Modafinil interactions

Do Not Exceed Recommended Dose Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. (Albuterol label, Warnings and precautions)

Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see Adverse Reactions ( 6.2 )] . taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive… (Amphetamine and dextroamphetamine label, Contraindications)

• Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (Apixaban label, Drug interactions)

Drug Interactions : Use with strong cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended because loss of efficacy may occur ( 5.5 , 7.1 ) (Apremilast label, Warnings and precautions)

CYP3A4 Inducers : Avoid concomitant use for greater than 14 days ( 7.1 ) (Aripiprazole label, Drug interactions)

PROVIGIL is contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . (Modafinil label, Contraindications)

Concomitant administration of BIXLENVO is contraindicated with: dofetilide due to the potential for increased dofetilide plasma concentrations and associated serious and/or life-threatening events. strong CYP3A inducers due to decreased plasma concentrations of BIC and LEN, which may result in the loss of therapeutic effect and development of resistance to BIXLENVO. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Contraindications)

Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. (Budesonide and formoterol label, Warnings and precautions)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (Buprenorphine label, Drug interactions)

Intervention: Concomitant use of VRAYLAR with a CYP3A4 inducer is not recommended [see Dosage and Administration ( 2.1 , 2.6 ) ] . (Cariprazine label, Drug interactions)

• Concomitant use of Strong CYP3A4 Inducers is not recommended. (Clozapine label, Drug interactions)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Codeine label, Boxed warning)

Moderate or Strong CYP3A4 inducers: Avoid concomitant use. (Daridorexant label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

Avoid concomitant use of other drugs that are also associated with similar cardiac effects (e.g., amphetamines, other sympathomimetic agents, atropine, amoxapine, scopolamine, antihistamines, other anticholinergic agents, amitriptyline, desipramine, other tricyclic antidepressants). (Dronabinol label, Warnings and precautions)

• CYP3A inducers: Avoid concomitant use. (Dronedarone label, Drug interactions)

Therefore, concomitant use with strong CYP3A inducers is not recommended [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . (Elexacaftor, tezacaftor, and ivacaftor label, Warnings and precautions)

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. (Fentanyl label, Boxed warning)

Preventing or Managing DI The concomitant use of ADDYI with CYP3A4 inducers is not recommended. (Flibanserin label, Drug interactions)

When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone [see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists] . (Fluticasone and salmeterol label, Warnings and precautions)

The increased risk of asthma-related death is considered a class effect of the long-acting beta 2 -adrenergic agonists, including formoterol fumarate inhalation solution. (Formoterol label, Warnings and precautions)

Should hypotension occur and a vasopressor be required, epinephrine must not be used since HALDOL DECANOATE may block its vasopressor activity, and paradoxically lower blood pressure. (Haloperidol label, Warnings and precautions)

In addition, discontinuation of a concomitantly used Cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentrations. (Hydrocodone and acetaminophen label, Boxed warning)

Avoid concomitant use of CYP3A4 inducers when using Corlanor. (Ivabradine label, Drug interactions)

Therefore, administration of potent enzyme inducers of CYP3A4 with ketoconazole tablets is not recommended. (Ketoconazole label, Drug interactions)

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

Do Not Exceed Recommended Dose Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. (Levalbuterol label, Warnings and precautions)

• Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects [see Adverse Reactions (6) , Drug Interactions (7.7) , and Overdosage (10) ] . (Liothyronine label, Boxed warning)

CYP3A4 inducers: Avoid concomitant use with CAPLYTA. (Lumateperone label, Drug interactions)

Strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. (Lurasidone label, Contraindications)

Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 12.3 ). (Macitentan label, Drug interactions)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in meperidine plasma concentration. (Meperidine label, Boxed warning)

John's Wort) Clinical Impact Significant decrease in plasma naldemedine concentrations, which may reduce efficacy [see Clinical Pharmacology (12.3) ] Intervention Avoid use of SYMPROIC with strong CYP3A inducers. (Naldemedine label, Drug interactions)

