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Drug overview for JUXTAPID (lomitapide mesylate):
Generic name: lomitapide mesylate (loe-MI-ta-pide)
Drug class: Microsomal Triglyceride Transfer Protein Inhibitors
Therapeutic class: Cardiovascular Therapy Agents
Lomitapide mesylate, an inhibitor of the microsomal triglyceride transfer protein (MTTP), is an antilipemic agent.
No enhanced Uses information available for this drug.
Generic name: lomitapide mesylate (loe-MI-ta-pide)
Drug class: Microsomal Triglyceride Transfer Protein Inhibitors
Therapeutic class: Cardiovascular Therapy Agents
Lomitapide mesylate, an inhibitor of the microsomal triglyceride transfer protein (MTTP), is an antilipemic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
JUXTAPID 5 MG CAPSULE
JUXTAPID 10 MG CAPSULE
JUXTAPID 20 MG CAPSULE
The following indications for JUXTAPID (lomitapide mesylate) have been approved by the FDA:
Indications:
Homozygous familial hypercholesterolemia
Professional Synonyms:
Familial homozygous hypercholesterolemia
Indications:
Homozygous familial hypercholesterolemia
Professional Synonyms:
Familial homozygous hypercholesterolemia
The following dosing information is available for JUXTAPID (lomitapide mesylate):
Dosage of lomitapide mesylate is expressed in terms of lomitapide.
The recommended initial adult dosage of lomitapide for management of homozygous familial hypercholesterolemia is 5 mg once daily; the initial dosage should be continued for at least 2 weeks. After 2 weeks (or longer), dosage may be increased gradually (i.e., at intervals of at least 4 weeks) in a stepwise manner (i.e., to 10, 20, 40, and then 60 mg once daily) based on safety and tolerability; liver function tests (or, at a minimum, ALT and AST concentrations) should be obtained prior to each dosage increase. The maintenance dosage of lomitapide should be individualized, taking into account the patient's goals and response to therapy; lomitapide dosage should not exceed 60 mg daily.
The recommended initial adult dosage of lomitapide for management of homozygous familial hypercholesterolemia is 5 mg once daily; the initial dosage should be continued for at least 2 weeks. After 2 weeks (or longer), dosage may be increased gradually (i.e., at intervals of at least 4 weeks) in a stepwise manner (i.e., to 10, 20, 40, and then 60 mg once daily) based on safety and tolerability; liver function tests (or, at a minimum, ALT and AST concentrations) should be obtained prior to each dosage increase. The maintenance dosage of lomitapide should be individualized, taking into account the patient's goals and response to therapy; lomitapide dosage should not exceed 60 mg daily.
Lomitapide mesylate is administered orally once daily. To reduce the risk of adverse GI effects, the drug should be administered without food, at least 2 hours after the evening meal. Lomitapide capsules should be swallowed whole with a glass of water; capsules should not be opened, crushed, dissolved, or chewed.
If a dose of lomitapide is missed, the next dose should be taken at the regularly scheduled time. If therapy is interrupted for longer than 1 week, patients should contact their healthcare provider before reinitiating therapy.
If a dose of lomitapide is missed, the next dose should be taken at the regularly scheduled time. If therapy is interrupted for longer than 1 week, patients should contact their healthcare provider before reinitiating therapy.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| JUXTAPID 5 MG CAPSULE | Maintenance | Adults take 1 capsule (5 mg) by oral route once daily on an empty stomach, at least 2 hours after the evening meal swallowing whole with water. |
| JUXTAPID 10 MG CAPSULE | Maintenance | Adults take 1 capsule (10 mg) by oral route once daily on an empty stomach, at least 2 hours after the evening meal swallowing whole with water. |
| JUXTAPID 20 MG CAPSULE | Maintenance | Adults take 3 capsules (60 mg) by oral route once daily on an empty stomach, at least 2 hours after the evening meal swallowing whole with water. |
| JUXTAPID 30 MG CAPSULE | Maintenance | Adults take 1 capsule (30 mg) by oral route once daily on an empty stomach, at least 2 hours after the evening meal swallowing whole with water. |
No generic dosing information available.
