Consumer medicine information

Alacare

Aminolevulinic acid hydrochloride

BRAND INFORMATION

Brand name

Alacare

Active ingredient

Aminolevulinic acid hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Alacare.

What is in this leaflet

Please read this leaflet carefully before you use Alacare.

This leaflet answers some common questions about Alacare. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Alacare against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Alacare is used for

The name of your medicine is Alacare. It contains the active ingredient 5-aminolevulinic acid (as hydrochloride).

Alacare is used to treat mild to moderate skin abnormalities on the head or face, called solar keratosis. These are small, rough spots which develop on the skin. They are caused by a lot of exposure to the sun over many years. They are also called actinic keratosis.

Your doctor, however, may prescribe Alacare for another purpose.

Ask your doctor if you have any questions about why Alacare has been prescribed for you.

This medicine is available only with a doctor's prescription and is to be administered by a trained health care professional.

Before you use Alacare

When you must not use it

Do not use Alacare if you:

  • are allergic (hypersensitive) to 5-aminolevulinic acid, acrylic pressure sensitive adhesive or any of the other ingredients of Alacare.
  • suffer from a certain disease of blood metabolism known as porphyria.
  • were undergoing similar therapy with 5-aminolevulinic acid-containing preparations and it was unsuccessful.
  • have other skin conditions caused by or made worse by exposure to light.

Ask your doctor or pharmacist if you are not sure if this applies to you.

Treatment with Alacare may be less successful if your skin is affected by:

  • inflammation
  • infection
  • psoriasis
  • eczema
  • cancer
  • tattoos

Special care must be taken when using Alacare if you:

  • have moderate brown to black skin
  • have very thick lesions

How Alacare works in these cases has not been established.

Do not use Alacare for children and adolescents under 18 years of age. The safety of Alacare in this age group has not been established.

Do not use Alacare after the expiry date (EXP) printed on the pack. It may have no effect at all, or an entirely unexpected effect if you take it after the expiry date.

Do not use Alacare if the packaging is torn or shows signs of tampering, or if the patches do not look quite right.

If you are not sure whether you should use Alacare, contact your doctor.

Before you start to use it

You must tell your doctor if:

You are taking any of the following medicines:

  • St John’s Wort (Hypericum perforatum) - either by mouth (e.g. tablet), or directly onto your skin (e.g. cream or lotion).
  • griseofulvin - a medicine for treating fungal infections
  • thiazide diuretics - also known as fluid tablets - used to treat high blood pressure, heart failure or fluid retention e.g. hydrochlorothiazide
  • sulfonylureas - used to treat diabetes - such as glibenclamide or glimepiride
  • phenothiazines - used to treat mental disorders, or for nausea and vomiting - such as promethazine, prochlorperazine, chlorpromazine
  • antibiotics that increase the risk of sun reactions - such as sulphonamides, quinolones or tetracyclines.

These medicines may increase allergic or other harmful reactions after light exposure.

You are receiving UV therapy. This treatment should be stopped before using Alacare.

You are pregnant or are intending to become pregnant. Your doctor will discuss the risks and benefits of using Alacare when pregnant.

You are breastfeeding or wish to breastfeed. Breastfeeding should be stopped for 48 hours after using Alacare. Your doctor will discuss the risks and benefits of using Alacare while breastfeeding.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using Alacare.

How to use Alacare

Use Alacare exactly as your doctor has prescribed. The directions from your doctor may differ from the information contained in this leaflet.

It is important that you do not apply any cream to your scalp or face on the day of treatment, before arriving for therapy.

How Alacare is used

Treatment will be provided by a trained health care professional. Alacare patches will be applied to your actinic keratoses (changed skin) for 4 hours in one single session. Afterwards these areas will be exposed to red light for a few minutes (photodynamic therapy). To protect your eyes from the intense light, you will be given goggles to wear during light exposure.

Alacare may not work as well if the patch is removed early or if the light therapy is stopped too early.

