Cystic fibrosis: Note: Efficacy and safety have not been established in patients with CF other than those homozygous for the F508del mutation.
Oral: Lumacaftor 200 mg/ivacaftor 125 mg: 2 tablets (lumacaftor 400 mg/ivacaftor 250 mg per dose) every 12 hours.
Missed dose: If a dose is missed ≤6 hours of the usual time it is taken, take the dose as soon as possible; otherwise, skip the missed dose and resume the normal dosing schedule.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
End-stage renal disease (ESRD): There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Hepatic impairment prior to treatment initiation:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Reduce the dose to 2 tablets (lumacaftor 400 mg/ivacaftor 250 mg per dose) in the morning and 1 tablet (lumacaftor 200 mg/ivacaftor 125 mg per dose) in the evening.
Severe impairment (Child-Pugh class C): Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, administer a maximum dose of 1 tablet (lumacaftor 200 mg/ivacaftor 125 mg per dose) every 12 hours or less frequently.
Hepatotoxicity during treatment: ALT or AST >5 times ULN (without concomitant elevated bilirubin) or >3 times ULN (with concomitant bilirubin >2 times ULN): Temporarily discontinue lumacaftor/ivacaftor; may resume if elevated transaminases resolved and after assessing benefits vs risks of continued treatment.
Refer to adult dosing.
(For additional information see "Lumacaftor and ivacaftor: Pediatric drug information")
Cystic fibrosis: Note: Orkambi is a fixed dose combination product; use caution when selecting dosage form.
Children 1 to <2 years (Ref):
Weight 7 to <9 kg: Oral: Lumacaftor 75 mg/ivacaftor 94 mg granule packet: 1 packet every 12 hours.
Weight 9 to <14 kg: Oral: Lumacaftor 100 mg/ivacaftor 125 mg granule packet: 1 packet every 12 hours.
Weight ≥14 kg: Oral: Lumacaftor 150 mg/ivacaftor 188 mg granule packet: 1 packet every 12 hours.
Children 2 to 5 years:
Weight <14 kg: Oral: Lumacaftor 100 mg/ivacaftor 125 mg granule packet: 1 packet every 12 hours.
Weight ≥14 kg: Oral: Lumacaftor 150 mg/ivacaftor 188 mg granule packet: 1 packet every 12 hours.
Children ≥6 to 11 years: Oral: Lumacaftor 100 mg/ivacaftor 125 mg tablets: 2 tablets every 12 hours (lumacaftor 200 mg/ivacaftor 250 mg per dose).
Children ≥12 years and Adolescents: Oral: Lumacaftor 200 mg/ivacaftor 125 mg tablets: 2 tablets every 12 hours (lumacaftor 400 mg/ivacaftor 250 mg per dose).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥1 year and Adolescents:
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl ≤30 mL/minute: There are no dosing adjustments provided in the manufacturer's labeling (not studied); use with caution.
End-stage renal disease: There are no dosing adjustments provided in the manufacturer's labeling (not studied); use with caution.
Hepatic impairment prior to initiation:
Children 1 to <2 years: Oral:
Weight 7 to <9 kg: Lumacaftor 75 mg/ivacaftor 94 mg granule packet:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 1 packet every morning and 1 packet every other evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 packet every morning or less often.
Weight 9 to <14 kg: Lumacaftor 100 mg/ivacaftor 125 mg granule packet:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 1 packet every morning and 1 packet every other evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 packet every morning or less often.
Weight ≥14 kg: Lumacaftor 150 mg/ivacaftor 188 mg granule packet:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 1 packet every morning and 1 packet every other evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 packet every morning or less often.
Children 2 to 5 years: Oral:
Weight <14 kg: Lumacaftor 100 mg/ivacaftor 125 mg granule packet:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 1 packet every morning and 1 packet every other evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 packet every morning or less often.
Weight ≥14 kg: Lumacaftor 150 mg/ivacaftor 188 mg granule packet:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 1 packet every morning and 1 packet every other evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 packet every morning or less often.
Children ≥6 to 11 years: Lumacaftor 100 mg/ivacaftor 125 mg tablets: Oral:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 2 tablets in the morning and 1 tablet in the evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 tablet every 12 hours or less often.
Children ≥12 years and Adolescents: Lumacaftor 200 mg/ivacaftor 125 mg tablets: Oral:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: Reduce the dose to 2 tablets in the morning and 1 tablet in the evening.
Severe impairment: Use with caution, weighing the risks and benefits of treatment. If therapy is appropriate, reduce the dose to 1 tablet every 12 hours or less often.
