THE DEPRESSANT EFFECTS OF OPIOID ANALGESICS ARE ENHANCED BY OTHER CNS DEPRESSANTS SUCH AS ALCOHOL, ANAESTHETICS, ANXIOLYTICS, HYPNOTICS, TRICYCLIC ANTIDEPRESSANTS, AND ANTIPSYCHOTICS. CYCLIZINE MAY COUNTERACT THE HAEMODYNAMIC BENEFITS OF OPIOIDS. CIMETIDINE INHIBITS THE METABOLISM OF SOME OPIOIDS, ESPECIALLY PETHIDINE.
THE ACTIONS OF OPIOIDS MAY IN TURN AFFECT THE ACTIVITIES OF OTHER DRUGS. FOR INSTANCE, THEIR GASTROINTESTINAL EFFECTS MAY DELAY ABSORPTION AS WITH MEXILETINE OR MAY BE COUNTERACTIVE AS WITH CISAPRIDE, METOCLOPRAMIDE, OR DOMPERIDONE. OPIOID PREMEDICANTS SUCH AS PAPAVERETUM HAVE BEEN REPORTED TO REDUCE SERUM CONCENTRATIONS OF CIPROFLOXACIN.
AGONIST/ANTAGONIST ANALGESICS (I.E., PENTAZOCINE, NALBUPHINE, BUTORPHANOL, AND BUPRENORPHINE) SHOULD BE ADMINISTERED WITH CAUTION TO A PATIENT WHO HAS RECEIVED OR IS RECEIVING A COURSE OF THERAPY WITH A PURE OPIOID AGONIST ANALGESIC SUCH AS HYDROMORPHONE. IN THIS SITUATION, MIXED AGONIST/ANTAGONIST ANALGESICS MAY REDUCE THE ANALGESIC EFFECT OF HYDROMORPHONE AND/OR MAY PRECIPITATE WITHDRAWAL SYMPTOMS IN THESE PATIENTS.
ALCOHOL.
RAPID RELEASE OR DOSE-DUMPING OF HYDROMORPHONE FROM A MODIFIED-RELEASE PREPARATION HAS BEEN ASSOCIATED WITH THE INGESTION OF ALCOHOL.
ANTIVIRALS.
INTERACTIONS BETWEEN OPIOID ANALGESICS AND RITONAVIR, OTHER HIV-PROTEASE INHIBITORS, OR REVERSE TRANSCRIPTASE INHIBITORS ARE COMPLEX, AND THE RESULTS OF THE LIMITED NUMBER OF STUDIES AND REPORTS IN VIVO HAVE NOT ALWAYS BORNE OUT PREDICTIONS ABOUT THE NATURE OF POTENTIAL INTERACTIONS.
SUBSTANTIAL DECREASES IN AUC AND IN THE PLASMA CONCENTRATION HAVE BEEN REPORTED FOR BOTH METHADONE AND FOR PETHIDINE WHEN GIVEN WITH RITONAVIR. IN THE CASE OF PETHIDINE, HOWEVER, PLASMA CONCENTRATIONS OF THE TOXIC METABOLITE NORPETHIDINE ARE GREATLY INCREASED, AND THE MANUFACTURERS OF RITONAVIR COUNSEL AGAINST SUCH COMBINED USE. THE HIV-PROTEASE INHIBITORS AMPRENAVIR, RITONAVIR AND NELFINAVIR MAY ALSO REDUCE METHADONE CONCENTRATIONS AND PROVOKE WITHDRAWAL SYMPTOMS IN DEPENDENT PATIENTS. PATIENTS REQUIRING METHADONE MAY NEED AN INCREASE IN THE DOSE. SIMILAR INTERACTIONS WITH METHADONE HAVE BEEN NOTED WITH THE NNRTIS EFAVIRENZ AND NEVIRAPINE AND THE NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR ABACAVIR. 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.
HISTAMINE H2-ANTAGONISTS.
HISTAMINE H2-ANTAGONISTS MAY ENHANCE THE EFFECTS OF SOME OPIOID ANALGESICS. CIMETIDINE WAS REPORTED TO ALTER THE CLEARANCE AND VOLUME OF DISTRIBUTION OF PETHIDINE WHEREAS RANITIDINE DID NOT. MORPHINE HAS BEEN CONSIDERED LESS LIKELY TO INTERACT WITH CIMETIDINE THAN PETHIDINE BECAUSE OF DIFFERENCES IN METABOLISM. HOWEVER, ALTHOUGH CIMETIDINE DID NOT AFFECT THE DISPOSITION OF MORPHINE IN HEALTHY SUBJECTS IN A STUDY THERE HAVE BEEN ISOLATED REPORTS OF POSSIBLE INTERACTIONS BETWEEN MORPHINE AND H2-ANTAGONISTS; APNOEA, CONFUSION, AND MUSCLE TWITCHING HAVE BEEN ASSOCIATED WITH CIMETIDINE PLUS MORPHINE, AND CONFUSION ASSOCIATED WITH RANITIDINE WITH MORPHINE. THERE HAS ALSO BEEN A REPORT OF A PATIENT RECEIVING REGULAR ANALGESIA WITH ORAL METHADONE AND SUBCUTANEOUS MORPHINE WHO BECAME UNRESPONSIVE 6 DAYS AFTER STARTING CIMETIDINE FOR PROPHYLAXIS OF PEPTIC ULCER; TREATMENT WITH NALOXONE WAS REQUIRED.