Wechselwirkungen von Suvorexant

• CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors. (Fachinformation zu Acalabrutinib, Arzneimittelwechselwirkungen)

…(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… (Fachinformation zu Alfuzosin, Gegenanzeigen)

Die Kombination von Alkohol mit sedierenden Arzneimitteln (Opioide, Benzodiazepine, Schlafmittel, Muskelrelaxanzien) kann gefährliche Schläfrigkeit, verlangsamte Atmung und eine Überdosierung verursachen. (NIAAA, Harmful Interactions: Mixing Alcohol with Medicines)

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

• 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) ] . (Fachinformation zu Alprazolam, Gegenanzeigen)

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) ] . (Fachinformation zu Apixaban, Arzneimittelwechselwirkungen)

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

• Avoid concurrent use of alcohol or other central nervous system (CNS) depressants with azelastine hydrochloride and fluticasone propionate nasal spray because further decreased alertness and impairment of CNS performance may occur. (Fachinformation zu Azelastin und Fluticason, Warnhinweise und Vorsichtsmaßnahmen)

…AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOD WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH ALCOHOL, BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Belladonna and opium suppositories expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to… (Fachinformation zu Belladonna und Opium, Boxed Warning (umrahmter Warnhinweis))

Concomitant administration of BIXLENVO with combined P-gp, UGT1A1, and strong CYP3A inhibitors is not recommended. (Fachinformation zu Bictegravir, Emtricitabin und Tenofoviralafenamid, Arzneimittelwechselwirkungen)

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

• Strong and Moderate CYP3A Inhibitors: Avoid concomitant use with BOSULIF. (Fachinformation zu Bosutinib, Arzneimittelwechselwirkungen)

Concomitant use of strong CYP3A4 inhibitors (e.g., azole antimycotics, HIV protease inhibitors) with CYCLOSET should be avoided. (Fachinformation zu Bromocriptin, Arzneimittelwechselwirkungen)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Buprenorphin, Boxed Warning (umrahmter Warnhinweis))

Concomitant use of opioids or a barbiturate with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Butalbital, Acetylsalicylsäure, Koffein und Codein, Boxed Warning (umrahmter Warnhinweis))

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Butalbital, Paracetamol, Koffein und Codein, Boxed Warning (umrahmter Warnhinweis))

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Butorphanol, Boxed Warning (umrahmter Warnhinweis))

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… (Fachinformation zu Cabozantinib, Arzneimittelwechselwirkungen)

CNS Depressants The concomitant use of EQUETRO and other CNS depressants can increase the risk of respiratory depression, profound sedation, hypotension, and syncope. (Fachinformation zu Carbamazepin, Arzneimittelwechselwirkungen)

Avoid concurrent use of Carbinoxamine Maleate Extended-Release Oral Suspension with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur. (Fachinformation zu Carbinoxamin, Warnhinweise und Vorsichtsmaßnahmen)

Avoid concurrent use of QUZYTTIR with alcohol or other CNS depressants because additional reduction in alertness and additional impairment of CNS performance may occur. (Fachinformation zu Cetirizin, Warnhinweise und Vorsichtsmaßnahmen)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Chlordiazepoxid, Warnhinweise)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Chlordiazepoxid und Clidiniumbromid, Warnhinweise)

…have a breathing problem such as emphysema or chronic bronchitis glaucoma trouble urinating due to an enlarged prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers When using this product excitability may occur, especially in children drowsiness may occur avoid alcoholic beverages alchohol, sedatives and tranquilizers… (Fachinformation zu Chlorphenamin, Warnhinweise)

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.). (Fachinformation zu Chlorpromazin, Gegenanzeigen)

Table 8: Drugs That are Affected by and Affecting Ciprofloxacin Drugs That are Affected by Ciprofloxacin Drug(s) Recommendation Comments Tizanidine Contraindicated Concomitant administration of tizanidine and ciprofloxacin is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see Contraindications ( 4.2 )]. (Fachinformation zu Ciprofloxacin, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Clobazam, Warnhinweise und Vorsichtsmaßnahmen)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Clonazepam, Warnhinweise)