Hepatotoxicity during treatment: Children ≥2 years and Adolescents:
ALT or AST >5 times ULN without concomitant elevated bilirubin: Temporarily discontinue lumacaftor/ivacaftor; may resume if elevated transaminases resolved and after assessing benefits vs risks of continued treatment.
ALT or AST >3 times ULN with concomitant bilirubin >2 times ULN: Temporarily discontinue lumacaftor/ivacaftor; may resume if elevated transaminases resolved and after assessing benefits vs risks of continued treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences listed are for adolescents and adults unless otherwise specified. Also see ivacaftor.
>10%:
Cardiovascular: Chest discomfort (children: ≤11%; adolescents and adults: ≤22%)
Gastrointestinal: Diarrhea (12%), nausea (13%), upper abdominal pain (13%)
Hepatic: Increased serum transaminases (including increased serum alanine aminotransferase, increased serum aspartate aminotransferase: children: 5% to 13%; adolescents and adults: <1%, increased serum bilirubin: adolescents and adults: <1%)
Nervous system: Headache (13%)
Respiratory: Changes in respiration (children: ≤11%; adolescents and adults: ≤22%), dyspnea (children ≤11%; adolescents and adults: ≤22%), increased bronchial secretions (11%), nasal congestion (17%), nasopharyngitis (13%), productive cough (18%)
1% to 10%:
Cardiovascular: Hypertension (≤1%)
Dermatologic: Skin rash (7%)
Endocrine & metabolic: Menstrual disease (10%; including amenorrhea, dysmenorrhea, heavy menstrual bleeding)
Gastrointestinal: Flatulence (7%)
Infection: Influenza (5%)
Nervous system: Fatigue (9%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (7%)
Respiratory: Rhinorrhea (6%), upper respiratory tract infection (10%)
<1%: Hepatic: Hepatic encephalopathy
Postmarketing:
Hepatic: Decompensated liver disease, hepatic failure
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema)
Nervous system: Exacerbation of depression (Mckinzie 2017), suicidal ideation (Mckinzie 2017), suicidal tendencies (Mckinzie 2017)
Ophthalmic: Cataract
There are no contraindications listed in the US labeling.
Canadian labeling: Hypersensitivity to lumacaftor, ivacaftor or any component of the formulation
Concerns related to adverse effects:
• Cataracts: Noncongenital lens opacities and cataracts have been reported in pediatric patients treated with lumacaftor/ivacaftor and ivacaftor; other risk factors were present in some cases (eg, corticosteroid use, exposure to radiation), but a possible risk related to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients.
• Hepatic effects: May increase hepatic transaminases with or without concomitant elevations in total serum bilirubin. Monitor ALT, AST, and bilirubin at baseline, every 3 months for the first year of therapy, and annually thereafter. Increased monitoring may be necessary in patients with a history of elevated hepatic transaminases or bilirubin. Temporarily discontinue treatment if ALT or AST >5 times ULN without concomitant elevated bilirubin or if ALT or AST >3 times ULN with concomitant bilirubin >2 times ULN.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported with lumacaftor/ivacaftor use. If signs and symptoms of severe hypersensitivity occur, discontinue use and treat appropriately; consider risk vs benefit prior to resuming therapy.
• Hypertension: Increased blood pressure has been observed; monitor blood pressure periodically during therapy.
• Respiratory effects: Use was associated with an increased incidence of respiratory events (eg, chest discomfort, dyspnea, and abnormal respirations); may result in drug discontinuation and may be serious (especially in patients with advanced lung disease [percent predicted FEV1 <40]). Careful monitoring during initiation of therapy is recommended in patients with a percent predicted FEV1 <40.
Disease-related concerns:
• Hepatic impairment: Use with caution; worsening of liver function (including hepatic encephalopathy) has been reported in patients with advanced liver disease. Liver function decompensation (including liver failure leading to death) has been reported in CF patients with preexisting cirrhosis with portal hypertension. Dosage adjustment is recommended in patients with moderate to severe (Child-Pugh class B or C) impairment.
• Renal impairment: Use with caution in patients with severe impairment (CrCl ≤30 mL/minute) or end-stage renal disease (ESRD).