The following drug interaction information is available for JUXTAPID (lomitapide mesylate):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Selected CYP3A4 Substrates/Mifepristone SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Mifepristone is an inhibitor of CYP3A4 and may increase levels and effects of drugs metabolized by this enzyme.(1) CLINICAL EFFECTS: Lovastatin, simvastatin and CYP3A4 substrates with a narrow therapeutic window such as alprazolam, cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, and tacrolimus or CYP3A4 substrates with a high first pass effect such as oral midazolam, sildenafil, and triazolam are particularly susceptible to significant toxicity.(1,2) PREDISPOSING FACTORS: Due to the need for continuous therapy and mifepristone's long half-life of 85 hours(1) which leads to accumulation, patients with endogenous Cushing's syndrome may be at an increased risk for toxicity. With pimozide, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(3) PATIENT MANAGEMENT: The US manufacturer of mifepristone for hypercortisolism due to endogenous Cushing's syndrome states use with lovastatin, simvastatin, CYP3A4 substrates with a narrow therapeutic range, or CYP3A4 substrates with a high first pass effect is contraindicated.(1) DISCUSSION: Administration of mifepristone 1200 mg daily for 10 days followed by a single dose of simvastatin 80 mg led to an increase of simvastatin and simvastatin acid (active metabolite) area-under-curve (AUC) of 10.4-fold and 15.7-fold, respectively. |
KORLYM, MIFEPREX, MIFEPRISTONE |
| Simvastatin (Greater Than 40 mg)/Lomitapide SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Lomitapide inhibits the metabolism of simvastatin via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of lomitapide may result in elevated levels of simvastatin and an increased risk of myopathy, including rhabdomyolysis.(1) PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. PATIENT MANAGEMENT: The dose of simvastatin should be reduced 50% when used concurrently with lomitapide. The dosage of simvastatin should be limited to 20 mg daily in most patients. A dosage of 40 mg may be used in patients who previously tolerated a daily dose of simvastatin of 80 mg for at least one year.(1,2) If concurrent therapy is deemed medically necessary, monitor patients for signs and symptoms of myopathy/rhabdomyolysis, including muscle pain/tenderness/weakness, fever, unusual tiredness, changes in the amount of urine, and/or discolored urine. DISCUSSION: Administration of lomitapide (60 mg daily for 7 days) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of simvastatin (40 mg) by 99% and 102%, respectively. The AUC and Cmax of simvastatin acid increased by 71% and 57%, respectively.(1,2) Administration of lomitapide (10 mg daily for 7 days) increased the AUC and Cmax of a single dose of simvastatin (20 mg) by 62% and 65%, respectively. The AUC and Cmax of simvastatin acid increased by 39% and 35%, respectively.(1,2) |
EZETIMIBE-SIMVASTATIN, FLOLIPID, SIMVASTATIN, VYTORIN |
| Lomitapide/Strong or Moderate CYP3A4 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Lomitapide is primarily metabolized via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inhibitor of CYP3A4 may result in high to very high levels of and toxicity from lomitapide.(1) PREDISPOSING FACTORS: The interaction may be more severe in patients with hepatic impairment or with end-stage renal disease.(1) PATIENT MANAGEMENT: Given the magnitude of this interaction and the potential toxicity of lomitapide, moderate and strong CYP3A4 inhibitors are contraindicated.(1) When possible use an alternative to the CYP3A4 inhibitor. If a moderate or strong CYP3A4 inhibitor is required, discontinue lomitapide. Due to its long half-life, it will take 1 to 2 weeks for remaining lomitapide to be eliminated; thus lomitapide adverse effects could occur after discontinuation. The US manufacturer of itraconazole states that concurrent use with lomitapide is contraindicated during and two weeks after itraconazole treatment.(4) DISCUSSION: Concurrent administration with ketoconazole (a strong inhibitor of CYP3A4) increased lomitapide area-under-curve (AUC) by 27-fold.(1) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, tucatinib, and voriconazole.(1-3,5) Moderate inhibitors of CYP3A4 include: amprenavir, aprepitant, atazanavir, avacopan, berotralstat, clofazimine, conivaptan, crizotinib, darunavir/ritonavir, diltiazem, dronedarone, duvelisib, erythromycin, fedratinib, fluconazole (also a CYP2C19 inhibitor), fluvoxamine, fosamprenavir, fosnetupitant, imatinib, isavuconazonium, lenacapavir, lefamulin, letermovir, netupitant, nilotinib, nirogacestat, schisandra, treosulfan and verapamil.(1-3) |
