Mirvaso^® Derm (Gel) Instructions for Use

Marketing Authorization Holder

Galderma, SA (Switzerland)

Manufactured By

Laboratoires Galderma (France)

Contact Information

GALDERMA SA (Switzerland)

ATC Code

D11AX21 (Brimonidine)

Active Substance

Brimonidine (Rec.INN registered by WHO)

Dosage Form

Mirvaso® Derm

Gel for external use 0.5%: 10 g or 30 g tubes

Dosage Form, Packaging, and Composition

Gel for external use opaque, from white to light yellow in color.

Excipients: carbomer – 12.5 mg, methylparahydroxybenzoate – 1 mg, phenoxyethanol – 4 mg, glycerol – 55 mg, titanium dioxide – 0.625 mg, propylene glycol – 55 mg, sodium hydroxide – to pH 6.0, purified water – to 1000 mg.

10 g – laminated tubes (1) – cardboard packs.
30 g – laminated tubes (1) – cardboard packs.
10 g – multilayer tubes (1) – cardboard packs.
30 g – multilayer tubes (1) – cardboard packs.

Clinical-Pharmacological Group

Selective alpha₂-adrenergic agonist used for rosacea

Pharmacotherapeutic Group

Facial erythema in rosacea treatment agent – selective alpha₂-adrenomimetic

Pharmacological Action

Brimonidine is a highly selective alpha₂-adrenergic receptor agonist: its affinity for alpha₂-adrenergic receptors is 1000 times greater than its affinity for alpha₁-adrenergic receptors.

Application to the facial skin of a highly selective alpha₂-adrenergic receptor agonist leads to a reduction in erythema due to direct vasoconstriction of the small blood vessels of the dermis.

Pharmacokinetics

Absorption

The absorption of brimonidine from Mirvaso^® Derm was studied in a clinical trial in 24 adult patients with facial erythema of rosacea. With daily application to the facial skin once a day for 29 days, no accumulation of the drug in the blood plasma was observed.

Metabolism

Brimonidine is extensively metabolized in the liver.

Excretion

Brimonidine and its metabolites are primarily excreted by the kidneys.

Indications

• Treatment of facial erythema in rosacea.

ICD codes

Dosage Regimen

For external use only.

A small amount of gel is applied in a thin layer to the skin of each of the 5 facial areas (forehead, chin, nose, cheeks) once a day in the presence of erythema.

When applying to the skin, Mirvaso^® Derm gel must be distributed evenly in a thin layer over the face, avoiding contact of the drug in the eyes, on the eyelids, lips, mouth, and nasal mucosa.

The gel should be applied only to the face.

The maximum recommended daily dose of the drug is 1 g (which approximately corresponds to the size of 5 match heads).

Treatment should be started with a small amount of gel (less than the maximum daily dose) for a duration of at least one week. Subsequently, the amount of the applied drug can be gradually increased, depending on its tolerability and the effectiveness of the treatment.

Hands must be washed after applying the drug.

Adverse Reactions

In clinical trials, the most frequently (1.2-3.3%) observed adverse reactions included redness, itching, flushing, and burning sensation of the skin. As a rule, these were mild or moderate reactions that did not lead to discontinuation of treatment. Cases of exacerbation of rosacea symptoms were reported in patients receiving treatment with Mirvaso^® Derm. Considering the data from all conducted clinical trials, cases of symptom exacerbation were noted in 16% of patients. No significant difference in the safety profile was found in elderly patients and patients aged 18 to 65 years.

In the post-registration period, frequent cases of increased redness, flushing, burning sensation of the skin, and blanching of the skin at the application site were noted.

In the post-registration period, infrequent cases of dizziness, as well as cases of bradycardia and hypotension (including orthostatic hypotension) with a frequency of “rare” were also reported, some of which led to hospitalization. In some cases, these adverse reactions occurred as a result of applying Mirvaso^® Derm gel after laser therapy.

Adverse reactions obtained during clinical trials and in the post-registration period (see Table 1) are classified by organ systems and frequency of occurrence. The frequency of adverse reactions was classified as follows: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from the available data).

Table 1

* Data on adverse reactions obtained in the post-registration period.

If any of the indicated side effects worsen or any other side effects not listed in the instructions are noted, you should immediately inform your doctor.

Contraindications

• Hypersensitivity to brimonidine or to any of the excipients;
• Children under 2 years of age (due to serious systemic risk);
• Children from 2 to 18 years of age (safety and efficacy of the drug for this age category have not been established);
• Concomitant use with monoamine oxidase inhibitors (MAOIs) (e.g., selegiline or moclobemide), and tricyclic (imipramine) and tetracyclic (maprotiline, mianserin and mirtazapine) antidepressants that affect noradrenergic transmission.

With caution pregnancy; impaired liver and kidney function (studies on the use of Mirvaso^® Derm in this category of patients have not been conducted).

Use in Pregnancy and Lactation

Pregnancy

Data on the use of brimonidine during pregnancy are limited or absent.

Reproductive toxicity studies in animals did not reveal any direct or indirect adverse effects of the drug. As a precautionary measure, it is recommended to avoid the use of Mirvaso^® Derm during pregnancy.

