Wechselwirkungen von Valproinsäure

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)

• Effects on Driving and Operating Machinery: Patients receiving • alprazolam XR should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs. (Fachinformation zu Alprazolam, Warnhinweise und Vorsichtsmaßnahmen)

Drug Class Drugs within class that are contraindicated with REYATAZ Alpha 1-adrenoreceptor antagonist Alfuzosin Anticonvulsants Carbamazepine, phenobarbital, phenytoin Antiarrhythmics Amiodarone (with ritonavir), quinidine (with ritonavir) Antimycobacterials Rifampin Antineoplastics Apalutamide, encorafenib, irinotecan, ivosidenib Antipsychotics Lurasidone (with… (Fachinformation zu Atazanavir, Gegenanzeigen)

• 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))

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

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))

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)] . (Fachinformation zu Bupropion, Gegenanzeigen)

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))

…diphosphate glucuronosyltransferase (UGT)1A1 enzyme induction, which may result in loss of virologic response [see Drug Interactions ( 7.2 , 7.3 ), Clinical Pharmacology ( 12.3 )] : o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin o Antimycobacterials: Rifampin, rifapentine Prior to initiation of VOCABRIA, note that use of CABENUVA (cabotegravir… (Fachinformation zu Cabotegravir, Gegenanzeigen)

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

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

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)

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

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)

If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. (Fachinformation zu Chinin, Arzneimittelwechselwirkungen)

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)

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

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

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))

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)

…elbasvir/grazoprevir Lipid 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… (Fachinformation zu Darunavir, Gegenanzeigen)

Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Anti-gout: colchicine, in patients with renal and/or hepatic impairment Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Cardiac Disorders: dronedarone, ivabradine, ranolazine Ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine… (Fachinformation zu Darunavir und Cobicistat, Gegenanzeigen)

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)

These drugs include, but are not limited to, the following: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin the androgen receptor inhibitor enzalutamide the antimycobacterials rifampin, rifapentine the cytotoxic agent mitotane St. (Fachinformation zu Doravirin, Gegenanzeigen)

Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine Herbal Products: St. (Fachinformation zu Elvitegravir, Cobicistat, Emtricitabin und Tenofovir, Gegenanzeigen)

…virologic response and possible resistance to COMPLERA or to the class of NNRTIs [see Warnings and Precautions (5.7) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ]: Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin Antimycobacterials: rifampin, rifapentine Glucocorticoid (systemic): dexamethasone (more than a single-dose)… (Fachinformation zu Emtricitabin, Rilpivirin und Tenofovir, Gegenanzeigen)

The concomitant use of ertapenem and valproic acid/divalproex sodium is generally not recommended. (Fachinformation zu Ertapenem, Warnhinweise und Vorsichtsmaßnahmen)

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

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)

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

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

• 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))

…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)

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

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. (Fachinformation zu Valproinsäure, 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, 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)

The concomitant use of PRIMAXIN and valproic acid/divalproex sodium is generally not recommended ( 5.3 , 7.3 ). (Fachinformation zu Imipenem und Cilastatin, Warnhinweise und Vorsichtsmaßnahmen)

To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made 5,6 . (Fachinformation zu Isoniazid, Arzneimittelwechselwirkungen)

Anticonvulsants Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. (Fachinformation zu Itraconazol, Arzneimittelwechselwirkungen)

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

This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. (Fachinformation zu Ketoconazol, Gegenanzeigen)

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

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

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

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))

…Non-opioid Analgesic (selective blocker of Nav1.8 sodium channels): suzetrigine PDE5 Inhibitor: sildenafil (Revatio ® ) when used for the treatment of pulmonary arterial hypertension Sedative/Hypnotics: triazolam, orally administered midazolam KALETRA is contraindicated with drugs that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations… (Fachinformation zu Lopinavir und Ritonavir, Gegenanzeigen)

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)

Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid The concomitant use of meropenem and valproic acid or divalproex sodium is generally not recommended. (Fachinformation zu Meropenem, Warnhinweise und Vorsichtsmaßnahmen)

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

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))