AKYNZEO, APONVIE, APREPITANT, APTIVUS, ATAZANAVIR SULFATE, CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CINVANTI, CLARITHROMYCIN, CLARITHROMYCIN ER, CLOFAZIMINE, CONIVAPTAN-D5W, COPIKTRA, CRESEMBA, DARUNAVIR, DIFLUCAN, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM-D5W, E.E.S. 200, E.E.S. 400, EMEND, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, EVOTAZ, FLUCONAZOLE, FLUCONAZOLE-NACL, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, FOSAMPRENAVIR CALCIUM, GENVOYA, GLEEVEC, IMATINIB MESYLATE, INREBIC, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MATZIM LA, MULTAQ, NEFAZODONE HCL, NOXAFIL, OGSIVEO, OMECLAMOX-PAK, ORLADEYO, PAXLOVID, POSACONAZOLE, PREVYMIS, PREZCOBIX, PREZISTA, RECORLEV, REYATAZ, SPORANOX, STRIBILD, SUNLENCA, SYMTUZA, TASIGNA, TAVNEOS, TIADYLT ER, TIAZAC, TOLSURA, TRANDOLAPRIL-VERAPAMIL ER, TUKYSA, TYBOST, VAPRISOL-5% DEXTROSE, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR, VERELAN PM, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, XALKORI, XENLETA, ZOKINVY, ZYDELIG, ZYKADIA |
| Lemborexant (Greater Than 5 mg)/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Inhibitors of CYP3A4 may inhibit the metabolism of lemborexant.(1) CLINICAL EFFECTS: Concurrent use of an inhibitor of CYP3A4 may result in increased levels of and effects from lemborexant, including somnolence, fatigue, CNS depressant effects, daytime impairment, headache, and nightmare or abnormal dreams.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The maximum recommended dose of lemborexant with concurrent use of a weak CYP3A4 inhibitors should not exceed 5 mg per dose.(1) DISCUSSION: Lemborexant is a CYP3A4 substrate. In a PKPB model, concurrent use of lemborexant with itraconazole increased area-under-curve (AUC) and concentration maximum (Cmax) by 3.75-fold and 1.5-fold, respectively. Concurrent use of lemborexant with fluconazole increased AUC and Cmax by 4.25-fold and 1.75-fold, respectively.(1) Weak inhibitors of CYP3A4 include: alprazolam, amiodarone, amlodipine, asciminib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, daridorexant, delavirdine, dihydroberberine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, rucaparib, selpercatinib, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan.(1,2) |
DAYVIGO |
There are 3 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Lomitapide (Less Than or Equal To 30 mg)/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of lomitapide.(1) Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Thus even weak CYP3A4 inhibitors may affect lomitapide exposure (AUC, area-under-curve). CLINICAL EFFECTS: Concurrent use of a weak inhibitor of CYP3A4 may result in 2-fold increases in lomitapide levels and toxicity from lomitapide.(1) PREDISPOSING FACTORS: This interaction may be more severe in patients with hepatic impairment or with end-stage renal disease.(1) PATIENT MANAGEMENT: The maximum lomitapide dose should be 30 mg daily for patients taking concomitant weak CYP3A4 inhibitors. Due to lomitapide's long half-life, it may take 1 to 2 weeks to see the full effect of this interaction. When initiating a weak CYP3A4 inhibitor in patients taking lomitapide 10 mg daily or more, decrease the dose of lomitapide by 50%. In patients taking lomitapide 5 mg daily, continue current dose. DISCUSSION: Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Based upon interactions with stronger inhibitors, weak inhibitors of CYP3A4 are predicted to increase lomitapide area-under-curve(AUC) 2-fold.(1) Weak CYP3A4 inhibitors linked to this interaction include alprazolam, amiodarone, amlodipine, asciminib, atorvastatin, azithromycin, Baikal skullcap, bicalutamide, blueberry juice, brodalumab, cannabidiol, capivasertib, cilostazol, cimetidine, ciprofloxacin, chlorzoxazone, clotrimazole, cranberry juice, cyclosporine, daridorexant, delavirdine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, larotrectinib, lacidipine, lapatinib, lazertinib, leflunomide, levamlodipine, linagliptin, lurasidone, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, rucaparib, selpercatinib, sitaxsentan, skullcap, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, vonoprazan, and zileuton.(1-3) |
ADDYI, AFINITOR, AFINITOR DISPERZ, ALPRAZOLAM, ALPRAZOLAM ER, ALPRAZOLAM INTENSOL, ALPRAZOLAM ODT, ALPRAZOLAM XR, AMIODARONE HCL, AMIODARONE HCL-D5W, AMLODIPINE BESILATE, AMLODIPINE BESYLATE, AMLODIPINE BESYLATE-BENAZEPRIL, AMLODIPINE-ATORVASTATIN, AMLODIPINE-OLMESARTAN, AMLODIPINE-VALSARTAN, AMLODIPINE-VALSARTAN-HCTZ, ARAVA, ASPRUZYO SPRINKLE, ATORVALIQ, ATORVASTATIN CALCIUM, AUBAGIO, AZITHROMYCIN, AZOR, BICALUTAMIDE, BRILINTA, CADUET, CASODEX, CHLORZOXAZONE, CILOSTAZOL, CIMETIDINE, CIMETIDINE HCL, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W, CLOTRIMAZOLE, CONJUPRI, CONSENSI, CYCLOSPORINE, CYCLOSPORINE MODIFIED, DAYBUE, DIPRIVAN, DUVYZAT, EMEND, EPIDIOLEX, EVEROLIMUS, EXFORGE, EXFORGE HCT, FLIBANSERIN, FOCINVEZ, FOSAPREPITANT DIMEGLUMINE, GENGRAF, GLYXAMBI, IBRANCE, ISONIAZID, ISTURISA, JAYPIRCA, JENTADUETO, JENTADUETO XR, JYNARQUE, KALYDECO, KATERZIA, LAPATINIB, LATUDA, LAZCLUZE, LEFLUNICLO, LEFLUNOMIDE, LEVAMLODIPINE MALEATE, LIPITOR, LORZONE, LOTREL, LURASIDONE HCL, LYNPARZA, MAVYRET, NEORAL, NEXTERONE, NORLIQVA, NORVASC, NOURIANZ, OLMESARTAN-AMLODIPINE-HCTZ, PACERONE, PAZOPANIB HCL, PRESTALIA, PROPOFOL, PROPOVEN (EUA), QELBREE, QUVIVIQ, RANOLAZINE ER, RETEVMO, RUBRACA, SAMSCA, SANDIMMUNE, SCEMBLIX, SILIQ, TAVALISSE, TELMISARTAN-AMLODIPINE, TERIFLUNOMIDE, TOLVAPTAN, TORPENZ, TRADJENTA, TRIBENZOR, TRIJARDY XR, TRUQAP, TYKERB, VITRAKVI, VOQUEZNA, VOQUEZNA DUAL PAK, VOTRIENT, XANAX, XANAX XR, XOLREMDI, ZEPATIER, ZILEUTON ER, ZITHROMAX, ZITHROMAX TRI-PAK, ZORTRESS, ZYFLO |
