Aspirin, ASA; Dipyridamole: (Moderate) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as barbiturates. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. Istradefylline: (Major) Avoid coadministration of istradefylline with primidone as istradefylline exposure and efficacy may be reduced. Glimepiride: (Minor) Barbiturates may induce the CYP2C9 metabolism of glimepiride. If primidone is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. Coadministration with another strong CYP3A4 inducer decreased the overall exposure of tivozanib by 52%. Caution should be exercised during concomitant use of any CNS-depressant drugs and any barbiturate; dosage reduction of one or both agents may be necessary. Triazolam: (Moderate) Additive CNS and/or respiratory depression may occur. Labetalol: (Moderate) Barbiturates can enhance the hepatic metabolism of beta-blockers that are significantly metabolized by the liver, such as labetaolol. Vortioxetine is extensively metabolized by CYP isoenzymes, primarily CYP2D6 and by CYP3A4 and other isoenzymes to a lesser extent. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. Nevirapine: (Moderate) Use caution and monitor for decreased efficacy of nevirapine if coadministered with barbiturates. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Oxazepam: (Moderate) Additive CNS and/or respiratory depression may occur with concurrent use. Hypnotic barbiturates are best avoided during ramelteon therapy; the manufacturer warns against using other medications for sleep concurrently with ramelteon. Admission), barbiturate anticonvulsive drug Primidone, CSIR NET JRF Antiepileptic drugs chemistry notes, Medicinal chemistry anti convulsant drugs lecture notes, CLONAZEPAM Synthesis, SAR, MCQ, Structure, Chemical Properties and Therapeutic Uses, VALPROIC ACID Synthesis, SAR, MCQ, Structure, Chemical Properties and Therapeutic Uses, https://www.youtube.com/watch?v=gs_jxI2xvUE, https://www.youtube.com/watch?v=RAs45lg55Z8&t=1s. Inducers of CYP3A4 such as phenobarbital may induce the hepatic metabolism of buprenorphine, which may lead to opiate withdrawal or inadequate pain control. Osimertinib: (Major) Avoid coadministration of primidone with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If primidone is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Neratinib: (Major) Avoid concomitant use of primidone with neratinib due to decreased efficacy of neratinib. Nimodipine: (Major) In epileptic patients taking phenobarbital with or without other enzyme-inducing anticonvulsants, there is a 7-fold decrease in the AUC of nimodipine due to hepatic enzyme induction. An enhanced effect of the displaced drug may occur. [67] Coadministration with another strong CYP3A4 inducer decreased the AUC of sotorasib by 51%. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. [12] He found it to have a similar anticonvulsant effect, but more specific, i.e. Trandolapril; Verapamil: (Major) Barbiturates have been shown to enhance the hepatic clearance of verapamil. It is recommended to avoid this combination when codeine is being used for cough. An interaction between barbiturates and mexiletine, however, may be possible. Brimonidine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates. Diphenhydramine; Ibuprofen: (Major) Because diphenhydramine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. Valproic Acid, Divalproex Sodium: (Moderate) Valproic acid inhibits phenobarbital metabolism, and most likely the metabolism of other barbiturates. Vorapaxar is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inducer decreased the composite AUC of enzalutamide plus N-desmethyl enzalutamide by 37%. Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of itraconazole. Use of more than one agent for hypnotic purposes may increase the risk for over-sedation, CNS effects, or sleep-related behaviors. Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Additive CNS depression may occur if barbiturates are co-used with sedating antihistamines, such as brompheniramine. A dose increase of the barbiturate may be necessary. (Moderate) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as barbiturates. The possibility exists that other factors leading to birth defects, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy. Bupivacaine; Meloxicam: (Minor) Bupivacaine is metabolized by CYP3A4. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. Queens of the Stone Age will bring Phantogram, Viagra Boys, the Armed, and Savages' Jehnny Beth on their fall North American tour. Ribociclib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Take primidone at around the same time(s) every day. Additionally, concomitant use of codeine with a barbiturate can decrease codeine concentrations, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. The exception is the use of levonorgestrel progestin IUDs, which have not been reported to interact and appear to maintain reliable efficacy. Acetaminophen; Chlorpheniramine: (Moderate) Additive CNS depression may occur if barbiturates are co-used with sedating antihistamines, such as chlorpheniramine. Educate patients about the risks and symptoms of respiratory depression and sedation. Ribociclib; Letrozole: (Major) Avoid coadministration of primidone with ribociclib due to decreased ribociclib exposure resulting decreased efficacy. The clinical significance of this interaction is uncertain, but the manufacturer recommends that these drugs not be co-administered. Patients should be monitored for loss of therapeutic effect if a barbiturate is added is added to aminophylline therapy. Netupitant, Fosnetupitant; Palonosetron: (Major) Netupitant is mainly metabolized by CYP3A4. Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. USP.org. Administer with meals to minimize indigestion or GI irritation. Tri-keto form is most stable in aqueous solution. Both drugs are well studied for this condition, unlike other therapies, and are recommended for initial treatment. Concomitant use may decrease exposure of ketoconazole and reduce its efficacy. Ceritinib is a CYP3A substrate and primidone is a strong CYP3A inducer. (Minor) Chronic therapy with barbiturates can increase the metabolism and decrease the effectiveness of acetaminophen. Levoleucovorin: (Minor) Limited data suggest that leucovorin and levoleucovorin may interfere with the activity of anticonvulsants such as barbiturates. When a medication is used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity as outlined by the OBRA guidelines.[60742]. Monitor for potential reduced cholesterol-lowering efficacy when barbiturates are co-administered with simvastatin, which is metabolized by CYP3A4. The authors speculated that this was due to improvements in diet, sun exposure, and exercise in response to earlier findings, and/or that this was because it was sunnier in London than in the Northern European countries, which had earlier reported this effect. Velpatasvir is a P-gp and CYP3A4 substrate. Acetaminophen; Aspirin; Diphenhydramine: (Major) Because diphenhydramine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. Temsavir is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. Coadministration may result in elevated primidone plasma concentrations. Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as primidone, may increase the risk of developing methemoglobinemia. In patients receiving either phenobarbital or primidone in combination with topiramate, there was a < 10% change in phenobarbital or primidone plasma concentrations; the effects on topiramate plasma concentrations were not evaluated. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. Glimepiride; Rosiglitazone: (Minor) Barbiturates may induce the CYP2C9 metabolism of glimepiride. Although not specifically studied with phenobarbital, other strong UGT1A1 inducers have been shown to decrease plasma concentrations of raltegravir, which may lead to HIV treatment failure or to the development of viral resistance. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. Coadministration of maraviroc and primidone is contraindicated in patients with CrCl less than 30 mL/min. Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. Higher caffeine doses may be needed after barbiturate administration. Caution should be exercised during concomitant use of anxiolytics, sedatives, and hypnotics and any barbiturate. (Major) Coadministration of primidone and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Thiotepa: (Major) Avoid the concomitant use of thiotepa and primidone if possible; increased metabolism to the active thiotepa metabolite may result in increased thiotepa toxicity (e.g., infection, bleeding, skin toxicity). Suvorexant: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Phenobarbital, which is a metabolite of primidone, directly interacts with GABA-A receptors and chloride channels. [7] It is taken by mouth. Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive CNS depression may occur if barbiturates are co-used with sedating antihistamines, such as dexchlorpheniramine. Coadministration of rifampin, another strong CYP3A4 inducer, with a single dose of apremilast resulted in a decrease in apremilast AUC and Cmax by 72% and 43%, respectively. Dexamethasone: (Moderate) Coadministration may result in decreased exposure to dexamethasone. The effects of aprepitant on tolbutamide were not considered significant. Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as primidone, may increase the risk of developing methemoglobinemia. It is recommended to avoid this combination when codeine is being used for cough. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. Monitor for additive CNS and respiratory effects, and warn about the potential effects to driving and other activities. Monitor for additive CNS and respiratory effects, and warn about the potential effects to driving and other activities. In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). The clinical significance of this effect is uncertain. Educate patients about the risks and symptoms of respiratory depression and sedation. Doravirine is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Because diphenhydramine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. Concomitant use with another strong CYP3A inducer reduced olutasidenib exposure by approximately 80%. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Coadministration may increase the risk of CNS depressant-related side effects. Appropriate dose adjustments necessary to ensure optimum levels of both anti-retroviral agent and the barbiturate are unknown. Only propranolol has been compared to primidone in a clinical trial. (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. All patients receiving concomitant barbiturate therapy should be closely monitored for neurological toxicity. CYP3A is responsible for both the formation and elimination of cariprazine's major active metabolites. Additive sedation or other CNS effects are also possible. [86], In 1954, Chalmers and Boheimer reported that the drug was associated with megaloblastic anemia. Patients should use caution when driving or operating machinery until they are aware of the effects of the drug. Lorazepam: (Moderate) Additive CNS and/or respiratory depression may occur with concurrent use. Azilsartan; Chlorthalidone: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. Ivacaftor is a sensitive CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Selpercatinib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Verapamil: (Major) Barbiturates have been shown to enhance the hepatic clearance of verapamil. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Monitor for signs of opioid withdrawal. Exemestane: (Major) If coadministration of exemestane with primidone is necessary, increase the dose of exemestane to 50 mg once daily after a meal. