*2.3.4 Fumaric acid esters and dimethyl fumarate*

*Healthcare Access - Regional Overviews*

synthesis of interleukin 2 [45].

to be ensured.

risk to the foetus [49].

*2.3.3 Acitretin*

fatigue [52].

pneumonitis and gastrointestinal toxicity [47, 48].

ritonavir, saquinavir) and octreotide [48].

eration and differentiation of keratinocytes [50].

3–6 months for a maximal response to acitretin [51].

ate, doxycycline, oral retinoids and phenytoin [53].

blood count should also be included.

by reversibly inhibiting the activation of CD4+ T cells, leading to a block on the

*Dosage and administration*. To induct psoriasis remission, the everyday dosage varies between 2.5 and 5 mg/kg, administered in two divided doses each day. Experts recommend it not be used continuously for longer than 1 whole year [46]. *Adverse effects*. Among the most important reported adverse effects of cyclosporine are renal toxicity, structural kidney damage, hypertension, liver toxicity, severe infections, high potassium levels, low magnesium levels, acne, tremors, headache,

*Laboratory tests recommended***.** Physical exam, patient history, QuantiFERON-TB

*Drug interactions*. Cyclosporine interacts with a large number of drugs such as antibiotics (ciprofloxacin, gentamicin, tobramycin, vancomycin, trimethoprim with sulfamethoxazole, azithromycin, erythromycin), nonsteroidal anti-inflammatory drugs, antifungals (amphotericin B, ketoconazole, fluconazole, itraconazole, terbinafine), ranitidine, cimetidine, birth control pills, tacrolimus, methotrexate, methylprednisone, allopurinol, colchicine, fenofibrate, gemfibrozil, statins, calcium channel blockers, amiodarone, bromocriptine, anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital), protease inhibitors (indinavir, nelfinavir,

It is contraindicated in the case of poorly controlled arterial hypertension, known malignancies or renal dysfunctions. As of yet, there have not been enough studies performed in humans to certify whether the drug affects the foetus or not. Nonetheless, the treatment is still to be avoided in pregnant women due to the role calcineurin inhibitors are believed to play in neural development. As such, cyclosporine should only be used in pregnancy if the benefits justify the hypothetical

Acitretin is a retinoid agent with substantial immunomodulatory and antiinflammatory effects, advocated in psoriasis for its capacity to modulate the prolif-

*Dosage and administration*. Acitretin is taken in a single oral dose, alongside the main meal. Therapeutic dosage varies between 25 and 50 mg/day. A simultaneous topical therapy is also suggested due to the slow onset of action, needing as long as

*Adverse effects***.** It can cause serious teratogenic effects on the exposed foetus, mucocutaneous dryness, hypertriglyceridemia, hepatotoxicity, toxic hepatitis, pancreatitis, hyperostosis, intracranial hypertension, alopecia, arthralgia and

*Laboratory tests recommended*. It is compulsory to take a pregnancy test before initiating the treatment; liver enzymes, lipid profile, renal function and complete

*Drug interactions***.** Acitretin interacts with retinoic acid supplements, methotrex-

The high teratogenicity of retinoids severely restricts their use in fertile women who should be appropriately counselled on the methods and importance of contraception [54]. Moreover, pregnancy should be circumvented for at least 3 years after

Gold for latent TB infection, renal function tests, complete blood count with differential and platelet count, magnesium level, potassium level, uric acid, lipids, glycaemia, bilirubin and liver enzymes are necessary before initiating therapy. The serum creatinine should be measured on two distinct occasions. Contraception has

**92**

Fumaric acid esters and dimethyl fumarate have been employed in the treatment of psoriasis for five decades, with substantial outcomes for patients [55]. Seemingly, dimethyl fumarate affects multiple cytokines and lymphocyte pathways, i.e. inhibiting the nuclear translocation and the transcriptional activity of the nuclear factor kappa-light-chain-enhancer of activated B-cells through its interaction with the intracellular reduced glutathione. It also transforms the T helper cells from the Th1 and the Th17 profile to a Th2 phenotype, subsequently reducing cytokine production and the proliferation of epithelial cells [56].

*Dosage and administration*. It is available as gastro-resistant tablets, being recommended to start with a low initial dose that may be subsequently increased in the following manner: in the first week, it is advised to take one 30 mg tablet, in the second week one 30 mg tablet can be taken twice daily, and during the third week one 30 mg tablet is taken three times per day. From the fourth week onwards, it can be switched to one 120 mg tablet, taken in the evening. Depending on the results, this dose can be increased with one 120 mg tablet per week, but the maximum daily dose should not exceed 720 mg [57].

*Adverse effects*. Among more regularly reported events are gastrointestinal disorders, flushing, haematological disturbances (lymphopenia, leukopenia, eosinophilia), loss of appetite, headache, paraesthesia, proteinuria, renal failure, Fanconi syndrome and fatigue [58].

*Reference tests*. Complete blood count, renal function and liver enzymes should be included.

*Drug interactions***.** Fumaric acid esters may interact with live vaccines, methotrexate, retinoids, cyclosporine, aminoglycosides, lithium, diuretics and nonsteroidal anti-inflammatory drugs [59].
