Tacrolimus efficacy

Several studies have assessed the clinical efficacy of cyclosporine versus tacrolimus. Most of the studies have shown similar longterm patient and allograft survival, whereas some renal transplant studies have demonstrated improved renal function in tacrolimus-treated patients. The most significant difference between the two agents appears to be their adverse-reaction profiles (Table 52-4). 

The evidence of the safety and efficacy of pimecrolimus was derived from studies primarily in patients with mild-to-moderate atopic dermatitis tacrolimus data was derived from moderate-to-severe patients. 

Tacrolimus, a macrolide, derives from a streptomyces species pharmacologically it resembles cyclosporin A, but is more potent and efficacious. 

Liver transplant recipients - Safety and efficacy in liver transplant recipients are unknown. If entecavir treatment is necessary for a liver transplant recipient who has received or is receiving an immunosuppressant that may affect renal function (eg, cyclosporine, tacrolimus), renal function must be carefully monitored before and during treatment with entecavir. 

Echinacea (Echinacea purpurea) Uses immune system stimulant prevention/Rx of colds, flu as supportive th apy for colds chronic infxns of the resp tract lower urinary tract Action Stimulates phagocytosis cytokine production T resp cellular activity topically exerts anesthetic, antimicrobial, anti-inflammatory effects Efficacy Not established may X severity duration of URI Available forms Caps w/ powdered herb equivalent to 300-500 mg, PO, tid pressed juice 6-9 mL, PO, once/d tine 2-4 mL, PO, tid (1 5 dilution) tea 2 tsp (4 g) of powdered herb in 1 cup of boiling water Noles/SE Fever, taste p -version, urticaria, angioedema Contra w/ autoimmune Dz, collagen Dz, progressive systemic Dz (TB, MS, collagen-vascular disorders), HIV, leukemia, may interfere w/ immunosuppressive therapy Interactions t Risk of disulfiram-like reaction W/ disulfiram, metronidazole T risk of exacerbation of HIV or AIDS W/ chinacea amprenavir, other protease inhibitors X effects OF azathioprine, basiliximab, corticosteroids, cyclosporine, daclizumab, econazole vag cream, muromonab-CD3, mycophenolate, prednisone, tacrolimus EMS Possible immunosuppression... 

Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimns and tacrolimus in the treatment of atopic dermatitis meta-analysis of randomised controlled trials. BMJ 2005 330 516-21. 

Henry ML. 1999. Cyclosporine and tacrolimus A comparison of efficacy and safety profiles. Clin Transplant. 13 209-220. 

Beck LA. The efficacy and safety of tacrolimus ointment a clinical review. J Am, Acad Dermatol. 2005 53 (suppl 2) S165-S170. 

TACROLIMUS ADEFOVIR DIPIVOXIL Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

TACROLIMUS GRAPEFRUIT JUICE t efficacy and t adverse effects of tacrolimus Unclear but probably due to inhibition of metabolism Avoid concomitant use. Measure levels if toxicity is suspected, l dose as necessary and monitor levels closely... 

TACROLIMUS PROTON PUMP INHIBITORS Possible t efficacy and adverse effects of immunosuppression Altered metabolism from CYP2C19 to CYP3A4 in patients with low CYP2C19 levels Monitor levels more closely... 

ACICLOVIR/ VALACICLOVIR ANTICANCER AND IMMUNOMODULATING DRUGS- 1. CICLOSPORIN 2. MYCOPHENOLATE 3. TACROLIMUS 1.1 nephrotoxicity 2. Possible T efficacy 3. t levels with protease inhibitors 1. Additive side-effect 2. Competition for renal excretion 3. Inhibition of CYP3A4-mediated metabolism of tacrolimus 1. Monitor renal function prior to concomitant therapy and monitor cidosporin levels 2. Monitor renal function particularly if on >4g valaciclovir 1 dose of aciclovir if there is a background of renal failure 3. Monitor clinical effects closely check levels... 

