b See Contraindications (4), Table 6 for orally administered midazolam. Benzodiazepines: midazolam (oral) triazolam ↑ midazolam ↑ triazolam Coadministration of REYATAZ with either orally administered midazolam or triazolam is contraindicated. Triazolam and orally administered midazolam are extensively metabolized by CYP3A4, and coadministration with REYATAZ can lead to the potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression [see Contraindications (4) ].
Source: FDA drug label - atazanavir
Sedatives/hypnotics: orally administered midazolam, triazolam ↑ midazolam ↑ triazolam Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Co-administration of triazolam or orally administered midazolam with darunavir may cause large increases in the concentrations of these benzodiazepines.
Source: FDA drug label - darunavir
Sedatives/hypnotics: orally administered midazolam, triazolam ↑ midazolam ↑ triazolam Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Co-administration of triazolam or orally administered midazolam with PREZCOBIX may cause large increases in the concentrations of these benzodiazepines.
Source: FDA drug label - darunavir ethanolate and cobicistat
Fosamprenavir calcium/ritonavir: ↔ Amprenavir ↔ Esomeprazole Sedative/hypnotics: Midazolam, triazolam ↑Midazolam ↑Triazolam Coadministration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression [see Contraindications (4)].
Source: FDA drug label - fosamprenavir calcium
Sedative/Hypnotics: triazolam, orally administered midazolam ↑ triazolam ↑ midazolam Contraindicated due to potential for prolonged or increased sedation or respiratory depression [see Contraindications (4)]. Sedative/Hypnotics: parenterally administered midazolam ↑ midazolam If lopinavir and ritonavir is co-administered with parenteral midazolam, close clinical monitoring for respiratory depression and/or prolonged sedation should be exercised and dosage adjustment should be considered.
Source: FDA drug label - lopinavir and ritonavir
Sedative/Hypnotics: triazolam, orally administered midazolam ↑ triazolam ↑ midazolam Contraindicated due to potential for prolonged or increased sedation or respiratory depression [see Contraindications (4) ] . Sedative/hypnotics: Parenteral midazolam ↑ midazolam Co-administration should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered.
Source: FDA drug label - ritonavir
Triazolobenzodiazepines and Other Related Benzodiazepines: Midazolam Use With Caution Midazolam: When oral midazolam is co‑administered with clarithromycin, dose adjustments may be necessary and possible prolongation and intensity of effect should be anticipated [see Warnings and Precautions ( 5.4 ) and Pharmacokinetics ( 12.3 )] . In postmarketing experience, erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines.
Source: FDA drug label - clarithromycin
Closely monitor patients for signs of reduced effectiveness when deferasirox is administered with drugs metabolized by CYP3A4 (e.g., alfentanil, aprepitant, budesonide, buspirone, conivaptan, cyclosporine, darifenacin, darunavir, dasatinib, dihydroergotamine, dronedarone, eletriptan, eplerenone, ergotamine, everolimus, felodipine, fentanyl, hormonal contraceptive agents, indinavir, fluticasone, lopinavir, lovastatin, lurasidone, maraviroc, midazolam, nisoldipine, pimozide, quetiapine, quinidine, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, tolvaptan, tipranavir, triazolam, ticagrelor, and vardenafil) [ see Clinical Pharmacology (12.3)].
Source: FDA drug label - deferasirox
COCs Increasing the Plasma Concentrations of CYP450 Enzymes : In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase. Two additional clinical drug-drug interaction studies using simvastatin and midazolam as marker substrates for CYP3A4 were each performed in 24 healthy postmenopausal women.
Source: FDA drug label - drospirenone and ethinyl estradiol
COCs Increasing the Plasma Concentrations of CYP450 Enzymes : In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.
Source: FDA drug label - drospirenone, ethinyl estradiol and levomefolate calcium and levomefolate calcium
COCs Increasing the Plasma Concentrations of CYP450 Enzymes: In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
( 7.3 ) Midazolam : Decreased exposure; monitor for suboptimal effect of midazolam. Midazolam Concomitant use of glycerol phenylbutyrate decreased the systemic exposure of midazolam. Monitor for suboptimal effect of midazolam in patients who are being treated with glycerol phenylbutyrate.
Source: FDA drug label - glycerol phenylbutyrate
Other Drug Interactions Caution is advised when midazolam is administered concomitantly with drugs that are known to inhibit the P450-3A4 enzyme system such as cimetidine (not ranitidine), erythromycin, diltiazem, verapamil, ketoconazole and itraconazole.