Avoid use with other central nervous system (CNS) depressants ( 5.3 ) (Fachinformation zu Clonidin, Warnhinweise und Vorsichtsmaßnahmen)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Codein, Boxed Warning (umrahmter Warnhinweis))

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) ] . (Fachinformation zu Colchicin, Gegenanzeigen)

Based on its structural similarity to TCAs, concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the… (Fachinformation zu Cyclobenzaprin, Arzneimittelwechselwirkungen)

Avoid use of PRADAXA Capsules and P-gp inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) [see Drug Interactions (7.1) and Use in Specific Populations (8.6) ] . (Fachinformation zu Dabigatran, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A4 inhibitors: Avoid concomitant use. (Fachinformation zu Daridorexant, Arzneimittelwechselwirkungen)

…modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam Co-administration of PREZISTA/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which… (Fachinformation zu Darunavir, Gegenanzeigen)

…modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam PREZCOBIX or PREZCOBIX PED is contraindicated in patients receiving certain co-administered drugs for which altered plasma concentrations… (Fachinformation zu Darunavir und Cobicistat, Gegenanzeigen)

Avoid concomitant use of strong CYP3A4 inhibitors. (Fachinformation zu Dasatinib, Arzneimittelwechselwirkungen)

• Avoid concomitant use of strong CYP3A4 inhibitors or inducers. (Fachinformation zu Dexamethason, Arzneimittelwechselwirkungen)

QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. (Fachinformation zu Dextromethorphan und Chinidin, Warnhinweise und Vorsichtsmaßnahmen)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Diazepam, Warnhinweise)

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. (Fachinformation zu Dihydroergotamin, Boxed Warning (umrahmter Warnhinweis))

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Dikaliumclorazepat, Warnhinweise)

CONTRAINDICATIONS Diphenoxylate hydrochloride and atropine sulfate is contraindicated in: • Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression (see WARNINGS ). (Fachinformation zu Diphenoxylat und Atropin, Gegenanzeigen)

Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. (Fachinformation zu Docetaxel, Arzneimittelwechselwirkungen)

Avoid concomitant use of Doxorubicin Hydrochloride Injection with inhibitors of CYP3A4, CYP2D6, or P-gp. (Fachinformation zu Doxorubicin, Arzneimittelwechselwirkungen)

…breathing problem such as emphysema or chronic bronchitis • glaucoma • trouble urinating due to an enlarged prostate gland Ask a doctor or pharmacist before use if you are taking • a sedative or any other sleep-aid • tranquilizers • any other antihistamines • any other drugs When using this product • avoid alcoholic beverages • do not drive a motor vehicle or operate… (Fachinformation zu Doxylamin, Warnhinweise)

Central nervous system (CNS) depressants: Concurrent use with alcohol or other CNS depressants is not recommended ( 5.1 ) (Fachinformation zu Doxylamin und Pyridoxin, Warnhinweise und Vorsichtsmaßnahmen)

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) ]. (Fachinformation zu Dutasterid und Tamsulosin, Warnhinweise und Vorsichtsmaßnahmen)

• 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) ]. (Fachinformation zu Eletriptan, Gegenanzeigen)

…Lipid-modifying Agents: lomitapide, lovastatin, simvastatin Phosphodiesterase-5 (PDE-5) Inhibitor: sildenafil when administered as REVATIO ® for the treatment of pulmonary arterial hypertension Sedative/hypnotics: triazolam, orally administered midazolam Coadministration of GENVOYA is contraindicated with drugs that: Are highly dependent on CYP3A for clearance and for which… (Fachinformation zu Elvitegravir, Cobicistat, Emtricitabin und Tenofovir, Gegenanzeigen)

…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)… (Fachinformation zu Eplerenon, Gegenanzeigen)

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. (Fachinformation zu Ergotamin und Koffein, Boxed Warning (umrahmter Warnhinweis))

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). (Fachinformation zu Erlotinib, Arzneimittelwechselwirkungen)

