No pharmaceutical opinion available for this interaction.
Lopinavir / ritonavir can inhibit the metabolism (CYP 3A4) and increase the plasma concentration of Tramadol.
Lopinavir / ritonavir may inhibit the metabolism (CYP2D6) and decrease the active metabolite formation of Tramadol.
3A4 (major), 13 identified metabolites, 5 of these metabolites are linked to the metabolism of ritonavir, transporters: MRP1, MRP2, OATP1A2, OATP1B1, P-gp
2C19 (strong), 1A2, 2C9 (moderate) UGT (moderate)
3A4 and 2D6 (strong), transporters: BCRP, MRP2, OATP1A2, OATP1B1, OATP1B3, OATP2B1, P-gp
2D6 : O-desmethyltramadol (M1), 3A4 and 2B6 : N-desmethyltramadol (M2) * See comments. UGT2B7 and 1A8, OCT1.
Possible decrease of clinical efficacy.
Possible increase of adverse effects.
Use this combination with caution.
Monitor the clinical efficacy and appearance of adverse effects.
Adjust dosage if necessary.
Hydromorphone and morphine.
Adverse effects of tramadol : dizziness, nausea, constipation, headache, seizures, suicidal tendencies, and serotonin syndrome including changes in mental status (agitation, hallucinations, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (hyperreflexia, incoordination) and gastrointestinal symptoms (nausea, vomiting, diarrhea).
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.
* M1 six times more powerful than parent molecule.
M2 (inactive metabolite) 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 and possible increase. Possible increase in the plasma concentration of tramadol due to the decrease in its transformation into M1 and M2 by CYP 2D6 and 3A4, respectively.
The interaction could be more important in slow metabolisers of 2D6. We observe in rapid metabolizers 2D6 M1/tramadol ratio 14 times higher compared to the 2D6 metabolizers slow.