Uses of Mitotane
Mitotane is used to treat adrenal cortical carcinoma (non-surgical) and Cushing’s syndrome.
Mechanism of action
- Adrenolytic agent.
- Dysfunction of the adrenal cortex, adrenal atrophy of the shingles and shingles of the shingles and eventually tumor death (via binding to mitochondrial proteins).
- Direct inhibition of the adrenal cortex and changes in the peripheral metabolism of steroids.
Pharmacokinetics of Mitotane
Absorption: 40%
Start of effect:
Antitumor effects at serum concentration of 14 μg / ml
Children 12.5-1.5 months to reach a serum concentration of 10 micrograms / ml, (observe therapeutic response earlier than this time)
Duration of action: Traceable serum concentration up to several months after discontinuation of the drug
Plasma peak: 3-5 hours
Metabolism: Liver and other tissues (to water-soluble metabolites)
Half-life: 159-18 days
Excretion: urine (10%), feces (17-1%)
Contraindications to the use of Mitotane
It should not be used in case of infection.
You can have side effects
Skin: Skin rash
Gastrointestinal: anorexia, diarrhea, nausea, vomiting
Central nervous system: depression, dizziness
Other complications (percentage unknown):
Cardiovascular: hot flashes, hypertension, postural hypotension
Endocrinology and metabolism: Insufficiency of the cortical part of the adrenal gland, the appearance of albumin in the urine, changes in hormone levels (decreased serum levels of androstenedione), decreased plasma testosterone levels (in men and women), growth retardation, gynecomastia, hypercholesterolemia, Elevated blood triglycerides, hypothyroidism, increased SHBG, ovarian cysts (bilateral, multiple)
Genitourinary: Blood in the urine, bleeding bladder inflammation
Hematology and oncology: neutropenia, increased bleeding time
Hepatic: Hepatitis, increased liver enzymes
Central nervous system: ataxia, toxicity of the central nervous system, confusion, dysarthria, generalized pain, headache, lethargy, mental retardation, anesthesia
Nervous, musculoskeletal: laxity
Ophthalmology: blurred vision, diplopia, cataracts, retinopathy, maculopathy
Miscellaneous: Fever
Mitotane drug interactions
General specifications of interactions:
CYP3A4 inductor (severe)
Intensifying CNS attenuating effects
Category X Interactions (Avoidance)
Abmasiclib, Alplicib, Hepatitis C Antiviral Combined Products, Apermilast, Aperpitant, Artemter, Asonaproir, Avapritinib, Oxitinib, Badacillin, Bortosomib, Bosutinib, Brigatinib, Capmatinib, Seripanib, Cariprazine, Cariprazine, Cariprazine Dynogest, Duravirine, Drondaron, Dulisib, Albasvir, Alexacafter / Tezacaphthor / Ivacaphthor, Oliglostat, Encorafenib, Interatinib, Ardafitinib, Etravirine, Federatinib, Flibanserin, Fos Aperpitant, Fos Netustipat, Fos Netustip Irinotecan, Isuoconazonium sulfate, Ibaradophylin, Ivoconazole, Iubradine, Icechanism, Lubrorcovation, Lulatinib, Lomatapurone, Lomatapon, Levaridone, Loridone, Loronidone, Luronidone, Loronidone, Loronidone, Luronidone, Loronidone, Loronidone, Mimulin, Mypressant, Midostaurin, MiffPriston, Navodipin, Nylosimin, Nissippine Nilotinib, Nimodipine, Nizoldipine, Olaparib, Palbicyclib, Panobinostat, Pemigatinib, Pazopanib, Pixidartinib, Pimavanserin, Pipe Rockin, Ponatinib, PunnabeTel, Rokomantine, Rogerazin, Rogerophenib, Rockhenib, Roflomel, Roflomin, Simpripatinib, Simpariire, Sonality, Surfinib, Titromicin, Tizacott, Tacoger, Tiger, Tuftin, Tilgurgron, Tilberry, Typecror, Tuftrover, Tilberror, Typhenol, Tilberry, Terabotin, Tocatinib, Abrogent, Olipristal, Opadacitinib, Valbenazine, Vandetanib, Valpatacavir, Ventoclax, Vincristine (Liposomal), Vinflonine, Vurapaxar, Voxilaprir, Zanobrotinib
Reduction of the effects of drugs by Mitotane
Ephrasebil, Acoronron Acetate, Alplinkib, Alplossib, Hepatitis C Hepatitis C combined, apylotamide, apical, opipylazole, aripperazole, arthemeter, ascorazol, aciprazole, ascorazol, acatritinib, aczotinib, benipuridol, bioelectinavir, botzophye, bosotinib, brevotazol, breposespagarazole , Brigatinib, Buspirone, Cabazitaxel, Cabosantinib, Calciphediol, Cannabidiol, Marijuana (Cannabis), Capamatinib, Cariprazine, Seritinib, Chlorpropamide, Clarithromycin, Clindamycin, Cytobic, Cytomycin, Cytomycin Substrates of CYP3A4 (high risk with its inducer), Dabrafenib, Daclatasovir, Dasabovir, Dacatinib, Deflazacort, Delamanide, Dexamethasone (systemic), Dinogen, Diethyl acetylbestrol, Duravirin, Dexolubisabone, Meth, Dexorubicin (Meth) Elbassuer, Alexacftor / Tezacaphthor / Ivacaphthor, Oliglostat, Encorafenib, Infortomob