Pimecrolimus

(BAN, USAN, rINN)
Pimecrolimus Chemical formula
Synonyms: ASM-981; Pimécrolimus; Pimecrolimús; Pimecrolimusum; Pimekrolimus; Pimekrolimuusi; SDZ-ASM-981. (3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-3-{(E)-2-[(1R,3R,4S)-4-Chloro-3methoxycyclohexyl]-1-methylvinyl}-8-ethyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy14,16-dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1c][1,4]oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone.
Cyrillic synonym: Пимекролимус.

💊 Chemical information

Chemical formula: C43H68ClNO11 = 810.5.
CAS — 137071-32-0.
ATC — D11AX15.
ATC Vet — QD11AX15.

💊 Adverse Effects and Precautions

As for topical tacrolimus. The most frequent adverse effects of topical pimecrolimus are a burning sensation, irritation, pruritus, erythema, and skin infections at the application site. Rarely anaphylactic reactions, sometimes severe, have been reported. Cases of lymphadenopathy have been reported in patients using pimecrolimus cream. Treatment with pimecrolimus should be stopped in patients who develop lymphadenopathy in the absence of a clear aetiology or in the presence of acute infectious mononucleosis. All patients should be monitored to ensure that the condition resolves.

Carcinogenicity.

Carcinogenicity studies in animals and reports of malignancies in patients treated with topical calcineurin inhibitors prompted the FDA to issue an alert about the possible risk and to make recommendations about the appropriate use of pimecrolimus and tacrolimus.

💊 Interactions

Alcohol intolerance, described as flushing, rash, burning, itching, or swelling, has occurred rarely after the consumption of alcohol by patients using topical pimecrolimus.

💊 Pharmacokinetics

There is minimal systemic absorption and no accumulation from topical use of pimecrolimus. Studies in animals and in vitro have found no evidence of metabolism in the skin. Pimecrolimus is absorbed from the gastrointestinal tract after oral doses, and is about 74 to 87% bound to plasma proteins. It is metabolised in the liver by the cytochrome P450 isoenzyme CYP3A subfamily. About 78% of a single dose is eliminated in the faeces as metabolites and less than 1% as unchanged pimecrolimus. Only about 2.5% of a dose is eliminated in the urine, as metabolites.
1. Van Leent EJM, et al. Low systemic exposure after repeated topical application of pimecrolimus (Elidel , SD Z ASM 981) in patients with atopic dermatitis. Dermatology 2002; 204: 63–8
2. Scott G, et al. Pharmacokinetics of pimecrolimus, a novel nonsteroid anti-inflammatory drug, after single and multiple oral administration. Clin Pharmacokinet 2003; 42: 1305–14
3. Zollinger M, et al. Pimecrolimus: absorption, distribution, metabolism, and excretion in healthy volunteers after a single oral dose and supplementary investigations in vitro. Drug Metab Dispos 2006; 34: 765–74.

💊 Uses and Administration

Pimecrolimus is a macrolactam ascomycin derivative related to tacrolimus that acts as a calcineurin inhibitor and has similar anti-inflammatory and immunosuppressant actions. It is used for short-term and intermittent long-term treatment of mild to moderate atopic eczema in non-immunocompromised patients over the age of 2 years when conventional therapies are ineffective or unsuitable. Pimecrolimus is applied twice daily as a 1% cream until signs and symptoms clear. Treatment should be stopped if there is no improvement after 6 weeks or if eczema is exacerbated. Oral forms of pimecrolimus are also being investigated for the treatment of psoriasis and atopic eczema.
1. Wellington K, Jarvis B. Topical pimecrolimus: a review of its clinical potential in the management of atopic dermatitis. Drugs 2002; 62: 817–40
2. Anonymous. Topical pimecrolimus (Elidel) for treatment of atopic dermatitis. Med Lett Drugs Ther 2002; 44: 48–50
3. Anonymous. Pimecrolimus cream for atopic dermatitis. Drug Ther Bull 2003; 41: 33–6
4. Papp K, et al. Effect of pimecrolimus cream 1% on the long-term course of pediatric atopic dermatitis. Int J Dermatol 2004; 43: 978–83
5. Meurer M, et al. Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis. Dermatology 2004; 208: 365–72
6. Ashcroft DM, et al. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. BMJ 2005; 330: 516–22
7. Papp KA, et al. Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a twoyear study. J Am Acad Dermatol 2005; 52: 240–6
8. Wolff K, et al. Efficacy and tolerability of three different doses of oral pimecrolimus in the treatment of moderate to severe atopic dermatitis: a randomized controlled trial. Br J Dermatol 2005; 152: 1296–1303.

Administration in infants.

A 6-week, double-blind, randomised study of 186 infants between the age of 3 and 23 months, followed by a 20-week open-label phase, showed that 1% pimecrolimus cream, applied twice daily was both safe and effective in mild to moderate atopic eczema.1 A review2 of data from 10 studies that included 1133 infants between 3 and 23 months of age who were treated for up to 2 years found that the level of systemic exposure to pimecrolimus was very low and comparable to that observed in older children and adults. Treatment was reported to be effective and there was no evidence of immunosuppression or an increase in the rate of infections. Licensed product information, however, does not recommend its use in patients under 2 years of age as the effect of pimecrolimus cream on the developing immune system in infants is unknown (for concerns about possible carcinogenicity see above).
1. Ho VC, et al. Safety and efficacy of nonsteroid pimecrolimus cream 1% in the treatment of atopic dermatitis in infants. J Pediatr 2003; 142: 155–62
2. Paul C, et al. Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years. Abstract: Pediatrics 2006; 117: 202–3. Full version: http://pediatrics.aappublications.org/cgi/reprint/117/1/e118 (accessed 27/09/07)

Lichen.