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

The use of LUNESTA with other sedative-hypnotics at bedtime or the middle of the night is not recommended. (Fachinformation zu Eszopiclon, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A inhibitor and P-gp inhibitor : Avoid coadministration. (Fachinformation zu Everolimus, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Ezetimib und Simvastatin, Gegenanzeigen)

• Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Fentanyl, Boxed Warning (umrahmter Warnhinweis))

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) ]. (Fachinformation zu Fesoterodin, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Flibanserin, Boxed Warning (umrahmter Warnhinweis))

CONTRAINDICATIONS Phenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. (Fachinformation zu Fluphenazin, Gegenanzeigen)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fachinformation zu Fluticason, Arzneimittelwechselwirkungen)

Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): May increase risk of systemic corticosteroid and cardiovascular effects. (Fachinformation zu Fluticason und Salmeterol, Arzneimittelwechselwirkungen)

…Hypericum perforatum ) Lipid modifying agents: Lomitapide, lovastatin, simvastatin Non-nucleoside reverse transcriptase inhibitor: Delavirdine PDE5 inhibitor: Sildenafil (Revatio) (for treatment of pulmonary arterial hypertension) Sedative/hypnotics: Midazolam, triazolam Hypersensitivity to fosamprenavir calcium or amprenavir (e.g., Stevens-Johnson syndrome). (Fachinformation zu Fosamprenavir, Gegenanzeigen)

• Respiratory Depression: May occur with NEURONTIN when used with concomitant central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. (Fachinformation zu Gabapentin, Warnhinweise und Vorsichtsmaßnahmen)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Hydrocodon, Boxed Warning (umrahmter Warnhinweis))

…ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;… (Fachinformation zu Hydrocodon und Chlorphenamin, Boxed Warning (umrahmter Warnhinweis))

…ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Hydrocodone bitartrate and homatropine methylbromide exposes patients and… (Fachinformation zu Hydrocodon und Homatropin, Boxed Warning (umrahmter Warnhinweis))

…LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P4503A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE AND IBUPROFEN TABLETS Addiction,… (Fachinformation zu Hydrocodon und Ibuprofen, Boxed Warning (umrahmter Warnhinweis))

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Hydrocodon und Paracetamol, Boxed Warning (umrahmter Warnhinweis))

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death . (Fachinformation zu Hydromorphon, Boxed Warning (umrahmter Warnhinweis))

Rarely, cardiac arrests and death have been reported in association with the combined use of hydroxyzine hydrochloride intramuscularly and other CNS depressants. (Fachinformation zu Hydroxyzin, Vorsichtsmaßnahmen)

• Strong CYP3A4 Inhibitors: Do not administer strong CYP3A4 inhibitors with CAMPTOSAR. (Fachinformation zu Irinotecan, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

…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 ) (Fachinformation zu Ivabradin, Gegenanzeigen)

Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death. (Fachinformation zu Ketamin, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Avoid strong CYP3A4 inhibitors. (Fachinformation zu Lapatinib, Arzneimittelwechselwirkungen)

Strong CYP3A4 Inhibitors: Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. (Fachinformation zu Larotrectinib, Arzneimittelwechselwirkungen)

Strong or moderate CYP3A inhibitors: Avoid concomitant use. (Fachinformation zu Lemborexant, Arzneimittelwechselwirkungen)

Avoid concurrent use of alcohol or other central nervous system depressants with XYZAL. (Fachinformation zu Levocetirizin, Warnhinweise und Vorsichtsmaßnahmen)

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Levorphanol, Boxed Warning (umrahmter Warnhinweis))

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) ]. (Fachinformation zu Lomitapid, Gegenanzeigen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Caution patients receiving LOREEV XR against operating machinery or driving a motor vehicle as well to avoid the concomitant use of alcohol and other CNS depressant drugs during treatment ( 5.4 , 7 ) (Fachinformation zu Lorazepam, Warnhinweise und Vorsichtsmaßnahmen)

• Strong CYP3A Inhibitors : Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. (Fachinformation zu Lorlatinib, Arzneimittelwechselwirkungen)

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 ). (Fachinformation zu Lovastatin, Gegenanzeigen)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. (Fachinformation zu Lurasidon, Gegenanzeigen)

Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . (Fachinformation zu Macitentan, Arzneimittelwechselwirkungen)

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 )]. (Fachinformation zu Maraviroc, Gegenanzeigen)

If concomitant use with another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases. (Fachinformation zu Metaxalon, Warnhinweise und Vorsichtsmaßnahmen)

Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Fachinformation zu Methadon, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Methylergometrin, Arzneimittelwechselwirkungen)

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS Personnel and Equipment for Monitoring and Resuscitation Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer… (Fachinformation zu Midazolam, Boxed Warning (umrahmter Warnhinweis))

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. (Fachinformation zu Mitapivat, Arzneimittelwechselwirkungen)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Morphin, Boxed Warning (umrahmter Warnhinweis))

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Nalbuphin, Boxed Warning (umrahmter Warnhinweis))

Risk of Recurrent Respiratory and CNS Depression : A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI using a new auto-injector with each dose while awaiting emergency medical assistance. (Fachinformation zu Nalmefen, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Naloxegol, Gegenanzeigen)

• Central Nervous System Depression Xyrem (sodium oxybate) is a CNS depressant. (Fachinformation zu Natriumoxybat, Boxed Warning (umrahmter Warnhinweis))

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

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

Therefore, the concomitant administration of NYMALIZE and strong CYP3A4 inhibitors should generally be avoided [ see Warnings and Precautions (5.3) ]. (Fachinformation zu Nimodipin, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Nisoldipin, Arzneimittelwechselwirkungen)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Oliceridin, Boxed Warning (umrahmter Warnhinweis))

• Avoid concurrent use of alcohol or other central nervous system depressants with olopatadine hydrochloride nasal solution (nasal spray) ( 5.2 ). (Fachinformation zu Olopatadin, Warnhinweise und Vorsichtsmaßnahmen)

• Avoid concurrent use of alcohol or other central nervous system (CNS) depressants with RYALTRIS because additional reductions in alertness and additional impairment of CNS performance may occur. (Fachinformation zu Olopatadin und Mometason, Warnhinweise und Vorsichtsmaßnahmen)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (Fachinformation zu Oxazepam, Warnhinweise)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Oxycodon, Boxed Warning (umrahmter Warnhinweis))

…LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Oxycodone hydrochloride tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to… (Fachinformation zu Oxycodon und Paracetamol, Boxed Warning (umrahmter Warnhinweis))

Risks From Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Oxymorphon, Boxed Warning (umrahmter Warnhinweis))

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Paracetamol und Codein, Boxed Warning (umrahmter Warnhinweis))

Strong CYP3A4 Inhibitors : Avoid coadministration of VOTRIENT with strong CYP3A4 inhibitors. (Fachinformation zu Pazopanib, Arzneimittelwechselwirkungen)

…MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Pentazocine and Naloxone Tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to… (Fachinformation zu Pentazocin und Naloxon, Boxed Warning (umrahmter Warnhinweis))

CONTRAINDICATIONS Perphenazine products are contraindicated in comatose or greatly obtunded patients and in patients receiving large doses of central nervous system depressants (barbiturates, alcohol, narcotics, analgesics, or antihistamines); in the presence of existing blood dyscrasias, bone marrow depression, or liver damage; and in patients who have shown… (Fachinformation zu Perphenazin, Gegenanzeigen)

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Pethidin, Boxed Warning (umrahmter Warnhinweis))

Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. (Fachinformation zu Phenelzin, Gegenanzeigen)

CNS depressants: Closely monitor for sedation and respiratory depression. (Fachinformation zu Phenobarbital, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

• Respiratory Depression : May occur with LYRICA when used with concomitant CNS depressants or in the setting of underlying respiratory impairment. (Fachinformation zu Pregabalin, Warnhinweise und Vorsichtsmaßnahmen)

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.). Do not use in pediatric surgery. (Fachinformation zu Prochlorperazin, Gegenanzeigen)

…PROMETHAZINE AND RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Promethazine HCl and Codeine Phosphate Oral Solution exposes patients and other users to the risks… (Fachinformation zu Promethazin und Codein, Boxed Warning (umrahmter Warnhinweis))

• Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (Fachinformation zu Propafenon, Warnhinweise und Vorsichtsmaßnahmen)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Remifentanil, Boxed Warning (umrahmter Warnhinweis))

• Strong CYP3A4 Inhibitors: Avoid concomitant administration. (Fachinformation zu Rimegepant, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Rivaroxaban, Warnhinweise und Vorsichtsmaßnahmen)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fachinformation zu Salmeterol, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Silodosin, Gegenanzeigen)

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) ] . (Fachinformation zu Simvastatin, Gegenanzeigen)

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) ]. (Fachinformation zu Sirolimus, Warnhinweise und Vorsichtsmaßnahmen)

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 )] . (Fachinformation zu Solifenacin, Arzneimittelwechselwirkungen)

Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . (Fachinformation zu Suzetrigin, Gegenanzeigen)

Effect of Other Drugs on TALZENNA Effect of P-gp Inhibitors Breast Cancer Avoid coadministration of TALZENNA with the following P-gp inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil. (Fachinformation zu Talazoparib, Arzneimittelwechselwirkungen)

• Should not be used in combination with strong inhibitors of CYP3A4. (Fachinformation zu Tamsulosin, Warnhinweise und Vorsichtsmaßnahmen)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Tapentadol, Boxed Warning (umrahmter Warnhinweis))

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 ) ] . (Fachinformation zu Thiotepa, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tolvaptan, Gegenanzeigen)

Avoid concomitant use HYCAMTIN capsules with P-gp inhibitors or BCRP inhibitors. (Fachinformation zu Topotecan, Arzneimittelwechselwirkungen)

Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided [see Warnings and Precautions (5.1) ] . (Fachinformation zu Toremifen, Boxed Warning (umrahmter Warnhinweis))

CYP3A inhibitors: Avoid concomitant strong CYP3A inhibitors ( 7.1 ) (Fachinformation zu Trabectedin, Arzneimittelwechselwirkungen)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Tramadol, Boxed Warning (umrahmter Warnhinweis))

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fachinformation zu Tramadol und Paracetamol, Boxed Warning (umrahmter Warnhinweis))

The use of RALDESY Should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic… (Fachinformation zu Trazodon, Warnhinweise und Vorsichtsmaßnahmen)

• Strong CYP3A Inhibitors and Inducers: Avoid coadministration with strong CYP3A inhibitors and inducers. (Fachinformation zu Tretinoin, Arzneimittelwechselwirkungen)

• Effects on Driving and Operating Heavy Machinery : Patients receiving triazolam should be cautioned against driving or operating heavy machinery, as well as avoiding concomitant use with alcohol and other CNS depressant drugs. (Fachinformation zu Triazolam, Warnhinweise und Vorsichtsmaßnahmen)

CONTRAINDICATIONS A known hypersensitivity to phenothiazines, comatose or greatly depressed states due to central nervous system depressants and, in cases of existing blood dyscrasias, bone marrow depression and preexisting liver damage. (Fachinformation zu Trifluoperazin, Gegenanzeigen)

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. (Fachinformation zu Ubrogepant, Gegenanzeigen)

For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. (Fachinformation zu Upadacitinib, Arzneimittelwechselwirkungen)

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (Fachinformation zu Vepdegestrant, Warnhinweise und Vorsichtsmaßnahmen)

Therefore, the concomitant use of strong CYP3A inhibitors with vincristine sulfate should be avoided. (Fachinformation zu Vincristin, Arzneimittelwechselwirkungen)

The use of zaleplon with other sedative-hypnotics at bedtime or the middle of the night is not recommended (see ). (Fachinformation zu Zaleplon, Warnhinweise)

The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended. (Fachinformation zu Zolpidem, Warnhinweise und Vorsichtsmaßnahmen)

P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (Fachinformation zu Afatinib, Arzneimittelwechselwirkungen)

Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants. (Fachinformation zu Allopurinol, Warnhinweise und Vorsichtsmaßnahmen)

CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. (Fachinformation zu Alosetron, Arzneimittelwechselwirkungen)

