Nefazodone interactions

• CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors. (Acalabrutinib label, Drug interactions)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Acetaminophen and codeine label, Boxed warning)

Alcohol – Although nefazodone did not potentiate the cognitive and psychomotor effects of alcohol in experiments with normal subjects, the concomitant use of nefazodone and alcohol in depressed patients is not advised. (Nefazodone label, Drug interactions)

…(Childs-Pugh categories B and C), since alfuzosin blood levels are increased in these patients [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir, since alfuzosin blood levels are increased [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . in… (Alfuzosin label, Contraindications)

Concomitant use of almotriptan tablets and potent CYP3A4 inhibitors should be avoided in patients with renal or hepatic impairment [see Clinical Pharmacology ( 12.3 )] . (Almotriptan label, Drug interactions)

• taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.5) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] . (Alprazolam label, Contraindications)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Serotonin Syndrome: Increased risk when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. (Amphetamine label, Warnings and precautions)

Serotonin Syndrome: Increased risk when coadministered with serotonergic agents (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans), but also during overdosage situations. (Amphetamine and dextroamphetamine label, Warnings and precautions)

For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3) ] . (Apixaban label, Drug interactions)

Do not use avanafil in patients taking strong CYP3A4 inhibitors [see Warnings and Precautions ( 5.2 ) and Dosage and Administration ( 2.3 )]. (Avanafil label, Drug interactions)

• Serotonergic Drugs: Concomitant use may result in serotonin syndrome. (Belladonna and opium label, Drug interactions)

Concomitant administration of BIXLENVO with combined P-gp, UGT1A1, and strong CYP3A inhibitors is not recommended. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Drug interactions)

Co-administration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with TRACLEER is not recommended. (Bosentan label, Drug interactions)

• Strong and Moderate CYP3A Inhibitors: Avoid concomitant use with BOSULIF. (Bosutinib label, Drug interactions)

Concomitant use of strong CYP3A4 inhibitors (e.g., azole antimycotics, HIV protease inhibitors) with CYCLOSET should be avoided. (Bromocriptine label, Drug interactions)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (Buprenorphine label, Drug interactions)

Serotonergic Drugs: Concomitant use may result in serotonin syndrome. (Buprenorphine and naloxone label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs SSRIs, and other serotonergic drugs, including buspirone, alone but particularly with concomitant use of other serotonergic drugs (including triptans), with drugs that impair metabolism of serotonin (in particular, MAOIs, including reversible MAOIs… (Buspirone label, Warnings)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Butalbital, acetaminophen, caffeine, and codeine label, Boxed warning)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Butalbital, aspirin, caffeine, and codeine label, Boxed warning)

…medical attention if they ‎experience symptoms of hyperalgesia, including worsening pain, increased ‎sensitivity to pain, or new pain [see WARNINGS ; ADVERSE REACTIONS ].‎ Serotonin Syndrome Inform patients that butorphanol tartrate could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. (Butorphanol label, Precautions)

Avoid taking a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) while taking COMETRIQ or reduce the dosage of COMETRIQ if concomitant use with strong CYP3A4 inhibitors cannot be avoided [see Dosage and Administration ( 2.2 ), Clinical Pharmacology… (Cabozantinib label, Drug interactions)

CONTRAINDICATIONS Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with nefazodone hydrochloride is contraindicated (see WARNINGS and PRECAUTIONS ). (Nefazodone label, Contraindications)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Codeine label, Boxed warning)

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors [see Drug Interactions (7) ] . (Colchicine label, Contraindications)

Hyperpyretic crisis seizures and deaths have occurred in patients who received cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitors drugs. (Cyclobenzaprine label, Contraindications)

Strong CYP3A4 inhibitors: Avoid concomitant use. (Daridorexant label, Drug interactions)

Avoid concomitant use of strong CYP3A4 inhibitors. (Dasatinib label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

• Avoid concomitant use of strong CYP3A4 inhibitors or inducers. (Dexamethasone label, Drug interactions)

Serotonergic Drugs The concomitant use of dextroamphetamine sulfate and serotonergic drugs increases the risk of serotonin syndrome. (Dextroamphetamine label, Drug interactions)

QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. (Dextromethorphan and quinidine label, Warnings and precautions)

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. (Dihydroergotamine label, Boxed warning)

Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. (Docetaxel label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Avoid concomitant use of Doxorubicin Hydrochloride Injection with inhibitors of CYP3A4, CYP2D6, or P-gp. (Doxorubicin label, Drug interactions)

…(12.3) ] • Concomitant use of drugs or herbal products that prolong the QT interval and might increase the risk of torsade de pointes, such as phenothiazine antipsychotics, tricyclic antidepressants, certain oral macrolide antibiotics, and Class I and III antiarrhythmics • Liver or lung toxicity related to the previous use of amiodarone • QTc interval >500 ms or… (Dronedarone label, Contraindications)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Drug-Drug Interactions Strong Inhibitors of Cytochrome P450 (CYP) 3A4 Tamsulosin-containing products, including JALYN, should not be coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole) as this can significantly increase tamsulosin exposure [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ]. (Dutasteride and tamsulosin label, Warnings and precautions)

• Recent use (i.e., within at least 72 hours) of the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir [see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ]. (Eletriptan label, Contraindications)

…Patients Eplerenone is contraindicated in all patients with: • serum potassium > 5.5 mEq/L at initiation, • creatinine clearance ≤ 30 mL/min, or • concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir) [see Drug Interactions (7.1) , Clinical Pharmacology (12.3)… (Eplerenone label, Contraindications)

WARNING Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine tartrate and caffeine tablets with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. (Ergotamine and caffeine label, Boxed warning)

Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin). (Erlotinib label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Consequently, estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A (see CONTRAINDICATIONS ). (Estazolam label, Warnings)

VYTORIN is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] . (Ezetimibe and simvastatin label, Contraindications)

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. (Fentanyl label, Boxed warning)

CYP3A4 Inhibitors Doses of Toviaz greater than 4 mg are not recommended in adult patients taking strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin [see Dosage and Administration (2.5) ]. (Fesoterodine label, Drug interactions)