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate. Disopyramide: (Moderate) Hepatic microsomal enzyme-inducing agents, such as barbiturates, have the potential to accelerate the hepatic metabolism of disopyramide, a CYP3A4 substrate. When eravacycline was administered with a strong CYP3A4/3A5 inducer, the eravacycline AUC was decreased by 35% and its clearance was increased by 54%. Additive dizziness, confusion, somnolence, and other CNS effects may also occur. Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Lenacapavir: (Contraindicated) Concurrent use of lenacapavir and barbiturates is contraindicated due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. Mifepristone: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as primidone. It is recommended to avoid this combination when codeine is being used for cough. Voriconazole: (Contraindicated) Voriconazole is contraindicated for use with long-acting barbiturates, such as primidone. In addition, phenobarbital may induce P-glycoprotein (P-gp), a drug efflux transporter for which dasabuvir, ombitasvir, paritaprevir, and ritonavir are substrates. Ixabepilone: (Major) Avoid concurrent use of ixabepilone and barbiturates due to decreased plasma concentrations of ixabepilone, which may reduce its efficacy. Primidone is a CYP3A4 inducer; dexamethasone is a CYP3A4 substrate. Barbiturates are CYP3A4 enzyme inducers and may cause decreased plasma concentrations of zolpidem; in some patients efficacy may be reduced. If methemoglobinemia occurs or is suspected, discontinue tetracaine and any other oxidizing agents. Ripretinib: (Major) Avoid coadministration of ripretinib with primidone. Higher lidocaine doses may be required; titrate to effect. (adsbygoogle = window.adsbygoogle || []).push({}); Pharmacophore solutions is an academia by the pharmacy people for the pharmacy people in the welfare of pharmacy education. In a drug interaction study, coadministration of a single dose of rivaroxaban 20 mg with food with a drug that is a combined P-gp and strong CYP3A4 inducer (rifampicin titrated up to 600 mg once daily) led to an approximate decrease of 50% in AUC and an approximate decrease of 22% in Cmax of rivaroxaban. [29][30][31] The populations usually said to be most at risk are institutionalized people, postmenopausal women, older men, people taking more than one anticonvulsant, and children, who are also at risk of rickets. Tapentadol: (Major) Concomitant use of tapentadol with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. To maintain a therapeutic dosage, serum concentrations of ethosuximide should be measured, especially if barbiturate therapy is added to or withdrawn from ethosuximide therapy. Pentazocine should be used cautiously in any patient receiving these agents, which may include barbiturates. Rimegepant is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. If coadministration cannot be avoided, increase the acalabrutinib dose to 200 mg PO twice daily. Clozapine: (Major) Coadministration of clozapine, a CYP3A4 substrate, with a potent inducer of CYP3A4, such as primidone, is not recommended. Coadministration may result in reduced systemic exposes to daclatasvir. Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. Pitolisant is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. If concurrent use is necessary, monitor for excessive sedation and somnolence. Concurrent use may decrease relugolix exposure and compromise the efficacy of relugolix therapy. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. Concomitant use may increase the risk for these adverse reactions. Primidone is a CYP3A4 inducer; prednisone is a CYP3A4 substrate. Concurrent use may result in additive CNS depression. It is likely that other barbiturates may exert the same effect. Ritonavir: (Major) Avoid concomitant use of ritonavir and barbiturates. Papaverine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation. Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by the concomitant use of primidone, a strong CYP3A inducer; both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate). Ethanol ingestion should be avoided during use of barbiturates due to the potential for additive CNS depressant effects; the lethal dose of a barbiturate is significantly less if alcohol is also ingested. Dasatinib is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. Bromocriptine is extensively metabolized by the liver via CYP3A4; phenobarbital, the active metabolite of primidone, is a strong inducer of CYP3A4. Concomitant administration of these drugs has not been formally evaluated. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with barbiturates. Also closely monitor everolimus whole blood trough concentrations in patients receiving everolimus for either kidney or liver transplant and adjust the dose as necessary to remain in the recommended therapeutic range. There is also a risk of additive CNS depression (drowsiness) when buspirone is given concomitantly with barbiturates. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively. It is also available in a chewable tablet formulation in Canada. If primidone is discontinued resume the recommended relugolix treatment dose of 120 mg once daily. During acute overdoses, barbiturates can enhance the formation of toxic acetaminophen metabolites. It is likely that all barbiturates exert the same effect as phenobarbital. When another strong CYP3A4 inducer, rifampin (600 mg once daily), was administered for 7 days before and 7 days after a single dose of rolapitant (180 mg), the mean Cmax and AUC of rolapitant were decreased by 30% and 85%, respectively; additionally, the mean half-life decreased from 176 hours to 41 hours. Primidone side effects. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects. If these drugs are administered concurrently, monitor patients for signs of primidone toxicity, such as confusion, excessive drowsiness, falls, unsteadiness, or difficulty walking, or nystagmus. Monitor for decreased response to prednisolone during concurrent use. Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Afatinib: (Major) Increase the daily dose of afatinib by 10 mg as tolerated if the concomitant use with primidone is necessary; resume the previous dose of afatinib 2 to 3 days after discontinuation of primidone. Monitor for additive CNS and respiratory effects, and warn about the potential effects to driving and other activities. Nintedanib: (Major) Avoid the use of barbiturates with nintedanib, as these drugs are expected to decrease the exposure of nintedanib and compromise its efficacy. Limit the use of opioid pain medications with barbiturates to only patients for whom alternative treatment options are inadequate. Caution should be exercised during concomitant use of anxiolytics, sedatives, and hypnotics and any barbiturate; dosage reduction of one or both agents may be necessary. Abiraterone is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. However, dosage adjustment is not likely to be needed. Clonazepam is a CYP3A4 substrate. Coadministration of CYP3A4 inducers, such as barbiturates, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy. Coadministration with another strong CYP3A inducer decreased the systemic exposure of a single dose of trabectedin by 31% compared to a single dose of trabectedin given alone. Rifampin may induce the metabolism of phenobarbital; coadministration may result in decreased phenobarbital plasma concentrations. Amlodipine; Benazepril: (Major) Barbiturates may induce the CYP3A4 metabolism of calcium-channel blockers such as amlodipine, and thereby reduce their oral bioavailability. Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Barbiturates may potentiate orthostatic hypotension when used concurrently with thiazide diuretics. Higher-dose hormonal regimens may be indicated where acceptable or applicable. Pramipexole: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction. Concurrent use may decrease the plasma concentrations of nevirapine leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Primidone is converted to phenobarbital in vivo, and phenobarbital is a potent inducer of the hepatic isoenzyme CYP3A4. Codeine; Guaifenesin: (Major) Concomitant use of codeine with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Educate patients about the risks and symptoms of respiratory depression and sedation. If concomitant use is necessary, monitor for decreased virologic response and decreased efficacy of the barbiturate. Smoothie. Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of codeine with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. Coadministration with another strong CYP3A4 inducer decreased selumetinib exposure by 51%. [83], It was brought to market a year later by the Imperial Chemical Industry, now known as AstraZeneca in the United Kingdom[53][84] and Germany. Phenobarbital may decrease quinidine half-life and corresponding AUC by about 50 to 60%. Primidone is metabolized to phenobarbital. For pediatric patients, concomitant use of maraviroc with a strong CYP3A inducer, without a strong CYP3A inhibitor, is not recommended. (Minor) Chronic therapy with barbiturates can increase the metabolism and decrease the effectiveness of acetaminophen. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. [40] Schaffer et al. Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with barbiturates may cause respiratory depression, hypotension, profound sedation, and death. ii. [37][38], Additionally, a coagulation defect resembling vitamin K deficiency has been observed in newborns of mothers taking primidone. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Discontinuation of a barbiturate may increase the risk of seizures, serotonin syndrome, and the risk of opioid-related adverse reactions, such as fatal respiratory depression. Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive CNS depression may occur if barbiturates are co-used with sedating antihistamines, such as chlorpheniramine. Educate patients about the risks and symptoms of respiratory depression and sedation. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Barbiturates are inducers of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. Thalidomide frequently causes drowsiness and somnolence. Primidone may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Vincristine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Calcitriol: (Moderate) Barbiturates can decrease the activity of vitamin D by increasing its metabolism. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Belumosudil is a CYP3A4 substrate and primidone, which is metabolized to phenobarbital, is a strong CYP3A inducer; concomitant use may result in decreased belumosudil exposure and reduced belumosudil efficacy. Green Tea: (Minor) Some green tea products contain caffeine. Ivacaftor is a sensitive CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Barbiturates induce CYP3A4; oxycodone is a CYP3A4 substrate. Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Additive CNS depression may occur if barbiturates are co-used with sedating antihistamines, such as chlorpheniramine. If concomitant use is necessary, do not use once daily dosing of lopinavir; ritonavir. Consider an alternative anticonvulsant when using elvitegravir. Coadministration with another strong CYP3A4 inducer decreased ponatinib exposure by 62%. Rasagiline: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including buprenorphine, butorphanol, dronabinol, THC, nabilone, nalbuphine, and anxiolytics, sedatives, and hypnotics. The severity of this interaction may be increased when additional CNS depressants are given. Barbiturates induce CYP3A4; oxycodone is a CYP3A4 substrate. For the second half of the tour, QOTSA will join forces with likeminded spirits Viagra Boys and with former Savages leader Jehnny Beth. 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