[MOL] Drug Interactions [00524] Medicine On Line


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[MOL] Drug Interactions



1. Cytochrome P-450 inhibitors:

Warning - Agents that impair drug metabolism of other drugs which share the same pathway increase concentrations of the co-administered drug.

DRUG CLASS LIKELIHOOD OF A DRUG INTERACTION ALTERNATIVES
HIV Protease inhibitors Ritonavir (Norvir®) strongest Indinavir (Crixivan®) intermed Nelfinavir (Viracept®)intermed Saquinavir (Fortovase®/ Invirase®) - weakest Saquinavir (Invirase®/Fortovase®) has less potential to cause drug interactions
Macrolides Erythromycin and clarithromycin (Biaxin®) are both inhibitors of CYP450, however, the inhibition may be greater with erythromycin Azithromycin (Zithromax®) is not metabolized by CYP450 and may be substituted if clinically warranted
Antifungals Listed by strength of inhibition:
Ketoconazole (Nizoral®) > Itraconazole (Sporanox®) > Fluconazole (Diflucan®)

Ketoconazole (Nizoral®) and Itraconazole (Sporanox®) are potent inhibitors of CYP450

Fluconazole (Diflucan®) is associated with less drug interactions when dosages of 200 mg or less are used. As dose is increased, there is a greater potential for drug interactions.
Topical antifungals such as clotrimazole (Mycelex®) troches and nystatin may be useful for prophylaxis of thrush or minor infections. For more severe fungal infections, amphotericin B (Fungizone®, Abelcet®, AmBisome®, Amphotec®) may be used
Non-nucleoside reverse transcriptase inhibitors Delavirdine (Rescriptor®) is a potent inhibitor of CYP450 potentially raising concentrations of other drugs While it may be beneficial in some cases to use delavirdine to increase concentrations of other drugs (e.g. protease inhibitors), alternatives in this class would be nevirapine and efavirenz (Sustiva; investigational) or perhaps nucleoside analogs (i.e., didanosine [Videx®], zidovudine [Retrovir®]) if clinically appropriate
H2 Antagonists Cimetidine (Tagamet®) is a CYP450 inhibitor with a high propensity for causing interactions Any other H2antagonist
i.e. Ranitidine (Zantac®)
or Famotidine (Pepcid®)

2. Cytochrome P-450 Inducers:

INDUCING DRUG STRENGTH ALTERNATIVES
Rifamycins:
Rifabutin (Mycobutin®) and Rifampin (Rifadin®, Rimactane®)
Potent inducers of CYP450 and may decrease concentrations of drugs metabolized by these pathways For patients receiving protease inhibitors, rifampin should be avoided.
However, rifabutin (Mycobutin®) may be used with indinavir (Crixivan®) and nelfinavir (Viracept®) at one-half the normal dose (150 mg/day). For ritonavir (Norvir®), rifabutin (Mycobutin®) is contraindicated, however some clinicians elect to use rifabutin on an every-other-day basis at one-half the normal dose (150 mg q M-W-F).
In patients requiring MAC prophylaxis, azithromycin (Zithromax®) or clarithromycin
(Biaxin®) may be substituted for rifabutin
HIV Protease inhibitors:
Nelfinavir (Viracept®) and Ritonavir (Norvir®)
Moderate inducers of CYP450, potentially decreasing concentrations of other drugs which are metabolized In this class Alternatives would be:
indinavir (Crixivan®)
saquinavir (Fortovase®)
delavirdine (Rescriptor®)
or perhaps nucleoside analogs, i.e.
didanosin e (Videx®)
zidovudine (Retrovir®) could be used if clinically appropriate
Non-nucleoside reverse
transcriptase inhibitors:
Nevirapine (Viramune®) Efavirenz ( Sustiva®; investigational)
Moderate inducers of CYP450, potentially decreasing concentrations of other drugs Alternatives in this class would be delavirdine or perhaps nucleoside analogs i.e.
didanosine (Videx®)
zidovudine (Retrovir®)
if clinically appropriate
Anticonvulsants:

Phenobarbital
Phenytoin
(Dilantin®)
Carbamazepine
(Tegretol®)

Major / moderate inducers of CYP450, potentially decreasing concentrations of other drugs. If clinically warranted, possible alternative anti-epileptics include:
valproic acid (Depakene®, Depakote®)
gabapentin (Neurontin®)
lamotrigine (Lamictal®)
topiramate (Topamax®)
tigabine (Investigational Tabitril®)

3. Metabolized drugs with narrow therapeutic indexes:

WARNING - All of these agents should be avoided, especially with potential P450 inhibitors, as they may produce serious or life-threatening side effects if their concentrations are increased or decreased.

CATEGORY DRUGS ALTERNATIVES / NOTES
Non-sedating antihistamines Terfenadine (Seldane®) Astemizole (Hismanal®) Newer non-sedating antihistamines such as fexofenadine (Allegra®) and loratadine (Claritin®) can be safely used with P450 inhibitors, as well as most over-the counter preparations
Antiarrythmics Flecainide (Tambocor®) Encainide (Enkaid®) Quinidine Antiarrhythmic therapy should be closely monitored and used with caution in patients receiving inhibitors of cytochrome P-450
Long-acting opiate analgesics Fentanyl (Sublimaze®, Duragesic®) Meperidine (Demerol®) Alternative analgesics include hydromorphone, codeine, and NSAIDs, particularly in patients receiving ritonavir (Norvir®)
Promotility agents Cisapride (Propulsid®)  
Long-acting benzodiazepines

Midazolam (Versed®) Triazolam (Halcion®)  
Ergotamines and dihydroergotamine Cafergot® Hydergine®D.H.E. 45®  
Illicit drugs Ecstacy/XTC/MDMA  
Coumarin anticoagulants Warfarin (Coumadin®)  
Oral contraceptives   Oral contraceptives should not be given concurrently with P450 inducers, as this can decrease their concentrations and lead to unwanted pregnancy

4. Renally cleared drugs with narrow therapeutic indices:

DRUG / NOTES ALTERNATIVES
Foscarnet (Foscavir®)
Ganciclovir (Cytovene®)
Adjust dose for renal function with these agents
Cidofovir (Vistide) may be used if clinically appropriate, but this agent can cause irreversible renal insufficiency
Aminoglycosides:
Gentamycin
Tobramycin
Amikacin

(Any drugs that are nephrotoxic may decrease aminoglycoside clearance and increase likelihood of aminoglycoside toxicity)

Other antibiotics covering gram – bacteria:
Aztreonam (Azactram®)
Broad Spectrum penicillins and cephalosporins



5. Drugs with specific requirements for absorption:

DRUGS REQUIREMENTS ALTERNATIVES
Ketoconazole (Nizoral®)
Itraconazole (Sporanox®)
Require an acidic gastric pH for optimal absorption - avoid in patients with achlorhydria or those receiving H2-antagonists, antacids, or proton pump inhibitors Fluconazole can be substituted if clinically appropriate. Topical antifungals such as clotrimazole (Mycelex®) troches and nystatin may be useful for prophylaxis of thrush or minor involvement. For more severe fungal infections, amphotericin B (Fungizone®, Abelcet®, AmBisome®, Amphotec®) may be used
Didanosine (Videx®) Must be taken on an empty stomach and separated from indinavir by one hour since the buffer component may impair indinavir (Crixivan®) absorption Administer didanosine (Videx®) once daily (investigational) on empty stomach to lessen inconvenience associated with indinavir. Can use alternative nucleoside analogs if clinically appropriate
Fluoroquinolones Must be separated from di- and trivalent cations (calcium products, antacids, iron preparations, DDI, etc) to avoid chelation and decreased therapeutic effect Separate quinolone from cations by 2-4 hours - administer quinolone first. Also, other antimicrobials with appropriate coverage (i.e. cephalosporins) may be used if clinically appropriate