Contraindications : התוויות נגד

4 CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients.
Patients with severe (Child-Pugh Class C) hepatic impairment..

Co-administration of PREZISTA/ritonavir is contraindicated with drugs that are highly dependent on cytochrome P450 3A (CYP3A) isoform for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). These drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed in Table 2 [also see Drug Interactions (7.3), Table 3].

Table 2: Drugs That Are Contraindicated With PREZISTA/ritonavir
Drug Class               Drugs within Class that   Clinical comment are contraindicated with
PREZISTA/ritonavir
Alpha 1adrenoreceptor Alfuzosin                    Potential for serious and/or life-threatening reactions antagonist                                         such as hypotension.
Ergot Derivatives        Dihydroergotamine,        Potential for serious and/or life-threatening events such Ergonovine, Ergotamine,   as acute ergot toxicity characterized by peripheral Methylergonovine          vasospasm and ischemia of the extremities and other tissues.

GI Motility Agent         Cisapride                      Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Neuroleptic               Pimozide , sertindole          Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Sedative/hypnotics        Orally administered            Triazolam and orally administered midazolam are Midazolam, Triazolam           extensively metabolized by CYP3A. Co-administration of triazolam or orally administered midazolam with
PREZISTA/ritonavir may cause large increases in the concentrations of these benzodiazepines. Potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression.
Herbal Products           St. John’s Wort                Patients taking PREZISTA/ritonavir should not use (Hypericum perforatum)         products containing St. John’s wort because co- administration may result in reduced plasma concentrations of darunavir. This may result in loss of therapeutic effect and development of resistance.
HMG CoA Reductase         Lovastatin, Simvastatin        Potential for serious reactions such as myopathy Inhibitors                                               including rhabdomyolysis. For dosing recommendation regarding atorvastatin and pravastatin, see Table 3:
Established and Other Potentially Significant Drug
Interactions: Alterations in Dose or Regimen May Be
Recommended Based on Drug Interaction Studies or
Predicted Interaction.


Antimycobacterial         Rifampin                       Rifampin is a potent inducer of CYP450 metabolism.
PREZISTA/ritonavir should not be used in combination with rifampin, as this may cause significant decreases in darunavir plasma concentrations. This may result in loss of therapeutic effect to PREZISTA.
PDE-5 inhibitor           Sildenafil for treatment of    A safe and effective dose for the treatment of pulmonary pulmonary arterial             arterial hypertension has not been established with hypertension ,                 PREZISTA/ritonavir.There is an increased potential for sildenafil-associated adverse events (which include visual avanafil (PDE-5                disturbances, hypotension, prolonged erection, and inhibitors)                    syncope).
Anti Allergic             Astemizole, Terfenadine
Anti HIV                  Co-administration with the combination product lopinavir/ritonavir antiarrhythmics            amiodarone, bepridil,
dronedarone,quinidine,
ranolazine, systemic lidocaine ticagrelor (antiplatelets) colchicine when used in patients with renal and/or hepatic impairment
(antigout)
Quetiapine

Due to the need for co-administration of PREZISTA with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.