Avoid co-administration of nifedipine with phenytoin or any known CYP3A4 inducer or consider an alternative antihypertensive therapy. (Nifedipine label, Drug interactions)

…contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. (Nirmatrelvir and ritonavir label, Contraindications)

Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs ( 7.1 ) -- - ---------- ------ USE IN SPECIFIC POPULATIONS---- -- -- --------- ---- Lactation: Not recommended; Lo Loestrin Fe can decrease milk production ( 8.2 ) (Norethindrone and ethinyl estradiol label, Drug interactions)

If a CYP3A4 inducer is discontinued, consider OLINVYK dosage reduction and monitor for signs of respiratory depression. (Oliceridine label, Drug interactions)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. (Oxycodone label, Boxed warning)

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. (Oxycodone and acetaminophen label, Boxed warning)

• CYP3A Inducers: Avoid concurrent use of IBRANCE with strong CYP3A inducers. (Palbociclib label, Drug interactions)

Strong CYP3A4 and P-glycoprotein (P-gp) inducers : Avoid using a strong inducer of CYP3A4 and/or P-gp during a dosing interval for ERZOFRI. (Paliperidone label, Drug interactions)

The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS ). (Phenelzine label, Contraindications)

…(8.1) ] With glaucoma [see Warnings and Precautions (5.3) ] With hyperthyroidism Taking or within 14 days of stopping a monoamine oxidase inhibitors [see Drug Interactions (7) ] With known hypersensitivity to phentermine, topiramate or any of the excipients in phentermine and topiramate extended-release capsules, or idiosyncrasy to the sympathomimetic amines. (Phentermine and topiramate label, Contraindications)

Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of NUPLAZID. (Pimavanserin label, Drug interactions)

Epinephrine Because of the potential for Promethazine to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with Promethazine Syrup overdose. (Promethazine label, Drug interactions)

ASPRUZYO Sprinkle is contraindicated in patients: Taking strong inhibitors of CYP3A [see Drug Interactions (7.1)] Taking inducers of CYP3A [see Drug Interactions (7.1)] With liver cirrhosis [see Use in Specific Populations (8.6)] Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) (4, 7.1) (Ranolazine label, Contraindications)

• Strong and Moderate CYP3A Inducers: Avoid concomitant administration. (Rimegepant label, Drug interactions)

Avoid concomitant use of XARELTO with drugs that are known combined P-gp and strong CYP3A inducers [see Drug Interactions (7.3) ] . (Rivaroxaban label, Warnings and precautions)

• Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended. (Roflumilast label, Warnings and precautions)

WARNING: ASTHMA-RELATED DEATH Long-acting beta 2 -adrenergic agonists (LABA), such as salmeterol, the active ingredient in SEREVENT DISKUS, as monotherapy (without inhaled corticosteroids [ICS]) increase the risk of asthma-related death. (Salmeterol label, Boxed warning)

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

Many patients who received Xyrem during clinical trials in narcolepsy were receiving central nervous system stimulants [see Clinical Trials ( 14 )]. (Sodium oxybate label, Boxed warning)

Inducers of CYP3A4 Strong CYP3A4 inducers should not be used with tamoxifen. (Tamoxifen label, Drug interactions)

Strong CYP3A4 inducers (e.g., rifampin): Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers, because of decreased exposure ( 7.2 , 12.3 ) (Tasimelteon label, Drug interactions)

Hypersensitivity Terbutaline sulfate is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any component of this drug product. (Terbutaline label, Contraindications)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; Zanaflex should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.7 ) (Tizanidine label, Warnings and precautions)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (Tramadol label, Boxed warning)

…(SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) tricyclic antidepressants other antidepressants, such as amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine amphetamines and methylphenidates medicines that can raise blood pressure (sympathomimetic medicine), such as pseudoephedrine, phenylephrine and ephedrine. (Tranylcypromine label, Boxed warning)

