intravenous doses of methyl aminolevulinate hydrochloride up to 500 mg/kg/day from Day 6 of gestation to Day 24 of lactation, there were no treatment-related effects on litter size, pup mortality, pup weights, and post weaning performance of the F1 animals including development and reproductive capacity. Only a slightly longer duration of gestation and a slight delay in pup physical development were noted in the 250 and 500 mg/kg/day groups. The NOAEL was 125 mg/kg/day methyl aminolevulinate hydrochloride (750 mg/m2, 290 times the MTHD based on mg/m2 comparisons and an estimated maximum systemic uptake of 1%).

Metvixia Cream, 16.8%, is available as the following:

2 gram aluminum tube, box of 1 (NDC 0299-6300-02)

Keep out of reach of children

For topical use only by physicians in the physician’s office. Dispense only to physicians and only to be applied by a physician.

Physicians should wear nitrile gloves when applying and removing Metvixia Cream. Vinyl and latex gloves do not provide adequate protection when using this product.

Store/Transport refrigerated, 2˚ - 8˚C (36˚ - 46˚F).

Use contents within one week after opening.

Should not be used after 24 hours out of refrigerator.