| Lomitapide (Less Than or Equal To 40 mg)/Hormonal Contraceptives SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Hormonal contraceptives are weak inhibitors of CYP3A4 and may inhibit the metabolism of lomitapide.(1) Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Thus even weak CYP3A4 inhibitors may affect lomitapide exposure (AUC, area-under-curve). CLINICAL EFFECTS: Concurrent use of a weak inhibitor of CYP3A4 may result in 2-fold increases in lomitapide levels and toxicity from lomitapide.(1) PREDISPOSING FACTORS: This interaction may be more severe in patients with hepatic impairment or with end-stage renal disease.(1) PATIENT MANAGEMENT: The maximum lomitapide dose should be 40 mg daily for patients taking hormonal contraceptives. Due to lomitapide's long half-life, it may take 1 to 2 weeks to see the full effect of this interaction. When initiating a hormonal contraceptive in patients taking lomitapide 10 mg daily or more, decrease the dose of lomitapide by 50%. In patients taking lomitapide 5 mg daily, continue current dose. DISCUSSION: Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Based upon interactions with stronger inhibitors, weak inhibitors of CYP3A4 are predicted to increase lomitapide area-under-curve(AUC) 2-fold.(1) |
AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, ANGELIQ, ANNOVERA, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL, CHATEAL EQ, COVARYX, COVARYX H.S., CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DESOGESTR-ETH ESTRAD ETH ESTRA, DOLISHALE, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, EEMT, EEMT H.S., ELINEST, ELURYNG, ENILLORING, ENPRESSE, ENSKYCE, ESTARYLLA, ESTRATEST F.S., ESTROGEN-METHYLTESTOSTERONE, ETHYNODIOL-ETHINYL ESTRADIOL, ETONOGESTREL-ETHINYL ESTRADIOL, FALMINA, FEMLYV, FINZALA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HALOETTE, ICLEVIA, ISIBLOOM, JAIMIESS, JASMIEL, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KELNOR 1-50, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEENA, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LEVORA-28, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUTERA, MARLISSA, MERZEE, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN 24 FE, MICROGESTIN FE, MILI, MONO-LINYAH, NATAZIA, NECON, NEXTSTELLIS, NIKKI, NORELGESTROMIN-ETH ESTRADIOL, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NUVARING, NYLIA, NYMYO, OCELLA, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, QUARTETTE, RECLIPSEN, RIVELSA, SAFYRAL, SETLAKIN, SIMLIYA, SIMPESSE, SPRINTEC, SRONYX, SYEDA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-NYMYO, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TRIVORA-28, TURQOZ, TWIRLA, TYBLUME, TYDEMY, VELIVET, VESTURA, VIENVA, VIORELE, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XULANE, YASMIN 28, YAZ, ZAFEMY, ZARAH, ZOVIA 1-35, ZUMANDIMINE |
| Eliglustat/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of eliglustat. If the patient is also taking an inhibitor of CYP2D6, eliglustat metabolism can be further inhibited.(1) CLINICAL EFFECTS: Concurrent use of an agent that is a weak inhibitor of CYP3A4 may result in elevated levels of and clinical effects of eliglustat, including prolongation of the PR, QTc, and/or QRS intervals, which may result in life-threatening cardiac arrhythmias.(1) PREDISPOSING FACTORS: If the patient is also taking an inhibitor of CYP2D6, is a poor metabolizer of CYP2D6, and/or has hepatic impairment, eliglustat metabolism can be further inhibited.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The concurrent use of eliglustat with weak inhibitors of CYP3A4 in poor metabolizers of CYP2D6 should be avoided.(1) The dosage of eliglustat with weak inhibitors of CYP3A4 in extensive metabolizers of CYP2D6 with mild (Child-Pugh Class A) hepatic impairment should be limited to 84 mg daily.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: Ketoconazole (400 mg daily), a strong inhibitor of CYP3A4, increased eliglustat (84 mg BID) maximum concentration (Cmax) and area-under-curve (AUC) by 4-fold and 4.4-fold, respectively, in extensive metabolizers. Physiologically-based pharmacokinetic (PKPB) models suggested ketoconazole would increase eliglustat Cmax and AUC by 4.4-fold and 5.4-fold, respectively, in intermediate metabolizers. PKPB models suggested ketoconazole may increase the Cmax and AUC of eliglustat (84 mg daily) by 4.3-fold and 6.2-fold, respectively, in poor metabolizers.(1) PKPB models suggested fluconazole, a moderate inhibitor of CYP3A4, would increase eliglustat Cmax and AUC by 2.8-fold and 3.2-fold, respectively, in extensive metabolizers and by 2.5-fold and 2.9-fold, respectively in intermediate metabolizers. PKPB models suggest that concurrent eliglustat (84 mg BID), paroxetine (a strong inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 16.7-fold and 24.2-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 7.5-fold and 9.8-fold, respectively.(1) PKPB models suggest that concurrent eliglustat (84 mg BID), terbinafine (a moderate inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 10.2-fold and 13.6-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 4.2-fold and 5-fold, respectively.(1) Weak inhibitors of CYP3A4 include: alprazolam, amlodipine, asciminib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, daridorexant, delavirdine, dihydroberberine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranolazine, resveratrol, roxithromycin, rucaparib, selpercatinib, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, and vonoprazan.(3,4) |
