7 DRUG INTERACTIONS
Table 3 includes clinically significant drug interactions with Sufentanil Citrate Injection.
| Inhibitors of CYP3A4 | |
| Clinical Impact: | The concomitant use of Sufentanil Citrate Injection and CYP3A4 inhibitors can increase the plasma concentration of sufentanil, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of Sufentanil Citrate Injection is achieved [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the sufentanil plasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to sufentanil. |
| Intervention: | If concomitant use is necessary, consider dosage reduction of Sufentanil Citrate Injection until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the Sufentanil Citrate Injection dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. |
| Examples: | Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), grapefruit juice. |
| CYP3A4 Inducers | |
| Clinical Impact: | The concomitant use of Sufentanil Citrate Injection and CYP3A4 inducers can decrease the plasma concentration of sufentanil [see Clinical Pharmacology (12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to sufentanil [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the sufentanil plasma concentration will increase [see Clinical Pharmacology (12.3)], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. |
| Intervention: | If concomitant use is necessary, consider increasing the Sufentanil Citrate Injection dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Sufentanil Citrate Injection dosage reduction and monitor for signs of respiratory depression. |
| Examples: | Rifampin, carbamazepine, phenytoin |
| Benzodiazepines and Other Central Nervous System (CNS) Depressants | |
| Clinical Impact: | The concomitant use of Sufentanil Citrate Injection with CNS depressants my result in decreased pulmonary artery pressure and may cause hypotension. Even small dosages of diazepam may cause cardiovascular depression when added to high dose or anesthetic dosages of Sufentanil Citrate Injection. As postoperative analgesia, concomitant use of Sufentanil Citrate Injection can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. |
| Intervention: | As postoperative analgesia, start with a lower dose of Sufentanil Citrate Injection and monitor patients for signs of respiratory depression, sedation, and hypotension. Fluids or other measures to counter hypotension should be available [see Warnings and Precautions (5.5)]. |
| Examples: | Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. |
| Serotonergic Drugs | |
| Clinical Impact: | The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions 5.5]. |
| Intervention: | If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Sufentanil Citrate Injection if serotonin syndrome is suspected. |
| Examples: | Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). |
| Monoamine Oxidase Inhibitors | |
| Clinical Impact: | MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2)]. |
| Intervention: | The use of Sufentanil Citrate Injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. |
| Examples: | phenelzine, tranylcypromine, linezolid |
| Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics | |
| Clinical Impact: | May reduce the analgesic effect of Sufentanil Citrate Injection and/or precipitate withdrawal symptoms. |
| Intervention: | Avoid concomitant use. |
| Examples: | butorphanol, nalbuphine, pentazocine, buprenorphine |
| Muscle Relaxants | |
| Clinical Impact: | Sufentanil may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. |
| Intervention: | Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Sufentanil Citrate Injection and/or the muscle relaxant as necessary. |
| Diuretics | |
| Clinical Impact: | Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. |
| Intervention: | Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. |
| Anticholinergic Drugs | |
| Clinical Impact: | The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. |
| Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when Sufentanil Citrate Injection is used concomitantly with anticholinergic drugs. |
| Nitrous oxide | |
| Clinical Impact: | Nitrous oxide has been reported to produce cardiovascular depression when given with higher doses of Sufentanil Citrate Injection. |
| Intervention: | Monitor patients for signs of cardiovascular depression that may be greater than otherwise expected. |