Avoid concomitant use with strong CYP3A inducers if possible. (Tretinoin label, Drug interactions)

Strong CYP3A4 Inducers: Should be avoided as concomitant use will result in reduction of ubrogepant exposure. (Ubrogepant label, Drug interactions)

• use of a long-acting beta 2 -adrenergic agonist (LABA), including vilanterol, one of the active ingredients in Umeclidinium and Vilanterol ELLIPTA, without an inhaled corticosteroid (ICS), in patients with asthma [see Warnings and Precautions ( 5.1 )] . (Umeclidinium and vilanterol label, Contraindications)

Strong CYP3A4 Inducers : Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended. (Upadacitinib label, Drug interactions)

Use of strong CYP3A4 inducers with INGREZZA or INGREZZA SPRINKLE Concomitant use is not recommended. (Valbenazine label, Drug interactions)

John's wort, a CYP3A4 inducer, in combination with zolpidem may decrease blood levels of zolpidem and is not recommended. (Zolpidem label, Drug interactions)

Acetazolamide decreases urinary excretion of amphetamine and may enhance the magnitude and duration of their effect. (Acetazolamide label, Drug interactions)

Sympathomimetics, Methylxanthines, Steroids In clinical studies, concurrent administration of aclidinium bromide and other drugs commonly used in the treatment of COPD including sympathomimetics (short-acting beta 2 agonists), methylxanthines, and oral and inhaled steroids showed no increases in adverse drug reactions. (Aclidinium label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

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

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

• Hypotension: Slow the infusion; as needed, add vasopressor drugs, positive inotropic agents, and volume expansion. (Amiodarone label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Strong CYP3A4 inducers Double the recommended dosage and further adjust based on clinical response. (Brexpiprazole label, Drug interactions)

Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology (12.3) ] , potentially resulting in decreased efficacy… (Buprenorphine and naloxone label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Other inhibitors and inducers of CYP3A4: Substances that inhibit CYP3A4, such as ketoconazole or ritonavir, may inhibit buspirone metabolism and increase plasma concentrations of buspirone while substances that induce CYP3A4, such as dexamethasone or certain anticonvulsants (phenytoin, phenobarbital, carbamazepine), may increase the rate of buspirone metabolism. (Buspirone label, Drug interactions)

Table 7: Clinically Significant Drug Interactions with INVOKANA UGT Enzyme Inducers Clinical Impact: UGT enzyme inducers decrease canagliflozin exposure which may reduce the effectiveness of INVOKANA. (Canagliflozin label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

• Strong inducer of CYP3A4 or CYP2C19: Consider dose increase of EPIDIOLEX. (Cannabidiol (prescription) label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

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

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Miscellaneous Cytochrome P450 Inducers: Efavirenz Nevirapine Rifampicin Rifabutin Rifapentine Use With Caution Inducers of CYP3A enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine will increase the metabolism of clarithromycin, thus decreasing plasma concentrations of clarithromycin, while increasing those of 14-OH-clarithromycin. (Clarithromycin label, Drug interactions)

Inducers of CYP3A4 and CYP3A5 Inducers of CYP3A4 and/or CYP3A5 may reduce plasma concentrations of clindamycin. (Clindamycin label, Drug interactions)

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

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

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Clinically Relevant Interactions Affecting DEXILANT When Coadministered with Other Drugs and Substances CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of dexlansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . (Dexlansoprazole label, Drug interactions)

Effects of PROVIGIL on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by PROVIGIL via inhibition of metabolic enzymes, with resultant higher systemic exposure. (Modafinil label, Drug interactions)

…drugs including dicyclomine hydrochloride: amantadine, antiarrhythmic agents of Class I (e.g., quinidine), antihistamines, antipsychotic agents (e.g., phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e.g., meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants, and other drugs having anticholinergic activity. (Dicyclomine label, Drug interactions)

