Three-time intake of ritonavir 500 mg twice a day increases AUC by 152%, and Tl/2 - 156 % (after a single dose of nelfinavir in a dose of 750 mg).
Other antiviral drugs
Nucleoside analogues - reverse transcriptase inhibitors. Clinically significant interactions between nelfinavir and nucleoside analogues (especially zidovudine + lamivudine, stavudine, and stavudine + didanosine) have not been observed. Because the didanosine in the form of tablets, with a buffer it is recommended to take on an empty stomach, nelfinavir should be taken while eating through 1 hour after didanosine or more than 2 hour before taking didanosine.
Non-nucleoside reverse transcriptase inhibitors. Safety and efficacy, the following combinations of drugs - not established.
Efavirenz. Combination with efavirenz increases AUC nelfinavir by 20%, while AUC Efavirenz does not change.Correction of the dose when they are simultaneously taken is not required.
Delavirdine Simultaneous appointment led to an increase AUC nelfinavir by 107% and the decrease AUC delavirdine by 31%.
Nevirapine. Clinically significant interactions between nelfinavir and nevirapine are not observed when they are taken concurrently, dosage adjustment is not required.
Other protease inhibitors. The safety and effectiveness of the combination of drugs listed below are not established. The results presented for ritonavir, indinavir and saquinavir were obtained in studies on interaction with a single dose.
Ritonavir. Simultaneous reception leads to an increase AUC Nelfinavir by 152% and a very slight change AUC ritonavir.
Indinavir: Simultaneous reception, led to an increase AUC nelfinavir by 83%, AUC indinavir - by 51%.
Saquinavir in soft gelatin capsules. Simultaneous reception led to an increase AUC nelfinavir by 18%, AUC saquinavir - 4 times.
Amprenavir. Simultaneous reception led to a slight increase AUC nelfinavir and amprenavir Cmin amprenavir on, 189%. Correction of the dose of these drugs is not required.
Inductors of enzymes of metabolism
Rifampin reduces AUC nelfinavir by 82%. Other powerful inducers CYP3A (eg, phenobarbital, carbamazepine, St. John's wort products) can also reduce nelfinavir plasma concentrations. If the patient receiving nelfinavir, you need treatment with the above drugs, then the doctor should look for an alternative to them.
Simultaneous administration of nelfinavir in a dose of 750 mg, 3 times a day and rifabutin at a dose of 300 mg once a day leads to a decrease AUC nelfinavir on. 32% and to increase AUC rifabutin by 207%. The simultaneous administration of nelfinavir, 750 mg of Z times daily, and rifabutin in a half-lower dose of 150 mg, 1 once a day - leads to a decrease AUC nelfinavir by 32% and to an increase AUC rifabutin by 83%. With-simultaneous admission, nelfinavir in a dose of 750 mg 3 times a day and rifabutin, the dose of the latter should be reduced to 150 mg 1 once a day (see "Special instructions").
Simultaneous reception of nelfinavir in a dose of 1250 mg 2 times a day and phenytoin at a dose of 300 mg 1 once a day did not change the concentration of nelfinavir in plasma. However, the AUF of phenytoin and the concentration of free phenytoin decreased by 29% and 28%, respectively.With simultaneous administration of dose adjustment, nelfinavir is not required, however, it is necessary to monitor phenytoin concentrations.
Inhibitors of metabolic enzymes Simultaneous administration of nelfinavir and a strong inhibitor CYP3A ketoconazole was accompanied by an increase AUC nelfinavir by 35%. This change is not considered clinically significant, so dose adjustment when concomitant administration of these drugs is not required. Given the metabolic characteristics, expect clinically significant drug interactions with other specific inhibitors CYP3A (fluconazole, itraconazole, clarithromycin, erythromycin) is not necessary, but it is impossible to exclude such possibility (see "Special instructions").
Inhibitors of HMG-CoA reductase. At simultaneous reception of nelfinavir in a dose of 1250 mg 2 times a day and simvastatin in a dose of 20 mg once a day AUC simvastatin increased by 506%. At-simultaneous reception of nelfinavir in a dose of 1250 mg 2 times a day and atorvastatin in a dose of 10 mg once a day - AUC Atorvastatin increased by 74%. Although reception with lovastatin was not specifically studied, it is expected that lovastatin can also interact with nelfinavir, as well as simvastatin. To avoid possible toxic effects, nelfinavir Do not administer simultaneously with simvastatin or lovastatin. Simultaneous reception of atorvastatin should be started with caution, with the lowest dose (see "Special instructions").
Methadone. Simultaneous reception of nelfinavir in a dose of 1250 mg twice a day and methadone in doses of 80 ± 21 mg once a day by HIV-infected patients participating in the methadone program reduced AUC methadone, by 47%, while none of the patients in this study did not develop withdrawal syndrome. However, due to pharmacokinetic changes, it is to be expected that withdrawal symptoms may appear in some patients receiving these drugs simultaneously, which will require an increase in the dose of methadone.
Other possible interactions
Nelfinavir increases concentrations, terfenadine in plasma, therefore, they should not be prescribed, at the same time to avoid severe or life-threatening arrhythmias. Since similar interactions are likely, with astemizole and cisapride, nelfinavir should not be prescribed simultaneously with these drugs. Although no special studies have been conducted on this subject, the agents with a pronounced, sedative effect, metabolized CYP3A, for example, triazolam or midazolam, should also not be used with nelfinavir, as their sedative effect may to lengthen.
Nelfinavir can increase plasma concentrations of other substances that are substrates for CYP3A (eg, calcium channel blockers, sildenafil, immunosuppressants, including
tacrolimus and ciclosporin), therefore, in such cases, patients need to be carefully monitored for signs of toxicityti attheir preparations (see "Special instructions").
Azithromycin. Simultaneous reception of nelfinavir in a dose of 1250 mg 2 times a day and a single dose 1200 mg azithromycin resulted in a slight decrease AUC nelfinavir and an increase in AUC azithromycin by 113%. Correction, doses of nelfinavir or azithromycin are not recommended. However, with the simultaneous administration of these drugs, patients should be carefully monitored for known side effects of azithromycin, such as an increase in hepatic enzyme activity and hearing impairment.
Oral contraceptives. Simultaneous reception of nelfinavir 750 mg three times a day and combined oral contraceptive containing 0.4 mg norethinodrel and 35 μg 17-α-ethinylestradiol for 7 days was accompanied by a 47% decrease in AUC of ethinylestradiol, a AUC norethinodrel - by 18%. Consideration should be given to the use of other contraceptive measures.