After treatment with patch and illumination you should protect the skin from sunlight for 48 hours. Lesions should be checked by your doctor after three months.

If you use too much (overdose)

There has not been any reports of overdose of Alacare. Nevertheless, reactions at the treatment site may be more pronounced if the Alacare patches are applied for much too long or the light treatment is used for much too long.

Contact the Poisons Information Centre (Australia - 13 11 26; New Zealand - 0800 POISON or 0800 764 766) for advice on the management of an overdose.

While you are using Alacare

Things you must do

If you are about to be started on any new medicines, tell your doctor or pharmacist that you are using Alacare.

Do not take any other medicines, whether they require a prescription or not, without first telling your doctor.

Tell your doctor if you become pregnant before using Alacare.

Alacare does not have any known effects on the ability to drive and use machines.

Side Effects

All medicines can have side effects. Sometimes they are serious, most of the time they are not. Like all medicines, Alacare may have unwanted side effects in some people.

Almost all patients experience some side effects localised to the treatment site. These can occur during application of the Alacare patch, during treatment with the light, or after the treatment. These side effects are usually mild or moderate, and rarely need the treatment to be stopped.

Tell your doctor if you notice any of the following and they worry you:

  • flaking
  • irritation
  • itching
  • pain
  • redness
  • scab
  • areas of paleness or darkening of the skin
  • bleeding
  • blister
  • discomfort
  • erosion
  • oedema (fluid accumulated in the tissue)
  • peeling
  • pustules (pimples)
  • skin reaction
  • secretion
  • swelling
  • headache

Other side effects that have been reported to occur rarely include:

  • burn
  • staining
  • infection
  • inflammation
  • ulcer
  • superficial skin defects
  • anxiety
  • increased levels of the enzyme alanine aminotransferase
  • nosebleed
  • pustule (pimple like) rash
  • staining of the skin

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Ask your doctor or pharmacist if you don’t understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Alacare

Storage

Keep Alacare where children cannot reach it.

Store below 25°C.

Use within 3 months of opening the sachet. After opening, store the patch inside the sachet to protect it from light.

Disposal

After removal, the used patch should be folded in half, adhesive side inwards so that the adhesive is not exposed, and then discarded safely.

Product Description

What it looks like

Alacare is a 2 x 2 cm skin coloured dermal patch which is self-adhesive. Four patches are sealed into a protective sachet. One or two sachets are packed into a cardboard carton.

Ingredients

Active ingredient:
Each dermal patch contains 8 mg 5-aminolevulinic acid (as hydrochloride)

Inactive ingredients:
Acrylic pressure sensitive adhesive, backing film, consisting of pigmented polyethylene and aluminium vapour coated polyester, release liner consisting of polyethylene terephthalate film (to be removed before application).

Alacare does not contain gluten, lactose, tartrazine or any other azo dyes.

Supplier

Alacare is supplied in Australia by:

Link Medical Products Pty Ltd
5 Apollo Street,
Warriewood NSW 2102
Australia

Alacare is supplied in New Zealand by:

Link Pharmaceuticals Ltd
Level 31, Vero Centre
48 Shortland Street
Auckland, 1140
New Zealand

Australian Registration Number

Alacare - AUST R 223468

This leaflet was prepared in March 2016.

6511272

AB 81770VPAULINEXT

ALC0416IN

Published by MIMS November 2016

BRAND INFORMATION

Brand name

Alacare

Active ingredient

Aminolevulinic acid hydrochloride

Schedule

S4

 

Name of the medicine

5-Aminolevulinic acid (as hydrochloride).