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))

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)

…(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). (Fachinformation zu Naltrexon und Bupropion, Gegenanzeigen)

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

…(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… (Fachinformation zu Nirmatrelvir und Ritonavir, 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 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)

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. (Fachinformation zu Valproinsäure, 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 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))

…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))

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. (Fachinformation zu Valproinsäure, 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 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)

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

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

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

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

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

…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))

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))

Table 2: Drugs That are Contraindicated with EDURANT and EDURANT PED Drug Class Contraindicated Drugs in Class Clinical Comment Anticonvulsants Carbamazepine Oxcarbazepine Phenobarbital Phenytoin Potential for significant decreases in rilpivirine plasma concentrations due to CYP3A enzyme induction, which may result in loss of virologic response. (Fachinformation zu Rilpivirin, Gegenanzeigen)

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… (Fachinformation zu Ritonavir, Boxed Warning (umrahmter Warnhinweis))

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

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (Fachinformation zu Sofosbuvir und Velpatasvir, 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 Tapentadol, Boxed Warning (umrahmter Warnhinweis))

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

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

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))

• 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)

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

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

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)

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

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. (Fachinformation zu Acetazolamid, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Albendazol, Warnhinweise und Vorsichtsmaßnahmen)

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)

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

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Amoxapine may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. (Fachinformation zu Amoxapin, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

…cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Monoamine Oxidase Inhibitors, Nonselective Beta-Adrenergic… (Fachinformation zu Articain und Adrenalin, Arzneimittelwechselwirkungen)

In addition, valproic acid and lithium pre-dose serum concentrations collected from an adjunctive therapy study were comparable between asenapine-treated patients and placebo-treated patients indicating a lack of effect of asenapine on valproic and lithium plasma levels. (Fachinformation zu Asenapin, Arzneimittelwechselwirkungen)

Patients should also be cautioned that the central nervous system depressant effects of intrathecal baclofen may be additive to those of alcohol and other CNS depressants. (Fachinformation zu Baclofen, Warnhinweise und Vorsichtsmaßnahmen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Sedatives/Hypnotics: midazolam (oral) triazolam ↑ midazolam (oral) ↑ triazolam Use caution when midazolam or triazolam is concomitantly administered with BIXLENVO. (Fachinformation zu Bictegravir, Emtricitabin und Tenofoviralafenamid, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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)

Central Nervous System (CNS) depressants Antihistamines have additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, antianxiety agents, etc.). Antihypertensive drugs Sympathomimetic may reduce the effects of antihypertensive drugs. (Fachinformation zu Brompheniramin, Pseudoephedrin und Dextromethorphan, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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)

Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets [see Warnings and Precautions (5.3) , Drug Interactions (7) ] . (Fachinformation zu Buprenorphin und Naloxon, 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)

All patients receiving concomitant barbiturate therapy should be closely monitored for neurological toxicity. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

All patients receiving concomitant barbiturate therapy should be closely monitored for neurological toxicity. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

• Additive sedative effects when used with other CNS depressants including alcohol (5.1) (Fachinformation zu Carisoprodol, Warnhinweise und Vorsichtsmaßnahmen)

The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Fachinformation zu Chlordiazepoxid, Warnhinweise)

Effects on the Ability to Drive or Operate Machinery As in the case of other preparations containing CNS-acting drugs, patients receiving Librax should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. (Fachinformation zu Chlordiazepoxid und Clidiniumbromid, Warnhinweise)

…procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine (Fachinformation zu Chloroprocain, Vorsichtsmaßnahmen)

Chlorpromazine A study involving the administration of 100 to 300 mg/day of chlorpromazine to schizophrenic patients already receiving valproate (200 mg BID) revealed a 15% increase in trough plasma levels of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Chlorzoxazone use should also be discontinued if a patient develops abnormal liver enzymes (e.g., AST, ALT, alkaline phosphatase and bilirubin.) The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Fachinformation zu Chlorzoxazon, Warnhinweise und Vorsichtsmaßnahmen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations Antibiotics Anticonvulsants Other Drugs/Dietary Supplements nafcillin carbamazepine bosentan St. (Fachinformation zu Ciclosporin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Clarithromycin, Arzneimittelwechselwirkungen)

