Opioids and especially benzodiazepines also increase the risk of potentially lethal respiratory depression.Strong inhibitors of the liver enzyme CYP3A4, such as ketoconazole, moderately increase buprenorphine concentrations; CYP3A4 inducers can theoretically decrease concentrations of buprenorphine. Pharmacology
Mechanism of action
Buprenorphine binds strongly to opioid receptors and acts as a pain-reducing medication in the central nervous system (CNS). It binds to the μ-opioid receptor with high affinity, which produces the analgesic effects in the CNS. It is a partial μ-opioid receptor agonist and a weak κ-opioid receptor antagonist. As the dose of buprenorphine increases, its analgesic effects reach a plateau, and then it starts to act like an antagonist. As a partial agonist, buprenorphine binds and activates the opioid receptors, but has only partia  efficacy at the receptor relative to a full agonist, even at maximal receptor occupancy. It is thus well-suited to treat opioid dependence, as it produces milder effects on the opioid receptor with lower dependence and habit-forming potential. Naloxone is a pure opioid antagonist that competes with opioid molecules in the CNS and prevents them from binding to the opioid receptors. Naloxones binding affinity is highest for the μ-opioid receptor, then the δ-opioid receptor, and lowest for the κ-opioid receptor. Naloxone has poor bioavailability, and is rapidly inactivated following oral administration. When injected, it exerts its full effects. The principle behind its function as a deterrent is as follows: when taken sublingually as prescribed, buprenorphines effects at the opioid receptor dominate, while naloxones effects are negligible due to the low oral absorption.
The most common side effects (in order of most to least common) of sublingual tablets include headaches, opioid withdrawal syndrome, pain, nausea, increased sweating, and difficulty sleeping. The most common side effects seen in film formulations are tongue pain, decreased sensation and redness in the mouth, headache, nausea, vomiting, excessive sweating, constipation, signs and symptoms of opioid withdrawal, sleeping difficulties, pain, and swelling of the extremities.Buprenorphine/naloxone has a milder side effect profile than methadone and limited respiratory effects, due to both agonist/antagonist effects. But buprenorphine/­naloxone may be less safe than methadone in people with stable liver disease, since it can elevate liver enzymes. Dependence and withdrawal
When taken in excess, buprenorphine/naloxone can produce dysphoric symptoms for non opioid-dependent/tolerant people because buprenorphine is a partial opioid agonist. The sublingual formulation of the buprenorphine/­naloxone combination was designed to reduce the potential to inject the medication in comparison to buprenorphine alone. If the combination is taken sublingually, as directed, the addition of naloxone does not diminish buprenorphines effects. When an opioid-dependent person dissolves and injects a combination sublingual tablet, a withdrawal effect may be triggered because of naloxones high parenteral bioavailability. While this mechanism can act to deter intravenous injection, the Suboxone formulation can still produce an opioid agonist "high" if used sublingually by non-dependent persons, leading to opioid dependence. Interactions
Buprenorphines sedating/narcotic effect is increased by other sedating substances, such as other opioids, benzodiazepines, first-generation antihistamines, alcohol, and antipsychotics.