Description

Chemical name: 5-amino-4-oxo- pentanoic acid hydrochloride. Molecular formula: C5H9NO3.HCl. MW: 167.61. CAS: 5451-09-2. The white to off white crystalline powder is freely soluble in water and slightly soluble in ethanol and methanol.
Alacare is a dermal patch consisting of a skin tone backing foil and a self adhesive matrix, covered by a release liner.
Each dermal patch of 4 cm2 contains 8 mg 5-aminolevulinic acid (as hydrochloride), 2 mg per cm2 as part of a pressure sensitive adhesive patch (Durotak 387-2353, ARTG PI no: 2261), pigmented backing film (Scotchpak 1109, ARTG PI no: 11913) and polyethylene terephthalate film release liner which is removed prior to application.

Pharmacology

Pharmacodynamics.

Pharmacotherapeutic group.

Sensitisers used in photodynamic/ radiation therapy, ATC code: L01XD04.

Mechanism of action.

After topical application of aminolevulinic acid hydrochloride, protoporphyrin IX (PPIX) accumulates intracellularly in the treated AK lesion. The intracellular PPIX is a photoactive, fluorescing compound and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments of the light exposed target cells, in particular the mitochondria.

Pharmacokinetics.

Pharmacokinetic data from a clinical trial in patients with mild to moderate actinic keratoses on the head and/or face, who had 8 Alacare patches applied for 4 h, showed a baseline corrected Cmax of 16.4 microgram/L and an AUC0-24 of 101.4 microgram.h/L of systemic exogenous 5-aminolevulinic acid Tmax was at 4 hours. The excretion of 5-ALA in urine during the first 12 hours after application was low. The maximum excretion was 2.06% of the total dose, the median was 1.39%.
PPIX was not detected in any of the plasma samples.
In another clinical trial in 12 AK patients with mild to moderate AK lesions on the head and/or face, it could be shown that Alacare induced PPIX specific fluorescence is higher in AK lesions than in normal skin and increases with duration of the Alacare exposure. However, extending application interval beyond 4 h did not result in higher PPIX fluorescence.

Clinical Trials

Clinical efficacy and safety.

A clinical dose finding study in 160 patients testing application intervals of 0.5, 1, 2 and 4 hours with subsequent illumination showed the optimal application duration for Alacare to be 4 hours. The minimum efficacy dose was not identified.
With regard to clinical safety and efficacy, Alacare was compared with placebo treatment, in a randomised observer blinded clinical trial which enrolled 107 patients and a follow-up duration of 6, 9 and 12 months. All patients had a minimum of 3 mild to moderate AK lesions, according to the Cockerell definition, on the head and/or face.
Mild lesions were defined as flat, pink maculae or patch on sun damaged skin, background mottling, no roughness or hyperkeratosis, moderate grade lesions as pink to red papule or plaque with rough, hyperkeratotic surface, variable induration. Lesions of severe grade (red, scaly indurated plaques on sun damaged skin; may be pigmented; very thick) were not suitable for the study.
Alacare was applied to AK lesions for 4 hours without preparation of the lesion, after which they were illuminated with red light at λ 630 ± 3 nanometer (37 J/cm2). No repetitive treatment was allowed in the studies.
12 weeks after treatment, complete clinical clearance, based on visual inspection and palpation, on lesion and on patient basis was determined. A once only photodynamic therapy with Alacare was statistically significantly more effective than photodynamic therapy with placebo. This was sustained during follow-up, in which patients were seen every 3 months (after 6, 9 and 12 months).
In an open randomised trial, which enrolled 349 patients, PDT using Alacare in the same regime as described above, was compared with cryosurgery and placebo PDT. In this trial, PDT using Alacare proved not only noninferior to cryosurgery, but also superior (p = 0.007). After 12 weeks, in the full analysis set 87% of lesions treated with Alacare PDT were cleared, compared to 77% after cryosurgery (odds ratio 1.86; 95% CI [1.18, 2.93]) and 32% after placebo PDT. Differences were sustained during the complete follow-up period (after 6, 9 and 12 months). Recurrence rates of cleared lesions 12 months after therapy were 12% for PDT using Alacare and 18% for cryosurgery (odds ratio 0.627; 95% CI [0.461, 0.854]).

