Buprenorphine, a semisynthetic opioid, is also less stimulating and produces less euphoria, less sedation and less risk of respiratory depression compared to methadone. Buprenorphine works to minimize withdrawal symptom and blocks the effects of illicit opiate drugs. Buprenorphine is commonly administered sublingually because it is poorly absorbed by the gastrointestinal system. The usual dose includes 2 mg to 32 mg daily with maximum dose effects occurring in the 16 mg to 32 mg range. Side effects include dry mouth, reduced respiratory rate, nausea, constipation and urinary retention. Buprenorphine maintenance therapy should be initiated in the early stages of substance abuse withdrawal because the drug can displace other opioid medications. Because concomitant dual diagnoses are common, clinicians must consider drug-to-drug interactions, specifically with selective serotonin reuptake inhibitors. Concomitant treatment with paroxetine (Paxil) and sertraline (Zoloft) inhibits CYP450 3A4 activity and increases therapeutic levels of buprenorphine. This result is also seen with metronidazole (Flagyl) and the macrolide antibiotics.