Special populations:
• Organ transplant recipients: Use is not recommended in cystic fibrosis patients who have undergone organ transplantation (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Orkambi: Lumacaftor 75 mg and ivacaftor 94 mg (14 ea); Lumacaftor 100 mg and ivacaftor 125 mg (56 ea); Lumacaftor 150 mg and ivacaftor 188 mg (56 ea)
Tablet, Oral:
Orkambi: Lumacaftor 100 mg and ivacaftor 125 mg [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigo carm) aluminum lake]
Orkambi: Lumacaftor 200 mg and ivacaftor 125 mg [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine)]
No
Pack (Orkambi Oral)
75-94 mg (per each): $497.98
100-125 mg (per each): $497.98
150-188 mg (per each): $497.98
Tablets (Orkambi Oral)
100-125 mg (per each): $248.99
200-125 mg (per each): $248.99
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Orkambi: Lumacaftor 75 mg and ivacaftor 94 mg (56 ea); Lumacaftor 100 mg and ivacaftor 125 mg (56 ea); Lumacaftor 150 mg and ivacaftor 188 mg (56 ea)
Tablet, Oral:
Orkambi: Lumacaftor 100 mg and ivacaftor 125 mg, Lumacaftor 200 mg and ivacaftor 125 mg [contains fd&c blue #1 (brilliant blue), fd&c blue #2 (indigotine,indigo carmine)]
Product is only available via authorized pharmacies and distributors. Further information is available at https://www.vrtx.com/authorized-distributors.
Oral: Tablets: Administer with fat-containing food (eg, eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products [eg, whole milk, cheese, and yogurt]).
Oral: Granules, tablets: Administer with a fat-containing meal or snack consumed just before or after dose (all formulations); examples of appropriate fat-containing foods include: Eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products (eg, whole milk, cheese, yogurt).
Granules: Mix entire contents of each packet of granules with 5 mL of an age-appropriate soft food or liquid (eg, pureed fruits, yogurt, pudding, milk, juice). Food should be at or below room temperature and the mixture should be completely consumed within 1 hour.
Missed dose: If a missed dose is identified within 6 hours, the patient should take the dose with fat-containing food. If more than 6 hours have elapsed after the usual dosing time, the patient should skip that dose and resume the normal schedule for the following dose. A double dose should not be taken to make up for the forgotten dose.
Cystic fibrosis: Treatment of cystic fibrosis (CF) in patients age 1 year and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.
Limitations of use: Efficacy and safety have not been established in patients with CF other than those homozygous for the F508del mutation.
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (Strong);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Abemaciclib. Risk X: Avoid
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease serum concentration of Abiraterone Acetate. Management: Avoid coadministration with strong CYP3A4 inducers. For patients treated with single-agent abiraterone who require therapy with a strong CYP3A4 inducers, abiraterone frequency may increased to twice daily. See full mono for details. Risk D: Consider Therapy Modification
Acalabrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Risk D: Consider Therapy Modification
Acoramidis: CYP3A4 Inducers (Strong) may decrease serum concentration of Acoramidis. Risk X: Avoid
Adagrasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Adagrasib. Risk X: Avoid
Alfacalcidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Alfacalcidol. Risk C: Monitor
ALfentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification
Alpelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Alpelisib. Risk X: Avoid
ALPRAZolam: CYP3A4 Inducers (Strong) may decrease serum concentration of ALPRAZolam. Risk C: Monitor
Amiodarone: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Amiodarone. CYP3A4 Inducers (Strong) may decrease serum concentration of Amiodarone. Risk C: Monitor
AmLODIPine: CYP3A4 Inducers (Strong) may decrease serum concentration of AmLODIPine. Risk C: Monitor
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid
Apixaban: CYP3A4 Inducers (Strong) may decrease serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification
Apremilast: CYP3A4 Inducers (Strong) may decrease serum concentration of Apremilast. Risk X: Avoid
Aprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Risk D: Consider Therapy Modification
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider Therapy Modification
Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk X: Avoid
Atazanavir: Lumacaftor and Ivacaftor may decrease serum concentration of Atazanavir. Atazanavir may increase serum concentration of Lumacaftor and Ivacaftor. Risk X: Avoid
Atogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Atorvastatin. Risk C: Monitor
Atrasentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Atrasentan. Risk X: Avoid
Avacopan: CYP3A4 Inducers (Strong) may decrease serum concentration of Avacopan. Risk X: Avoid
Avanafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Axitinib. Risk X: Avoid
Barnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Barnidipine. Risk C: Monitor
Bedaquiline: CYP3A4 Inducers (Strong) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Bedaquiline. Risk X: Avoid
Belumosudil: CYP3A4 Inducers (Strong) may decrease serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Benidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Benidipine. Risk C: Monitor
Benperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Benperidol. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor
Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Betamethasone (Systemic). Risk C: Monitor
Bictegravir: CYP3A4 Inducers (Strong) may decrease serum concentration of Bictegravir. Risk C: Monitor
