Lysodren® therapy

What is Lysodren®?

Lysodren® (Mitotane) is an adrenal cytotoxic active substance – an antineoplastic agent which suppresses production of adrenal cortex corticosteroid hormones. 1,2

Lysodren® role in ACC

Only FDA approved treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC) 1

WARNING: Patients treated with Lysodren are at an increased risk for developing ADRENAL CRISIS in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma, or infection occurs or develops, temporarily discontinue Lyosdren and administer exogenous steroids. Montior patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs.

How Lysodren® works

Research on the mode of action of mitotane suggests two main biological effects:

  • A direct cytotoxic effect on adrenal cortical cells, mediated through mitochondrial alterations and inhibition of sterol-O-acyl transferase 1 (SOAT1) 2
  • Inhibition of corticosteroid synthesis by modifying the peripheral metabolism of cortisol and directly suppressing the production of corticosteroids from the adrenal cortex 1,4

Management of advanced ACC not amenable to radical resection

Practice Guidelines on the management of adrenocortical carcinoma in adults5

ACC: adrenocortical carcinoma: EDP: etoposide, doxorubicin, cisplatin
Adapted from Fassnacht M, et al. Eur J Endocrinol.2018;179(4):G1-G46.

Reference notes from Practice Guidelines

  1. Only in selected patients (with severe hormone excess)
  2. The following factors might guide the decision: site of disease involvement, tumor burden, symptoms, tumor grade/Ki67 index
  3. The following factors might guide the decision: site of disease involvement, tumor burden, symptoms, tumor grade/Ki67 index, and importantly kinetics of tumor growth
  4. Radiotherapy, radiofrequency ablation, cryo-ablation, microwave ablation, (chemo-) embolization
  5. Few panellists favored cisplatin + etoposide
  6. Contact specialized center

Lysodren® dosing and monitoring the therapeutic window

Lysodren® is available as 500 mg tablets.1 The total daily dose should be divided into three or four doses with food.1

The recommended treatment schedule is to start the patient at 2000 mg to 6000 mg orally, in three to four divided doses per day with food. Titrate LYSODREN to achieve a plasma level of 14 to 20 mg/L1

Time taken to reach target levels of Lysodren® and observe clinical benefits varies from patient to patient but typically requires a minimum of 4 months of continuous treatment. 6

Finding and maintaining the Lysodren® therapeutic window

Optimal Plasma Concentration Target

Mitotane Plasma Level Monitoring is to be performed on a regular and individual basis to reach/maintain an optimal therapeutic window.6

REFERENCES

1. Lysodren® prescribing information.
2. Waszut U, Szyszka P, Dworakowska D. Understanding mitotane mode of action, J Physiol Pharmacol 2017; 68 (1):13-26.
3. Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma, N Engl J Med 2012; 366(23):2189-97.
4. Ghataore L, Chakraborti I, Aylwin S, et al. Effects of mitotane treatment on human steroid metabolism: implications for patient management, Endocr Connect 2012; 1(11):37-47.
5. Fassnacht M, et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018;179(4):G1-G46.
6. Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2009;23(2):273-89.

Lysodren Adverse Events1

Reported Adverse Reactions include:

  • Metabolism and nutrition disorders: Anorexia
  • Gastrointestinal disorders: Epigastric discomfort, nausea, vomiting, diarrhea
  • Nervous system disorders: Depression, dizziness, or vertigo
  • Confusion, headache, ataxia, mental impairment, weakness, dysarthria, paresthesia, polyneuropathy, movement disorder, balance disorder, dysgeusia
  • Skin and subcutaneous tissue disorders: Rash, pruritus, hypersensitivity reactions
  • Blood and lymphatic system disorders: Leukopenia, anemia, thrombocytopenia, prolonged bleeding time, hematuria, hemorrhagic cystitis
  • Endocrine: growth retardation, hypothyroidism
  • Eye disorders: maculopathy, visual blurring, diplopia, lens opacity, retinopathy
  • Hepatobiliary disorders: hepatitis, elevation of liver enzymes, liver injury (hepatocellular/cholestatic/mixed)
  • Reproductive system and breast disorders: gynecomastia, hypogonadism (in males)
  • Hypercholesterolemia, hypertriglyceridemia
  • Decreased plasma androstenedione, decreased plasma testosterone in females, increased sex hormone binding globulin in females and males, decreased blood free testosterone in males
  • Musculoskeletal disorders: muscular weakness, generalized aching
  • General disorders: fever
  • Renal and urinary disorders: Albuminuria/proteinuria
  • Vascular disorders: Hypertension, orthostatic hypotension, flushing
  • Infections: opportunistic infection

INDICATION AND IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING ON ADRENAL CRISIS IN THE SETTING OF SHOCK, SEVERE TRAUMA OR INFECTION

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What is LYSODREN®?

