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CYP3A4 enzyme

The enzyme CYP3A4 (full name: Cytochrome P450 3A4) is involved in the metabolisation of xenobiotics, such as drugs. Around 30-50% of all drugs are metabolised by CYP3A4. Drugs that can be metabolised by the enzyme CYP3A4 include:

  • Cytostatics such as docetaxel, tamoxifen, paclitaxel, cyclophosphamide, vincristine and irinotecan
  • Antidepressants such as citalopram, norfluoxetine, sertraline, mirtazapine, nefadozone and venlafaxine
  • Antipsychotics such as haloperidol, risperidone, pimozide and quetiapine
  • Opioids such as codeine, tramadol, methadone and fentanyl
  • Benzodiazepines such as midazolam and diazepam
  • Statins such as atorvastatin and simvastatin (not: pravastatin and rosuvastatin)
  • Calcium channel blockers such as diltiazem, verapamil, amlodipine and nisoldipine
  • Antiarrhythmic drugs such as amiodarone, dronedarone and quinidine
  • Antihistamines such as terfenadine, astemizole and chlorphenamine
  • Glucocorticoids such as budesonide, hydrocortisone and dexamethasone

Although CYP3A4 is involved in the metabolisation of 30-50% of all prescribed drugs, little is known about the clinical implications of variant alleles. This is due in part to the relatively low frequency of most variant alleles and the recently identified *22 variant. Consequently, no statements are made regarding individual drugs on the basis of CYP3A4 genotyping.

Genetic predisposition
The activity of the enzyme CYP3A4 varies from one individual to another. As a result, the efficacy of a drug can differ from person to person, as can the risk of potential side effects. This variation can be partly explained by genetic variations in the CYP3A4 gene. Although a large number of drugs are (partly) metabolised by the enzyme CYP3A4, we do not currently know of any specific dose adjustments based on genotyping.
When a genotype is determined variations in the CYP3A4 gene are indicated by two so-called alleles. Each allele has a name consisting of an asterisk (*) and a number. An example of a possible CYP3A4 genotype is CYP3A4*1/*22.
At iGene we determine the following variants (alleles) of the CYP3A4 gene:
CYP3A4*2-*20, *22, *26 and other (classified as CYP3A4*1).

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