Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease.

Article Details

Citation

Kuper JI, D'Aprile M

Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease.

Clin Pharmacokinet. 2000 Sep;39(3):203-14. doi: 10.2165/00003088-200039030-00003.

PubMed ID
11020135 [ View in PubMed
]
Abstract

Therapeutic and prophylactic regimens directed specifically against Mycobacterium avium complex (MAC) are increasingly being used in patients infected with the human immunodeficiency virus (HIV). Several of the drugs used in the management of MAC have been associated with significant drug interactions involving the cytochrome P450 (CYP) enzyme system. This enzyme system is also highly influenced by other drugs used in the management of patients with HIV, particularly the protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and azole antifungals. This article reviews the published concentrations or subtherapeutic concentrations of other drugs have been described. In particular, concurrent use of rifabutin with clarithromycin or fluconazole has resulted in increased concentrations of rifabutin and an accompanying increase in the incidence of rifabutin toxicities, including uveitis and leucopenia. Similar results have been seen when rifabutin is combined with protease inhibitors or delavirdine. The macrolides, clarithromycin and azithromycin, have also been associated with significant drug interactions. Clarithromycin has a higher affinity for CYP than azithromycin and, thus, is more frequently associated with clinically significant drug interactions. Clarithromycin is an inhibitor of CYP and may result in toxic concentrations of other drugs metabolised by this enzyme system. Such interactions have been described with rifabutin and the statin lipid-lowering agents. In addition, nevirapine and efavirenz have been shown to significantly reduce clarithromycin concentrations, whereas the protease inhibitors and delavirdine may increase clarithromycin concentrations. Other drugs used in the management of patients with MAC are not metabolised by CYP and thus have a lower incidence of interactions, although the absorption of ciprofloxacin may be impaired when it is given with products containing multivalent cations, such as didanosine. However, clinicians must remain vigilant for drug interactions when reviewing a patient's medication profile, keeping in mind both interactions that have been described in the literature and those that may be predicted based upon known pharmacokinetic profiles.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
6-Deoxyerythronolide BCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
AVE9633Cytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Brefeldin ACytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Bryostatin 1Cytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
CandicidinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
CarbomycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Coltuximab ravtansineCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
DirithromycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
DoramectinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
EpofolateCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Epothilone DCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
EprinomectinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
FlurithromycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
GPI-1485Cytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
IxabepiloneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
KitasamycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
KOS-1584Cytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Lorvotuzumab mertansineCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
MidecamycinCytochrome P450 3A4ProteinHumans
No
Substrate
Inhibitor
Details
MiocamycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
MitemcinalCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
OleandomycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
PatupiloneCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
PimecrolimusCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
RidaforolimusCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
RokitamycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
SagopiloneCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
SelamectinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
SolithromycinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
TildipirosinCytochrome P450 3A4ProteinHumans
No
Inhibitor
Details
Drug Interactions
DrugsInteraction
Clarithromycin
Nelfinavir
The serum concentration of Clarithromycin can be increased when it is combined with Nelfinavir.
Clarithromycin
Indinavir
The serum concentration of Clarithromycin can be increased when it is combined with Indinavir.
Clarithromycin
Ritonavir
The serum concentration of Clarithromycin can be increased when it is combined with Ritonavir.
Clarithromycin
Amprenavir
The serum concentration of Clarithromycin can be increased when it is combined with Amprenavir.
Clarithromycin
Tipranavir
The serum concentration of Clarithromycin can be increased when it is combined with Tipranavir.