Acute Porphyria Drugs

Acute Porphyria Drug Database

L04AX02 - Thalidomide
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 thalidomide that can be confused with an acute porphyric attack are constipation, vomiting and parasthesia. There are some reports of amenorrhoea as a side effect from use of thalidomide, but this is not mentioned as a side effect in the SPC of the drug (Passeron 2001, Frances 2002, Ordi 1998, Gutierrez-Roderigues 1989, Gompel 1999).
Rationale
Thalidomide is mainly metabolized non enzymatically. There are no data pointing to clinical CYP induction or inhibition.
Chemical description
Thalidomide is a phthalimide glutarimide with tertiary and secondary cyclic amines.
Therapeutic characteristics
Thalidomide has anti-inflammatory and immunomodulating effects and is used in combination with melphalan and corticosteroids as first line treatment of patients with untreated multiple myeloma, aged 65 years or more, or ineligible for high dose chemotherapy. It is also used in the treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum. It is administered orally.
Metabolism and pharmakokinetics
Thalidomide mainly undergoes non-enzymatic hydrolysis in plasma to multiple metabolites. It is listed as a substrate for CYP 1A1, 1A2, 2C9, 2E1 and 2C19, a weak inhibitor of CYP 2C19 and as an enhancer of 3A5 mediated metabolism (Zhou 2009). Thalidomide has shown to increase the metabolism of midazolam and ciclosporine by a proposed mechanism that involves heterotropic cooperativity of CYP 3A5 (Okada et al. 2008). However, thalidomide has minimal hepatic CYP catalyzed metabolism, and interactions with CYP is not observed and not probable.
Preclinical data
In a study on rats, treatment with thalidomide showed no effect on the urinary porphyrin excretion, but thalidomide was believed to have an effect on the activity of CYP 450 (Tsambaos 1994).
Published experience
One report of uneventful use by a woman with AIP (Filiotou 2002).
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.

References

  1. Scientific articles
  2. Francã¨s C, et al. Transient secondary amenorrhea in women treated by thalidomide. Eur J Dermatol. 2002; 12: 63â-5. PMID 38904376. #3358
  3. Zhou, S.F., Zhou, Z.W. et al. Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development. Current Medicinal Chem 2009; 16: 3480-3675. #2353
  4. Filiotou A, Vaiopoulos G et al. Acute intermittent porphyria and systemic lupus erythematosus: report of a case and review of the literature. Lupus. 2002;11(3):190-2. PMID 11999885. #2339
  5. Gompel A, Frances C et al. Ovarian failure with thalidomide treatment in complex aphthosis: comment on the concise communication by Ordi et al. Arthritis Rheum 1999; 42: 2259-60. PMID 10524707. #3359
  6. Gutierrez-Rodriguez O, Starusta-Bacal P et al. Treatment of refractory rheumatoid arthritis - the thalidomide experience. J Rheumatol 1989; 16: 158-63. PMID 2746563. #4617
  7. Niwa T, Murayama N, Yamazaki H. Heterotropic cooperativity in oxidation mediated by cytochrome p450. Curr Drug Metab. 2008 Jun;9(5):453-62. PMID 18537580. #2344
  8. Ordi J, Cortes F, Martinez N et al. Thalidomide induces amenorrhea in patients with lupus disease. Arthritis Rheum 1998; 41: 2273-5. PMID 9870886. #4618
  9. Passeron T, et al.. Thalidomide-induced amenorrhoea: two cases. Br J Dermatol. 2001; 144: 1292â-3. PMID 11422077. #4619
  10. Teo SK, Sabourin PJ et al. Metabolism of thalidomide in human microsomes, cloned human cytochrome P-450 isozymes, and Hansens disease patients. J Biochem Mol Toxicol. 2000;14(3):140-7. PMID 10711629. #3360
  11. Trapnell CB, Donahue SR et al. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther. 1998 Dec;64(6):597-602. #2351
  12. Tsambaos D, Bolsen K et al. Effects of oral thalidomide on rat liver and skin microsomal P450 isozyme activities and on urinary porphyrin excretion: interaction with oral hexachlorobenzene. Arch Dermatol Res. 1994;286(6):347-9. PMID 7979550. #2352
  13. Drug reference publications
  14. Sweetman SC, editor. Martindale: The complete drug reference. Thalidomide. Pharmaceutical Press 2009. #2347
  15. Summary of Product Characteristics
  16. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Thalidomide celegene. #2350
Similar drugs
Explore alternative drugs in similar therapeutic classes L04A / L04AX or go back.
 
© NAPOS 2024
An unhandled error has occurred. Reload 🗙