Perampanel interactions

Patients taking FYCOMPA should avoid the use of alcohol [see Drug Interactions (7.3) ] . (Perampanel label, Warnings and precautions)

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

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

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

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

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

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

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. (Buprenorphine label, Boxed warning)

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions (5.3) and Drug Interactions (7.3)] . (Bupropion label, Contraindications)

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. (Butorphanol label, Boxed warning)

Avoid concurrent use of QUZYTTIR with alcohol or other CNS depressants because additional reduction in alertness and additional impairment of CNS performance may occur. (Cetirizine label, Warnings and precautions)

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 )]. (Ciprofloxacin label, Drug interactions)

Avoid use with other central nervous system (CNS) depressants ( 5.3 ) (Clonidine label, Warnings and precautions)

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. (Codeine label, Boxed warning)

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

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… (Cyclobenzaprine label, Drug interactions)

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

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

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

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. (Divalproex (valproate) label, Boxed warning)

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

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

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

The use of LUNESTA with other sedative-hypnotics at bedtime or the middle of the night is not recommended. (Eszopiclone label, Warnings and precautions)

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

IT IS NOT KNOWN WHETHER CONCOMITANT USE OF OTHER ANTIEPILEPTIC DRUGS AND/OR OTHER DRUGS AFFECT THE INCIDENCE OF HEPATIC FAILURE. (Felbamate label, Boxed warning)

• 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. (Fentanyl label, Boxed warning)

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

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

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

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

Seizures: HALDOL DECANOATE is generally not recommended in patients receiving antiseizure drugs or who have a history of seizures or EEG abnormalities. (Haloperidol label, Warnings and precautions)

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. (Hydrocodone and acetaminophen label, Boxed warning)

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 . (Hydromorphone label, Boxed warning)

Rarely, cardiac arrests and death have been reported in association with the combined use of hydroxyzine hydrochloride intramuscularly and other CNS depressants. (Hydroxyzine label, Precautions)

To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made 5,6 . (Isoniazid label, Drug interactions)

Anticonvulsants Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. (Itraconazole label, Drug interactions)

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

Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death. (Ketamine label, Drug interactions)

This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. (Ketoconazole label, Contraindications)

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

Avoid concurrent use of alcohol or other central nervous system depressants with XYZAL. (Levocetirizine label, Warnings and precautions)

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. (Levorphanol label, Boxed warning)

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 ) (Lorazepam label, Warnings and precautions)

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

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

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

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. (Meperidine label, Boxed warning)

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 )]. (Methadone label, Boxed warning)

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 ResuscitationOnly personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer… (Midazolam label, Boxed warning)

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. (Morphine label, Boxed warning)

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. (Nalbuphine label, Boxed warning)

…(e.g., buprenorphine) use, or acute opiate withdrawal [see Warnings and Precautions (5.4) and Drug Interactions (7.2) ] Patients undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions (5.3) and Drug Interactions (7.7) ] Concomitant administration of monoamine oxidase inhibitors (MAOI). (Naltrexone and bupropion label, Contraindications)

…(selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial hypertension (PAH) • Sedative/hypnotics: triazolam, oral midazolam • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin • Vasopressin receptor antagonists: tolvaptan ➢ Drugs that… (Nirmatrelvir and ritonavir label, Contraindications)

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

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. (Oliceridine label, Boxed warning)

Avoid concurrent use of alcohol or other central nervous system depressants with olopatadine hydrochloride nasal spray ( 5.2 ). (Olopatadine label, Warnings and precautions)

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. (Oxycodone label, Boxed warning)

…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… (Oxycodone and acetaminophen label, Boxed warning)

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. (Oxymorphone label, Boxed warning)

…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… (Pentazocine and naloxone label, Boxed warning)

Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. (Phenelzine label, Contraindications)

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

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

WARNING: DRUG-DRUG INTERACTIONS LEADING TO POTENTIALLY SERIOUS AND/OR LIFE THREATENING REACTIONS Co-administration of NORVIR with several classes of drugs including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism… (Ritonavir label, Boxed warning)

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

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

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

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

Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )]. (Sodium oxybate label, Boxed warning)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (Sofosbuvir and velpatasvir label, Drug interactions)

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

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

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. (Tapentadol label, Boxed warning)

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. (Tramadol label, Boxed warning)

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… (Trazodone label, Warnings and precautions)

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

• 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. (Triazolam label, Warnings and precautions)

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

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

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. (Valproic acid label, Boxed warning)

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

The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended. (Zolpidem label, Warnings and precautions)

By decreasing the gastrointestinal absorption of primidone, acetazolamide may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. (Acetazolamide label, Drug interactions)

Risk of Neurologic Symptoms: Neurocysticercosis patients may experience cerebral hypertensive episodes, seizures or focal neurologic deficits after initiation of therapy; begin appropriate steroid and anticonvulsant therapy. (Albendazole label, Warnings and precautions)

Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants. (Allopurinol label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

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

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Anticonvulsants Salicylic acid can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels. (Aspirin and dipyridamole label, Drug interactions)