Source: FDA drug label - itraconazole
Other Drug Interactions Caution is advised when midazolam is administered concomitantly with drugs that are known to inhibit the P450-3A4 enzyme system such as cimetidine (not ranitidine), erythromycin, diltiazem, verapamil, ketoconazole and itraconazole.
Source: FDA drug label - ketoconazole
Caution should be exercised when paclitaxel is concomitantly administered with known substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4.
Source: FDA drug label - paclitaxel
7 DRUG INTERACTIONS CYP3A4 Substrates (e.g., midazolam): Efficacy of concomitant drugs may be decreased; monitor for suboptimal efficacy and consider increasing the dose of the concomitant drug. ( 7.1 ) 7.1 CYP3A4 Substrates Concomitant use of Xermelo may decrease the efficacy of drugs that are CYP3A4 substrates (e.g., midazolam) by decreasing their systemic exposure.
Source: FDA drug label - telotristat ethyl
Prevention or Management Midazolam Closely monitor patients for signs or symptoms of increased or prolonged central nervous system effects (e.g., somnolence and confusion) and refer to the CYP3A substrate prescribing information for dosage adjustments when used concomitantly with VOQUEZNA TRIPLE PAK.
Source: FDA drug label - vonoprazan fumarate and amoxicillin
80% increase Midazolam Similar to diazepam.
Source: FDA drug label - aminophylline
Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - aprepitant
Effects of Armodafinil 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 armodafinil via induction of metabolic enzymes, which results in lower systemic exposure.
Source: FDA drug label - armodafinil
CYP3A Substrate (e.g., Midazolam) — Coadministration of atomoxetine (60 mg BID for 12 days) with midazolam, a model compound for CYP3A4 metabolized drugs (single dose of 5 mg), resulted in 15% increase in AUC of midazolam.
Source: FDA drug label - atomoxetine
CYP3A Substrate (e.g., Midazolam) — Coadministration of atomoxetine (60 mg BID for 12 days) with midazolam, a model compound for CYP3A4 metabolized drugs (single dose of 5 mg), resulted in 15% increase in AUC of midazolam.
Source: FDA drug label - atomoxetine hydrochloride
Concomitant use of REZUROCK with sensitive CYP3A substrates (e.g., midazolam) is predicted to increase CYP3A substrate exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.
Source: FDA drug label - belumosudil
Clinical studies have shown that with coadministration of bicalutamide, mean midazolam (a CYP 3A4 substrate) levels may be increased 1.5-fold (for C max ) and 1.9-fold (for AUC).
Source: FDA drug label - bicalutamide
7.6 Drugs without Clinically Significant Interactions with BIKTARVY Based on drug interaction studies conducted with BIKTARVY or the components of BIKTARVY, no clinically significant drug interactions have been observed when BIKTARVY is combined with the following drugs: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.
Source: FDA drug label - bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate
7.4 Drugs without Clinically Significant Interactions with Cabotegravir Based on drug interaction study results, the following drugs can be coadministered with cabotegravir (non-antiretrovirals) or given after discontinuation of cabotegravir (antiretrovirals and non-antiretrovirals) without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, and rilpivirine [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - cabotegravir
7.5 Drugs without Clinically Significant Interactions Cabotegravir Based on drug interaction study results, the following drugs can be coadministered with cabotegravir (non-antiretrovirals and rilpivirine) or given after discontinuation of cabotegravir (antiretrovirals and non-antiretrovirals) without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, and rilpivirine [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - cabotegravir and rilpivirine
7.4 Drugs without Clinically Significant Interactions with Cabotegravir Based on drug interaction study results, the following drugs can be coadministered with cabotegravir without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl estradiol, rifabutin, and rilpivirine [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - cabotegravir sodium
In addition, carbamazepine causes, or would be expected to cause, decreased levels of the following drugs, for which monitoring of concentrations or dosage adjustment may be necessary: acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, citalopram, clonazepam, clozapine, corticosteroids (e.g., prednisolone, dexamethasone), cyclosporine, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, ethosuximide, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, mianserin, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, sertraline, sirolimus, tadalafil, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide.
Source: FDA drug label - carbamazepine
7.4 CYP3A4 Substrates Darifenacin (30 mg daily) did not have a significant impact on midazolam (7.5 mg) pharmacokinetics [ see Clinical Pharmacology (12.3)] .
