Interactions of drugs is a common occurrence in medicine, and many side effects, intolerances, idiosyncratic reactions and "allergies" may be as a result of certain drug interactions with combinations of drugs. 

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With opioids, there are many interactions with other drugs, some of which are dangerous, while some cause only side effects.  

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Benzodiazepines- interactions with opioids are one of the most frequent causes of death.  Benzodiazepines, including Xanax (alprazolam), Klonopin (clonazepam), Valium (diazepam), Librium (chlordiazepoxide), Restoril (temazepam), Serax (oxazepam), Halcion (triazolam), Ativan (lorazepam), etc. are commonly overprescribed in the US for anxiety, panic disorders, sleeplessness, and a number of other conditions.  Over 50,000,000 prescriptions per year are written for benzodiazepines, making it one of the most prescribed classes of drugs in the US. Approximately 35-50% of all opioid related deaths are in patients also using one of the benzodiazepines, but 82% of overdose deaths involving buprenorphine also involve benzodiazepines.  Criteria are very loose for prescribing and most doing the prescribing ever even test the patients to see if it is doing any good.  Some doctors have the patients on the drugs for decades, and the patient long ago forgot why he was taking the drugs.    

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Alcohol- Approximately 22% of all opioid related deaths are in patients actively drinking alcohol.  This strong interaction depends on the amount of alcohol and the patient's tolerance. 

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Other opioids- Many patients have more than one opioid in their system at any one time.  The combined effect of these drugs may result in death. 

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Sleeping Aids- Ambien, chloral hydrate, diphenhydramine (Benadryl), and others may result in respiratory depression when used in concert with opioids.  

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Carisoprodol (Soma)- Soma is not a muscle relaxant since it does not have any measurable effect on muscle tone.  It is a centrally acting drug that is sedating and is converted in the body into a very sedating antipsychotic drug.  The combination of Soma plus a benzodiazepine plus and opioid is called the holy trinity due to the very desired by addicts effects.  However many deaths have been reported to have resulted from this combination due to respiraty depression, therefore under no circumstances should the patient have the combination of the three drug classes. 

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Other sedating drugs- Tricyclic antidepressants (especially amitriptyline), Tetracyclic antidepressants (trazodone), other muscle relaxants such as tizanidine, high dose baclofen, other sleeping agents, anticonvulsants, etc. can combine sedation to the point they may depress sensorium and respiration. Quiatipine (Seroquel) is not indicated for sleep disturbances but many doctors use this drug off label, causing extreme sedation when combined with opioids.  GHB is a drug used to treat narcolepsy, but is also commonly used as a street drug. Storm Chaser Joel Taylor overdosed and died from this drug on a cruise in 2018. 

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Buprenorphine interactions- Taking buprenorphine 30 min to hours after taking another opioid may result in fulminant withdrawal symptoms (abdominal cramps, sweating, pain everywhere, nausea, diarrhea).  The only deaths with buprenorphine in adults is when the person is either using alcohol or benzodiazepines with the drug.  This is why these are prohibited when in buprenorphine programs.