Contraindicated with Strong or Moderate CYP3A4 Inhibitors The concomitant use of ADDYI and moderate or strong CYP3A4 inhibitors increases flibanserin concentrations, which can cause severe hypotension and syncope [see Warnings and Precautions (5.2) ] . (Flibanserin label, Boxed warning)

THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTIDEPRESSANT OVERDOSE. (Flumazenil label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fluticasone label, Drug interactions)

Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): May increase risk of systemic corticosteroid and cardiovascular effects. (Fluticasone and salmeterol label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Intervention Avoid concomitant use of FOCINVEZ Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy… (Fosaprepitant label, Drug interactions)

Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of granisetron and other serotonergic drugs. (Granisetron label, Warnings and precautions)

Cytochrome P450 3A4 Interaction The concomitant use of HYSINGLA ER with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Hydrocodone label, Boxed warning)

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and acetaminophen tablets with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Hydrocodone and acetaminophen label, Boxed warning)

Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Polistirex and Chlorpheniramine Polistirex with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. (Hydrocodone and chlorpheniramine label, Boxed warning)

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and homatropine methylbromide with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. (Hydrocodone and homatropine label, Boxed warning)

Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Bitartrate and Ibuprofen Tablets with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which may cause potentially fatal respiratory depression. (Hydrocodone and ibuprofen label, Boxed warning)

• Serotonergic Drugs : Concomitant use may result in serotonin syndrome. (Hydromorphone label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

• Strong CYP3A4 Inhibitors: Do not administer strong CYP3A4 inhibitors with CAMPTOSAR. (Irinotecan label, Drug interactions)

Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs. (Nefazodone label, Warnings)

…bradycardia [see Warnings and Precautions ( 5.3 )] • Severe hepatic impairment [see Use in Specific Populations ( 8.6 )] • Pacemaker dependence (heart rate maintained exclusively by the pacemaker) [see Drug Interactions ( 7.3 )] • Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors [see Drug Interactions ( 7.1 )] Acute decompensated heart failure ( 4 ) (Ivabradine label, Contraindications)

Avoid strong CYP3A4 inhibitors. (Lapatinib label, Drug interactions)

Strong CYP3A4 Inhibitors: Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. (Larotrectinib label, Drug interactions)

Strong or moderate CYP3A inhibitors: Avoid concomitant use. (Lemborexant label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. (Levorphanol label, Precautions)

Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs. (Nefazodone label, Warnings)

Serotonin Syndrome: Increased risk when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. (Lisdexamfetamine label, Warnings and precautions)

If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. (Lithium label, Warnings and precautions)

Concomitant administration of JUXTAPID with moderate or strong CYP3A4 inhibitors, as this can increase JUXTAPID exposure [see Warnings and Precautions (5.6) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ]. (Lomitapide label, Contraindications)

LOREEV XR should not be used in such patients without adequate antidepressant therapy. (Lorazepam label, Warnings and precautions)

• Strong CYP3A Inhibitors : Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. (Lorlatinib label, Drug interactions)

Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and cobicistat-containing products) (see WARNINGS , Myopathy/Rhabdomyolysis ). (Lovastatin label, Contraindications)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. (Lurasidone label, Contraindications)

Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . (Macitentan label, Drug interactions)

SELZENTRY is contraindicated in patients with severe renal impairment or ESRD (creatinine clearance [CrCl] less than 30 mL per minute) who are concomitantly taking potent CYP3A inhibitors or inducers [see Warnings and Precautions ( 5.3 )]. (Maraviroc label, Contraindications)

Cytochrome P450 3A4 Interaction The concomitant use of DEMEROL Injection with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Meperidine label, Boxed warning)

Serotonin syndrome has resulted from concomitant use of metaxalone (within the recommended dosage range) and other serotonergic drugs [see Warnings and Precautions (5.1) ]. (Metaxalone label, Drug interactions)

Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

Serotonin Syndrome: Increased risk when coadministered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. (Methamphetamine label, Warnings and precautions)

Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs. (Nefazodone label, Warnings)

Although there have been no reports of such interactions with methylergonovine alone, strong and moderate CYP 3A4 inhibitors should not be co-administered with methylergonovine. (Methylergonovine label, Drug interactions)

• Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone. (Milnacipran label, Warnings and precautions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. (Mitapivat label, Drug interactions)

• Serotonergic Drugs: Concomitant use may result in serotonin syndrome. (Morphine label, Drug interactions)

Patients concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1) and Clinical Pharmacology… (Naloxegol label, Contraindications)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 , 7.2 )] . (Nilotinib label, Boxed warning)

Therefore, the concomitant administration of NYMALIZE and strong CYP3A4 inhibitors should generally be avoided [ see Warnings and Precautions (5.3) ]. (Nimodipine label, Drug interactions)

CYP3A4 inhibitors and inducers : SULAR is substrate of CYP3A4 and coadministration of SULAR with any known inducer or inhibitor of CYP3A4 should be avoided in general. (Nisoldipine label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Serotonergic Drugs : Concomitant use may result in serotonin syndrome. (Oliceridine label, Drug interactions)

Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Ondansetron Injection and other serotonergic drugs. (Ondansetron label, Warnings and precautions)

Cytochrome P450 3A4 Interaction The concomitant use of Oxycodone Hydrochloride Oral Solution with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Oxycodone label, Boxed warning)

Cytochrome P450 3A4 Interaction The concomitant use of oxycodone hydrochloride tablets with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (Oxycodone and acetaminophen label, Boxed warning)

Serotonergic Drugs : Concomitant use may result in serotonin syndrome. (Oxymorphone label, Drug interactions)

Avoid concomitant use of strong CYP3A inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole). (Palbociclib label, Drug interactions)

Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of POSFREA and other serotonergic drugs. (Palonosetron label, Warnings and precautions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Strong CYP3A4 Inhibitors : Avoid coadministration of VOTRIENT with strong CYP3A4 inhibitors. (Pazopanib label, Drug interactions)

Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. (Pentazocine and naloxone label, Precautions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

CONTRAINDICATIONS Coadministration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine with nefazodone hydrochloride is contraindicated (see WARNINGS and PRECAUTIONS ). (Nefazodone label, Contraindications)

…prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine HCl. (Promethazine label, Drug interactions)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. (Promethazine and codeine label, Boxed warning)

…prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine. (Promethazine and dextromethorphan label, Drug interactions)

• Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (Propafenone label, Warnings and precautions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs. (Nefazodone label, Warnings)

• Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Remifentanil label, Warnings and precautions)

• Strong CYP3A4 Inhibitors: Avoid concomitant administration. (Rimegepant label, Drug interactions)

Use with P-gp and Strong CYP3A Inhibitors or Inducers Avoid concomitant use of XARELTO with known combined P-gp and strong CYP3A inhibitors [see Drug Interactions (7.2) ] . (Rivaroxaban label, Warnings and precautions)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Salmeterol label, Drug interactions)

Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs. (Nefazodone label, Warnings)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Severe renal impairment (CCr < 30 mL/min) Severe hepatic impairment (Child-Pugh score ≥ 10) Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) [see DRUG INTERACTIONS (7.1) ] Patients with a history of hypersensitivity to silodosin or any of the ingredients in silodosin capsules… (Silodosin label, Contraindications)

ZOCOR is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] . (Simvastatin label, Contraindications)

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ]. (Sirolimus label, Warnings and precautions)

The dosage of Solifenacin succinate tablets greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors [see Dosage and Administration ( 2.4 )] . (Solifenacin label, Drug interactions)

Combining St. John's wort with antidepressants and other serotonergic drugs increases the risk of serotonin syndrome. (NCCIH, St. John's Wort)

CYP3A Inhibitors Concomitant use of BELSOMRA with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) is not recommended [see Clinical Pharmacology (12.3) ]. (Suvorexant label, Drug interactions)

Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . (Suzetrigine label, Contraindications)

• Should not be used in combination with strong inhibitors of CYP3A4. (Tamsulosin label, Warnings and precautions)

Avoid co-administration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with TEPADINA due to the potential effects on efficacy and toxicity [see Clinical Pharmacology ( 12.3 ) ] . (Thiotepa label, Drug interactions)

Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology (12.3) ] . (Ticagrelor label, Drug interactions)

…dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS [see Warnings and Precautions (5.2) ] Unable to sense or respond to thirst Hypovolemic hyponatremia Taking strong CYP3A inhibitors [see Warnings and Precautions (5.5) ] Anuria Hypersensitivity (e.g., anaphylactic shock, rash generalized) to tolvaptan or any components of the product [see Adverse… (Tolvaptan label, Contraindications)

Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided [see Warnings and Precautions (5.1) ] . (Toremifene label, Boxed warning)

CYP3A inhibitors: Avoid concomitant strong CYP3A inhibitors ( 7.1 ) (Trabectedin label, Drug interactions)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (Tramadol label, Boxed warning)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (Tramadol and acetaminophen label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

• Strong CYP3A Inhibitors and Inducers: Avoid coadministration with strong CYP3A inhibitors and inducers. (Tretinoin label, Drug interactions)

The coadministration of triazolam and nefazodone causes a significant increase in the plasma level of triazolam (see WARNINGS and PRECAUTIONS ), and a 75% reduction in the initial triazolam dosage is recommended if the two drugs are to be given together. (Nefazodone label, Contraindications)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

UBRELVY is contraindicated: With concomitant use of strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 )] In patients with a history of serious hypersensitivity to ubrogepant or any component of UBRELVY. (Ubrogepant label, Contraindications)

For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. (Upadacitinib label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (Vepdegestrant label, Warnings and precautions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

Therefore, the concomitant use of strong CYP3A inhibitors with vincristine sulfate should be avoided. (Vincristine label, Drug interactions)

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. (Nefazodone label, Boxed warning)

• Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone. (Ziprasidone label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. (Albuterol label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. (Alosetron label, Drug interactions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Amlodipine label, Drug interactions)

HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations… (Nefazodone label, Drug interactions)

CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Amlodipine and benazepril label, Drug interactions)

• Increased exposure of amlodipine when coadministered with CYP3A inhibitors Olmesartan medoxomil ( 7.2 ): • Nonsteroidal anti-inflammatory drugs (NSAIDS) may lead to increased risk of renal impairment and loss of antihypertensive effect. (Amlodipine and olmesartan label, Drug interactions)

Amlodipine Impact of Other Drugs on Amlodipine CYP3A Inhibitors Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Amlodipine and valsartan label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

MAO inhibitors, tricyclic antidepressants and drugs that prolong the QTc interval may potentiate effect on the cardiovascular system. (Arformoterol label, Drug interactions)

CYP2D6 inhibitors and CYP3A4 Inhibitors : See full prescribing information for ABILIFY MAINTENA dosage modifications when used concomitantly with CYP2D6 inhibitors and/or CYP3A4 inhibitors for greater than 14 days ( 7.1 ) (Aripiprazole label, Drug interactions)

The administration of local anesthetic solutions containing epinephrine to patients receiving monoamine oxidase inhibitors, nonselective beta-adrenergic antagonists, or tricyclic antidepressants may produce severe, prolonged hypertension. (Articaine and epinephrine label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations… (Nefazodone label, Drug interactions)

CYP3A4/5 Inhibitors Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. (Axitinib label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Use of Cytochrome P450 3A4 Inhibitors Ritonavir and other strong cytochrome P450 3A4 (CYP3A4) inhibitors can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )] . (Azelastine and fluticasone label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Amphetamines may enhance the effects of tricyclic antidepressants. (Benzphetamine label, Drug interactions)

Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. (Bortezomib label, Drug interactions)

Strong CYP2D6 REXULTI may be administered without dosage adjustment in patients with MDD when administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine). or CYP3A4 inhibitors Administer half of recommended dosage. (Brexpiprazole label, Drug interactions)

Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines. (Brimonidine label, Drug interactions)

Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines. (Brimonidine and timolol label, Drug interactions)

Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the co-administration of PULMICORT FLEXHALER with ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to… (Budesonide label, Warnings and precautions)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Budesonide and formoterol label, Warnings and precautions)

…Interactions with MARCAINE WITH EPINEPHRINE Risk of Severe, Persistent Hypertension Due to Drug Interactions Between MARCAINE WITH EPINEPHRINE and Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Administration of MARCAINE WITH EPINEPHRINE (containing a vasoconstrictor) in patients receiving monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants may… (Bupivacaine label, Warnings and precautions)

