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Prescribing Information can be found at the bottom of this page.

Skilarence® (dimethyl fumarate) is an oral treatment option for moderate-to-severe plaque psoriasis in adults in need of systemic treatment.1

Skilarence® contains the active substance dimethyl fumarate (DMF), a fumaric acid ester (FAE). The main activity of DMF and its main metabolite monomethyl fumarate (MMF) has not been elucidated but is considered to be immunomodulatory and anti-inflammatory.1

Skilarence® presentation:

Skilarence® is an oral treatment available in two gastro-resistant tablet strengths:1

  • The 30 mg presentation is used to initiate treatment and it may help you find the optimal dose for the individual needs of each patient.
  • The 120 mg presentation is used for the later phase of up-titration and usually for treatment maintenance.

The tablets are taken one to three times per day, with a maximum daily dose of 720 mg (six tablets).1 The usual maintenance dose required during treatment with FAEs is usually around 2-4 tablets per day.2

Administration:

Skilarence® dosing can be adapted for each patient according to the response to therapy and the occurrence of any side effects.2

Please advise your patients not to crush, divide, dissolve or chew Skilarence® tablets.

How to start Skilarence®2

  • It is recommended to begin treatment with a low initial dose with subsequent gradual increases1
  • If treatment success is observed before the maximum dose is reached, no further increase of dose is necessary1

  • The maximum daily dose allowed is 720 mg1
  • After clinically relevant improvement, dose can be progressively reduced to find the maintenance dose required by the individual1
  • If a particular dose increase is not tolerated, it may be temporarily reduced to the last tolerated dose.1
  • Response to treatment usually starts to be observed after three weeks, improves over time and can be expected to be maintained for at least up to 24 months, according to experience with related products containing dimethyl fumarate1,3
  • Skilarence® allows for flexible dosing that can be tailored to each patient.1

Skilarence® is contraindicated in the following cases:1

  • Hypersensitivity to DMF or to any of its excipients
    Skilarence® contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption are advised not to take this medicinal product.
  • Severe gastrointestinal disorders
    Skilarence® may cause gastrointestinal disorders.
  • Severe hepatic or renal impairment
    Skilarence® has not been studied in patients with severe renal or hepatic impairment, however, some cases of renal toxicity have been reported during post-marketing surveillance with FAEs.
  • Lymphopenia/leukopenia:
    Skilarence® is contraindicated in patients with a baseline lymphocyte count of <1.0×109 and/or a leukocyte count of <3.0×109.
  • Pregnancy and breast-feeding
    There is limited data from the use of DMF in pregnant women. It is unknown whether DMF or its metabolites are excreted in human milk.

Based on the pharmacology of DMF, a need for dose adjustment is neither needed in the elderly nor in patients with mild-to-moderate renal or hepatic impairment.1

The safety and efficacy of Skilarence® in paediatric patients below the age of 18 years have not been established.1

Interactions and combination with other treatments:1

  • There is no evidence for Skilarence® interaction with cytochrome P450 and the most common efflux and uptake transporters, thus no interactions are expected with medicinal products metabolised or transported by these systems.
  • No drug interaction studies with Skilarence® have been performed.
  • Combination of Skilarence® with other systemic anti-psoriatic therapy (both non-biologic and biologic) might have additive effects on the immune system. Caution is advised when switching patients from such therapies to Skilarence®.
  • Caution is also advised with concomitant use of medicines with nephrotoxic potential (methotrexate, cyclosporine, aminoglycosides, diuretics, NSAIDs or lithium) since they may increase the potential for renal adverse reactions (e.g. proteinuria) in patients taking Skilarence®.
  • In cases of severe or prolonged diarrhoea during treatment with Skilarence®, absorption of other medicinal products may be affected. If your patient is taking oral contraceptives, their efficacy may be reduced. It is recommended to advise her to use an alternative contraceptive method.
  • Please advise your patients to avoid consumption of large quantities of strong alcoholic drinks (more than 50 mL of containing 30% alcohol by volume). Alcohol may increase the frequency of gastrointestinal adverse reactions.

Adverse events and its management

Before patients start treatment, it is recommend that they be informed of potential gastrointestinal adverse events and ways to deal with them.