Use with CNS Depressants Clemastine has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.). Use in Activities Requiring Mental Alertness Patients should be warned about engaging in activities requiring mental alertness such as driving a car or operating appliances, machinery, etc. (Fachinformation zu Clemastin, Warnhinweise)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Cholestyramine Cholestyramine, when concurrently administered with valproic acid, led to, on average, a 14% decrease in plasma levels of valproic acid in a study conducted in 6 healthy subjects administered valproic acid oral solution and cholestyramine. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

CNS Depressants Antihistamines may have additive effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, tranquilizers, antianxiety agents. (Fachinformation zu Cyproheptadin, Warnhinweise)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Risk increases when used with other central nervous system (CNS) depressants. (Fachinformation zu Daridorexant, Warnhinweise und Vorsichtsmaßnahmen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Use with CNS Depressants CORPHENA Oral Solution has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.). Use in Activities Requiring Mental Alertness Patients should be warned about engaging in activities requiring mental alertness such as driving a car or operating appliances, machinery, etc. (Fachinformation zu Dexchlorpheniramin, Warnhinweise)

Co-administration of valproate (1,500 mg daily) increased the free fraction of diazepam (10 mg) by 90% in healthy volunteers (n = 6). (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Exercise caution when prescribing ZIPSOR with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics). (Fachinformation zu Diclofenac, Warnhinweise und Vorsichtsmaßnahmen)

Exercise caution when prescribing diclofenac sodium/misoprostol with concomitant drugs that are known to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics). (Fachinformation zu Diclofenac und Misoprostol, Warnhinweise und Vorsichtsmaßnahmen)

The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. (Fachinformation zu Dikaliumclorazepat, Warnhinweise)

The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Fachinformation zu Dimenhydrinat, Warnhinweise)

Drug Interactions Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc). (Fachinformation zu Diphenhydramin, Arzneimittelwechselwirkungen)

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose. (Fachinformation zu Doxepin, Warnhinweise und Vorsichtsmaßnahmen)

Barbiturates and Anti-Epileptics Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. (Fachinformation zu Doxycyclin, Arzneimittelwechselwirkungen)

Seizures and Seizure-like Activity : Weigh the potential risk versus benefits before prescribing dronabinol oral solution to patients with a history of seizures, including those requiring anti-epileptic medication or with other factors that lower the seizure threshold. (Fachinformation zu Dronabinol, Warnhinweise und Vorsichtsmaßnahmen)

Following the administration of droperidol, the dose of other CNS depressant drugs should be reduced. (Fachinformation zu Droperidol, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant. (Fachinformation zu Emtricitabin und Tenofovir, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Although behaviors such as sleep-driving may occur with sedative-hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with sedative-hypnotics appears to increase the risk of such behaviors, as does the use of sedative-hypnotics at doses exceeding the maximum recommended dose. (Fachinformation zu Estazolam, Warnhinweise)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Anticonvulsants - In a pharmacokinetic study, maximum plasma concentrations of felodipine were considerably lower in epileptic patients on long-term anticonvulsant therapy (e.g., phenytoin, carbamazepine, or phenobarbital) than in healthy volunteers. (Fachinformation zu Felodipin, Arzneimittelwechselwirkungen)

Exacerbated by other CNS depressants, and in settings where flibanserin concentrations are increased. (Fachinformation zu Flibanserin, Warnhinweise und Vorsichtsmaßnahmen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Possible risk factors for seizures include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent cyclic antidepressant poisoning. (Fachinformation zu Flumazenil, Warnhinweise)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) (Fachinformation zu Fluoxetin, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Effects of VYKOURA on Other Drugs Certain Antiepileptic Drugs Increase monitoring for seizure activity in patients taking certain concomitant antiepileptic drugs. (Fachinformation zu Folinsäure (Leucovorin), Arzneimittelwechselwirkungen)

Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population . (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Corticosteroids, valproic acid, or haloperidol : May increase plasma ammonia level; monitor ammonia levels closely. (Fachinformation zu Glycerolphenylbutyrat, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Glycopyrroniumbromid, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Strong CYP3A4 Inducers Exposure to irinotecan or its active metabolite SN-38 is substantially reduced in adult and pediatric patients concomitantly receiving the CYP3A4 enzyme-inducing anticonvulsants phenytoin, phenobarbital, carbamazepine, or St. (Fachinformation zu Irinotecan, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ ledipasvir ↓ sofosbuvir Coadministration of ledipasvir and sofosbuvir with carbamazepine, phenytoin, or phenobarbital is expected to decrease the concentration of ledipasvir and sofosbuvir, leading to reduced therapeutic effect of ledipasvir and sofosbuvir. (Fachinformation zu Ledipasvir und Sofosbuvir, Arzneimittelwechselwirkungen)

Risk increases with dose and use with other central nervous system (CNS) depressants. (Fachinformation zu Lemborexant, Warnhinweise und Vorsichtsmaßnahmen)

Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ lenacapavir Concomitant administration of carbamazepine, oxcarbazepine, phenobarbital, or phenytoin may result in loss of therapeutic effect and development of resistance. (Fachinformation zu Lenacapavir, Arzneimittelwechselwirkungen)

Effects of Leucovorin Products on Other Drugs Antiepileptic Drugs Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the frequency of seizures in susceptible children. (Fachinformation zu Levofolinsäure (Levoleucovorin), Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, 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)

…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 (Fachinformation zu Lidocain und Prilocain, Arzneimittelwechselwirkungen)

Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs : Lofexidine tablets potentiates the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs. (Fachinformation zu Lofexidin, Warnhinweise und Vorsichtsmaßnahmen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

• Coadministration of meclizine hydrochloride with other CNS depressants, including alcohol, may result in increased CNS depression ( 7.1 ). (Fachinformation zu Meclozin, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Anticonvulsants In patients taking an anticonvulsant (e.g., valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of mefloquine may reduce seizure control by lowering the plasma levels of the anticonvulsant. (Fachinformation zu Mefloquin, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

…procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine (Fachinformation zu Mepivacain, Arzneimittelwechselwirkungen)

Additive Effects Since the effects of meprobamate and alcohol or meprobamate and other CNS depressants or psychotropic drugs may be additive,appropriate caution should be exercised with patients who take more than one of these agents simultaneously. (Fachinformation zu Meprobamat, Warnhinweise)

Patients receiving ATMEKSI (methocarbamol) Oral Suspension should be cautioned about combined effects with alcohol and other CNS depressants [ see Drug Interactions (7.1) ]. (Fachinformation zu Methocarbamol, Warnhinweise und Vorsichtsmaßnahmen)

All patients receiving concomitant barbiturate therapy should be closely monitored for neurological toxicity. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, 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)

Valproic Acid, Haloperidol, or Corticosteroids : May increase plasma ammonia level; monitor ammonia levels closely. (Fachinformation zu Natriumphenylbutyrat, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Valproic acid may increase the exposure to nifedipine during concomitant therapy. (Fachinformation zu Nifedipin, Vorsichtsmaßnahmen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Co-administration of valproate (500 mg BID) and olanzapine (5 mg) to healthy adults (n=10) caused 15% reduction in C max and 35% reduction in AUC of olanzapine. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Co-administration of valproate (500 mg BID) and olanzapine (5 mg) to healthy adults (n=10) caused 15% reduction in C max and 35% reduction in AUC of olanzapine. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Patients should be warned that the effects of alcohol or other CNS-depressant drugs may be additive to those of Oxazepam, possibly requiring adjustment of dosage or elimination of such agents. (Fachinformation zu Oxazepam, Warnhinweise)

If the patient is being treated with an anticonvulsant agent, increased dosage of that agent may be required when perphenazine products are used concomitantly. (Fachinformation zu Perphenazin, Warnhinweise)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Concomitant Use with Midazolam : Noxafil can prolong hypnotic/sedative effects. (Fachinformation zu Posaconazol, Warnhinweise und Vorsichtsmaßnahmen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

…cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine The administration of local anesthetic injections containing… (Fachinformation zu Prilocain und Adrenalin, Arzneimittelwechselwirkungen)

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. (Fachinformation zu Prochlorperazin, Vorsichtsmaßnahmen)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine… (Fachinformation zu Promethazin, Warnhinweise)

The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine… (Fachinformation zu Promethazin und Dextromethorphan, Warnhinweise)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. (Fachinformation zu Protriptylin, Arzneimittelwechselwirkungen)

The use of alcohol and other CNS depressants may increase the risk of such behaviors. (Fachinformation zu Ramelteon, Warnhinweise und Vorsichtsmaßnahmen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Rifampin A study involving the administration of a single dose of valproate (7 mg/kg) 36 hours after 5 nights of daily dosing with rifampin (600 mg) revealed a 40% increase in the oral clearance of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproate therapy is instituted in patients taking anticoagulants. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Reduced Rocuronium Bromide Injection activity possible : Anticonvulsants. (Fachinformation zu Rocuronium, Arzneimittelwechselwirkungen)

…cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine NAROPIN should be used with caution in patients receiving… (Fachinformation zu Ropivacain, Arzneimittelwechselwirkungen)

Inhibitors of Folate Synthesis (e.g., methotrexate, valproic acid, phenobarbital, trimethoprim) Clinical Impact In vitro and in vivo nonclinical data suggest that drugs that inhibit folate synthesis may decrease the bioavailability of endogenous BH4 by inhibiting the enzyme dihydrofolate reductase, which is involved in the recycling (regeneration) of BH4. (Fachinformation zu Sapropterin, Arzneimittelwechselwirkungen)

Weigh this potential risk against the benefits before prescribing TRANSDERM SCŌP to patients with a history of seizures, including those receiving anti-epileptic medication or who have risk factors that can lower the seizure threshold. (Fachinformation zu Scopolamin, 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)

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Strong CYP3A Inducers c : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.10 )]. (Fachinformation zu Tacrolimus, Arzneimittelwechselwirkungen)

Although behaviors such as “sleep-driving” may occur with temazepam capsules alone at therapeutic doses, the use of alcohol and other CNS depressants with temazepam capsules appear to increase the risk of such behaviors, as does the use of temazepam capsules at doses exceeding the maximum recommended dose. (Fachinformation zu Temazepam, Warnhinweise)

Alcohol or Other Sedating Drugs Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence [see Warnings and Precautions (5.7) ] . (Fachinformation zu Tetrabenazin, Arzneimittelwechselwirkungen)

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

Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed ( 7.1, 7.2 ) (Fachinformation zu Tinidazol, Arzneimittelwechselwirkungen)

Sedation: Zanaflex may interfere with everyday activities; sedative effects of Zanaflex, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 ) (Fachinformation zu Tizanidin, Warnhinweise und Vorsichtsmaßnahmen)

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)… (Fachinformation zu Tranylcypromin, Arzneimittelwechselwirkungen)

Intervention: Patients should be counseled that RALDESY may enhance the response to alcohol, barbiturates, and other CNS depressants. (Fachinformation zu Trazodon, Arzneimittelwechselwirkungen)

Oral Contraceptive Steroids Administration of a single-dose of ethinyloestradiol (50 mcg)/levonorgestrel (250 mcg) to 6 women on valproate (200 mg BID) therapy for 2 months did not reveal any pharmacokinetic interaction. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. (Fachinformation zu Trifluoperazin, Vorsichtsmaßnahmen)

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)

Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Drug Interactions The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. (Fachinformation zu Vincristin, 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)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Anticonvulsant therapy can be given if clinically indicated. (Fachinformation zu Cefalexin, Warnhinweise und Vorsichtsmaßnahmen)

Anticonvulsant therapy should be continued in patients with known seizure disorders. (Fachinformation zu Cefazolin, Warnhinweise und Vorsichtsmaßnahmen)

