mitotane

Action and Spectrum

Actions and spectrum: 

mitotane is an antineoplastic medication that is used to treat adrenal cortical carcinoma, a rare type of cancer that originates in the outer layer of the adrenal gland. mitotane belongs to the group of medications called adrenocortical suppressants, and it works by blocking the production of cortisol and other hormones in the adrenal gland, leading to tumor cell death. 

mitotane is classified as a type II cytotoxic agent that acts through alkylating agents by modifying DNA and proteins in cancer cells, leading to their death. It is also believed to increase the production of enzymes in the liver that breaks down cortisol, which can help to control symptoms in patients with adrenal cortical carcinoma. 

Drug Interaction

Adverse Reaction

Frequency defined

>10%

Weakness (12%)

Diarrhea (13%)

Vertigo (15%)

Skin rash (15%)

Anorexia (24%)

Lethargy/somnolence (25%)

Vomiting (37%)

Nausea (39%)

Frequency not defined

Eye: diplopia, toxic retinopathy, Visual blurring, lens opacity

Cardiovascular: orthostatic hypotension, flushing

Decrease in protein bound iodine

Genitourinary: hemorrhagic cystitis, Hematuria, and albuminuria

Generalized aching and hyperpyrexia

Post marketing Reports

Blood and lymphatic disorders: prolonged bleeding time, Neutropenia

Psychiatric disorders: Confused state

Nervous system disorders: dysarthria, ataxia, Neuropsychological disturbance, headache, mental impairment

Eye disorders: Maculopathy

Hepatobiliary disorders: elevation of liver enzymes, Hepatitis

Reproductive system and breast disorders: ovarian macrocysts, Gynecomastia, hypogonadism in males

Fever

Black Box Warning

mitotane does not have any black box warning.

Contraindication / Caution

Contraindication:

Those who have a history of hypersensitivity to mitotane or any other substance which is used in the formulation should not take this. It is contraindicated to patients who have conditions like severe hepatic or renal dysfunction, pregnancy, or adrenocortical insufficiency.

Caution:

Hepatic dysfunction: Mitotane can cause hepatotoxicity. Patients who have hepatic impairment must be monitored closely.

Adrenal insufficiency: Mitotane can cause adrenal insufficiency. Patients who have adrenal diseases must be monitored for symptoms like weakness, fatigue and hypotension.

Interactions with other medications: Mitotane can interact with medications. Patient must be monitored for any drug interactions and dosage must be adjusted as per the need.

Neurological effects: Mitotane can lead to confusion, dizziness, ataxia. Patient must warn not to drive heavy  machinery which need activeness.

Skin reactions: Mitotane can lead to skin reactions like rash and pruritus. Patient must inform to healthcare provider if there is any skin reaction.

Pregnancy and lactation: Mitotane is contraindicated during pregnancy and lactation. This is because it has potential to harm to fetus or nursing infant.

Renal dysfunction: Mitotane is secreted by kidney. Patient who has renal impairment must be monitored closely. 

Comorbidities:

Liver disease: Mitotane is metabolized in the liver. Patients who have liver disease may have severe side effects.  They also have difficulty to metabolize the drug.

Hypothyroidism: Mitotane can cause hypothyroidism. Patients who already have hypothyroidism may need close attention to the levels of thyroid hormone during the mitotane consumption.

Renal impairment: Mitotane is secreted by kidney. Patients who have renal impairment may have severe side effects.

Diabetes: Mitotane can lead to changes in metabolism of glucose. Patients who have diabetes may need close monitoring to the blood glucose levels.

Osteoporosis: Mitotane can lead to bone loss. Patients who have osteoporosis may need close monitoring to the bone density.

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category: D

Lactation: mitotane is excreted in breast milk, and its use during lactation is not recommended.

 Pregnancy category:

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester.
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women.
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women.
• Category N: There is no data available for the drug under this category.

Pharmacology

Mitotane is an antineoplastic medication. It has an adrenocortical activity. It acts mainly on the adrenal cortex by destroying cells and reducing the production of glucocorticoids and androgens. It helps to treat adrenal carcinoma. It has a complex pharmacology. The exact mechanism is not fully understood. It induces the cytochrome P450 enzyme system in adrenal gland. It leads to the formation of reactive metabolites which can lead to destruction of the adrenal cortex cells.

It also has anti-angiogenic effects which can help in antineoplastic activity. It has a sedative effect on the CNS.

Pharmacodynamics:

Mitotane is a cytotoxic agent. It inhibits the synthesis of adrenal steroids. It destroys particular adrenocortical cells by damaging the inner mitochondrial membrane and endoplasmic reticulum (ER) in these cells. It reduces the production of cortical, aldosterone, and adrenal androgens. This is because it can penetrate the adrenal cortex and accumulate in the lip droplets of adrenocortical cells. This can lead to reduces adrenal steroidogenesis in the treatment.

Pharmacokinetics:

Absorption

Mitotane is given orally. It is absorbed by GI tract with plasma contractions of 2 to 6 hours after the single dosage. The bioavailability is highly variable from 15 to 40% because it has a poor solubility and different absorption rate.

Distribution

Mitotane is highly lipophilic. It distributed to adipose tissue. It accumulated in there. The half life is many months. It also goes to other tissues like lungs, kidney, liver, and brain.

Metabolism

Mitotane is metabolized in the liver by the cytochrome P450 enzymes. CYP3A4 forms many metabolites like o,p’-DDD (dichlorodiphenyldichloroethane).  It is an active metabolite which has a therapeutic effects of mitotane.

Elimination and excretion

The elimination of mitotane is a slow process. The half life is about 18 to 159 days. It excreted in the feces and very small amounts in the urine.

Adminstartion

Mitotan is available in the tablet form. It is given with food which can improve the absorption. The duration and dosage is depends on the condition of patient and response to the treatment. The dosage must not be increased than the prescribed dosage. It must be taken at the same time for every day to maintain the regularity of drug in the body.

Patient Information Leaflet

Generic Name: mitotane

Pronounced: [ MYE-toe-tane ]

Why do we use mitotane?

Mitotane is used to treat adrenal cortical carcinoma. It is rare type of cancer which can affect he outer layer of the adrenal gland. It is used to manage Cushing’s syndrome. It is also used as a off-label medication to treat breast and prostate cancer.