Sympathomimetics Epinephrine Can increase the risk of cardiac arrhythmias. (Digoxin label, Drug interactions)

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. (Divalproex (valproate) label, Drug interactions)

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

If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists. (Dorzolamide and timolol label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

• Drugs that potentiate the effects of epinephrine include sympathomimetics, beta blockers, tricyclic antidepressants, MAO inhibitors, COMT inhibitors, clonidine, doxapram, oxytocin, levothyroxine sodium, and certain antihistamines. (Epinephrine label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

• Sympathomimetic drugs: Dose adjustment needed ( 7 ) (Esmolol label, Drug interactions)

Table 4: Clinically Relevant Interactions Affecting Esomeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (Esomeprazole label, Drug interactions)

Drugs that Induce CYP3A4 (Rifampicin) Racemic zopiclone exposure was decreased 80% by concomitant use of rifampicin, a potent inducer of CYP3A4. (Eszopiclone label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Interaction With Strong Inhibitors and Inducers of CYP3A4 Coadministration of Zortress with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) or strong CYP3A4 inducers (e.g., rifampin, rifabutin) is not recommended without close monitoring of everolimus whole blood trough… (Everolimus label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

CYP3A4 Inducers No dosing adjustments are recommended in the presence of CYP3A4 inducers, such as rifampin and carbamazepine. (Fesoterodine label, Drug interactions)

Limited data in patients receiving known enzyme inducers ( phenytoin, phenobarbital, carbamazepine ) indicate only a 30% increase in the rate of flecainide elimination. (Flecainide label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

…somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid. (Glimepiride label, Drug interactions)

…olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), thyroid hormones, phenytoin, nicotinic acid, and calcium channel blocking drugs. (Glipizide label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Concomitant administration of inducers of CYP3A4 may lead to decreases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions, including adrenal crisis. (Hydrocortisone label, Drug interactions)

CYP3A4 inducers may decrease Gleevec C max and area under curve (AUC). (Imatinib label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

…Insulin Aspart Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin aspart label, Drug interactions)

…Insulin Degludec Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin degludec label, Drug interactions)

…Effect of LEVEMIR Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin detemir label, Drug interactions)

…Glargine-yfgn Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin glargine label, Drug interactions)

…Effect of LYUMJEV Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin lispro label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Monoamine Oxidase (MAO) Inhibitors Caution should be used when concomitantly administering MAO inhibitors and PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Concomitant Use with CYP3A Inducers Use of KALYDECO with strong CYP3A inducers, such as rifampin, substantially decreases the exposure of ivacaftor, which may reduce the therapeutic effectiveness of KALYDECO. (Ivacaftor label, Warnings and precautions)

Sympathomimetics and Vasopressin : Sympathomimetics and vasopressin may enhance the sympathomimetic effects of ketamine [see Drug Interactions ( 7.2 )] . (Ketamine label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Clinically Relevant Interactions Affecting PREVACID or PREVACID SoluTab When Coadministered with Other Drugs CYP2C19 OR CYP3A4 Inducers Clinical Impact: Decreased exposure of lansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . (Lansoprazole label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

Sympathomimetics Concurrent use may of sympathomimetics and levothyroxine may increase the effects of sympathomimetics or thyroid hormone. (Levothyroxine label, Drug interactions)

Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. (Lidocaine label, Drug interactions)

Strong P-glycoprotein/CYP3A4 inducer: The efficacy of TRADJENTA may be reduced when administered in combination (e.g., with rifampin). (Linagliptin label, Drug interactions)

Monoamine Oxidase (MAO) Inhibitors Caution should be used when concomitantly administering MAO inhibitors and PROVIGIL. (Modafinil label, Drug interactions)

Additionally, in studies of another stimulant, there was slowing of the increase in height [see Adverse Reactions (6.1) ] . (Lisdexamfetamine label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

