Monograph
L04AD02 - Tacrolimus |
Propably not porphyrinogenic |
PNP |
Important Information
Patients on immunosuppressive therapy have an increased risk of infections. Since infections have a potential to trigger acute porphyric attacks vigilance is motivated regarding signs or symptoms of infection and/or possible symptoms of a porphyric attack. Side effects like nausea and vomiting may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
Infections are common in patients using immunosuppressants and since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended. Common adverse reactions of tacrolimus that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Tacrolimus is a substrate of CYP 3A4, but does not induce or irreversible inhibit cytochrome P450 enzymes.
Chemical description
Macrolide immunosuppressant.
Therapeutic characteristics
Tacrolimus is a calcineurin inhibitor with highly potent immunosuppressive properties. It is used as prophylaxis and treatment of transplant rejection. It is administered orally or as an intravenous or intramuscular injection.
Metabolism and pharmacokinetics
Tacrolimus is widely metabolised in the liver, primarily by the cytochrome P450-3A4. Tacrolimus is also considerably metabolised in the intestinal wall. Tacrolimus is a weak inhibitor of Cyp3A4, but is not listed among mechanism-based CYP inhibitors. It has shown to increased blood levels of phenytoin, but it probably has no major potential to inhibit the Cyp metabolism of other drugs.
Published experience
Reports of uneventful use:
Barone et al. J Clin pharmacol 2003 (tolerated in 1 patient with AIP).
Turton-Weeks et al. Prog Transplant 2001(tolerated in 1 patient with AIP).
Telkes G et al. Transplant Proc. 2013 (tolerated in 1 patient With HCP).
IPNet drug reports
Uneventful use reported in 2 patients with acute porphyria.
References
| # |
Citation details |
PMID |
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| * | Scientific articles |
| 1. |
Christians U, Jacobsen W, Benet L Z, Lampen A, Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clinical Pharmacokinetics. 41(11):813-851, 2002.
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| 2. |
Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83â-448.
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| 3. |
The tolerability of newer immunosuppressive medications in a patient with acute intermittent porphyria. Journal of Clinical Pharmacology 2001; 41(1):113-115.
Barone GM, Gurley BJ, Anderson KE, Ketel BL, Abul-Ezz SR. |
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| 4. |
Tacrolimus: a further update of its use in the management of organ transplantation.
Scott LJ, McKeage K, Keam SJ, Plosker GL. Drugs. 2003;63(12):1247-97. |
12790696 |
| 5. |
Kidney transplantation in hereditary coproporphyria using tacrolimus and mycophenolate mofetil: a case report.
Telkes G, Pusztai A et al. Transplant Proc. 2013;45(10):3703-4. |
24315002 |
| 6. |
Pretransplant evaluation of a patient with acute intermittent porphyria. Progress in Transplantation 2001; 11(3):214-216.
Turton-Weeks S, Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR et al. |
11949465 |
| * | Drug reference publications |
| 7. |
Sweetman SC, editor. Martindale: The complete drug reference. Tacrolimus. Pharmaceutical Press 2009.
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| * | Government bodies |
| 8. |
European Public Assessment Report, Advagraf (Scientific discussion).European Medicines Agency (EMEA). Accessible from: emea.europa.eu
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| * | Summary of Product Characteristics |
| 9. |
The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Prograf.
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