25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. (Fachinformation zu Aminophyllin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Amlodipin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Amlodipin und Atorvastatin, Arzneimittelwechselwirkungen)

CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Fachinformation zu Amlodipin und Benazepril, Arzneimittelwechselwirkungen)

• 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. (Fachinformation zu Amlodipin und Olmesartan, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Amlodipin und Valsartan, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

LIPITOR plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. (Fachinformation zu Atorvastatin, Arzneimittelwechselwirkungen)

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

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. (Fachinformation zu Bortezomib, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Use with CNS depressants may result in an additive or potentiating effect. (Fachinformation zu Brimonidin, Arzneimittelwechselwirkungen)

Use with CNS depressants may result in an additive or potentiating effect. (Fachinformation zu Brimonidin und Timolol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Budesonid, Warnhinweise und Vorsichtsmaßnahmen)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Fachinformation zu Budesonid und Formoterol, Warnhinweise und Vorsichtsmaßnahmen)

Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. (Fachinformation zu Bupivacain, Warnhinweise und Vorsichtsmaßnahmen)

Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. (Fachinformation zu Bupivacain und Adrenalin, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Triazolam/flurazepam: Coadministration of buspirone with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine. (Fachinformation zu Buspiron, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Chinin, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Ciclesonid, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Cilostazol, Arzneimittelwechselwirkungen)

Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. (Fachinformation zu Cinacalcet, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. (Fachinformation zu Clindamycin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. (Fachinformation zu Darifenacin, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Moderate or strong CYP3A4 inhibitors: Give one third of the recommended dosage of EMFLAZA ( 7.1 ) (Fachinformation zu Deflazacort, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Desogestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Alcohol or other sedating drugs: May have additive sedation and somnolence ( 7.5 ) (Fachinformation zu Deutetrabenazin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of dexlansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Fachinformation zu Dexlansoprazol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Digoxin: Monitor digoxin concentrations ( 7.3 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

…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 organic cation transport,… (Fachinformation zu Dofetilid, Arzneimittelwechselwirkungen)

Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. (Fachinformation zu Doravirin, Arzneimittelwechselwirkungen)

Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. (Fachinformation zu Doxazosin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Effects of Other Drugs on Dronedarone Ketoconazole and Other Potent CYP3A Inhibitors Concomitant use of ketoconazole as well as other potent CYP3A inhibitors such as itraconazole, voriconazole, ritonavir, clarithromycin, and nefazodone is contraindicated because exposure to dronedarone is significantly increased [see Contraindications (4) , Clinical Pharmacology… (Fachinformation zu Dronedaron, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Consider monitoring serum potassium concentration in high-risk patients who take a strong CYP3A4 inhibitor long-term and concomitantly. (Fachinformation zu Drospirenon und Ethinylestradiol, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

P-gp Inhibitors Treatment of NVAF Based on clinical experience from the ENGAGE AF-TIMI 48 study, dose reduction in patients concomitantly receiving P-gp inhibitors resulted in edoxaban blood levels that were lower than in patients who were given the full dose. (Fachinformation zu Edoxaban, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Concomitant Use with CYP3A Inhibitors Exposure to elexacaftor, tezacaftor and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. (Fachinformation zu Elexacaftor, Tezacaftor und Ivacaftor, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. (Fachinformation zu Emtricitabin und Tenofovir, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Emtricitabin, Rilpivirin und Tenofovir, Arzneimittelwechselwirkungen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Estradiol, Arzneimittelwechselwirkungen)

…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,… (Fachinformation zu Estradiol und Dienogest, Arzneimittelwechselwirkungen)

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. (Fachinformation zu Estradiol und Norethisteron, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Etonogestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Felodipin, Arzneimittelwechselwirkungen)

Concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) via P-gp inhibition; however, concomitant P-gp inhibitor use had no attributable effect on safety or treatment outcome of fidaxomicin-treated adult patients in controlled clinical trials. (Fachinformation zu Fidaxomicin, Arzneimittelwechselwirkungen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