Source: FDA drug label - darifenacin
7.4 CYP3A4 Substrates Darifenacin (30 mg daily) did not have a significant impact on midazolam (7.5 mg) pharmacokinetics [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - darifenacin hydrobromide
This effect is shown in Table 3 for intravenous midazolam (25-50 µg/kg) and intravenous fentanyl (3-6 µg/kg) in patients of two different age groups. Table 3 SUPRANE MAC with Fentanyl or Midazolam Mean ± SD (percent reduction) Dose 18-30 years 31-65 years No fentanyl 6.4 ± 0.0 6.3 ± 0.4 3 µg/kg fentanyl 3.5 ± 1.9 (46%) 3.1 ± 0.6 (51%) 6 µg/kg fentanyl 3.0 ± 1.2 (53%) 2.3 ± 1.0 (64%) No midazolam 6.9 ± 0.1 5.9 ± 0.6 25 µg/kg midazolam - 4.9 ± 0.9 (16%) 50 µg/kg midazolam - 4.9 ± 0.5 (17%) 7.2 Neuromuscular Blocking Agents Anesthetic concentrations of desflurane at equilibrium (administered for 15 or more minutes before testing) reduced the ED 95 of succinylcholine by approximately 30% and that of atracurium and pancuronium by approximately 50% compared to N 2 O/opioid anesthesia ( see Table 4 ).
Source: FDA drug label - desflurane
Examples desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine 7.2 Drugs Having No Clinically Important Interactions with Desvenlafaxine Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with desvenlafaxine [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - desvenlafaxine
Examples desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine 7.2 Drugs Having No Clinically Important Interactions with desvenlafaxine Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with desvenlafaxine [see CLINICAL PHARMACOLOGY (12.3)].
Source: FDA drug label - desvenlafaxine er
Examples desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine 7.2 Drugs Having No Clinically Important Interactions with PRISTIQ Based on pharmacokinetic studies, no dosage adjustment is required for drugs that are mainly metabolized by CYP3A4 (e.g., midazolam), or for drugs that are metabolized by both CYP2D6 and CYP3A4 (e.g., tamoxifen, aripiprazole), when administered concomitantly with PRISTIQ [see Clinical Pharmacology (12.3) ].
Source: FDA drug label - desvenlafaxine succinate
Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam. No pharmacokinetic interactions between dexmedetomidine and isoflurane, propofol, alfentanil and midazolam have been demonstrated.
Source: FDA drug label - dexmedetomidine
Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam. No pharmacokinetic interactions between Dexmedetomidine Injection and isoflurane, propofol, alfentanil and midazolam have been demonstrated.
Source: FDA drug label - dexmedetomidine hydrochloride
Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam. No pharmacokinetic interactions between dexmedetomidine and isoflurane, propofol, alfentanil and midazolam have been demonstrated.
Source: FDA drug label - dexmedetomidine hydrochloride in 0.9% sodium chloride
midazolam, pimozide, simvastatin) is necessary when XELSTRYM is co-administered [see CLINICAL PHARMACOLOGY (12.3) ].
Source: FDA drug label - dextroamphetamine
No significant adverse interactions with commonly used premedications or drugs used during anesthesia and surgery (including atropine, scopolamine, glycopyrrolate, diazepam, hydroxyzine, d-tubocurarine, succinylcholine, and other nondepolarizing muscle relaxants) or topical local anesthetics (including lidocaine, dyclonine HCl and Cetacaine) have been observed in adults or pediatric patients.
Source: FDA drug label - midazolam
Benzodiazepines : Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the C max by 2-fold, compared to placebo. The elimination half-life of midazolam and triazolam also increased (1.5- to 2.5-fold) during coadministration with diltiazem. These pharmacokinetic effects seen during diltiazem coadministration can result in increased clinical effects (e.g., prolonged sedation) of both midazolam and triazolam.
Source: FDA drug label - diltiazem hydrochloride
7.2 Effect of PIFELTRO on Other Drugs No clinically significant changes in concentration were observed for the following agents when co-administered with doravirine: dolutegravir, lamivudine, TDF, elbasvir and grazoprevir, ledipasvir and sofosbuvir, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, and midazolam [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - doravirine
Benzodiazepines: oral midazolam ↓ midazolam Consider increasing the dose of midazolam by no more than 2-fold and individualize midazolam therapy based on the patient’s response.
Source: FDA drug label - elagolix and estradiol and norethisterone
No clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following drugs: buprenorphine, itraconazole, ketoconazole, lorazepam, methadone, midazolam, naloxone, norbuprenorphine, norgestimate/ethinyl estradiol, and sertraline.
Source: FDA drug label - emtricitabine and tenofovir alafenamide
Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus, may increase the pharmacologic effect of these benzodiazepines.
Source: FDA drug label - erythromycin
Triazolobenzodiazepines (such as triazolam and alprazolam) and Related Benzodiazepines Erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines.