CERDELGA |
There are 7 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Lovastatin; Simvastatin (Less than or Equal To 40 mg)/Lomitapide SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Lomitapide inhibits the metabolism of lovastatin and simvastatin via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of lomitapide may result in elevated levels of lovastatin or simvastatin and an increased risk of myopathy, including rhabdomyolysis.(1) PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. PATIENT MANAGEMENT: The dose of simvastatin should be reduced 50% when used concurrently with lomitapide. The dosage of simvastatin should be limited to 20 mg daily in most patients. A dosage of 40 mg may be used in patients who previously tolerated a daily dose of simvastatin of 80 mg for at least one year.(1,2) Similar reductions should be considered for lovastatin.(1) DISCUSSION: Administration of lomitapide (60 mg daily for 7 days) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of simvastatin (40 mg) by 99% and 102%, respectively. The AUC and Cmax of simvastatin acid increased by 71% and 57%, respectively.(1,2) Administration of lomitapide (10 mg daily for 7 days) increased the AUC and Cmax of a single dose of simvastatin (20 mg) by 62% and 65%, respectively. The AUC and Cmax of simvastatin acid increased by 39% and 35%, respectively.(1,2) |
ALTOPREV, EZETIMIBE-SIMVASTATIN, LOVASTATIN, SIMVASTATIN, VYTORIN, ZOCOR |
| Warfarin/Lomitapide SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Lomitapide is a weak CYP2C9 inhibitor and a weak CYP3A inhibitor which may decrease the metabolism of both the S-enantiomer and R-enantiomer of warfarin, respectively.(2-4) CLINICAL EFFECTS: Concurrent use of lomitapide may result in elevated levels of warfarin and INR.(1) Concurrent use of warfarin and lomitapide may increase the risk for bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). Pharmacogenomic information: patients with a CYP2C9 intermediate metabolizer genotype, and/or 1-2 copies of a reduced function VKORC1 gene are expected to be more susceptible to this interaction. Although patients with a pre-existing CYP2C9 poor metabolizer genotype are expected to be less susceptible to effects from this drug combination, their reduced function genotypes (e.g. CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3) result in an inherently higher warfarin half-life and risk for warfarin-associated bleeding. CYP2C9 poor metabolizers generally require lower anticoagulant doses and more time (>2 to 4 weeks) to achieve effective and safe anticoagulation than patients without these CYP2C9 variants. PATIENT MANAGEMENT: Monitor INRs frequently until stable in patients who start lomitapide therapy, or have the lomitapide dose adjusted.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. Discontinue anticoagulation in patients with active pathologic bleeding. DISCUSSION: Administration of lomitapide (60 mg daily for 7 days) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a R-warfarin by 28% and 14%, respectively, following the administration of a single dose of warfarin (10 mg). The AUC and Cmax of S-warfarin increased by 30% and 15%, respectively. INR values increased by 22%.(1) In clinical trials for lomitapide, one of five patients receiving concurrent warfarin had to withdraw from the trial as a result of difficulty in controlling INR values.(1) |
JANTOVEN, WARFARIN SODIUM |
| Lomitapide/Bile Acid Sequestrants; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants and sevelamer may decrease the gastrointestinal absorption of lomitapide. CLINICAL EFFECTS: Simultaneous administration of a bile acid sequestrant or sevelamer may result in decreased absorption and effectiveness of lomitapide.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: For maximal bioavailability, the manufacturer of lomitapide states lomitapide and bile acid sequestrant administration should be separated by at least 4 hours.(1) Although used for hyperphosphatemia, sevelamer is linked to this monograph due to its structural and pharmacologic similarities to colesevelam. Both agents are non-absorbed cross linked polymers with a high affinity for bile acids.(2) DISCUSSION: Lomitapide maximal systemic concentrations occur approximately 6 hours after administration. Although an interaction study has not been performed, the manufacturer of lomitapide recommends separating bile acid sequestrant administration for a minimum of 4 hours before or after lomitapide dose.(1) |
CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, RENVELA, SEVELAMER CARBONATE, SEVELAMER HCL, WELCHOL |
| Tacrolimus/Moderate and Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate and weak inhibitors of CYP3A4 may inhibit the metabolism of tacrolimus.(1) CLINICAL EFFECTS: Concurrent use of a CYP3A4 inhibitor may result in elevated levels of and toxicity from tacrolimus, including nephrotoxicity, neurotoxicity, and prolongation of the QTc interval and life-threatening cardiac arrhythmias, including torsades de pointes.(1) PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The US manufacturer of tacrolimus recommends monitoring tacrolimus whole blood trough concentrations and reducing tacrolimus dose if needed.(1) Consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study of 26 renal transplant recipients, conjugated estrogens 3.75 mg daily increased the tacrolimus dose-corrected concentration of tacrolimus by 85.6%. Discontinuation of the conjugated estrogens led to a decrease in tacrolimus concentration of 46.6%.(3) A case report describes a 65-year-old kidney transplant recipient who was stable on tacrolimus 9 mg per day with trough levels of 5 to 7.5 ng/mL. Ten days after starting on estradiol gel 0.5 mg per day, her tacrolimus level rose to 18.3 ng/mL and serum creatinine (Scr) rose from 1.1 mg/dL at baseline to 2 mg/dL. Tacrolimus dose was reduced by 60%, and trough levels and Scr normalized after two weeks.(4) A study of 16 healthy volunteers found that elbasvir 50 mg/grazoprevir 200 mg daily increased the area-under-curve (AUC) of tacrolimus by 43%, while the maximum concentration (Cmax) of tacrolimus was decreased by 40%.(5) An analysis of FAERS data from 2004-2017, found a significant assoc ation between transplant rejection and concurrent use of tacrolimus and clotrimazole (reporting odds ration 1.92, 95% CI). A retrospective study of 7 heart transplant patients on concurrent tacrolimus and clotrimazole troche showed a significant correlation between tacrolimus trough concentration and AUC after clotrimazole discontinuation. Tacrolimus clearance and bioavailability after clotrimazole discontinuation was 2.2-fold greater (0.27 vs. 0.59 L/h/kg) and the trough concentration decreased from 6.5 ng/mL at 1 day to 5.3 ng/mL at 2 days after clotrimazole discontinuation.(7) A retrospective study of 26 heart transplant patients found that discontinuation of concurrent clotrimazole with tacrolimus in the CYP3A5 expresser group had a 3.3-fold increase in apparent oral clearance and AUC of tacrolimus (0.27 vs. 0.89 L/h/kg) compared to the CYP3A5 non expresser group with a 2.2-fold mean increase (0.18 vs. 0.39 L/h/kg).(8) A study of 6 adult kidney transplant recipients found that clotrimazole (5-day course) increased the tacrolimus AUC 250% and the blood trough concentrations doubled (27.7 ng/ml versus 27.4 ng/ml). Tacrolimus clearance decreased 60% with coadministration of clotrimazole.(9) A case report describes a 23-year-old kidney transplant recipient who was stable on tacrolimus 5 mg twice daily, mycophenolate mofetil 30 mg daily, prednisone (30 mg daily tapered over time to 5 mg), and clotrimazole troche 10 mg four times daily. Discontinuation of clotrimazole resulted in a decrease in tacrolimus trough levels from 13.7 ng/ml to 5.4 ng/ml over a period of 6 days. Clotrimazole was restarted with tacrolimus 6 mg resulting in an increased tacrolimus level of 19.2 ng/ml.(10) A retrospective study in 95 heart transplant recipients on concurrent clotrimazole and tacrolimus found a median tacrolimus dose increase of 66.7% was required after clotrimazole discontinuation. Tacrolimus trough concentration was found to have decreased 42.5% after clotrimazole discontinuation.(11) A retrospective study in 65 pancreas transplant patients on concurrent tacrolimus, clotrimazole, cyclosporine, and prednisone found that clotrimazole discontinuation at 3 months after transplantation may cause significant tacrolimus trough level reductions.(12) Moderate CYP3A4 inhibitors linked to this monograph include: aprepitant, berotralstat, clofazimine, conivaptan, fluvoxamine, lenacapavir, letermovir, netupitant, nirogacestat, and tofisopam.(6) Weak CYP3A4 inhibitors linked to this monograph include: alprazolam, avacopan, baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, chlorzoxazone, cimetidine, cranberry juice, daclatasvir, daridorexant, delavirdine, diosmin, estrogens, flibanserin, fosaprepitant, fostamatinib, ginkgo biloba, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lazertinib, linagliptin, lomitapide, lumateperone, lurasidone, peppermint oil, piperine, propiverine, ranitidine, resveratrol, rimegepant, simeprevir, sitaxsentan, skullcap, suvorexant, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan-amoxicillin.(6) |
ASTAGRAF XL, ENVARSUS XR, PROGRAF, TACROLIMUS, TACROLIMUS XL |