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

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

…agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration… (Methadone label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin) : Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. (Methylprednisolone label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. (Nintedanib label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Effects of PROVIGIL on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by PROVIGIL via inhibition of metabolic enzymes, with resultant higher systemic exposure. (Modafinil label, Drug interactions)

Phenytoin, Carbamazepine, and Rifampin In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. (Ondansetron label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

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

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Risk of Abuse and Dependence Phentermine is related chemically and pharmacologically to amphetamine (d- and d l l-amphetamine) and other related stimulant drugs that have been extensively abused. (Phentermine label, Warnings and precautions)

Pressor Effect with Concomitant Oxytocic Drugs Oxytocic drugs potentiate the increasing blood pressure effect of sympathomimetic pressor amines including BIORPHEN [see Drug Interactions (7.1) ] , with the potential for hemorrhagic stroke. (Phenylephrine label, Warnings and precautions)

Effects of PROVIGIL on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by PROVIGIL via inhibition of metabolic enzymes, with resultant higher systemic exposure. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Strong CYP3A4 Inducers: Decreased exposure of WAKIX; consider dosage adjustment of WAKIX ( 2.6 , 7.1 ) (Pitolisant label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

CYP 3A4 inducers (e.g. barbiturates, phenytoin, carbamazepine, and rifampin): Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of prednisolone and require that the dosage of Orapred be increased. (Prednisolone label, Drug interactions)

CYP 3A4 inducers and inhibitors: May, respectively, increase or decrease clearance of corticosteroids, necessitating dose adjustment. (Prednisone label, Drug interactions)

Effects of PROVIGIL on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by PROVIGIL via inhibition of metabolic enzymes, with resultant higher systemic exposure. (Modafinil label, Drug interactions)

• Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose up to 5 fold when used in combination with a chronic treatment (more than 7-14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. (Quetiapine label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Rifampin (strong CYP enzyme inducer): Decreases exposure to and effects of ramelteon. (Ramelteon label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Monoamine Oxidase (MAO) Inhibitors Caution should be used when concomitantly administering MAO inhibitors and PROVIGIL. (Modafinil label, Drug interactions)

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

Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. (Risperidone label, Drug interactions)

Anesthetic: meperidine ↓ meperidine/ ↑ normeperidine (metabolite) Dosage increase and long-term use of meperidine with ritonavir are not recommended due to the increased concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant activity (e.g., seizures). (Ritonavir 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)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Monoamine Oxidase (MAO) Inhibitors Caution should be used when concomitantly administering MAO inhibitors and PROVIGIL. (Modafinil label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Beta-2-Receptor Stimulants Beta-agonists such as albuterol, terbutaline and isoproterenol may have to be administered in increased dosages when used concomitantly with sotalol. (Sotalol label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Circulatory Shock Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with trimethoprim-sulfamethoxazole products in patients with history of recent (days to weeks) exposure to sulfamethoxazole and trimethoprim. (Sulfamethoxazole and trimethoprim label, Warnings)

Strong CYP3A inducers: Efficacy may be reduced ( 7.2 ). (Suvorexant label, Drug interactions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (Tacrolimus label, Warnings and precautions)

CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase CIALIS exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: CIALIS for use as needed: no more than 10 mg every 72 hours CIALIS for once daily use: dose not to exceed 2.5 mg CYP3A4 inducers (e.g. rifampin) decrease CIALIS exposure ( 7.2 ). (Tadalafil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

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

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. (Terbinafine label, Drug interactions)

Use of tiagabine HCl without enzyme-inducing antiepileptic drugs results in blood levels about twice those attained in the studies on which current dosing recommendations are based (see DOSAGE AND ADMINISTRATION ). (Tiagabine label, Warnings)

If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists. (Timolol label, Warnings and precautions)

CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse reactions ( 7.2 ) (Tinidazole label, Drug interactions)