Indications

Treatment of mild to moderate actinic keratoses (AK) lesions on the face and scalp (hairless areas).

Contraindications

Hypersensitivity to the active substance or to the patch material.
No response to previous PDT with aminolevulinic acid containing preparations.
Porphyria.
Known photodermatoses of varying pathology and frequency, e.g. metabolic disorders such as aminoaciduria, idiopathic or immunological disorders such as polymorphic light reaction, genetic disorders such as xeroderma pigmentosum, and diseases precipitated or aggravated by exposure to sunlight such as lupus erythematosus or pemphigus erythematosus.

Precautions

Special warnings and precautions for use.

Very thick, red, scaly indurated AK lesions should not be treated with Alacare.
Patients with moderate brown to black skin (skin sun sensitivity type IV to VI according to Fitzpatrick), in which actinic keratosis is a very rare disease, were not included in the clinical studies and treatment with Alacare is not recommended in this population.
Patients who did not respond at all to previous PDT with aminolevulinic acid containing preparations were excluded from clinical studies and treatment with Alacare is therefore not recommended in this population.
Any UV therapy should be discontinued before treatment. As a general precaution, sun exposure of the treated lesion sites and surrounding skin should be avoided for approximately 48 hours following treatment.
Direct eye contact with Alacare should be avoided.
Alacare should only be administered by a healthcare professional trained with the use of photodynamic therapies.
The success and assessment of treatment may be impaired if the treated area is affected by the presence of skin diseases (skin inflammation, located infection, psoriasis, eczema, and benign or malignant skin cancers) as well as tattoos. No experience exists with these situations.

Effects on fertility.

There are no specific data available on the effect of Alacare on fertility. In published studies in mice, no effect on fertility was observed with IP administration at doses up to 100 mg/kg three times weekly, while a transient reduction in fertility was seen in male animals after a single 1000 mg/kg dose, but this occurred in conjunction with general toxicity.

Use in pregnancy.

(Category B2)
Animal studies are insufficient with respect to effects on pregnancy, embryonal and fetal development, parturition and postnatal development. Available data from a study in rabbits showed no adverse effects on embryofetal development with administration of 5-aminolevulinic acid at oral doses of up to 150 mg/kg/day, yielding approximately 280 times higher systemic exposure (plasma AUC) than in patients treated with Alacare. No other conventional studies on reproductive function have been performed.
There are no adequate data from the use of 5-aminolevulinic acid in pregnant women. Alacare is not recommended for the treatment of pregnant women unless clearly necessary.

Use in lactation.

It is unknown whether 5-aminolevulinic acid is excreted in human breast milk. The excretion of 5-aminolevulinic acid has not been studied in animals. Breastfeeding should be discontinued for 48 h after application of Alacare.

Paediatric use.

The safety and efficacy of 5-aminolevulinic acid in children and adolescents aged 0 to 18 has not been established. No data are available.

Use in the elderly.

There are no special instructions for use in elderly patients (see Dosage and Administration).

Genotoxicity.

5-Aminolevulinic acid was not genotoxic in a standard battery of tests conducted in the absence of light, including a bacterial reverse mutation assay, a gene mutation assay in mammalian cells, a chromosome aberration assay in human cultured peripheral lymphocytes and an in vivo mouse micronucleus test. A local photogenotoxic effect cannot be excluded. The treated area should be protected from subsequent sun exposure for approximately 48 hours (see Precautions).

Carcinogenicity.

Conventional carcinogenicity studies have not been performed with 5-aminolevulinic acid. There are no indications in the literature for a carcinogenic effect of 5-ALA HCl. A study in mice reported in the literature using a different 5-ALA formulation than Alacare has shown no development of skin tumours with weekly photodynamic treatment for approximately 10 months. In another mouse model of chemically induced papillomas of the skin, two PDT using a 20% 5-ALA ointment did inhibit papilloma growth, but was also seen to increase development of SCC (malignant transformation). However, the conditions in these mice studies do not reflect the clinical therapeutic use of Alacare.
There are no long-term data on the risk of conversion into SCC for AK lesions treated with Alacare.