| Lemborexant (Less Than or Equal To 5 mg)/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of CYP3A4 may inhibit the metabolism of lemborexant.(1) CLINICAL EFFECTS: Concurrent use of an inhibitor of CYP3A4 may result in increased levels of and effects from lemborexant, including somnolence, fatigue, CNS depressant effects, daytime impairment, headache, and nightmare or abnormal dreams.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The maximum recommended dose of lemborexant with concurrent use of a weak CYP3A4 inhibitors should not exceed 5 mg per dose.(1) DISCUSSION: Lemborexant is a CYP3A4 substrate. In a PKPB model, concurrent use of lemborexant with itraconazole increased area-under-curve (AUC) and concentration maximum (Cmax) by 3.75-fold and 1.5-fold, respectively. Concurrent use of lemborexant with fluconazole increased AUC and Cmax by 4.25-fold and 1.75-fold, respectively.(1) Weak inhibitors of CYP3A4 include: alprazolam, amiodarone, amlodipine, asciminib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, daridorexant, delavirdine, dihydroberberine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, rucaparib, selpercatinib, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan.(1,2) |
DAYVIGO |
| Ubrogepant/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of ubrogepant.(1) CLINICAL EFFECTS: Concurrent use of ubrogepant with weak CYP3A4 inhibitors may result in an increase in exposure of ubrogepant.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when used concomitantly with weak CYP3A4 inhibitors. Initial dose of ubrogepant should not exceed 50 mg when used concomitantly with weak inhibitors of CYP3A4. A second dose may be given within 24 hours but should not exceed 50 mg when used concurrently with weak CYP3A4 inhibitors.(1) DISCUSSION: Coadministration of ubrogepant with verapamil, a moderate CYP3A4 inhibitor, resulted in a 3.5-fold and 2.8-fold increase in area-under-curve (AUC) and concentration maximum (Cmax), respectively. No dedicated drug interaction study was conducted to assess concomitant use with weak CYP3A4 inhibitors. The conservative prediction of the maximal potential increase in ubrogepant exposure with weak CYP3A4 inhibitors is not expected to be more than 2-fold.(1) Weak inhibitors of CYP3A4 include: alprazolam, amiodarone, amlodipine, asciminib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, delavirdine, dihydroberberine, diosmin, elagolix, everolimus, flibanserin, fosaprepitant, fostamatinib, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, mavorixafor, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, resveratrol, roxithromycin, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan.(2,3) |
UBRELVY |
| Sirolimus Protein-Bound/Slt Moderate and Weak CYP3A4 Inhibit SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate and weak CYP3A4 inhibitors may inhibit the metabolism of sirolimus by CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of moderate or weak CYP3A4 inhibitors may result in elevated levels of and side effects from sirolimus.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sirolimus protein-bound injection (Fyarro) states a dose reduction to 56 mg/m2 is recommended when used concurrently with moderate or weak CYP3A4 inhibitors. Concurrent use with strong CYP3A4 inhibitors should be avoided.(1) DISCUSSION: In an open, randomized, cross-over trial in 18 healthy subjects, concurrent single doses of diltiazem (120 mg) and sirolimus (10 mg) increased sirolimus area-under-curve (AUC) and maximum concentration (Cmax) by 60% and by 43%, respectively. Sirolimus apparent oral clearance and volume of distribution decreased by 38% and 45%, respectively. There were no effects on diltiazem pharmacokinetics or pharmacodynamics.(2) In a study in 26 healthy subjects, concurrent sirolimus (2 mg daily) with verapamil (180 mg twice daily) increased sirolimus AUC and Cmax by 2.2-fold and 2.3-fold, respectively. The AUC and Cmax of the active S-enantiomer of verapamil each increased by 1.5-fold. Verapamil time to Cmax (Tmax) was increased by 1.2 hours.(2) Moderate and weak CYP3A4 inhibitors linked to this monograph include: alprazolam, amlodipine, aprepitant, avacopan, azithromycin, berberine, berotralstat, bicalutamide, blueberry, brodalumab, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clofazimine, conivaptan, daclatasvir, daridorexant, delavirdine, diosmin, entrectinib, erythromycin, estrogen, flibanserin, fluvoxamine, fosaprepitant, fosnetupitant, fostamatinib, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lazertinib, lenacapavir, levamlodipine, linagliptin, lomitapide, lumateperone, lurasidone, mavorixafor, netupitant, omeprazole, osilodrostat, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, resveratrol, rimegepant, roxithromycin, scutellarin, simeprevir, sitaxsentan, suvorexant, ticagrelor, tofisopam, tolvaptan, trofinetide and vonoprazan.(3,4) |
FYARRO |
The following contraindication information is available for JUXTAPID (lomitapide mesylate):
Drug contraindication overview.
Lomitapide mesylate is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C); patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations; women who are pregnant; and patients receiving concomitant therapy with moderate or potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4.