…Interactions with MARCAINE WITH EPINEPHRINE Risk of Severe, Persistent Hypertension Due to Drug Interactions Between MARCAINE WITH EPINEPHRINE and Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Administration of MARCAINE WITH EPINEPHRINE (containing a vasoconstrictor) in patients receiving monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants may… (Bupivacaine and epinephrine label, Warnings and precautions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

• Tricyclic antidepressants: risk of hypertension and dyskinesia reported during concomitant use with carbidopa/levodopa ( 7.4 ) (Carbidopa, levodopa, and entacapone label, Drug interactions)

Clinically Significant Drug Interactions with VRAYLAR Strong or Moderate CYP3A4 Inhibitors Clinical Impact: Concomitant use of VRAYLAR with a strong or moderate CYP3A4 inhibitor increases the exposures of cariprazine and its major active metabolite, didesmethylcariprazine (DDCAR), compared to use of VRAYLAR alone [see Clinical Pharmacology ( 12.3 ) ]. (Cariprazine label, Drug interactions)

Since the sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously. (Carisoprodol label, Warnings and precautions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Drug Interactions The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or hypertension. (Chloroprocaine label, Precautions)

In a drug interaction study, co-administration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of des-ciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. (Ciclesonide label, Drug interactions)

Inhibitors of CYP3A4 or CYP2C19 Inhibitors of CYP3A4 Coadministration of strong (e.g., ketoconazole) and moderate (e.g., erythromycin, diltiazem and grapefruit juice) CYP3A4 inhibitors can increase exposure to cilostazol. (Cilostazol label, Drug interactions)

Cimetidine When nefazodone (200 mg BID) and cimetidine (300 mg QID) were coadministered for one week, no change in the steady-state pharmacokinetics of either nefazodone or cimetidine was observed compared to each dosed alone. (Nefazodone label, Drug interactions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

…syndrome, uncorrected electrolyte imbalance, such as hypokalemia or hypomagnesemia and cardiac disease, such as heart failure, myocardial infarction, or bradycardia), and patients receiving Class IA antiarrhythmic agents (quinidine, procainamide), or Class III antiarrhythmic agents (amiodarone, sotalol), tricyclic antidepressants, macrolides, and antipsychotics. (Ciprofloxacin label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. (Clindamycin label, Drug interactions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

…Interactions The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs. (Clonazepam label, Drug interactions)

Tricyclic antidepressants Clinical Implication Concomitant use of tricyclic antidepressants with clonidine can increase blood pressure and may counteract the hypotensive effects of clonidine. (Clonidine label, Drug interactions)

The actions of the benzodiazepines may be potentiated by barbiturates, narcotics, phenothiazines, monoamine oxidase inhibitors or other antidepressants. (Clorazepate label, Drug interactions)

Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively. (Nefazodone label, Drug interactions)

CYP2D6 and CYP3A4 Inhibitors Concomitant treatment with CLOZARIL and CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline) can increase clozapine levels and lead to adverse reactions [see Clinical Pharmacology ( 12.3 )] . (Clozapine label, Drug interactions)

Sympathomimetics, postganglionic blocking agents, and tricyclic antidepressants: Concomitant administration may increase the risk of cardiovascular adverse reactions. (Cocaine label, Drug interactions)

Concomitant administration of itraconazole, a strong CYP3A4 inhibitor, with DUAVEE, resulted in increases in bazedoxifene exposure (40%) and, to a lesser extent, conjugated estrogens exposure (9% for baseline-adjusted total estrone, 5% for total equilin), compared to DUAVEE alone [see Pharmacokinetics (12.3) ] . (Conjugated estrogens and bazedoxifene label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Moderate or strong CYP3A4 inhibitors: Give one third of the recommended dosage of EMFLAZA ( 7.1 ) (Deflazacort label, Drug interactions)

…that may Increase Risk of Hyponatremia Concomitant administration of DESMODA with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, NSAIDs, lamotrigine, sulfonylureas, particularly chlorpropamide, oxybutynin… (Desmopressin label, Drug interactions)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Desogestrel and ethinyl estradiol label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of dexlansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Dexlansoprazole label, Drug interactions)

…be given to the pharmacology of the agents employed particularly with compounds that may potentiate or be potentiated by the action of Valium, such as phenothiazines, antipsychotics, anxiolytics/sedatives, hypnotics, anticonvulsants, narcotic analgesics, anesthetics, sedative antihistamines, narcotics, barbiturates, MAO inhibitors and other antidepressants. (Diazepam label, Drug interactions)

…drugs including dicyclomine hydrochloride: amantadine, antiarrhythmic agents of Class I (e.g., quinidine), antihistamines, antipsychotic agents (e.g., phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e.g., meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants, and other drugs having anticholinergic activity. (Dicyclomine label, Drug interactions)

Cardiovascular-Active Drugs Digoxin – When nefazodone (200 mg BID) and digoxin (0.2 mg QD) were coadministered for 9 days to healthy male volunteers (n = 18) who were phenotyped as CYP2D6 extensive metabolizers, C max , C min , and AUC of digoxin were increased by 29%, 27%, and 15%, respectively. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

Concomitant medications were grouped as ACE inhibitors, oral anticoagulants, calcium channel blockers, beta blockers, cardiac glycosides, inducers of CYP3A4, substrates and inhibitors of CYP3A4, substrates and inhibitors of P-glycoprotein, nitrates, sulphonylureas, loop diuretics, potassium sparing diuretics, thiazide diuretics, substrates and inhibitors of tubular… (Dofetilide label, Drug interactions)

Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. (Doravirine label, Drug interactions)

Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. (Doxazosin label, Drug interactions)

Concomitant use of other drugs that cause dizziness, confusion, sedation, or somnolence such as CNS depressants may increase this effect (e.g., barbiturates, benzodiazepines, lithium, opioids, buspirone, scopolamine, antihistamines, tricyclic antidepressants, other anticholinergic agents, and muscle relaxants). (Dronabinol label, Warnings and precautions)