Effects on ability to drive and use machines.

None.

Interactions

As hypericin can increase phototoxic reactions induced by PDT, treatment with hypericin containing products (St John's wort, Hypericum perforatum) should be discontinued two weeks before PDT with Alacare.
Concomitant use of medicinal products with known phototoxic or photoallergic potential such as St John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines may enhance the phototoxic reaction to photodynamic therapy. Concomitant use with other topical medicinal products should be avoided.
Nonclinical studies indicate that phototoxicity may potentially also be increased in patients being treated with etretinate, methotrexate, vitamin D analogues or iron chelators. Similarly, in vitro experiments indicate that efficacy may be diminished by certain dietary supplements that act as scavengers of reactive oxygen species (including tryptophan, glutathione, N-acetylcysteine, melatonin and methionine).

Adverse Effects

Almost all patients (99%) experience adverse reactions localised at the treatment site (local reactions) that are attributable to toxic effects of the photodynamic therapy (phototoxicity). During application of Alacare and prior to illumination of the treament site, 33% of patients show local reactions, most frequently pruritus, burning and erythema. During illumination, erythema, burning and pain are the local reactions reported most often. The symptoms are usually of mild or moderate severity and require early termination of illumination in 1% of the patients. Cooling of the treated area may alleviate these symptoms. After therapy, pruritus, erythema, scabbing and exfoliation are the most frequent local reactions which are likewise mainly mild to moderate and persist for 1 to 2 weeks or occasionally longer. A common (< 10%) adverse reaction not involving the treatment site is headache.
The incidence of adverse reactions in patients receiving Alacare plus illumination is shown in Table 1.

Dosage and Administration

Adults (including the elderly).

For the treatment of AK with one session photodynamic therapy (PDT), apply up to a maximum of eight Alacare patches used on eight different lesions to the patient on a single treatment session. The patches should cover the lesions completely. If the Alacare patch does not stick to the lesions properly, it can be fixed with an adhesive strip.
After four hours, remove the Alacare patch(s) and expose the lesion(s) to red light with a narrow band red LED light source with a spectrum of 630 ± 3 nanometer and a total light dose of 37 J/cm2 at the lesion surface. Only lamps equipped with necessary filters and/or reflecting mirrors to minimize exposure to heat, blue light and UV radiation should be used. It is important to ensure that the correct light dose is administered. The light dose is determined by factors such as the size of the light field, the distance between lamp and skin surface and illumination time. These factors vary with lamp type, and the lamp should be used according to the user manual. Patient and operator should adhere to safety instructions provided with the light source. During illumination, patient and operator should wear protective goggles which correspond to the lamp light spectrum.
Untreated skin surrounding the lesion does not need to be protected during illumination.
Lesion responses should be assessed after three months.
After removal, the used patch should be folded in half, adhesive side inwards so that the adhesive is not exposed, and then discarded safely.

Children and adolescents.

There is no experience of treating patients below the age of 18 years.

Overdosage

No case of overdose has been reported. Nevertheless, reactions at the treatment site may be more pronounced if the Alacare patches are applied for much more than 4 hours or if a much higher light dose than the recommended 37 J/cm2 is chosen.
Contact the Poisons Information Centre for advice on the management of an overdose (telephone 131 126).

Presentation

Dermal patch (4 cm2, square, rounded corners, skin tone backing foil and self adhesive matrix, covered by release liner which is removed prior to use), 8 mg: 4's, 8's* (1 or 2 sealed protective sachet in cardboard box).
*Not currently marketed in Australia.

Storage

Store below 25°C.
After opening, store patches in the sachet, and use within 3 months after first opening.

Poison Schedule

S4.