Rufinamide interactions

Combining alcohol with sedating medicines (opioids, benzodiazepines, sleep medicines, muscle relaxants) can cause dangerous drowsiness, slowed breathing, and overdose. (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. (Alprazolam label, Warnings and precautions)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Buprenorphine label, Boxed warning)

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

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

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

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

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

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

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

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

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

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

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

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

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Hydrocodone and acetaminophen label, Boxed warning)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

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

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. (Baclofen label, Warnings and precautions)

Sedatives/Hypnotics: midazolam (oral) triazolam ↑ midazolam (oral) ↑ triazolam Use caution when midazolam or triazolam is concomitantly administered with BIXLENVO. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Drug interactions)

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, post menopausal status, tobacco use, advance age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. (Budesonide label, Warnings and precautions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. (Budesonide and formoterol label, Warnings and precautions)

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) ] . (Buprenorphine and naloxone label, Warnings and precautions)

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

Butalbital, acetaminophen and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. (Butalbital, acetaminophen, and caffeine label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

• Additive sedative effects when used with other CNS depressants including alcohol (5.1) (Carisoprodol label, Warnings and precautions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

…Effect Increase by <16 to 70% c) Dependent on concentration of valproate Primidone Not Investigated Decrease by 25 to 46% c) ’ d) Independent of dose or concentration of primidone Benzodiazepines e) Not Investigated No Effect a) Predictions are based on BANZEL concentrations at the maximum recommended dose of BANZEL. b) Maximum changes predicted to be in pediatric… (Rufinamide label, Drug interactions)

Therefore, dosage of anticonvulsants, including barbiturates, should not be reduced if chlorpromazine is started. (Chlorpromazine label, Precautions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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

Risk increases when used with other central nervous system (CNS) depressants. (Daridorexant label, Warnings and precautions)

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

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

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

…Effect Increase by <16 to 70% c) Dependent on concentration of valproate Primidone Not Investigated Decrease by 25 to 46% c) ’ d) Independent of dose or concentration of primidone Benzodiazepines e) Not Investigated No Effect a) Predictions are based on BANZEL concentrations at the maximum recommended dose of BANZEL. b) Maximum changes predicted to be in pediatric… (Rufinamide label, Drug interactions)

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

The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Dimenhydrinate label, Warnings)

Drug Interactions Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc). (Diphenhydramine label, Drug interactions)

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. (Doxepin label, Warnings and precautions)

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

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. (Dronabinol label, Warnings and precautions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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. (Felodipine label, Drug interactions)

Exacerbated by other CNS depressants, and in settings where flibanserin concentrations are increased. (Flibanserin label, Warnings and precautions)

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

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids), should be monitored and treated with established standards of care. (Fluticasone label, Warnings and precautions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. (Fluticasone and salmeterol label, Warnings and precautions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Risk increases with dose and use with other central nervous system (CNS) depressants. (Lemborexant label, Warnings and precautions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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

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. (Lofexidine label, Warnings and precautions)

• Coadministration of meclizine hydrochloride with other CNS depressants, including alcohol, may result in increased CNS depression ( 7.1 ). (Meclizine label, Drug interactions)

MPA Injectable Suspension, USP can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids). (Medroxyprogesterone label, Warnings and precautions)

Patients receiving ATMEKSI (methocarbamol) Oral Suspension should be cautioned about combined effects with alcohol and other CNS depressants [ see Drug Interactions (7.1) ]. (Methocarbamol label, Warnings and precautions)

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care. (Mometasone label, Warnings and precautions)

WARNINGS AND PRECAUTIONS Risk of Recurrent Respiratory and CNS Depression : Due to the duration of action of naloxone relative to the opioid, respiratory and CNS depression may recur after the first dose of naloxone. (Naloxone label, Warnings and precautions)

Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. (Norethindrone label, Drug interactions)

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. (Norgestimate and ethinyl estradiol label, Drug interactions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Phenytoin: The decrease in clearance of phenytoin estimated at typical levels of rufinamide (C avss 15 μg/mL) is predicted to increase plasma levels of phenytoin by 7 to 21%. (Rufinamide label, Drug interactions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. (Prochlorperazine label, Precautions)

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… (Promethazine label, Warnings)

As with other sedative medications, there is wide interpatient variability in DIPRIVAN dosage requirements, and these requirements may change with time. (Propofol label, Warnings and precautions)

The use of alcohol and other CNS depressants may increase the risk of such behaviors. (Ramelteon label, Warnings and precautions)

Effects of Other AEDs on BANZEL Potent cytochrome P450 enzyme inducers, such as carbamazepine, phenytoin, primidone, and phenobarbital, appear to increase the clearance of BANZEL (see Table 6). (Rufinamide label, Drug interactions)

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. (Scopolamine label, Warnings and precautions)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Suvorexant label, Warnings and precautions)

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 )]. (Tacrolimus label, Drug interactions)

…Effect Increase by <16 to 70% c) Dependent on concentration of valproate Primidone Not Investigated Decrease by 25 to 46% c) ’ d) Independent of dose or concentration of primidone Benzodiazepines e) Not Investigated No Effect a) Predictions are based on BANZEL concentrations at the maximum recommended dose of BANZEL. b) Maximum changes predicted to be in pediatric… (Rufinamide label, Drug interactions)

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) ] . (Tetrabenazine label, Drug interactions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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

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 ) (Tizanidine label, Warnings and precautions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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

Intervention: Patients should be counseled that RALDESY may enhance the response to alcohol, barbiturates, and other CNS depressants. (Trazodone label, Drug interactions)

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

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

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

…ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3 . (Warfarin label, Drug interactions)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (Rufinamide label, Drug interactions)

Guanethidine or similarly acting compounds; thyroid medication; alcohol, barbiturates and other CNS depressants; and disulfiram – see WARNINGS section. (Amitriptyline label, Drug interactions)

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

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

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

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

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

John’s Wort [ Hypericum perforatum ]; anticonvulsants: carbamazepine, phenobarbital, phenytoin; efavirenz, nevirapine). (Everolimus label, Drug interactions)

Examples: Anticonvulsants: phenytoin, carbamazepine and oxcarbazepine Antibiotics: rifampicin and rifabutin Barbiturates: phenobarbital and primidone Antiretrovirals: efavirenz and nevirapine Estrogen and Estrogen Containing Products Clinical Impact: Oral estrogen and estrogen-containing oral contraceptives may interact with hydrocortisone by increasing serum… (Hydrocortisone label, Drug interactions)

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

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

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

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

Hormonal contraceptives may be less effective with BANZEL; use additional non-hormonal forms of contraception ( 7.3 ) (Rufinamide label, Drug interactions)

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