LYSODREN is a prescription medicine used to treat people with cancer of the adrenal glands (adrenocortical carcinoma) that is functional (when the adrenal glands make more corticosteroid hormone than normal) or nonfunctional (when the adrenal glands make less corticosteroid hormone than normal) and the cancer cannot be removed by surgery.

IMPORTANT SAFETY INFORMATION INCLUDING WARNINGS

What is the most important information I should know about LYSODREN®?

LYSODREN can cause serious side effects including:

Adrenal Insufficiency and Adrenal Crisis.
  • Adrenal Insufficiency. LYSODREN can cause your adrenal glands to stop making enough corticosteroid hormones (adrenal insufficiency) or make this problem worse in people with cancer of the adrenal glands (adrenocortical carcinoma). Your healthcare provider may temporarily stop, reduce your dose, or permanently stop treatment with LYSODREN if you develop adrenal insufficiency during treatment.
  • Adrenal Crisis. LYSODREN can cause your adrenal glands to suddenly stop making enough corticosteroid hormones (adrenal crisis). You are at increased risk for developing adrenal crisis if you experience shock, severe injury, or infection during treatment with LYSODREN. Adrenal crisis may lead to death. Tell your healthcare provider right away if you get an injury, infection, or other illness during treatment with LYSODREN. Your healthcare provider will temporarily stop LYSODREN if shock, severe injury, or infections happen during treatment. Tell your healthcare provider if you have any planned surgery
Your healthcare provider will check your levels of corticosteroid hormones during treatment and may give you corticosteroid medicine if you develop adrenal gland problems. Tell your healthcare provider right away if you develop any signs or symptoms of adrenal gland problems, including:

  • severe weakness
  • confusion
  • pain in the lower back and legs
  • stomach (abdominal) pain
  • nausea, vomiting, or diarrhea
  • feeling lightheaded or dizzy
  • passing out
  • feeling very tired
  • decreased appetite
  • weight loss
  • areas of darkened skin
  • craving salt
  • low blood sugar
  • feeling irritable or depressed
  • hair loss
What should I tell my doctor before taking LYSODREN®?

  • have an injury, infection or illness
  • plan to have surgery. Tell your healthcare providers you are taking LYSODREN. You may need to stop taking LYSODREN before any surgery and dental procedures.
  • have cysts on your ovaries
  • have liver or kidney problems
  • have bleeding problems
  • are pregnant or plan to become pregnant. LYSODREN can harm your unborn baby.
  • are breastfeeding or plan to breastfeed. LYSODREN can pass into your breast milk and may harm your baby
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking LYSODREN with certain other medicines may affect the way LYSODREN and the other medicines work and may increase your risk of side effects.
Especially tell your healthcare provider if you take:

  • spironolactone
  • hormonal birth control
  • warfarin
  • midazolam or other CYP3A substrates
What are the most common side effects of LYSODREN®?

The most common side effects of LYSODREN include:

  • Eating disorders (Anorexia)
  • Upper stomach area (abdominal) discomfort
  • Nausea (upset stomach)
  • Vomiting
  • Diarrhea
  • Depression
  • Dizziness or lightheadedness
  • Rash
  • High cholesterol
  • Increase of triglycerides
  • Decreased thyroid hormones
  • Decreased testosterone (in males)
These are not all of the possible side effects of LYSODREN. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Pharmacy, Inc. at 1-844-LYSODREN (1-844-597-6373) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full US Prescribing Information, including boxed warning, for LYSODREN® (mitotane), tablets.

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Tel: +33 (0) 1 40 33 94 14 / Fax: +33 (0) 1 40 33 30 87
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Last updated: March 2024; LYS – US – 0047

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