Acute Porphyria Drugs

Acute Porphyria Drug Database

G04BD08 - Solifenacin
Propably not porphyrinogenic
PNP
Rationale
Solifenacin is extensively metabolized by Cyp3A4, but it has no capacity for Cyp-induction or significant Cyp-inhibition.
Chemical description
Dihydroisoquinoline tertiary amine.
Therapeutic characteristics
Solifenacin is an anticholinergic spasmolytic used in the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and increased urinary frequency. It is administered orally. Common adverse reactions of solifenacin that can be confused with an acute porphyric attack are constipation, nausea and abdominal pain. Side effects such as nausea may be potentially porphyrinogenic through reduction in caloric intake. Urinary infection is an uncommon side effect but may also potentially be porphyrinogenic.
Metabolism and pharmakokinetics
Solifenacin is eliminated mainly via hepatic metabolism by Cyp3A4, and only 3-13 % is excreted as unchanged drug in urine. The absolute bioavailability is about 90%. Solifenacin has a high fraction of plasma protein-binding (93-96%). Solifenacin doses not influence the activities of Cyps 1A1, 1A2, 2C9, 2D6 and 3A4, but shows weak and clinically insignificant inhibitory potential for Cyp 2C19 and p-glycoprotein.(Doroshyenko 2009). In a well-controlled therapeutic trial solifenacin did not interact with the metabolism of ethinyl estradiol or levonorgestrel administered in oral contraception. (Taekema-Roelvink 2005).
IPNet drug reports
Uneventful use reported in 2 patients with acute porphyria.

References

  1. Scientific articles
  2. Doroshyenko, O., Fur, U. Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet. 2009;48(5):281-302 #1550
  3. Taekema-Roelvink M. E.J., Swart P.J., Pharmacokinetic interaction of solifenacin with an oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women: a double-blind, placebo-controlled study. Clin Ther. 2005;27(9):1403-10. PMID 16291413. #1553
  4. Drug reference publications
  5. Sweetman SC, editor. Martindale: The complete drug reference. Solifenacin succinate. Pharmaceutical Press 2009. #1552
  6. Summary of Product Characteristics
  7. Norwegian medicines agency. Summary of Product Characteristics (SPC). Vesicare. #1551
  8. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Vesicare. #1554
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