Possible pharmacodynamic interactions can occur between droperidol and potentially arrhythmogenic agents such as class I or III antiarrhythmics, antihistamines that prolong the QT interval, antimalarials, calcium channel blockers, neuroleptics that prolong the QT interval, and antidepressants. (Droperidol label, Drug interactions)

Consider monitoring serum potassium concentration in high-risk patients who take a strong CYP3A4 inhibitor long-term and concomitantly. (Drospirenone and ethinyl estradiol label, Warnings and precautions)

Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Concomitant Use with CYP3A Inhibitors Exposure to elexacaftor, tezacaftor and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. (Elexacaftor, tezacaftor, and ivacaftor label, Warnings and precautions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Drugs Inducing or Inhibiting CYP3A Enzymes Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of RPV [see Contraindications (4) , Warnings and Precautions (5.7) , and Clinical Pharmacology (12.3) ] . (Emtricitabine, rilpivirine, and tenofovir label, Drug interactions)

• Drugs that potentiate the effects of epinephrine include sympathomimetics, beta blockers, tricyclic antidepressants, MAO inhibitors, COMT inhibitors, clonidine, doxapram, oxytocin, levothyroxine sodium, and certain antihistamines. (Epinephrine label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects. (Estradiol label, Drug interactions)

…exposure at steady state. [See Clinical Pharmacology (12.3).] Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors like azole antifungals (for example, ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem,… (Estradiol and dienogest label, Drug interactions)

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. (Estradiol and norethindrone label, Drug interactions)

Additive effects occur with concomitant use of other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use. (Eszopiclone label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Concomitant administration of strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma estrogen and/or progestin concentrations. (Etonogestrel and ethinyl estradiol label, Drug interactions)

CCR5 antagonists maraviroc ↔ etravirine ↓ maraviroc When Etravirine is co-administered with maraviroc in the absence of a potent CYP3A inhibitor (e.g., ritonavir boosted protease inhibitor), the recommended dose of maraviroc is 600 mg twice daily. (Etravirine label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

Coadministration of CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several-fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism. (Felodipine label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations… (Nefazodone label, Drug interactions)

• MAO inhibitors, tricyclic antidepressants and drugs that prolong QTc interval may potentiate effect on the cardiovascular system. (Formoterol label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…prolongation and the potential for torsades de pointes, the use of FOSCAVIR should be avoided in combination with agents known to prolong the QT interval including Class IA (e.g., quinidine or procainamide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents, phenothiazines, tricyclic antidepressants, and certain macrolides and fluoroquinolones. (Foscarnet label, Drug interactions)

Avoid co-administration of CONTEPO with drugs known to prolong the QT interval, such as class IA or class III antiarrhythmic medications, tricyclic antidepressants, macrolides, and antipsychotics [see Warnings and Precautions ( 5.2 )] . (Fosfomycin label, Drug interactions)

…Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine,… (Fosphenytoin label, Drug interactions)

• CYP3A4 Inhibitor: Monitor adverse reactions if concomitant use with IRESSA. (Gefitinib label, Drug interactions)

Other Anticholinergic Drugs There is potential for an additive interaction between glycopyrrolate and concomitantly used anticholinergic drugs (e.g., tricyclic antidepressants, anti-epileptics, class I antiarrhythmics, anti­-spasmodics, amantadine) resulting in increased anticholinergic adverse reactions. (Glycopyrrolate label, Drug interactions)

…Interactions: Effect of other Drugs on INTUNIV Concomitant Drug Name or Drug Class Clinical Rationale and Magnitude of Drug Interaction Clinical Recommendation Strong and moderate CYP3A4 inhibitors, e.g., ketoconazole, fluconazole Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in an increase… (Guanfacine label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Haloperidol – When a single oral 5 mg dose of haloperidol was coadministered with nefazodone (200 mg BID) at steady state, haloperidol apparent clearance decreased by 35% with no significant increase in peak haloperidol plasma concentrations or time of peak. (Nefazodone label, Drug interactions)

Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions associated with the use of excessive doses. (Hydrocortisone label, Drug interactions)

• CYP3A4 Inhibitors: Use in combination with CYP3A4 inhibitors could decrease the effectiveness of ifosfamide. (Ifosfamide label, Drug interactions)

The dose of FANAPT should be reduced in patients co-administered a strong CYP2D6 or CYP3A4 inhibitor. (Iloperidone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Monoamine Oxidase Inhibitors or Tricyclic Antidepressants Ipratropium Bromide and Albuterol Sulfate Inhalation Solution should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents because the action of albuterol sulfate on the cardiovascular… (Ipratropium and albuterol label, Drug interactions)

Drugs that may potentiate clinical response of Isoproterenol Clinical Impact The effects of isoproterenol may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine. (Isoproterenol label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Strong CYP3A4 or CYP2C9 Inhibitors Patients with renal or hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to VIMPAT. (Lacosamide label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Lansoprazole label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Monoamine oxidase inhibitors (MAOs) or tricyclic antidepressants : May potentiate effect of albuterol on the cardiovascular system. (Levalbuterol label, Drug interactions)

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

Antidepressant Therapy Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and levothyroxine may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. (Levothyroxine label, Drug interactions)

Clinically Significant Drug Interactions The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. (Lidocaine label, Drug interactions)

…Adverse Reactions Due to Drug Interactions with FLAVALTA Risk of Severe, Persistent Hypertension Due to Drug Interactions Between FLAVALTA and Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Administration of FLAVALTA (containing a vasoconstrictor, epinephrine) in patients receiving monoamine oxidase inhibitors (MAOI), or tricyclic antidepressants may result… (Lidocaine and epinephrine label, Warnings and precautions)

Antidepressant Therapy Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and liothyronine sodium may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. (Liothyronine label, Drug interactions)

Drug Interactions Effects of Other Drugs on Loperamide Concomitant use of loperamide hydrochloride capsules with inhibitors of CYP3A4 (e.g., itraconazole) or CYP2C8 (e.g., gemfibrozil) or inhibitors of P-glycoprotein (e.g., quinidine, ritonavir) can increase exposure to loperamide. (Loperamide label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Monitor all antidepressant-treated patients, especially during the initial few months of anti-depressant drug therapy, and at times of dosage changes. (Lumateperone label, Warnings and precautions)