Source: FDA drug label - erythromycin ethylsuccinate
Erythromycin has been reported to decrease the clearance of triazolam, midazolam and related benzodiazepines, and thus may increase the pharmacological effect of these benzodiazepines.
Source: FDA drug label - erythromycin lactobionate
7.9 Midazolam (CYP3A4/5 Substrate) Single-dose administration of midazolam to healthy volunteers following administration of multiple-dose everolimus indicated that everolimus is a weak inhibitor of CYP3A4/5. Dose adjustment of midazolam or other CYP3A4/5 substrates is not necessary when everolimus is coadministered with midazolam or other CYP3A4/5 substrates [see Clinical Pharmacology ( 12.5 )] .
Source: FDA drug label - everolimus
(See PRECAUTIONS .) Midazolam: The effect of fluconazole on the pharmacokinetics and pharmacodynamics of midazolam was examined in a randomized, cross-over study in 12 volunteers. In addition, a 7.5 mg dose of midazolam was orally ingested on the first day, 0.05 mg/kg was administered intravenously on the fourth day, and 7.5 mg orally on the sixth day. Fluconazole reduced the clearance of IV midazolam by 51%.
Source: FDA drug label - fluconazole
Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam.
Source: FDA drug label - fluoxetine
Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam.
Source: FDA drug label - fluoxetine hydrochloride
Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4(alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ].
Source: FDA drug label - fosaprepitant
Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - fosaprepitant dimeglumine
7.2 Effect of NOURIANZ on Other Drugs CYP3A4 Substrates Coadministration of NOURIANZ 20 mg with a CYP3A4 substrate (midazolam) did not affect the CYP3A4 substrate exposure, while concomitant administration of NOURIANZ 40 mg increased the CYP3A4 substrate (atorvastatin) C max and AUC inf by 1.5-fold [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - istradefylline
Co-administration with oral midazolam, a sensitive CYP3A substrate, increased midazolam exposure 1.5-fold, consistent with weak inhibition of CYP3A by ivacaftor.
Source: FDA drug label - ivacaftor
o Midazolam Midazolam is a 3A4 substrate. There was no effect of lacosamide (200 mg single dose or repeat doses of 400 mg/day given as 200 mg BID) on the pharmacokinetics of midazolam (single dose, 7.5 mg), indicating no inhibitory or inducing effects on CYP3A4.
Source: FDA drug label - lacosamide
Midazolam : Following coadministration of lapatinib and midazolam (CYP3A4 substrate), 24-hour systemic exposure (AUC) of orally administered midazolam increased 45%, while 24-hour AUC of intravenously administered midazolam increased 22%.
Source: FDA drug label - lapatinib
Examples Alfentanil, avanafil, buspirone, conivaptan b , dabigatran etexilate, darifenacin, darunavir, digoxin, ebastine, everolimus, fexofenadine, ibrutinib, lomitapide, lovastatin, lurasidone, midazolam, naloxegol, nisoldipine, saquinavir, simvastatin, sirolimus, tacrolimus, tipranavir b , triazolam, and vardenafil.
Source: FDA drug label - levoketoconazole
From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate is co-administered [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - lisdexamfetamine
From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when VYVANSE is co-administered [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - lisdexamfetamine dimesylate
Other CNS Depressants One case was reported of inadequate sedation with chloral hydrate and later with oral midazolam due to a possible interaction with methylphenidate administered chronically in a 2-year-old boy with a history of Williams syndrome. The sedative effect of midazolam HCl syrup is accentuated by any concomitantly administered medication which depresses the central nervous system, particularly opioids (e.g., morphine, meperidine, and fentanyl), propofol, ketamine, nitrous oxide, secobarbital and droperidol. Consequently, the dose of midazolam HCl syrup should be adjusted according to the type and amount of concomitant medications administered and the desired clinical response [see DOSAGE AND ADMINISTRATION] .
Source: FDA drug label - midazolam hydrochloride
7 DRUG INTERACTIONS Effects of Modafinil 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 modafinil via induction of metabolic enzymes, which results in lower systemic exposure.
Source: FDA drug label - modafinil
7 DRUG INTERACTIONS 7.1 Midazolam (CYP3A4 substrate) In healthy subjects, concomitant administration of a single 8 mg oral dose of Moxidectin Tablets did not have an effect on the pharmacokinetics of midazolam [ see Clinical Pharmacology ( 12.3 ) ].
Source: FDA drug label - moxidectin
Midazolam When administered with netupitant, the systemic exposure to midazolam was significantly increased. Consider the potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) when administering these drugs with AKYNZEO [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - netupitant and palonosetron
No interaction was observed in healthy subjects between midazolam and nifedipine.
Source: FDA drug label - midazolam
In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam.