There are a few case reports1,2 of benefit from pimecrolimus 1% cream in the management of oral lichen planus. In most cases it was applied twice daily, and in some cases adhesive gel or paste was also used. Improvement in oral lesions occurred within 2 to 4 weeks in 3 cases.1 In a placebocontrolled study3 of 20 patients with oral erosive lichen planus, pimecrolimus 1% cream was applied twice daily for 4 weeks. Although pain scores were reduced with pimecrolimus, the reduction in erythema was not maintained. There was also a trend towards an improvement in ulceration but changes in scores were not statistically significant. Topical pimecrolimus has also been tried in the management of genital lichen planus. In a series4of 11 women, 9 experienced benefit after 4 to 6 weeks of treatment; with follow-up of up to 10 months, 6 of them had experienced a complete response and 3 a partial response. The resolution of signs and symptoms of lichen sclerosus has been reported in 7 female patients (aged 4 to 48 years) with the use of topical pimecrolimus 1% cream twice daily for 3 to 4 months.5,6 A poor response was reported in a 62year-old woman who used the cream less frequently because of burning and stinging.5
1. Esquivel-Pedraza L, et al. Treatment of oral lichen planus with topical pimecrolimus 1% cream. Br J Dermatol 2004; 150: 771–3
2. Dissemond J, et al. Pimecrolimus in an adhesive ointment as a new treatment option for oral lichen planus. Br J Dermatol 2004; 150: 782–4
3. Swift JC, et al. The effectiveness of 1% pimecrolimus cream in the treatment of oral erosive lichen planus. J Periodontol 2005; 76: 627–35
4. Lonsdale-Eccles AA, Velangi S. Topical pimecrolimus in the treatment of genital lichen planus: a prospective case series. Br J Dermatol 2005; 153: 390–4
5. Goldstein AT, et al. Pimecrolimus for the treatment of vulvar lichen sclerosus: a report of 4 cases. J Reprod Med 2004; 49: 778–80
6. Boms S, et al. Pimecrolimus 1% cream for anogenital lichen sclerosus in childhood. BMC Dermatol 2004; 4: 14. Available at: http://www.biomedcentral.com/1471-5945/4/14 (accessed 27/09/07)

Psoriasis.

Topical pimecrolimus may have some benefit1 in the treatment of psoriasis. Although studies have generally found it to be less effective than topical corticosteroids or topical calcipotriol,2-4 one study2 in patients with chronic plaque psoriasis did report that pimecrolimus 1% ointment applied under occlusion had a similar efficacy to clobetasol propionate 0.05% ointment. Oral pimecrolimus is also under investigation and has reduced disease severity in dose-finding studies in patients with chronic plaque psoriasis.5,6
1. Gribetz C, et al. Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study. J Am Acad Dermatol 2004; 51: 731–8
2. Mrowietz U, et al. The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. Br J Dermatol 1998; 139: 992–6
3. Mrowietz U, et al. An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion. Acta Derm Venereol 2003; 83: 351–3
4. Kreuter A, et al. 1% Pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study. Arch Dermatol 2006; 142: 1138–43
5. Rappersberger K, et al. Pimecrolimus identifies a common genomic anti-inflammatory profile, is clinically highly effective in psoriasis and is well tolerated. J Invest Dermatol 2002; 119: 876–87
6. Gottlieb AB, et al. Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial. Br J Dermatol 2005; 152: 1219–27.

Seborrhoeic dermatitis.

Small studies1,2 suggest that topical pimecrolimus has a similar efficacy to topical corticosteroids in the treatment of seborrhoeic dermatitis. It has also been effective in a few cases that had not responded to topical corticosteroids.3
1. Rigopoulos D, et al. Pimecrolimus cream 1% vs. betamethasone 17-valerate 0.1% cream in the treatment of seborrhoeic dermatitis: a randomized open-label clinical trial. Br J Dermatol 2004; 151: 1071–5
2. Firooz A, et al. Pimecrolimus cream, 1%, vs hydrocortisone acetate cream, 1%, in the treatment of facial seborrheic dermatitis: a randomized, investigator-blind, clinical trial. Arch Dermatol 2006; 142: 1066–7
3. Cunha PR. Pimecrolimus cream 1% is effective in seborrhoeic dermatitis refractory to treatment with topical corticosteroids. Acta Derm Venereol 2006; 86: 69–70.

💊 Preparations

Proprietary Preparations

Arg.: Elidel; Austral.: Elidel; Austria: Elidel; Belg.: Elidel; Braz.: Elidel; Canad.: Elidel; Chile: Elidel; Cz.: Elidel; Denm.: Elidel; Fin.: Elidel; Fr.: Elidel; Ger.: Douglan; Elidel; Gr.: Aregen; Elidel; Hong Kong: Elidel; Hung.: Elidel; Indon.: Elidel; Israel: Elidel; Ital.: Elidel; Malaysia: Elidel; Mex.: Elidel; Neth.: Elidel; Norw.: Elidel; NZ: Elidel; Philipp.: Elidel; Pol.: Elidel; Port.: Aregen; Elidel; Rus.: Elidel (Элидел); S.Afr.: Elidel; Singapore: Elidel; Spain: Elidel; Isaplic; Rizan; Swed.: Elidel; Switz.: Elidel; Thai.: Elidel; Tu rk.: Elidel; UK: Elidel; USA: Elidel; Venez.: Elidel.
Published January 07, 2019.