Appendix

Appendix I:

Substrates, inducers or inhibitors of cytochrome P450 CYP3A4 isoform

KEY: Inducers: Red. Inhibitors: Blue. Substrates: Black. *Inducer OR inhibitor AND substrate

This is not a fully comprehensive list. For full prescribing information please consult the Summary of Product Characteristics (SPC) provided by the manufacturer.

There are a number of human liver P450 enzyme isoforms including CYP1A2, 2A6, 2C19, 2D6, 2E1, 3A4, 3A5, 4A11 and 7. CYP3A4 is responsible for more than 60% of prescribed drugs metabolised by the liver.

Prescribed drugs which are substrates, inducers or inhibitors of the CYP3A4 isoform of cytochrome P450 include the following, listed by therapeutic category:

Cardiovascular System:

  • Antiarrhythmic agents
    Amiodarone, quinidine
  • Calcium channel blockers
    Bepridil, diltiazem, lercanidipine, verapamil*; Dihydropyridienes: Amlodipine, felodipine, isradipine, nicardipine, nifedipine*, nisoldipine
  • Cholesterol lowering agents
    HMG-Co A reductase inhibitors: Simvastatin,lovastatin, atorvastatin
  • Diuretics
    Spironolactone

Central Nervous System:

  • Anticonvulsants
    Barbiturates; Benzodiazepines: Alprazolam, diazepam, flurazepam, midazolam, trizolam; Carbamazepine*; Hydantoins: Phenytoin
  • Antidepressants
    Fluoxetine, fluvoxamine, nefazodone*, paroxetine*, reboxetine, sertraline*, venlafaxine*
  • Antipsychotic agents
    Ziprasidone; Serotonin 5HT-4 receptor agonists: Pimozide
  • Drugs for demenia
    Parasympathomimetic/cholinergic agents: Galantamine
  • Migraine
    Ergot alkaloids, ergotamine; Selective 5HT-1 receptor agonists: Eletriptan
  • Nausea and vertigo
    Domperidone
  • Opiate agonists
    Alfentanil, fentanyl, methadone, sufentanil
  • Obesity agents
    Central appetite suppressants: Sibutramine
  • Substances of abuse
    Cocaine, tetrahydrocannabinol

Endocrine System:

  • Female sex hormones
    Ethinyloestradiol, progesterone
  • Glucocorticosteroids
    Dexamethasone
  • Male sex hormones
    Testosterone
  • Other endocrine drugs
    Bromocriptine

Gastro-Intestinal System:

  • Ulcer healing drugs
    H2-antagonist: Cimetidine; Proton pump inhibitors:
    Esomeprazole, omeprazole
  • Gastro-motility drugs
    Cisapride

Herbals and Natural Substances:

  • St John's Wort, grapefruit juice

Infections:

  • Antibiotics
    Combination antibiotics: quinupristin+dalfopristin; Macrolides: Clarithromycin*, erythromycin*, troleandomycin, elithromycin; Quinolones: Norfloxacin, ciprofloxacin; Sulphonamides: Sulphamethoxazole
  • Antifungals
    Azole antifungals: Fluconazole, itraconazole*, ketoconazole*, miconazole, voriconazole
  • Antituberculosis agents
    Rifampicin
  • Antileprotic drugs
    Dapsone
  • Antivirals
    Non nucleoside analogues: Didanosine, nevirapine, delaviridine and efavirenz; Protease inhibitors:
    Amprenavir, atazanavir*, indinavir*, nelfinavir*, ritonavir*, saquinavir*

Malignant Disease and Immunosuppression:

  • Hormone antagonists
    Exemestane, paclitaxel, tamoxifen
  • Immunosuppressive agents
    Ciclosporin*, sirolimus, tacrolimus
  • Other antineoplastic agents
    Bexarotene, imatinib, paclitaxel

Musculoskeletal disorders:

  • Local anaesthetics
    Levobupivicaine, lidocaine
  • Miscellaneous analgesics
    Acetaminophen
  • NSAIDs
    Coxibs: Parecoxib, valdecoxib

Obstetrics and Gynaecology:

  • Drugs used in obstetrics
    Mifepristone
  • Oral contraceptives
    Gestodene

Respiratory System:

  • Antihistamines
    Astemizole, loratadine, terfenadine
  • Lukotriene-receptor antagonists
    Montelukast
  • Respiratory corticosteroids
    Budesonide, fluticasone
  • Xanthines
    Theophylline

Urology:

  • Erectile Dysfunction
    PDE-5 inhibitors: Sildenafil, tadalafil, vardenafil
  • Urinary Incontinence/Overactive Bladder
    Cholinergic receptor antagonists: Tolterodine