Source: FDA drug label - olanzapine and fuoxetine
7.5 Benzodiazepines Metabolized by CYP3A4 Concomitant administration of posaconazole with midazolam increases the midazolam plasma concentrations by approximately 5-fold. Increased plasma midazolam concentrations could potentiate and prolong hypnotic and sedative effects.
Source: FDA drug label - posaconazole
7.2 Drugs without Clinically Significant Interactions with ISENTRESS or ISENTRESS HD ISENTRESS In drug interaction studies performed using ISENTRESS film-coated tablets 400 mg twice daily dose, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of the following: ethinyl estradiol/norgestimate, methadone, midazolam, lamivudine, tenofovir disoproxil fumarate, etravirine, darunavir/ritonavir, or boceprevir.
Source: FDA drug label - raltegravir
This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Midazolam Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral ranitidine at a dose of 150 mg twice daily. However, in another interaction study in 8 volunteers receiving IV midazolam, a 300 mg oral dose of ranitidine increased midazolam exposure by about 9%.
Source: FDA drug label - ranitidine
In a placebo-controlled study where saquinavir or placebo was administered orally as a 1200 mg dose, three times a day, for 5 days (n=12), a 56% reduction in the clearance of midazolam following a single 0.05 mg/kg IV dose was observed.
Source: FDA drug label - midazolam
Dosage adjustments of the drugs metabolized by CYP2C8 (e.g., repaglinide) and CYP3A4/5 (e.g., midazolam, sirolimus and tacrolimus) may be necessary if they are given concurrently with spironolactone.
Source: FDA drug label - spironolactone
Because of potential drug-drug interactions, consider dose adjustment of CYP1A2 substrates (e.g., theophylline, caffeine), CYP2B6 substrates (e.g., sertraline, thiotepa), and CYP3A4 substrates (e.g., midazolam, triazolam, quinidine), as clinically appropriate, when administered concomitantly with DIACOMIT.
Source: FDA drug label - stiripentol
Strong CYP3A Inducers Strong CYP3A inhibitor/inducer, based on reported effect on exposures to tacrolimus along with supporting in vitro CYP3A inhibitor/inducer data, or based on drug-drug interaction studies with midazolam (sensitive CYP3A probe substrate).
Source: FDA drug label - tacrolimus
Strong CYP3A Inducers Strong CYP3A inhibitor/inducer, based on reported effect on exposures to tacrolimus along with supporting in vitro CYP3A inhibitor/inducer data, or based on drug-drug interaction studies with midazolam (sensitive CYP3A probe substrate).
Source: FDA drug label - tacrolimus extended-release capsules
Midazolam or Lovastatin) — Tadalafil had no significant effect on exposure (AUC) to midazolam or lovastatin.
Source: FDA drug label - tadalafil
Potential for tezacaftor/ivacaftor to affect other drugs 7.4 CYP3A Substrates Co-administration of SYMDEKO with midazolam (oral), a sensitive CYP3A substrate, did not affect midazolam exposure.
Source: FDA drug label - tezacaftor and ivacaftor
80% increase Midazolam Similar to diazepam.
Source: FDA drug label - theophylline
80% increase Midazolam Similar to diazepam.
Source: FDA drug label - theophylline anhydrous
A phenotypic cocktail study was conducted with 16 healthy volunteers to quantify the influence of 10 days of APTIVUS/ritonavir capsule administration on the activity of hepatic CYP1A2 (caffeine), 2C9 (warfarin), 2C19 (omeprazole), 2D6 (dextromethorphan) and the activity of intestinal and hepatic CYP3A4/5 (midazolam) and P-glycoprotein (P-gp) (digoxin). Benzodiazepines: Parenterally administered midazolam ↑ Midazolam Midazolam is extensively metabolized by CYP3A4. Increases in the concentration of midazolam are expected to be significantly higher with oral than parenteral administration.
Source: FDA drug label - tipranavir
7.5 Effect of Toremifene on CYP3A4 Substrates In a study of 20 healthy subjects, 2 mg midazolam once daily (days 6 and 18) coadministered with toremifene as a 480 mg loading dose followed by 80 mg once daily for 16 days. Following coadministration on days 6 and 18 relevant increases in midazolam and α-hydroxymidazolam Cmax and AUC were not observed. Following coadministration on day 18 midazolam and α-hydroxymidazolam Cmax and AUC were reduced by less than 20%.
Source: FDA drug label - toremifene citrate
Midazolam (CYP3A4 Inhibition) Significantly Increased Increased plasma exposures may increase the risk of adverse reactions and toxicities related to benzodiazepines.
Source: FDA drug label - voriconazole