Concomitant Respiratory Medications SPIRIVA RESPIMAT has been used concomitantly with short-acting and long-acting sympathomimetic (beta-agonists) bronchodilators, methylxanthines, oral and inhaled steroids, antihistamines, mucolytics, leukotriene modifiers, cromones, and anti-IgE treatment without increases in adverse reactions. (Tiotropium label, Drug interactions)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (Tofacitinib label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. (Treprostinil label, Warnings and precautions)

Hepatic enzyme inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin): Drugs which induce hepatic microsomal drug metabolizing enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. (Triamcinolone label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

Effects of PROVIGIL on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by PROVIGIL via induction of metabolic enzymes, which results in lower systemic exposure. (Modafinil label, Drug interactions)

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. (Valproic acid label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Modafinil label, Warnings and precautions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of PROVIGIL. (Modafinil label, Drug interactions)

Warfarin More frequent monitoring of prothrombin times/INR should be considered whenever PROVIGIL is coadministered with warfarin [see Clinical Pharmacology ( 12.3 )] . (Modafinil label, Drug interactions)

Multiple-dose administration of the potent CYP3A4 inducer rifampin (600 mg every 24 hours, q24h, for 14 days), however, reduced zaleplon C max and AUC by approximately 80%. (Zaleplon label, Drug interactions)

The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, tramadol, meperidine, methadone, lithium, tryptophan, buspirone, amphetamines, and St. (Ziprasidone label, Warnings and precautions)

CYP3A4 Inducers If co-administration with a potent CYP3A4 inducer is necessary, the patient should be closely monitored and the dose of ZONISAMIDE and other drugs that CYP3A4 substrates may need to be adjusted [see Clinical Pharmacology ( 12.3 )] . (Zonisamide label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel-blocking drugs, and isoniazid. (Acarbose label, Drug interactions)

Severe reactions have required intervention with vasopressor agents and supportive measures. (Benzonatate label, Warnings)

Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with PROVIGIL and for one month after discontinuation of PROVIGIL treatment. (Modafinil label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. (Empagliflozin and metformin label, Drug interactions)

TAF is not an inhibitor or inducer of CYP3A in vivo . (Emtricitabine and tenofovir label, Drug interactions)

Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with PROVIGIL and for one month after discontinuation of PROVIGIL treatment. (Modafinil label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. (Glyburide label, Drug interactions)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Glyburide and metformin label, Drug interactions)

Atypical Antipsychotics (e.g., olanzapine and clozapine), Corticosteroids, Danazol, Diuretics, Estrogens, Glucagon, Isoniazid, Niacin, Oral Contraceptives, Phenothiazines, Progestogens (e.g., in oral contraceptives), Protease inhibitors, Somatropin, Sympathomimetic Agents (e.g., albuterol, epinephrine, terbutaline) and Thyroid Hormones. (Insulin regular (human) label, Drug interactions)

ATROVENT HFA has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids commonly used in the treatment of COPD. (Ipratropium label, Drug interactions)

Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with MPA Injectable Suspension, USP. (Medroxyprogesterone label, Drug interactions)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Metformin label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Pioglitazone and metformin label, Drug interactions)

These effects are responsive to discontinuation of DIPRIVAN, intravenous fluid administration, and/or vasopressor therapy. (Propofol label, Warnings and precautions)

CYP3A4 Substrates An in vitro study has suggested that rifaximin induces CYP3A4 [see Clinical Pharmacology ( 12.3 )] . (Rifaximin label, Drug interactions)

Strong CYP3A inducers: Strong inducers of CYP3A (for example, rifampin, phenytoin, carbamazepine, phenobarbital or St. (Riociguat label, Drug interactions)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Sitagliptin and metformin label, Drug interactions)

Drugs Having No Clinically Important Interactions with SAPHRIS No dosage adjustment of SAPHRIS is necessary when administered concomitantly with paroxetine (see Table 12 in Drug Interactions ( 7.1 ) for paroxetine dosage adjustment), imipramine, cimetidine, valproate, lithium, or a CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampin). (Asenapine 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)