Cimetidine and Ranitidine Cimetidine and ranitidine do not affect the clearance of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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

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

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

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

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

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

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)

Concurrent use of alcohol and other CNS depressants (such as hypnotic sedatives and tranquilizers) with doxylamine succinate and pyridoxine hydrochloride delayed-release tablets is not recommended. (Fachinformation zu Doxylamin und Pyridoxin, Arzneimittelwechselwirkungen)

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

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

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

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

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

Antiepileptics The activity of antiepileptic drugs might be impaired if co-administered with PLAQUENIL. (Fachinformation zu Hydroxychloroquin, Arzneimittelwechselwirkungen)

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

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

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

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

Effect on Ketone and Thyroid Function Tests Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Effect on Ketone and Thyroid Function Tests Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Effect on Ketone and Thyroid Function Tests Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Therefore, ambulatory patients should be warned about activities requiring alertness (e.g., operating vehicles or machinery) and about concomitant use of alcohol and other CNS depressants. (Fachinformation zu Loxapin, Warnhinweise)

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Anticonvulsants, psychotropic, hormone preparations, corticosteroids, antithyroid agents, cyproheptadine: may affect the results of the metyrapone test. (Fachinformation zu Metyrapon, Arzneimittelwechselwirkungen)

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

There have been reports that valproic acid can induce hyperammonemia through inhibition of the synthesis of N-acetylglutamate, a co-factor for carbamyl phosphate synthetase. (Fachinformation zu Natriumphenylacetat und Natriumbenzoat, Arzneimittelwechselwirkungen)

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

Moderate and weak CYP3A4 inhibitors include alprozalam, ameprenavir, amiodarone, aprepitant, atazanavir, cimetidine, cyclosporine, diltiazem, erythromycin, fluconazole, fluoxetine, isoniazid, oral contraceptives, quinuprestin/dalfopristin, valproic acid, and verapamil. (Fachinformation zu Nimodipin, Arzneimittelwechselwirkungen)

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

Effect on Ketone and Thyroid Function Tests Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Cimetidine and Ranitidine Cimetidine and ranitidine do not affect the clearance of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

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

Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

Effect on Ketone and Thyroid Function Tests Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

These data suggest that GH may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, and cyclosporine). (Fachinformation zu Tesamorelin, Arzneimittelwechselwirkungen)

Effect on Ketone and Thyroid Function Tests Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. (Fachinformation zu Valproinsäure, Warnhinweise und Vorsichtsmaßnahmen)

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

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

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

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

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed Antacids A study involving the co-administration of valproate 500 mg with commonly administered antacids (Maalox, Trisogel, and Titralac - 160 mEq doses) did not reveal any effect on the extent of absorption of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Clozapine In psychotic patients (n = 11), no interaction was observed when valproate was co-administered with clozapine. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Haloperidol A study involving the administration of 6 to 10 mg/day of haloperidol to schizophrenic patients already receiving valproate (200 mg BID) revealed no significant changes in valproate trough plasma levels. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Lithium Co-administration of valproate (500 mg BID) and lithium carbonate (300 mg TID) to normal male volunteers (n = 16) had no effect on the steady-state kinetics of lithium. (Fachinformation zu Valproinsäure, 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)

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed Antacids A study involving the co-administration of valproate 500 mg with commonly administered antacids (Maalox, Trisogel, and Titralac - 160 mEq doses) did not reveal any effect on the extent of absorption of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed Antacids A study involving the co-administration of valproate 500 mg with commonly administered antacids (Maalox, Trisogel, and Titralac - 160 mEq doses) did not reveal any effect on the extent of absorption of valproate. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed Acetaminophen Valproate had no effect on any of the pharmacokinetic parameters of acetaminophen when it was concurrently administered to three epileptic patients. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)

Drugs for which either no interaction or a likely clinically unimportant interaction has been observed Acetaminophen Valproate had no effect on any of the pharmacokinetic parameters of acetaminophen when it was concurrently administered to three epileptic patients. (Fachinformation zu Valproinsäure, Arzneimittelwechselwirkungen)