Lomitapide mesylate is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C); patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations; women who are pregnant; and patients receiving concomitant therapy with moderate or potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4.
There are 4 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Alcohol use disorder |
| Hepatic cirrhosis |
| Lactation |
| Pregnancy |
There are 3 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Disease of liver |
| Malabsorption states |
There are 0 moderate contraindications.
The following adverse reaction information is available for JUXTAPID (lomitapide mesylate):
Adverse reaction overview.
Adverse effects reported in 10% or more of patients receiving lomitapide in the pivotal study include diarrhea, nausea, dyspepsia, vomiting, abdominal pain, weight loss, chest pain, abdominal discomfort, abdominal distention, constipation, flatulence, influenza, nasopharyngitis, increased ALT, fatigue, gastroenteritis, back pain, pharyngolaryngeal pain, gastroesophageal reflux disease, defecation urgency, rectal tenesmus, fever, headache, dizziness, nasal congestion, angina pectoris, and palpitations.
Adverse effects reported in 10% or more of patients receiving lomitapide in the pivotal study include diarrhea, nausea, dyspepsia, vomiting, abdominal pain, weight loss, chest pain, abdominal discomfort, abdominal distention, constipation, flatulence, influenza, nasopharyngitis, increased ALT, fatigue, gastroenteritis, back pain, pharyngolaryngeal pain, gastroesophageal reflux disease, defecation urgency, rectal tenesmus, fever, headache, dizziness, nasal congestion, angina pectoris, and palpitations.
There are 6 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Gastroenteritis Increased alanine transaminase Increased aspartate transaminase |
| Rare/Very Rare |
|---|
|
Hepatitis Severe diarrhea Steatosis of liver |
There are 28 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Chest pain Diarrhea Dyspepsia Nausea Pharyngitis Sore throat Vomiting |
Abdominal distension Angina Back pain Constipation Dizziness Essential fatty acid deficiency Fatigue Fecal urgency Fever Flatulence Gastroesophageal reflux disease Headache disorder Influenza Nasal congestion Palpitations Tenesmus Vitamin E deficiency Weight loss |
| Rare/Very Rare |
|---|
|
Alopecia Myalgia |
The following precautions are available for JUXTAPID (lomitapide mesylate):
Safety and efficacy of lomitapide have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| Lomitapide | 1 Day – 18 Years | Safety and efficacy not established. |
Category X. (See Users Guide.) (See Cautions: Contraindications and also see Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Other Warnings and Precautions, in Cautions.) To monitor pregnancy outcomes in women who have been exposed to lomitapide, a pregnancy registry has been established. Clinicians are encouraged to enroll patients who become pregnant while receiving lomitapide in the registry; women also may enroll themselves in the registry by calling 877-902-4099 or visiting http://www.juxtapid.com.
| Drug/Drug Class | Severity | Precaution Description | Pregnancy Category Description |
|---|---|---|---|
| Lomitapide | 1 | Based on drug pharmacology and animal data, dev tox may occur | Contraindicated or not recommended. Existing fda teratogenicity category (if available) is augmented by information supporting a more severe warning. |
It is not known whether lomitapide is distributed into human milk. Because many drugs are distributed into human milk and because of the potential for tumorigenicity (demonstrated in animal studies), a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Contraindicated
Absolute contraindication. (Human data usually available to support recommendations.) This drug should not be given to breast feeding mothers.
Contraindicated
Absolute contraindication. (Human data usually available to support recommendations.) This drug should not be given to breast feeding mothers.
| Drug Name | Excretion Potential | Effect on Infant | Notes |
|---|---|---|---|
| Lomitapide | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Potential for serious adverse events, mfg does not recommend |
Clinical studies of lomitapide did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. Dosage should be selected with caution. (See Dosage and Administration: Special Populations.)
The following prioritized warning is available for JUXTAPID (lomitapide mesylate):
WARNING: Lomitapide may rarely cause serious (possibly fatal) liver disease. This medication increases fat in the liver, which may also increase the risk for liver disease. Careful monitoring by your doctor may decrease your risk.
Lab and/or medical tests (such as liver function) should be done before starting treatment and while you are taking this medication. Keep all medical and lab appointments. Get medical help right away if you have any symptoms of liver damage, such as nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.
To receive lomitapide in the United States, you must understand, agree to, and carefully follow the requirements of the REMS Program for this medication. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.
WARNING: Lomitapide may rarely cause serious (possibly fatal) liver disease. This medication increases fat in the liver, which may also increase the risk for liver disease. Careful monitoring by your doctor may decrease your risk.
Lab and/or medical tests (such as liver function) should be done before starting treatment and while you are taking this medication. Keep all medical and lab appointments. Get medical help right away if you have any symptoms of liver damage, such as nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.
To receive lomitapide in the United States, you must understand, agree to, and carefully follow the requirements of the REMS Program for this medication. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.
The following icd codes are available for JUXTAPID (lomitapide mesylate)'s list of indications:
| Homozygous familial hypercholesterolemia | |
| E78.01 | Familial hypercholesterolemia |
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