LIPITOR plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. (Atorvastatin label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Use with CNS depressants may result in an additive or potentiating effect. (Brimonidine label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Triazolam/flurazepam: Coadministration of buspirone with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine. (Buspirone label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Antiepileptics: Carbamazepine Use With Caution Carbamazepine: Concomitant administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. (Clarithromycin label, Drug interactions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations Antibiotics Anticonvulsants Other Drugs/Dietary Supplements nafcillin carbamazepine bosentan St. (Cyclosporine label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. (Darifenacin label, Drug interactions)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

Alcohol or other sedating drugs: May have additive sedation and somnolence ( 7.5 ) (Deutetrabenazine label, Drug interactions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Exercise caution when prescribing Diclofenac Potassium with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics). (Diclofenac label, Warnings and precautions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Barbiturates and Anti-Epileptics Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. (Doxycycline label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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… (Dronedarone label, Drug interactions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

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

Alcohol and Other CNS Depressants The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. (Perampanel label, Drug interactions)

Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant. (Emtricitabine and tenofovir label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. (Everolimus label, Drug interactions)

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

Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) (Fluoxetine label, Drug interactions)

Potential Pimozide Interaction Pimozide is metabolized by the cytochrome P4503A4 isoenzyme, and it has been demonstrated that ketoconazole, a potent inhibitor of CYP3A4, blocks the metabolism of this drug, resulting in increased plasma concentrations of parent drug. (Fluvoxamine label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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). (Ivacaftor label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients with History of Allergy or Rash to Other Antiepileptic Drugs The risk of rash may be increased in patients with a history of allergy or rash to other AEDs. (Lamotrigine label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Strong CYP3A4 inhibitors : Maximum recommended dosage is 80 mg once daily ( 7 ). (Levomilnacipran label, Drug interactions)

Contraceptives With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40% [see Clinical Pharmacology (12.3) ] . (Perampanel label, Drug interactions)

Contraceptives With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40% [see Clinical Pharmacology (12.3) ] . (Perampanel label, Drug interactions)

…prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sufonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine (Lidocaine and prilocaine label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

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

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

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. (Naloxone label, Warnings and precautions)

CYP3A inhibitors such as fluconazole, itraconazole, clarithromycin, erythromycin, nefazodone, fluoxetine, saquinavir, indinavir, and nelfinavir may result in increased exposure to nifedipine when co-administered. (Nifedipine label, Drug interactions)

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

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Drug Interactions and Decreased Vitamin Absorption ORLISTAT may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs [see Drug Interactions (7) ]. (Orlistat label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Alcohol and Other CNS Depressants The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. (Perampanel label, Drug interactions)

• Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. (Pioglitazone label, Drug interactions)

Strong CYP2C8 inhibitors (e.g., gemfibrozil): Limit ACTOPLUS MET dose to 15 mg/850 mg daily. (Pioglitazone and metformin label, Drug interactions)

Concomitant Use with Midazolam : Noxafil can prolong hypnotic/sedative effects. (Posaconazole label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (Perampanel label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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). (Tacrolimus label, Warnings and precautions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. (Theophylline label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed ( 7.1, 7.2 ) (Tinidazole label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

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… (Tofacitinib label, Drug interactions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Excessive reduction of blood glucose (additive effect) f CNS depressant agents (including opioids, alcohol, sedatives, hypnotics) Use with caution d Increased CNS depression Dietary supplements containing sympathomimetics Contraindicated a Antidepressants including but not limited to: Other MAOIs (e.g., linezolid, intravenous methylene blue, selective MAOIs)… (Tranylcypromine label, Drug interactions)

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

Concurrent use of alcohol or other CNS depressants with trihexyphenidyl HCl may cause increased sedative effects. (Trihexyphenidyl label, Drug interactions)

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

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

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

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and ODV. (Venlafaxine label, Drug interactions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors ( 2.4 , 7 ). (Vilazodone label, Drug interactions)

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

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. (Voriconazole label, Drug interactions)

Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. (Warfarin label, Drug interactions)

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

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (Perampanel label, Warnings and precautions)

Anticonvulsant therapy can be given if clinically indicated. (Cephalexin label, Warnings and precautions)

Repaglinide (CYP2C8 Substrates) The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. (Clopidogrel label, Drug interactions)

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

The “gasping syndrome” is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations. (Epoetin alfa label, Warnings and precautions)

Seizures Although anticonvulsant effects of racemic citalopram have been observed in animal studies, Escitalopram Capsules have not been systematically evaluated in patients with a seizure disorder. (Escitalopram label, Warnings and precautions)

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

Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). (Perampanel label, Drug interactions)

Antiepileptics The activity of antiepileptic drugs might be impaired if co-administered with PLAQUENIL. (Hydroxychloroquine label, Drug interactions)

Antiepileptic Drugs Sporadic cases of seizures have been reported during concomitant use of ketorolac tromethamine and antiepileptic drugs (phenytoin, carbamazepine). (Ketorolac label, Drug interactions)

Effect on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . (Leflunomide label, Drug interactions)

Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). (Perampanel label, Drug interactions)

…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),… (Prazosin label, Drug interactions)

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)]. (Ranolazine label, Drug interactions)

Effect of AUBAGIO on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . (Teriflunomide label, Drug interactions)

…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) ]. (Montelukast label, Drug interactions)