Ketoconazole (Potent Inhibitor of CYP3A4) Coadministration of a single 500 mg oral dose of mefloquine with 400 mg of ketoconazole once daily for 10 days in 8 healthy volunteers resulted in an increase in the mean C max and AUC of mefloquine by 64% and 79%, respectively, and an increase in the mean elimination half-life of mefloquine from 322 hours to 448 hours. (Mefloquine label, Drug interactions)

Likewise, solutions of mepivacaine containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result. (Mepivacaine label, Warnings)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Drug interactions Additive anticholinergic effects may result from concomitant use with antipsychotics, tricyclic antidepressants, and other drugs with anticholinergic effects. (Methscopolamine label, Drug interactions)

Similarly, there were no changes in the pharmacokinetic parameters of nefazodone or HO-NEF; however, the mean AUC levels of the nefazodone metabolites mCPP and triazole-dione increased by 3 to 6 fold and 1.3 fold, respectively. (Nefazodone label, Drug interactions)

Cytochrome P450-3A4 Inhibitors: May result in prolonged sedation due to decreased plasma clearance of midazolam. (Midazolam label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Mometasone label, Warnings and precautions)

Pharmacokinetic studies between moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. (Moxifloxacin label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as 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… (Nalbuphine label, Drug interactions)

Moderate (e.g., fluconazole, atazanavir, aprepitant, diltiazem, erythromycin) and Strong (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir, saquinavir) CYP3A Inhibitors Clinical Impact Increase in plasma naldemedine concentrations [see Clinical Pharmacology (12.3) ] Intervention Monitor for potential naldemedine-related adverse reactions [see Adverse… (Naldemedine label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…as ketoconazole, fluconazole, itraconazole, clarithromycin, erythromycin (Azithromycin, although structurally related to the class of macrolide antibiotic is void of clinically relevant CYP3A4 inhibition), grapefruit, nefazodone, fluoxetine, saquinavir, indinavir, nelfinavir, and ritonavir may result in increased exposure to nifedipine when co-administered. (Nifedipine label, Drug interactions)

Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. (Nintedanib label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Norelgestromin and ethinyl estradiol label, Drug interactions)

Substances increasing the systemic concentrations of HCs: Co-administration of certain HCs and strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase the systemic concentrations of progestins, including norethindrone. (Norethindrone label, Drug interactions)

CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. (Norethindrone and ethinyl estradiol label, Drug interactions)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Norgestimate and ethinyl estradiol label, Drug interactions)

Concomitant administration of CYP3A4 inhibitors such as itraconazole, fluconazole, grapefruit juice or ketoconazole may increase plasma hormone concentrations. (Norgestrel and ethinyl estradiol label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

• Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): • Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. (Olmesartan, amlodipine, and hydrochlorothiazide label, Drug interactions)

Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the mometasone furoate plasma concentration and potentially increase the risk for adverse reactions. (Olopatadine and mometasone label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Omeprazole label, Drug interactions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Omeprazole and sodium bicarbonate label, Drug interactions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

Co-administration with strong cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole) increases the systemic exposure of oxybutynin. (Oxybutynin label, Drug interactions)

Exposure of Paricalcitol Injection will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . (Paricalcitol label, Drug interactions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Agonistic Effects (increase in BIORPHEN blood pressure effect) can occur with monoamine oxidase inhibitors (MAOI), oxytocin and oxytocic drugs, tricyclic antidepressants, angiotensin and aldosterone, atropine, steroids, norepinephrine transporter inhibitors, ergot alkaloids. (Phenylephrine label, Drug interactions)

However, due to the nonlinear pharmacokinetics of phenytoin, the failure to observe a significant effect on the single-dose pharmacokinetics of phenytoin does not preclude the possibility of a clinically significant interaction with nefazodone when phenytoin is dosed chronically. (Nefazodone label, Drug interactions)

Acute cardiac arrest may be possible during treatment with tricyclic antidepressants; therefore, Anticholium should only be considered as an antidote for this indication while the patient has continuous ECG monitoring. (Physostigmine label, Warnings and precautions)

Strong CYP3A4 Inhibitors: Reduce NUPLAZID dose to 10 mg once daily. (Pimavanserin label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations… (Nefazodone label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations… (Nefazodone label, Drug interactions)

CYP 3A4 inhibitors (e.g., ketoconazole, macrolide antibiotics): Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects. (Prednisolone label, Drug interactions)

CYP 3A4 Inhibitors (e.g., Ketoconazole, Macrolide Antibiotics) Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to increased risk of corticosteroid side effects. (Prednisone label, Drug interactions)

…Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine The administration of local anesthetic injections containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or hypertension. (Prilocaine and epinephrine label, Drug interactions)

Published clinical reports indicate primaquine may inhibit CYP3A4 enzyme activity and thus may lead to increased exposure of oral CYP3A4 substrate drugs when co-administered with Primaquine phosphate Tablets. (Primaquine label, Drug interactions)

Propranolol – The coadministration of nefazodone (200 mg BID) and propranolol (40 mg BID) for 5.5 days to healthy male volunteers (n = 18), including 3 poor and 15 extensive CYP2D6 metabolizers, resulted in 30% and 14% reductions in C max and AUC of propranolol, respectively, and a 14% reduction in C max for the metabolite, 4-hydroxypropranolol. (Nefazodone label, Drug interactions)

It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. (Quetiapine label, Warnings and precautions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

Although a causal relationship between a specific drug and the arrhythmia was not established in this case, erythromycin is a CYP3A4 inhibitor and has been shown to increase quinine plasma levels when used concomitantly. (Quinine label, Warnings and precautions)

Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution. (Ramelteon label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co‑administered. (Repaglinide label, Drug interactions)

Effect of Other Drugs on Rifabutin Pharmacokinetics Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin. (Rifabutin label, Drug interactions)

…5-HT 3 Receptor Antagonists Ondansetron Decrease exposure Statins Metabolized by CYP3A4 Simvastatin Decrease exposure Thiazolidinediones Rosiglitazone Decrease AUC by 66% Tricyclic Antidepressants Nortriptyline A tuberculosis treatment regimen including rifampin (600 mg/day), isoniazid (300 mg/day), pyrazinamide (500 mg 3× per day), and pyridoxine (25 mg) was… (Rifampin label, Drug interactions)