and Dutin, Interatinib, Enzalotamide, Aravacycline, Ardafitinib, Erlotinib, Steriol (systemic and topical), Etoposide Vazid Phosphate, Etravirin, Orolimus, Ovgliptin, Exemestane, Federatinib, Fentanyl, Flibanserin, Fos Aperpitant, Fos Netopitant, Fustamatinib, Jefitinib, Jamie Gliptin, Glascovidir, Heparin, Celpazovir, Glacaproir and Glacaproir Imatinib, Irinotan Products, Isuoconazonium sulfate, Iabradine, Ivoconazole, Iocidibin, Icazamib, Ketoconazole, LaPatinib, Lepatinib, Lefamolin, Leboxolin, Lymbokorith, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Laurethinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Lurlatinib, Laurethinib Lumatapon, lomatoprone, loronidone, luroniston, mimimulin, macantan, manidypine, marvarox, maperidine, methylphenisolone, mirdog, nalemadine, nyloxel, natagulinidine, nilotinib, nifedipine, nilotinib, semi-based, nilotinib, hemp, uisolidate, olaprostinib Ox Carbazpin, Palbicyclib, Panobinostat, Pazopanib, Pemigatinib, Prampanel, Paxidartinib, Pimavanserin, Pipraquin, Pitolisant, Pulatosumb and Dutin , Ponatinib, Predator, prednisolone (systemic), prednisone, luminid, Propafonon, Ramothye, Ranolazine, Robukestine, Rogerigenib, Ribysteism, Rigpent, Riperinib, Reflomilandone, Rolapitant, Roflomin, Roxolitinib, Saxaglipinib, Celoprinib, Slvmtynyb, sertraline, Symprvyr, sirolimus, Svnydgyb, sorafenib, sufentanil, Sanytynyb, tadalafil, tamoxifen, Tazymltyvn, Tazmtvstat, telithromycin, Tmsyrvlymvs, Ttrahydrvkanabydyvl, Ttrahydrvkanabydyvl Vkanabydyvl, Tzakaftvr and Ayvakaftvr, thiotepa, Tyagabyn, Tykagrlvr, Tvfasytynyb, Tvlvaptan, Tvrmyfn, Trabktdyn , Tropisterone, abrogent, odenafil, olipristal, opadacitinib, valbenazine, vandetanib, valpatasovir, vemorafenib, ventoclax, vilazodone, vincristine (liposomal), vinflonazole, vorapox, vorapox
Reducing the effects of Mitotane by drugs
Spironolactone
Enhanced effects of drugs by Mitotane:
Clarithromycin, Doxercalciferol, Ifosfamide, Lorlatinib, Tiotapa
Increased effects of Mitotane by drugs:
Clarithromycin
Warnings
- Therapeutic drug concentrations should be monitored every 4-8 weeks until reaching the target concentration and then every 3 months (using gas chromatography-flame ionization
technique). - At the beginning of treatment of children (with adrenocortical cancer), the serum concentration of the drug should be monitored every 2-4 weeks until reaching a concentration of 10 micrograms / ml and then every 1-2 weeks (even after reaching the target concentration of 14-20 micrograms / ml Liters). Dose adjustment should be made according to the narrow treatment window and drug accumulation.
- Adrenal function, free cortisol levels, adrenocorticotropin (ACTH), TSH and free thyroxine are monitored periodically during treatment.
- The patient should be monitored for central nervous system toxicity (confusion, depression, extreme fatigue, changes in speech and balance), adrenal crisis and ovarian macrocysts (vaginal bleeding and / or pelvic pain) and the patient should be warned to report these symptoms. Report speed.
- Behavioral and neurological examinations are recommended.
- It is necessary to check other medications used by the patient to adjust the dose if necessary or to use alternative therapy.
- The patient should be reminded of the need for regular medication and completion of treatment.
Mitotane drug recommendations
- Initial treatment should be performed in a hospital until the dose is stabilized.
- The dose should be adjusted according to the maximum tolerable dose for each patient and based on the presence of side effects and improvement of clinical responses.
- Treatment with glucocorticoids may also be necessary in patients treated with mitotane, especially in long-term treatment. After stopping treatment with mitotane, steroid treatment should be continued until the adrenal cortex returns to normal.
- Continuous treatment with the maximum tolerable amount of mitotane seems to be more effective than intermittent treatment.
- The duration of treatment also depends on the clinical response. Only 15% of patients who have been treated with the maximum tolerable dose for three months but have not responded to treatment show a clinical response by continuing treatment.
- It is recommended that in the event of shock or severe trauma, treatment with mitotane be discontinued immediately and temporarily, and that steroids be given, as decreased adrenal function may impair the natural response to these stresses.
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