Breastfeeding period

It is unknown whether Brimonidine and its metabolites are excreted in breast milk. In this regard, the risk for newborns and infants cannot be excluded. The decision to discontinue breastfeeding or the use of Mirvaso^® Derm should be made taking into account the importance of the drug for the mother.

Pediatric Use

Contraindications: children under 2 years of age (due to serious systemic risk); children from 2 to 18 years of age (safety and efficacy of the drug for this age category have not been established).

Special Precautions

Mirvaso^® Derm should not be applied to irritated skin (including after laser therapy) or open wounds, or to the area around the eyes. In case of severe irritation or allergy, treatment with the drug should be discontinued.

Mirvaso^® Derm can be used in conjunction with other medicinal products used to treat inflammatory elements of rosacea and with cosmetic products. They can be applied to the skin only after Mirvaso^® Derm has dried, and not immediately before it.

Erythema and flushing. The effect of Mirvaso^® Derm begins to weaken several hours after application. In some patients, recurrence of erythema and flushing in a more severe form than observed before treatment was described. Most of these cases were noted within the first 2 weeks after starting treatment.

Some patients receiving therapy with Mirvaso^® Derm experienced flushing. The time of onset varied from 30 minutes to several hours after gel application. In most cases, erythema and flushing resolved after discontinuation of the drug.

In case of worsening erythema, the use of Mirvaso^® Derm should be suspended. Symptomatic measures, such as cooling compresses, taking NSAIDs and antihistamines, may alleviate the symptoms.

After resuming the use of Mirvaso^® Derm, cases of exacerbation of erythema and flushing in an aggravated form were noted. After a temporary break in treatment, resumption of Mirvaso^® Derm use should begin with a test application of the drug to a small area of facial skin at least 1 day before transitioning to treatment with the drug applied to the entire facial skin surface.

The recommended dose and frequency of application must be strictly observed: once a day, in a very thin layer.

Avoid increasing the maximum daily dose and/or frequency of application, as the safety of increased daily doses or multiple daily applications has not been established.

Concomitant use with systemic alpha-adrenergic receptor agonists may enhance the side effects of this class of drugs in patients with

• Severe or uncontrolled, or unstable cardiovascular diseases;
• Depression, cerebral or coronary circulatory insufficiency, Raynaud’s disease, orthostatic hypotension, thromboangiitis obliterans, scleroderma, or Sjögren’s syndrome.

Excipients

One gram of gel contains 1 mg of methylparahydroxybenzoate (E218), which may cause allergic reactions (possibly delayed type). This product also contains 55 mg of propylene glycol (E1520) per gram, equivalent to 5.5% w/w, which may cause skin irritation.

Effect on ability to drive vehicles and operate machinery

The drug does not affect or insignificantly affects the ability to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

There is no information on brimonidine overdose with external use in adult patients.

Symptoms of accidental oral ingestion of the drug may include such overdose phenomena of alpha₂-adrenergic receptor agonists as arterial hypotension, weakness, vomiting, drowsiness, lethargy, bradycardia, arrhythmia, miosis, apnea, hypotension, hypothermia, respiratory depression, and convulsions.

During a clinical trial, 2 cases of serious adverse events caused by accidental ingestion of Mirvaso^® Derm by young children were noted. The symptoms observed in children corresponded to the known symptoms of overdose of alpha₂-adrenergic receptor agonists in young children and completely resolved within 24 hours.

Treatment of overdose upon oral ingestion includes supportive and symptomatic therapy, and it is necessary to maintain airway patency.

Drug Interactions

No studies on the interaction of the drug with other medicinal products have been conducted.

Monoamine oxidase inhibitors (MAOIs) may theoretically interfere with the absorption of brimonidine and potentially lead to increased systemic side effects, such as arterial hypotension, and also affect the metabolic process and absorption of circulating amines.

The possibility of additive or potentiating action should be considered when using brimonidine concomitantly with drugs that depress the CNS (alcohol, barbiturates, opiates, sedatives, or anesthetics).

There are no data on the effect of brimonidine on the level of circulating catecholamines. Nevertheless, caution is recommended when prescribing brimonidine to patients receiving drugs that can affect the metabolism of amines and increase their concentration in the blood, such as chlorpromazine, methylphenidate, reserpine.

Caution is recommended with the concomitant use of brimonidine or a change in its dose in the treatment of ophthalmic diseases.

Caution is recommended at the start of treatment or when changing the dose of co-administered systemic drugs (regardless of their dosage form) that may interact with alpha-adrenergic receptor agonists or affect their action, i.e., are agonists or antagonists of alpha-adrenergic receptors (e.g., isoprenaline, prazosin).

In some patients, Brimonidine can cause a clinically insignificant decrease in blood pressure, so caution should be exercised when using such drugs as antihypertensive agents and/or cardiac glycosides concomitantly with Mirvaso^® Derm.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F). Do not freeze.

Shelf Life

Shelf life – 2 years. Do not use after the expiration date.

After opening the tube, the drug should be stored at a temperature not exceeding 25°C (77°F) for no more than 6 months.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.