• CYP3A4 Inhibitor: Monitor adverse reactions if concomitant use with IRESSA. (Fachinformation zu Gefitinib, Arzneimittelwechselwirkungen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Hydrocortison, Arzneimittelwechselwirkungen)

• CYP3A4 Inhibitors: Use in combination with CYP3A4 inhibitors could decrease the effectiveness of ifosfamide. (Fachinformation zu Ifosfamid, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Potential for other drugs to affect ivacaftor CYP3A inhibitors: Reduce KALYDECO dosage in patients aged 6 months and older when co-administered with strong CYP3A inhibitors (e.g., ketoconazole) or moderate CYP3A inhibitors (e.g., fluconazole). (Fachinformation zu Ivacaftor, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Konjugierte Estrogene und Bazedoxifen, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Fachinformation zu Lansoprazol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Levonorgestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. (Fachinformation zu Lidocain und Adrenalin, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Loperamid, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Mefloquin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Concurrent use of metyrosine with alcohol or other CNS depressants can increase their sedative effects. (Fachinformation zu Metirosin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

…mifepristone is contraindicated. [See Contraindications (4.3)] 5.6 Use of Strong CYP3A Inhibitors Mifepristone should be used with caution in patients taking ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole,… (Fachinformation zu Mifepriston, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Fachinformation zu Mometason, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Naldemedin, Arzneimittelwechselwirkungen)

WARNINGS AND PRECAUTIONS Risk of Recurrent Respiratory and CNS Depression : Due to the duration of action of naloxone relative to the opioid, respiratory and CNS depression may recur after the first dose of naloxone. (Fachinformation zu Naloxon, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (Fachinformation zu Naproxen und Esomeprazol, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

…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. (Fachinformation zu Nifedipin, Arzneimittelwechselwirkungen)

Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. (Fachinformation zu Nintedanib, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Norelgestromin und Ethinylestradiol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Norethisteron, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. (Fachinformation zu Norethisteron und Ethinylestradiol, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Norgestimat und Ethinylestradiol, Arzneimittelwechselwirkungen)

Concomitant administration of CYP3A4 inhibitors such as itraconazole, fluconazole, grapefruit juice or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Norgestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

• Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): • Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. (Fachinformation zu Olmesartan, Amlodipin und Hydrochlorothiazid, Arzneimittelwechselwirkungen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Fachinformation zu Omeprazol, Arzneimittelwechselwirkungen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Fachinformation zu Omeprazol und Natriumhydrogencarbonat, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Exposure of Paricalcitol Injection will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . (Fachinformation zu Paricalcitol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Prednisolon, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Prednison, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Primaquin, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co‑administered. (Fachinformation zu Repaglinid, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

• Concomitant P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine): Caution should be exercised when concomitant use of XIFAXAN and a P-glycoprotein inhibitor is needed. (Fachinformation zu Rifaximin, Warnhinweise und Vorsichtsmaßnahmen)

Coadministration of EDURANT or EDURANT PED and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine. (Fachinformation zu Rilpivirin, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Roflumilast, Arzneimittelwechselwirkungen)

• Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). (Fachinformation zu Romidepsin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Ropivacain, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (Fachinformation zu Saxagliptin, Arzneimittelwechselwirkungen)

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (Fachinformation zu Saxagliptin und Metformin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin) increase SILDENAFIL ORAL FILM exposure. (Fachinformation zu Sildenafil, Arzneimittelwechselwirkungen)

Monitor QT interval more frequently when SUTENT is concomitantly administered with strong CYP3A4 inhibitors or drugs known to prolong QT interval. (Fachinformation zu Sunitinib, Warnhinweise und Vorsichtsmaßnahmen)

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (Fachinformation zu Tacrolimus, Warnhinweise und Vorsichtsmaßnahmen)

…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 )] . (Fachinformation zu Tadalafil, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Telmisartan und Amlodipin, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Temsirolimus, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. (Fachinformation zu Theophyllin, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Tinidazol, Arzneimittelwechselwirkungen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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 ). (Fachinformation zu Tolterodin, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Triamcinolon, Arzneimittelwechselwirkungen)