…levonorgestrel Immunosuppressants Cyclosporine, tacrolimus Methylxanthines Theophylline Narcotic analgesics Methadone Phosphodiesterase-5 (PDE-5) Inhibitors Sildenafil Thyroid preparations Levothyroxine Tricyclic antidepressants Amitriptyline, nortriptyline 7.5 Other Interactions The conversion of PRIFTIN to 25-desacetyl rifapentine is mediated by an esterase enzyme. (Rifapentine label, Drug interactions)

Coadministration of EDURANT or EDURANT PED and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine. (Rilpivirine label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic exposure and may result in increased adverse reactions. (Roflumilast label, Drug interactions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

• Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). (Romidepsin label, Drug interactions)

Coadministration of a selective and potent inhibitor of CYP3A4, ketoconazole (100 mg bid for 2 days with ropivacaine infusion administered 1 hour after ketoconazole) caused a 15% reduction in in vivo plasma clearance of ropivacaine. (Ropivacaine label, Drug interactions)

HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations… (Nefazodone label, Drug interactions)

Strong CYP3A4 Inhibitors: Reduce, interrupt, or discontinue JAKAFI/JAKAFI XR doses as recommended except in patients with acute or chronic graft-versus-host-disease. (Ruxolitinib label, Drug interactions)

Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). (Saxagliptin label, Drug interactions)

Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). (Saxagliptin and metformin label, Drug interactions)

Concomitant use of other drugs that cause central nervous system (CNS) adverse reactions (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics) or have anticholinergic properties (e.g., other belladonna alkaloids, sedating antihistamines, meclizine, tricyclic antidepressants, and muscle relaxants) may increase this effect [see Drug Interactions ( 7.1 )] . (Scopolamine label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin) increase SILDENAFIL ORAL FILM exposure. (Sildenafil label, Drug interactions)

The concurrent use of Xyrem with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and… (Sodium oxybate label, Warnings and precautions)

The efficacy of tricyclic antidepressants can decrease when coadministered with sulfamethoxazole and trimethoprim. (Sulfamethoxazole and trimethoprim label, Drug interactions)

Monitor QT interval more frequently when SUTENT is concomitantly administered with strong CYP3A4 inhibitors or drugs known to prolong QT interval. (Sunitinib label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

…Physicians should be aware that CIALIS for once daily use provides continuous plasma tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol [see Drug Interactions ( 7.1 , 7.2 , 7.3 )] . (Tadalafil label, Warnings and precautions)

CYP3A4 Inhibitors Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. (Telmisartan and amlodipine label, Drug interactions)

The benzodiazepines, including temazepam, produce additive CNS-depressant effects when co-administered with other CNS depressants such as alcohol, barbiturates, antipsychotics, sedative/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants, and anesthetics. (Temazepam label, Drug interactions)

Co-administration with Inducers or Inhibitors of CYP3A Metabolism Agents Inducing CYP3A Metabolism: Strong inducers of CYP3A4/5 such as dexamethasone, carbamazepine, phenytoin, phenobarbital, rifampin, rifabutin, and rifampacin may decrease exposure of the active metabolite, sirolimus. (Temsirolimus label, Warnings and precautions)

…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6. (Nefazodone label, Drug interactions)

Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Terbutaline sulfate should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, since the action of terbutaline sulfate on the vascular system may be potentiated. (Terbutaline label, Precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

FEV 1 measurements taken when theophylline and nefazodone were coadministered did not differ from baseline dosage (i.e., when theophylline was administered alone). (Nefazodone label, Drug interactions)

Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole. (Tinidazole label, Drug interactions)

The CNS depressant effects of Zanaflex with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions ( 7.4 )] . (Tizanidine label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

Drug Interactions CYP3A4 Inhibitors Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see CLINICAL PHARMACOLOGY, Variability in Metabolism and Drug-Drug Interactions ). (Tolterodine label, Drug interactions)

Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with KENALOG-40 Injection may cause increased plasma concentration of triamcinolone leading to adverse reactions. (Triamcinolone label, Drug interactions)

Increase in Plasma Concentrations of ella Associated with Co-Administered Drugs CYP3A4 inhibitors such as itraconazole or ketoconazole increase plasma concentrations of ella [see Pharmacokinetics (12.3) ] . (Ulipristal label, Drug interactions)

Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of Umeclidinium and Vilanterol ELLIPTA with ketoconazole and other known strong cytochrome P450 3A4 (CYP3A4) inhibitors (including, but not limited to, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone,… (Umeclidinium and vilanterol label, Warnings and precautions)

Immunosuppressive Agents There have been reports of increased blood concentrations of cyclosporine and tacrolimus into toxic ranges when patients received these drugs concomitantly with nefazodone. (Nefazodone label, Drug interactions)

In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA and INGREZZA SPRINKLE concentrations may be higher and QT prolongation clinically significant [see Clinical Pharmacology ( 12.2 )] . (Valbenazine label, Warnings and precautions)

Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, cobicistat, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. (Vardenafil label, Warnings and precautions)

Drugs Suspected of Causing SIADH Use with drugs suspected of causing SIADH (e.g., SSRIs, tricyclic antidepressants, haloperidol, chlorpropamide, enalapril, methyldopa, pentamidine, vincristine, cyclophosphamide, ifosfamide, felbamate) may increase the pressor effect in addition to the antidiuretic effect of Vasostrict ® . (Vasopressin label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

CYP3A4 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP3A4 which increases the exposure of CYP3A4 substrates when coadministered [see Clinical Pharmacology (12.3) ]. (Viloxazine label, Drug interactions)

Inhibitors of CYP3A4: May cause earlier onset and/or increased severity of adverse reactions ( 7.1 ) (Vinorelbine label, Drug interactions)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (Nefazodone label, Warnings)

Warfarin – There were no effects on the prothrombin or bleeding times or upon the pharmacokinetics of R-warfarin when nefazodone (200 mg BID) was administered for 1 week to subjects who had been pretreated for 2 weeks with warfarin. (Nefazodone label, Drug interactions)

