MIRVASO Gel Ref.[6613] Active ingredients: Brimonidine

Mirvaso should not be applied on irritated skin (including following laser therapy) or open wounds. In case of severe irritation or contact allergy, the treatment with the medicinal product should be discontinued.

Exacerbation of rosacea symptoms is very common in patients treated with Mirvaso. Across all clinical studies, 16% of patients receiving Mirvaso experienced an event of symptom exacerbation. Treatment should be initiated with a small amount of gel and the dose increased gradually, based on tolerability and response to treatment (see section 4.2).

Erythema and flushing

The effect of Mirvaso topical gel begins to diminish hours after application. In some patients, erythema and flushing were reported to return with greater severity than was present at baseline. Most of the cases were observed within the first 2 weeks of starting the treatment (see section 4.8).

The onset of flushing relative to application of Mirvaso topical gel varied, ranging from approximately 30 minutes to several hours (see section 4.8).

In the majority of these cases, erythema and flushing resolved after discontinuation of Mirvaso topical gel.

In case worsening of erythema occurs, Mirvaso topical gel should be discontinued. Symptomatic measures, such as cooling, NSAID and antihistamines, may help in alleviating symptoms.

Recurrences of aggravated erythema and flushing have been reported after re-administration of Mirvaso topical gel. Prior to resuming treatment after temporary discontinuation due to aggravated erythema or flushing, perform a test application on a small area of the face for at least one day before full facial application is resumed.

It is important to inform the patient not to exceed the recommended maximum dose (5 pea size amounts) and frequency of application (once daily).

Mirvaso should not be applied close to the eyes.

Concomitant use of other systemic alpha adrenergic receptor agonists

The concomitant use of other systemic alpha adrenergic receptor agonists may potentiate the undesirable effects of this class of medicinal products in patients:

• with severe or unstable or uncontrolled cardiovascular disease;
• with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, thrombangiitis obliterans, scleroderma, or Sjögren’s syndrome.

Other

Any increase in the daily amount applied above 5 pea sized amounts and/or increase in frequency of daily application of the medicinal product should be avoided, since the safety of higher daily doses or repeated daily application has not been assessed.

The medicinal product contains methylparahydroxybenzoate (E218) which may cause allergic reactions (possibly delayed), and propylene glycol (E1520) which may cause skin irritation.

No interaction studies have been performed.

Mirvaso is contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy and patients on tricyclic or tetracyclic antidepressants which affect noradrenergic transmission (see section 4.3).

The possibility of an additive or potentiating effect with central nervous system depressants (alcohol, barbiturates, opiates, sedatives, or anaesthetics) should be considered.

No data on the level of circulating catecholamines after Mirvaso administration are available. Caution, however, is advised in patients taking substances which can affect the metabolism and uptake of circulating amines e.g. chlorpromazine, methylphenidate, reserpine.

Caution is advised when initiating (or changing the dose of) a concomitant systemic substance (irrespective of pharmaceutical form) which may interact with alpha adrenergic receptor agonists or interfere with their activity i.e. agonists or antagonists of the adrenergic receptor e.g. (isoprenaline, prazosin).

Brimonidine may cause clinically insignificant decreases in blood pressure in some patients. Caution is therefore advised when using medicinal products such as anti-hypertensives and/or cardiac glycosides concomitantly with brimonidine.

Pregnancy

There are no or limited amount of data from the use of brimonidine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Mirvaso during pregnancy.

Breast-feeding

It is unknown whether brimonidine/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Mirvaso should not be used during breast-feeding.

Fertility

Brimonidine did not present any special reproductive or developmental hazard in animal species.

Mirvaso has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reactions are erythema, pruritus, flushing and skin burning sensation, all occurring in 1.2 to 3.3% of patients in clinical studies. They are typically mild to moderate in severity, and usually do not require discontinuation of treatment. Aggravated erythema, flushing and skin burning sensation have been reported during the post-marketing period (see section 4.4).

Tabulated list of adverse reactions

The adverse reactions are classified by System Organ Class and frequency, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data) and were reported with Mirvaso either in clinical studies, or during the post-marketing experience (identified by an asterix (*) in Table 1).

Table 1. Adverse reactions:

^* Adverse reactions reported from post-marketing data.

Description of selected adverse reactions

Bradycardia and hypotension

Post-marketing cases of bradycardia, hypotension (including orthostatic hypotension) and dizziness have been reported, some of which required hospitalisation. Some cases involved application of Mirvaso following laser procedures (see section 4.4).

Other special populations

Elderly patients

No meaningful differences in the safety profiles were observed between the elderly subject population and subjects 18 to 65 years of age.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.