Adverse events with Skilarence® are usually mild and can be managed without discontinuation of the treatment.1

The following table shows the adverse events of Skilarence® in decreasing frequency:1

*Additional adverse reactions reported with Fumaderm, a related medicinal product containing dimethyl fumarate along with other fumaric acid esters

Recommendations to help your patients address most common adverse events:

Gastrointestinal events

They have a frequency of 62.7% and may occur particularly in the first three months after starting treatment.1
Gastrointestinal tolerability can be improved by following the dose titration schedule on initiating Skilarence® treatment and by taking Skilarence® with food.1

Flushing

Flushing occurs mainly in the first few weeks of treatment, with a frequency of 20,8%.1
If flushing is significant, a temporary reduction in the dose may be considered.1

Lymphopenia

Lymphopenia are most likely to occur during the first three months of treatment, does not generally lead to treatment discontinuation and reverts after treatment is stopped.1

Risk of Progressive multifocal leukoencephalopathy (PML):

PML is a rare, opportunistic viral infection of the central nervous system that occurs due to reactivation of the John Cunningham Virus (JCV), a human polyomavirus latent in approximately 50–80% of adults.4,5 If the patient has had a previous infection with JCV, he or she may develop PML as a result of being exposed to risk factors such as previous immunosuppressive treatment, persistent moderate or severe lymphopenia, concomitant disorders that affect the immune system, or genetic or environmental factors.1
Persistent moderate or severe lymphopenia under treatment with DMF is also considered a risk factor for PML. Patients who develop lymphopenia should be monitored for signs and symptoms of opportunistic infections, particularly for symptoms indicative of PML, such us progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision and changes in thinking, memory and orientation, leading to confusion and personality changes.1 If PML is suspected, treatment with Skilarence® should be stopped immediately and further appropriate neurological and radiological examinations performed.

It is crucial to follow the recommended monitoring guidance for Skilarence®.

Renal dysfunction and Fanconi syndrome

Functional disorders of the kidney occur occasionally under Skilarence® treatment. It is recommended to monitor the renal function and urine status, and dose reduction or discontinuation must be considered if Fanconi syndrome is detected in order to prevent renal impairment or osteomalacia.1

Signs of Fanconi syndrome are proteinuria, glucosuria (with normal blood sugar levels), hyperaminoaciduria, phosphaturia (possibly concurrent with hypophosphatemia), and it can occur without elevated creatinine levels or low glomerular filtration rate.1

Monitoring helps to manage adverse events

Before and during treatment, a complete blood count with differential and a urine test to monitor renal and hepatic function should be performed periodically.1

Treatment should not be initiated if leukocytes <3.0×109/L and lymphocytes <1.0×109/L or other pathological results are identified.1

How to monitor correctly:1

Every 3 monthsIf lab results correspond toAction
 

Lymphocytes

≥0.7×109 cells/L and
<1.0×109/L
Monthly monitoring
(until values ≥1.0×109 cells/L for 2 consecutive tests)
<0.7×109 cells/LStop treatment
if lab result is confirmed in second test continue monitoring until levels return to normal
 

Leukocytes

<3.0×109 cells/LStop treatment
Marked decreaseCareful monitoring
Hepatic EnzymesIf clinically relevant changes occurConsider dose reduction or treatment discontinuation
Renal function
& Urine status

Adapted from Skilarence® Summary of Product Characteristics.1
Please refer to Summary of Product Characteristics before prescribing. Lymphocytes and leukocytes are monitored based on a complete blood count including differential.

References

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1. Skilarence® Summary of Product Characteristics. Almirall.

2. Reich K, Thaci D, Mrowietz U, Kamps A, Neureither M, Luger T. Efficacy and safety of fumaric acid esters in the long-term treatment of psoriasis–a retrospective study (FUTURE). Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology: JDDG. 2009;7(7):603-711.

3. Patient Information Leaflet (PIL) Skilarence®. Almirall.

4. Balak DMW., Hajdarbegovic E, Bramer WM, Neumann MHA and Thio HB. Progressive multifocal leukoencephalopathy associated with fumaric acid esters treatment in psoriasis patients. J Eur Acad Dermatol Venereol. 2017

5. Khalili K, White MK, Lublin F, Ferrante P, Berger JR. Reactivation of JC virus and development of PML in patients with multiple sclerosis. Neurology. 2007;68:985-990

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UK-IEDMF-2100002

March 2021

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