7 DRUG INTERACTIONS
Table 2 includes clinically significant drug interactions with alfentanil injection.
| Inhibitors of CYP3A4 and CYP2D6 | |
| Clinical Impact: | The concomitant use of alfentanil injection and CYP3A4 inhibitors can increase the plasma concentration of alfentanil, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of alfentanil injection and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of alfentanil injection is achieved [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the alfentanil 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 alfentanil. |
| Intervention: | If concomitant use is necessary, consider dosage reduction of alfentanil injection until stable drug effects are achieved [see Dosage and Administration (2.2)]. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the alfentanil injection dosage until stable drug effects are achieved [see Dosage and Administration (2.2)]. Monitor for signs of opioid withdrawal. |
| Examples: | Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) |
| CYP3A4 Inducers | |
| Clinical Impact: | The concomitant use of alfentanil injection and CYP3A4 inducers can decrease the plasma concentration of alfentanil [see Clinical Pharmacology (12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to alfentanil [see Warnings and Precautions (5.13)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the alfentanil 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 alfentanil injection dosage until stable drug effects are achieved [see Dosage and Administration (2.2)]. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider alfentanil injection dosage reduction and monitor for signs of respiratory depression. |
| Examples: | Rifampin, carbamazepine, phenytoin |
| Benzodiazepines and Other Central Nervous System (CNS) Depressants | |
| Clinical Impact: | Diazepam administered immediately prior to or in conjunction with high doses of alfentanil injection may produce vasodilation and hypotension, and may result in delayed recovery. Both the magnitude and duration of central nervous system and cardiovascular effects may be enhanced when alfentanil injection is administered in combination with other CNS depressants such as barbiturates, tranquilizers, opioids, or inhalation general anesthetics. Postoperative respiratory depression may be enhanced or prolonged by these agents. |
| Intervention: | Monitor patients receiving alfentanil injection and benzodiazepines or other CNS depressants for hypotension patients and prolonged respiratory depression and sedation. In such cases of combined treatment, the dose of one or both agents should be reduced. Limited clinical experience indicates that requirements for volatile inhalation anesthetics are reduced by 30% to 50% for the first sixty (60) minutes following alfentanil induction [see Warnings and Precautions (5.2)]. |
| 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 (5.7]. |
| Intervention: | If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue alfentanil 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: | Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported rarely with alfentanil. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2)] |
| Intervention: | When alfentanil injection is administered to patients who have received MAO inhibitors within 14 days, monitor patients for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension as needed. |
| Examples: | phenelzine, tranylcypromine, linezolid |
| Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics | |
| Clinical Impact: | May reduce the analgesic effect of Alfentanil injection and/or precipitate withdrawal symptoms. |
| Intervention: | Avoid concomitant use. |
| Examples: | butorphanol, nalbuphine, pentazocine, buprenorphine |
| Muscle Relaxants | |
| Clinical Impact: | Alfentanil 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 alfentanil 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 alfentanil injection is used concomitantly with anticholinergic drugs. |
| Cimetidine | |
| Clinical Impact: | Cimetidine reduces the clearance of alfentanil, extending the duration of action. |
| Intervention: | Use smaller alfentanil doses for prolonged administration and monitor closely for respiratory depression and other effects of alfentanil. |
| Nitrous oxide | |
| Clinical Impact: | Nitrous oxide has been reported to produce cardiovascular depression when given with higher doses of alfentanil injection. |
| Intervention: | Monitor patients for signs of cardiovascular depression that may be greater than otherwise expected. |