Drug-Induced Liver Injury Caused by the Histrelin (Vantus®) Subcutaneous Implant

Ricker, Jonathan; Foody, William F.; Shumway, Nathan M.; Shaw, Jon A.

doi:10.1097/smj.0b013e3181c376a6

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…It may be that changes observed in the blood lipid profile are caused by direct action of analogs on liver cells. In animal models the GnRH agonist histrelin has been safely administered to both rats and rabbits [42]. However, Chester et al [32] investigated long-term toxicity of the GnRH antagonist detirelix and noted a significant dose-dependent increase in AST and ALT activity in blood of rats of both sexes.…”

Section: Discussionmentioning

confidence: 99%

“…Freundl et al [46], using leuprorelin in patients treated for endometriosis, detected only slight changes in ALT, AST and LDH activities in blood. In men with advanced prostate cancer who were treated with histrelin implant, the most common adverse effects were hot flashes, implant site reaction, renal impairment, testicular atrophy, nausea, fatigue, and gynecomastia [42]. Nevertheless, only 8.7% of these patients developed hepatic impairment, defined as occasional random anomalous laboratory values.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, only 8.7% of these patients developed hepatic impairment, defined as occasional random anomalous laboratory values. In some clinical reports there were only a few cases of liver toxicity manifested by transiently elevated enzymes in a hepatocellular pattern – AST, ALT and alkaline phosphatase after the initiation of histrelin treatment [42]. The liver biopsy revealed marked necro-inflammatory injury with bridging necrosis, which favors a typical pattern for medication- or toxin-mediated hepatocellular damage.…”

Section: Discussionmentioning

confidence: 99%

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Zmiany morfologiczne i enzymatyczne wywołane długoterminowym podawaniem samicom szczura niskiej dawki agonisty i antagonisty gonadoliberyny.

et al. 2012

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SummaryBackgroundLong-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects.Material/MethodsWe investigated whether a 3-months administration of a low dose (6 μg/kg b.w.) of dalarelin – a new agonist, and cetrorelix – a known antagonist of GnRH to female rats causes morphological changes in pituitary gland, ovaries, uterus and liver (HE and VG staining); effects on pituitary, hepatic and blood enzyme activities (histochemical and kinetic methods, respectively), and on the blood lipid profile (colorimetric methods); and to what extent these changes are reversible.ResultsApplying analogs effectively inhibited ovulation, affected the uterine endometrium and changed histological appearance of the liver (e.g., steatosis). They altered activities of marker enzymes of cellular respiration, gluconeogenesis and intracellular digestion in the liver and, partially in the pituitary gland, caused undesirable changes in the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a concentration of cholesterol HDL fraction and triglycerides in the blood. Both morphological and enzymatic effects were more evident after antagonist administration; changes in the blood lipid profile were more evident after agonist administration. In both analogs histological and enzymatic changes persisted a relatively long time after the discontinuation of the treatment.ConclusionsThe low dose of dalarelin and cetrorelix is sufficient to cause limited damage of hepatic cells and may modify the function of pituitary, ovaries, uterus and liver as well as other organs, even after discontinuation of the treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Zmiany morfologiczne i enzymatyczne wywołane długoterminowym podawaniem samicom szczura niskiej dawki agonisty i antagonisty gonadoliberyny.

et al. 2012

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Current awareness: Pharmacoepidemiology and drug safety

2010

Pharmacoepidemiology and Drug

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 23 sections: 1 Reviews; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Teratogens/fetal exposure; 20 Antidiabetic Agents; 21 Contrast Agents; 22 Bone Conservation Agents; 23 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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