No pharmaceutical opinion available for this interaction.
Elvitegravir / Cobicistat can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Tramadol.
Elvitegravir / Cobicistat may inhibit the metabolism (CYP2D6) and decrease the active metabolite formation of Tramadol.
Elvitegravir 3A4 and then UGT1A1/3; Cobicistat 3A4 (major) and 2D6 (minor)
Elvitegravir : 2C9 (moderate)
Cobicistat : 3A4 and 2D6 (potent), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3
2D6 (major) : mono-O-desméthyltramadol (M1), 3A4 and 2B6 (minor) : nortramadol (M2) * See comments.
Possible decrease of clinical efficacy.
Possible increase of adverse effects.
Monitor the clinical efficacy and appearance of adverse effects.
Adjust the dose depending on the effectiveness.
Hydromorphone and morphine.
Signs and symptoms of opioid withdrawal : craving for opioids, irritability, myalgias, muscle spasms, flushing, abdominal pain, nausea, vomiting, diarrhea, restlessness, diaphoresis, lacrimation, rhinorrhea, mydriasis, yawning, piloerection (goose flesh), tachycardia, tremulousness.
Signs and symptoms of opioid toxicity miosis, euphoria, dysphoria, drowsiness, confusion, excessive sedation, decreased alertness, hallucinations, dizziness, bradycardia, myoclonus, hypotension, prolonged or recurrent respiratory depression.
* M1 six times more powerful than parent molecule and M2 (about 1/5 strength of M1) and go through 2D6 transformed in M5 weakly active (less than M1).
Possible reduction of the analgesic effect due to the decrease in the formation of the active metabolite M1. We observe in rapid metabolizers 2D6 M1/tramadol ratio 14 times higher compared to the 2D6 metabolizers slow.