CYP3A and Drug Interactions

CYP3A and Drug Interactions
Serious adverse interactions between drugs is a problem faced by primary care physicians during the day today practice Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly
CYP3A4 CYP3A4, which is more commonly
expressed than CYP3A5, and usually accounts for most CYP3A
activity in vivo, about 50% of the drugs are metabolized by this enzyme
invitro testing of new drugs to predict CYP-related interactions.
using Liver microsomes and CYP3A-overexpressing
cells is available. the drug companies. May also do studies in healthy volunteers.
what happens in a patient depends on the potency of
the inhibitor or inducer, whether there are alternate elimination
pathways, and how serious the symptoms are.
CYP3A inhibitors can be classified as very potent or
moderate. is currently considered a potent
A drug causes more than a 5-fold increase
in the plasma concentration of another drug

GRAPEFRUIT JUICE — In usual quantities, grapefruit
juice is a moderate inhibitor because it inhibits only
intestinal and not hepatic CYP3A.4
this is mainly a problem in the USA.
not a problem in India .


In general most of the drugs in the HIV protease inhibitors,
macrolide-type antibiotics and azole antifungals are CYP3A inhibitors, butthere may be differences in the potency of
inhibition within a class.





Drugs Metabolized Mainly by CYP3A
primary care physicians; simvastatin oxybutynin
Xanax
HIV medications
Erythromycin
Fentanyl
Amiodarone
Carbamazepine
Sildenafil
are mainly the drugs to be watched.

in alphabetic order by class of drugs

Anticholinergics: darifenacin (Enablex), oxybutynin (Ditropan*),
solifenacin (VESicare), tolterodine (Detrol*)
Benzodiazepines: alprazolam (Xanax*), midazolam (Versed*),
triazolam (Halcion*)
Calcium channel blockers: diltiazem (Cardizem*), felodipine
(Plendil), nimodipine (Nimotop), nifedipine (Adalat*), nisoldipine
(Sular), nitrendipine, verapamil (Calan*)
Chemotherapeutic agents: cyclophosphamide (Cytoxan*),
erlotinib (Tarceva), ifosfamide (Ifex), tamoxifen (Nolvadex*),
vinblastine (Velban*), vincristine (Oncovin*)
HIV protease inhibitors: amprenavir (Agenerase), atazanavir
(Reyataz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir
(Norvir), saquinavir (Invirase, Fortovase)
HMG-CoA Reductase Inhibitors: atorvastatin (Lipitor),
lovastatin (Mevacor*), simvastatin (Zocor)
Immunosuppressive agents: cyclosporine (Neoral,
Sandimmune*), tacrolimus (Prograf)
Macrolide-type antibiotics: clarithromycin (Biaxin), erythromycin
(Erythrocin*), telithromycin (Ketek), troleandomycin (TAO)
Opioids: alfentanyl (Alfenta*), fentanyl (Sublimaze*), sufentanil
(Sufenta*)
Steroids: budesonide (Pulmicort), cortisol, 17 ß-estradiol,
progesterone
Others: amiodarone (Cordarone*), carbamazepine (Tegretol*),
delavirdine (Rescriptor), efavirenz (Sustiva), nevirapine
(Viramune), quinidine (Quinidex*), repaglinide (Prandin),
sildenafil (Viagra), tadalafil (Cialis), trazodone (Desyrel*),
vardenafil (Levitra)



Amprenavir
carbamazepine ciprofloxacin (Cipro*) diltiazem
fluconazole (Diflucan) erythromycin)
phenytoin (Dilantin*) grapefruit juice
norfloxacin (Noroxin) verapamil
Amiodarone
atazanavir
cisapride
clarithromycin (Biaxin)
clarithromycin phenobarbital
indinavir
itraconazole
Ketoconazole
nefazodone
nelfinavir
ritonavir
telithromycin
troleandomycin
voriconazole
Carbamazepin efavirenz nevirapine (Viramune)
efavirenz (Sustiva)
Phenytoin
Phenobarbital
Rifabutin
rifampin rifapentine (Priftin)
St. John’s Wort

DRUGS FOR OVERACTIVE BLADDER

All of these drugs are only modestly more effective than placebo for this indication.

( Enablex) and solifenacin, ( VESIcare)
like oxybutynin, tolterodine and trospium, are
muscuranic receptor antagonists.
although in animal studies solifenacin had an increased affinity to bladder Smooth muscle cells and less to the salivary gland cells in clinical practice. This might mean less dry mouth
and darifenacin has an increased affinity to M3, receptor than to the M1 receptor, so theoretically it has less CNS effects.
but on the whole cost-effectiveness Ditropan is as good as any other medication.


DRUGS FOR OVERACTIVE BLADDER
Darifenacin hydrobromide —
Enablex(Novartis) 7.5-15 mg PD once/d2 100$(7.5-, 15-mg ER tabs)
Oxybutynin chloride —
average generic price 5 mg PC bid or tid 25$(5-mg IR tabs; syrup)
Ditropan 75$
Ditropan XL 5-30 mg PC once/d 100 $(5-, 10-, 15-mg ER tabs)
Oxytrol I patch 2x/wk 90$(39 cm2 transdermal patch) (39 mgld)
Solifenacin succinate — VESicare 5 mg PC once/d4 100 $(5-, 10-mg tabs)
Tolterodine tartrate —
Detrol 1-2mg P0 bid5 100 $(1-. 2-mg IR tabs)
Detrol LA 2-4 mg P0 once/d5 100 $(2-. 4-mg ER caps)
Trospium chloride —
Sanctura (20 mg PC bid 90 $ Odyssey) (20-mg tabs)