ADEFOVIR DIPIVOXIL 1. ANTIBIOTICS -aminoglycosides, vancomycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - cidosporin, tacrolimus 3. ANTIFUNGALS-amphotericin, 4. ANTIPROTOZOALS-pentamidine 5. ANTIVIRALS - cidofovir, foscarnet sodium, tenofovir Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

GRAPEFRUIT JUICE SIROLIMUS, TACROLIMUS Possibly T efficacy and T adverse effects of sirolimus Possibly t bioavailability via inhibition of intestinal CYP3A4 and effects of P-gp Avoid concomitant use... 

Spencer CM, Goa KL, Gilhs JC. Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation. Drugs 1997 54 925-975. 

Sperrcer CM, Goa KL, Gillis JC (1997) Tacrolimus. Air update of its phai macology aird cliirical efficacy iir tire mairagemeirt of orgair ti airsplairtadoir. Drugs 54 925—975. 

Amphotericin colloidal dispersion has been compared with amphotericin deoxycholate in a prospective, randomized, double-blind study in the empirical treatment of fever and neutropenia in 213 patients (25). Patients were stratified by age and concomitant use of ciclosporin or tacrolimus and then randomized to receive ABCD (4 mg/kg/day) or amphotericin deoxycholate (0.8 mg/ kg/day) for 14 days. Renal dysfunction was less likely to develop and occurred later with ABCD than with amphotericin deoxycholate. Likewise, the absolute and percentage fall in the serum potassium concentration from baseline to the end of therapy was greater with amphotericin deoxycholate than ABCD. However, probable or possible infusion-related hypoxia and chills were more common with ABCD than amphotericin deoxycholate. There was a therapeutic response in 50% of the patients who received ABCD and 43% of those who received amphotericin deoxycholate. Thus, ABCD was of comparable efficacy and less nephrotoxic than amphotericin deoxycholate, but infusion-related events were more common with ABCD. 

In a study of the safety and efficacy of simvastatin in hyperlipidemia after renal transplantation in 15 patients, the Cmax and AUC of simvastatin were increased seven-fold by ciclosporin (260). In contrast, in 17 patients, tacrolimus had no effect. Although there were no complications, such as myopathy or rhabdomyolysis, creatine kinase activity must be monitored during co-administra-tion of simvastatin and ciclosporin. 

Jablonska S, Rustin M. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group. Arch Dermatol 2000 136(8) 999-1006. 

Kang S, Lucky AW, Pariser D, Lawrence I, Hanifin JM. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 2001 44(Suppl l) S58-64. 

Kramer BK, Montagnino G, Del Castillo D, Margreiter R, Sperschneider H, Olbricht CJ, Kruger B, Ortuho J, Kohler H, Kunzendorf U, Stummvoll HK, Tabernero JM, Muhibacher F Rivero M, Arias M European Tacrolimus vs Cyclosporin Microemulsion Renal Transplantation Study Group. Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation 2 year follow-up results. Nephrol Dial Transplant 2005 20 968-973. 

Meiser B, Kaczmarek I, Mueller M, Groetzner J, Weis M, Knez A, Stempfle FlU, Klauss V, Schmoeckel M, Reichart B, Ueberfuhr P. Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is highly efficacious. J Heart Lung Transplant 2007 ... 

When compared with the standard formulation, the microemulsion formulation has demonstrated equivalent or superior efficacy in kidney, liver, and heart transplant recipients. Other areas of research include CSA as monotherapy and as rescue therapy for patients who are unable to tolerate tacrolimus. 

Pimecrolimus and tacrolimus are calcineurin inhibitors capable of exerting a local immunomodulating effect that may serve to normalize hyperproliferation of epidermis. As topical agents, tacrolimus and pimecrolimus are approved for the treatment of atopic dermatitis however, regulatory approval regarding the efficacy of these agents in psoriasis is yet to be completed. 

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