Concurrent use of alcohol or other CNS depressants with trihexyphenidyl may cause increased sedative effects. (Fachinformation zu Trihexyphenidyl, Arzneimittelwechselwirkungen)

The recent use of other drugs that cause CNS depression or EPS symptoms may also increase the risk; consider reducing the dosage or discontinuing the drug. (Fachinformation zu Trimethobenzamid, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Ulipristal, Arzneimittelwechselwirkungen)

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,… (Fachinformation zu Umeclidiniumbromid und Vilanterol, Warnhinweise und Vorsichtsmaßnahmen)

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 )] . (Fachinformation zu Valbenazin, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Vardenafil, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

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) ]. (Fachinformation zu Viloxazin, Arzneimittelwechselwirkungen)

Inhibitors of CYP3A4: May cause earlier onset and/or increased severity of adverse reactions ( 7.1 ) (Fachinformation zu Vinorelbin, Arzneimittelwechselwirkungen)

Eszopiclone (CYP3A4 Inhibition) Not Studied In Vivo or In Vitro , but Drug Plasma Exposure Likely to be Increased which may Increase the Sedative Effect of Eszopiclone Dose reduction of eszopiclone is recommended. (Fachinformation zu Voriconazol, Arzneimittelwechselwirkungen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. (Fachinformation zu Warfarin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Zafirlukast, Vorsichtsmaßnahmen)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Fachinformation zu Suvorexant, Warnhinweise und Vorsichtsmaßnahmen)

Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. (Fachinformation zu Dapagliflozin, Arzneimittelwechselwirkungen)

Antihistamines Amphetamines may counteract the sedative effect of antihistamines. (Fachinformation zu Dexamfetamin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Disopyramid, Arzneimittelwechselwirkungen)

In Drug-Induced CNS and Respiratory Depression Doxapram alone may not stimulate adequate spontaneous breathing or provide sufficient arousal in patients who are severely depressed either due to respiratory failure or to CNS depressant drugs, but may be used as an adjunct to established supportive measures and resuscitative techniques. (Fachinformation zu Doxapram, Warnhinweise)

The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. (Fachinformation zu Dutasterid, Arzneimittelwechselwirkungen)

The “gasping syndrome” is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations. (Fachinformation zu Epoetin alfa, Warnhinweise und Vorsichtsmaßnahmen)

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

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes. (Fachinformation zu Famciclovir, Arzneimittelwechselwirkungen)

Effect of SUNLENCA on Other Drugs Lenacapavir is a moderate inhibitor of CYP3A. (Fachinformation zu Lenacapavir, Arzneimittelwechselwirkungen)

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 . (Fachinformation zu Memantin und Donepezil, Arzneimittelwechselwirkungen)

…to date with the following: (1) cardiac glycosides– digitalis and digoxin; (2) hypoglycemics–insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; (3) tranquilizers and sedatives–chlordiazepoxide, diazepam, and phenobarbital; (4) antigout–allopurinol, colchicine, and probenecid; (5) antiarrhythmics–procainamide, propranolol (see WARNINGS however),… (Fachinformation zu Prazosin, Arzneimittelwechselwirkungen)

Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Concomitant use of ASPRUZYO Sprinkle with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir is contraindicated [see Contraindications (4), Clinical Pharmacology (12.3)]. (Fachinformation zu Ranolazin, Arzneimittelwechselwirkungen)

Clinically Significant Interactions Affecting Other Drugs CYP3A Substrates Where Small Concentration Changes May Lead to Serious Adverse Reactions Clinical Impact Ritlecitinib is a CYP3A inhibitor. (Fachinformation zu Ritlecitinib, Arzneimittelwechselwirkungen)

However, no formal drug-drug interaction studies between zileuton and CYP3A4 inhibitors, such as ketaconazole, have been conducted. (Fachinformation zu Zileuton, Arzneimittelwechselwirkungen)

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) .]… (Fachinformation zu Desloratadin, Arzneimittelwechselwirkungen)

…adjustment is needed when SINGULAIR is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, fexofenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3) ]. (Fachinformation zu Montelukast, Arzneimittelwechselwirkungen)