INCREASED RISK OF RESPIRATORY DEPRESSION, AND HYPOTENSION WITH HALOTHANE. RESPIRATORY DEPRESSANT EFFECT ENHANCED BY LIDOCAINE. THE DEPRESSANT EFFECTS OF OPIOID ANALGESICS ARE ENHANCED BY OTHER CNS DEPRESSANTS SUCH AS ALCOHOL, CNS DEPRESSANTS,BENZODIAZEPINES, ANAESTHETICS, HYPNOTICS, TRICYCLIC ANTIDEPRESSANTS, PHENOTHIAZINES, ANTIPSYCHOTICS & ANXIOLYTICS. INCOMPATIBLE WITH SOLUBLE BARTITURATES. CYCLIZINE MAY COUNTERACT THE HAEMODYNAMIC BENEFITS OF OPIOIDS. CIMETIDINE INHIBITS THE METABOLISM OF SOME OPIOIDS, ESPECIALLY PETHIDINE. PETHIDINE WHEN GIVEN WITH RITONAVIR, PLASMA CONCENTRATIONS OF THE TOXIC METABOLITE NORPETHIDINE ARE GREATLY INCREASED. THE HIV-PROTEASE INHIBITORS AMPRENAVIR AND NELFINAVIR MAY ALSO REDUCE METHADONE CONCENTRATIONS AND PROVOKE WITHDRAWAL SYMPTOMS IN DEPENDENT PATIENTS. PATIENTS REQUIRING METHADONE MAY NEED AN INCREASE IN THE DOSE OF THIS DRUG IF GIVEN WITH AMPRENAVIR, NELFINAVIR, OR RITONAVIR. SIMILAR INTERACTIONS WITH METHADONE HAVE BEEN NOTED WITH THE NNRTIS EFAVIRENZ AND NEVIRAPINE AND THE NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR ABACAVIR; AGAIN, A DOSE INCREASE IN METHADONE MAY BE REQUIRED. THE HIV-PROTEASE INHIBITORS INDINAVIR AND SAQUINAVIR DO NOT APPEAR TO INTERACT WITH METHADONE. RITONAVIR IS PREDICTED TO REDUCE PLASMA CONCENTRATIONS OF MORPHINE.
IN CONTRAST, AN INCREASE IN AUC AND IN ELIMINATION HALF-LIFE HAS BEEN REPORTED IN SUBJECTS GIVEN FENTANYL WITH RITONAVIR. THE MANUFACTURERS OF RITONAVIR ALSO CONSIDER THAT INCREASED PLASMA CONCENTRATIONS OF DEXTROPROPOXYPHENE AND TRAMADOL, WITH AN INCREASED LIKELIHOOD OF OPIOID TOXICITY, MAY OCCUR IF EITHER DRUG IS GIVEN DURING RITONAVIR TREATMENT. ORAL ANTICOAGULANTS EFFECT IS INCREASED BY OPIOID ANALGESICS.
OPIOIDS GASTROINTESTINAL EFFECTS MAY DELAY ABSORPTION OF SOME DRUGS AND MAY BE COUNTERACTIVE WITH CISAPRIDE, DOMPERIDON OR METOCLOPRAMIDE. MAY CAUSE SEVERE AND SOMETIMES FATAL SIDEEFFECTS WHEN GIVEN IN PATIENTS WHO ARE ON MAOIS.
HISTAMINE H2-ANTAGONISTS MAY ENHANCE THE EFFECTS OF SOME OPIOID ANALGESICS.
MORPHINE HAS BEEN CONSIDERED LESS LIKELY TO INTERACT WITH CIMETIDINE THAN PETHIDINE BECAUSE OF DIFFERENCES IN METABOLISM.