mitotane: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
mitotane: clinical details
Prescribing considerations
- Initiate and supervise treatment in a specialist setting experienced in adrenocortical carcinoma.
- Anticipate adrenal suppression; glucocorticoid and sometimes mineralocorticoid replacement may be required.
- Rapid cytotoxicity can cause infarction or haemorrhage in large metastatic masses; assess whether surgical reduction is appropriate before treatment.
- Mitotane accumulates in adipose tissue, so concentrations and interactions can persist long after interruption.
- Consider prolonged bleeding time when planning surgery or invasive procedures.
Contraindications and cautions
- Hypersensitivity to mitotane or an excipient
- Breastfeeding
- Concomitant spironolactone
- Use is not recommended in severe hepatic or severe renal impairment; exercise caution with lesser impairment
Monitoring
- Mitotane plasma concentration, aiming for the SmPC therapeutic window and avoiding concentrations associated with neurological toxicity
- Clinical tolerance and regular neurological and behavioural assessment
- Adrenal function and adequacy of steroid replacement, using free cortisol and ACTH where appropriate
- Full blood count, liver function and triglycerides
- Bleeding risk before surgery or dental procedures
- Gynaecological symptoms and periodic ovarian ultrasound in premenopausal women
- Thyroid function and neuropsychological development in children and adolescents
Clinical pharmacology
Mitotane is lipophilic, is stored predominantly in adipose tissue and has highly variable, prolonged elimination. It damages or inhibits the adrenal cortex, alters steroid metabolism and induces hepatic cytochrome P450 enzymes, particularly CYP3A4.
Formulation and product differences
- The selected product is a scored oral tablet supplied in a bottle.
- Caregivers should use disposable gloves; pregnant people should not handle the tablets.
- Store in the original packaging and dispose of unwanted tablets according to local cytotoxic-waste requirements.
mitotane preparations and strengths
Tablet
Route: Oral
Strengths: 500 mg
mitotane interactions
Mitotane has persistent enzyme-inducing effects, so the specialist or pharmacist should review all prescribed, non-prescribed and herbal products.
Spironolactone
Must not be combined with mitotane because it may block mitotane's action.
Warfarin and other coumarin anticoagulants
Mitotane accelerates their metabolism, so anticoagulant effect and requirements can change and need close monitoring.
CYP3A4 substrates, including sunitinib, etoposide and midazolam
Mitotane can alter their blood concentrations through enzyme induction, including after mitotane has been stopped.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.