As zafirlukast is known to be an inhibitor of CYP3A4 in vitro , it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with zafirlukast. (Zafirlukast label, Precautions)

Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Zaleplon label, Warnings)

Additive effects occur with concomitant use of other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use [see Drug Interactions (7.1) ] . (Zolpidem label, Warnings and precautions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Paralytic ileus, hyperthermia and heat stroke, all of which have sometimes been fatal, have occurred in patients taking anticholinergic-type antiparkinsonism drugs, including benztropine mesylate, in combination with phenothiazines and/or tricyclic antidepressants. (Benztropine label, Warnings)

Such individuals are referred to commonly as “poor metabolizers” of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants. (Nefazodone label, Drug interactions)

CYP1A2 Isozyme – Nefazodone and its metabolites have been shown in vitro not to inhibit CYP1A2. (Nefazodone label, Drug interactions)

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa-levodopa preparations. (Carbidopa label, Drug interactions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

CYP1A2 Isozyme – Nefazodone and its metabolites have been shown in vitro not to inhibit CYP1A2. (Nefazodone label, Drug interactions)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

Such individuals are referred to commonly as “poor metabolizers” of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants. (Nefazodone label, Drug interactions)

Although potent inhibitors of cytochrome P450 3A4 (e.g., ketoconazole) have not been studied clinically, in vitro studies have shown that erythromycin and oleandomycin inhibit the metabolism of disopyramide. (Disopyramide label, Drug interactions)

In contrast, drugs that are inhibitors of cytochrome P450 isozymes, e.g., antidepressants, may be expected to have little effect on valproate clearance because cytochrome P450 microsomal mediated oxidation is a relatively minor secondary metabolic pathway compared to glucuronidation and beta-oxidation. (Divalproex (valproate) label, Drug interactions)

The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. (Dutasteride label, Drug interactions)

TAF is a weak inhibitor of CYP3A in vitro . (Emtricitabine and tenofovir label, Drug interactions)

Effects of Other Drugs on HALAVEN No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P-glycoprotein (P-gp) inhibitors. (Eribulin label, Drug interactions)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes. (Famciclovir label, Drug interactions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Serotonin Syndrome Serotonin syndrome may occur with frovatriptan succinate, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors [ see Drug Interactions (7.3) ]. (Frovatriptan label, Warnings and precautions)

…quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmics, certain antipsychotics (e.g., ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine), certain antidepressants (e.g., citalopram, fluoxetine), certain antibiotics (e.g., azithromycin, erythromycin, clarithromycin, gatifloxacin, moxifloxacin); and others (e.g., pentamidine, methadone,… (Hydroxyzine label, Precautions)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Effect of Other Drugs on the Metabolism of Donepezil Inhibitors of CYP3A4 (e.g., ketoconazole) and CYP2D6 (e.g., quinidine), inhibit donepezil metabolism in vitro . (Memantine and donepezil label, Drug interactions)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

CYP1A2 Isozyme – Nefazodone and its metabolites have been shown in vitro not to inhibit CYP1A2. (Nefazodone label, Drug interactions)

Serotonin Syndrome Serotonin syndrome may occur with naratriptan tablets, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors [see Drug Interactions (7.3)]. (Naratriptan label, Warnings and precautions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

The safety and efficacy of combination therapy with phentermine and any other drug products for weight loss including prescribed drugs, over-the-counter preparations, and herbal products, or serotonergic agents such as selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established. (Phentermine label, Warnings and precautions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Serotonin Syndrome Serotonin syndrome may occur with triptans, including MAXALT particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5) ] . (Rizatriptan label, Warnings and precautions)

General Anesthetics – Little is known about the potential for interaction between nefazodone and general anesthetics; therefore, prior to elective surgery, nefazodone hydrochloride should be discontinued for as long as clinically feasible. (Nefazodone label, Drug interactions)

Hyponatremia : Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including nefazodone. (Nefazodone label, Warnings)

Serotonin Syndrome Serotonin syndrome may occur with IMITREX tablets, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.4)] . (Sumatriptan label, Warnings and precautions)

Serotonin Syndrome Serotonin syndrome may occur with sumatriptan and naproxen sodium tablets, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Contraindications (4) and Drug Interactions (7.1)] . (Sumatriptan and naproxen label, Warnings and precautions)

Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone),… (Tapentadol label, Warnings and precautions)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

In most cases, patients were using concomitant medications (antidepressants, antipsychotics, stimulants, narcotics) that are thought to lower the seizure threshold. (Tiagabine label, Warnings)

Some cases presented with features resembling neuroleptic malignant syndrome. (Nefazodone label, Warnings)

Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents because of the secondary anticholinergic activities of these medications. (Trihexyphenidyl label, Drug interactions)

In contrast, drugs that are inhibitors of cytochrome P450 isozymes, e.g., antidepressants, may be expected to have little effect on valproate clearance because cytochrome P450 microsomal mediated oxidation is a relatively minor secondary metabolic pathway compared to glucuronidation and beta-oxidation. (Valproic acid label, Drug interactions)

CYP1A2 Isozyme – Nefazodone and its metabolites have been shown in vitro not to inhibit CYP1A2. (Nefazodone label, Drug interactions)

Serotonin Syndrome Serotonin syndrome may occur with triptans, including zolmitriptan, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions ( 7.5 )] . (Zolmitriptan label, Warnings and precautions)

Inhibitors of Cytochrome P450 3A4 In controlled clinical studies co-administration of desloratadine with ketoconazole, erythromycin, or azithromycin resulted in increased plasma concentrations of desloratadine and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3) .]… (Desloratadine label, Drug interactions)

No interaction with the tricyclic antidepressant imipramine was shown in a single-dose study with entacapone without coadministered levodopa and dopa-decarboxylase inhibitor. (Entacapone label, Precautions)

Commonly Administered Drugs: Population analysis showed that commonly administered drugs (e.g., selegiline, amantadine, tricyclic antidepressants, benzodiazepines, ibuprofen, thiazides, antihistamines, anticholinergics) did not affect the clearance of ropinirole. (Ropinirole label, Drug interactions)