Bisoprolol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bisoprolol. Risk C: Monitor
Blonanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bortezomib. Risk X: Avoid
Bosutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bosutinib. Risk X: Avoid
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor
Brexpiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Decrease brexpiprazole to original dose over 1 to 2 weeks if the strong CYP3A4 inducer is discontinued. Risk D: Consider Therapy Modification
Brigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Brigatinib. Risk X: Avoid
Bromocriptine: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromocriptine. Risk C: Monitor
Bromperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromperidol. Risk C: Monitor
Brotizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Brotizolam. Risk C: Monitor
Buprenorphine: CYP3A4 Inducers (Strong) may decrease serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inducers (Strong) may decrease serum concentration of BusPIRone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed. Risk D: Consider Therapy Modification
Butorphanol: CYP3A4 Inducers (Strong) may decrease serum concentration of Butorphanol. Risk C: Monitor
Cabazitaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabazitaxel. Risk C: Monitor
Cabozantinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider Therapy Modification
Calcifediol: CYP3A4 Inducers (Strong) may increase serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor
Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabidiol. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Cannabidiol. Risk C: Monitor
Cannabis: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor
Capivasertib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capivasertib. Risk X: Avoid
Capmatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capmatinib. Risk X: Avoid
Cariprazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cariprazine. Risk X: Avoid
Ceritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ceritinib. Risk X: Avoid
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease serum concentration of ChlorproPAMIDE. Risk C: Monitor
Cilnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cilnidipine. Risk C: Monitor
Citalopram: CYP3A4 Inducers (Strong) may decrease serum concentration of Citalopram. Risk C: Monitor
Clarithromycin: May increase serum concentration of Lumacaftor and Ivacaftor. Specifically, the concentration of ivacaftor may be increased. Lumacaftor and Ivacaftor may increase serum concentration of Clarithromycin. Management: Consider alternatives to this combination due to the potential for impaired clarithromycin efficacy. If initiating or resuming lumacaftor/ivacaftor after an interruption of 7 days or more, dose reductions are required. See full mono for details. Risk D: Consider Therapy Modification
Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
ClonazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of ClonazePAM. Risk C: Monitor
CloZAPine: CYP3A4 Inducers (Strong) may decrease serum concentration of CloZAPine. Management: Avoid use with strong CYP3A4 inducers when possible. If combined, monitor patients closely and consider clozapine dose increases. Clozapine dose reduction and further monitoring may be required when strong CYP3A4 inducers are discontinued. Risk D: Consider Therapy Modification
Cobicistat: Lumacaftor and Ivacaftor may decrease serum concentration of Cobicistat. Cobicistat may increase serum concentration of Lumacaftor and Ivacaftor. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced cobicistat efficacy. Lumacaftor/ivacaftor dose adjustments may be required; see full interact monograph for details. Risk D: Consider Therapy Modification
Cobimetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inducers (Strong) may decrease serum concentration of Colchicine. Risk C: Monitor
Copanlisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Copanlisib. Risk X: Avoid
Crinecerfont: CYP3A4 Inducers (Strong) may decrease serum concentration of Crinecerfont. Management: Double the morning and evening doses of crinecerfont during coadministration with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
Crizotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Crizotinib. Risk X: Avoid
CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of CycloSPORINE (Systemic). Management: Monitor closely for reduced cyclosporine concentrations when combined with strong CYP3A4 inducers. Cyclosporine dose increases will likely be required to maintain adequate serum concentrations. Risk D: Consider Therapy Modification
CYP2B6 Substrates (High risk with Inducers): Lumacaftor and Ivacaftor may decrease serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor
CYP2C19 Substrates (High risk with Inducers): Lumacaftor and Ivacaftor may decrease serum concentration of CYP2C19 Substrates (High risk with Inducers). Risk C: Monitor
CYP2C8 Substrates (High Risk with Inhibitors or Inducers): Lumacaftor and Ivacaftor may decrease serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor
CYP2C9 Substrates (High Risk with Inhibitors or Inducers): Lumacaftor and Ivacaftor may decrease serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid
CYP3A4 Inhibitors (Strong): May increase serum concentration of Lumacaftor and Ivacaftor. Management: When initiating or resuming lumacaftor/ivacaftor after a therapy interruption of 7 days or more, reduce the lumacaftor/ivacaftor dose to 1 tablet daily or 1 packet of oral granules every other day for the first week, and then resume the standard dose. Risk D: Consider Therapy Modification
Cyproterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Cyproterone. Risk C: Monitor
Daclatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Daclatasvir. Risk X: Avoid
Dapsone (Systemic): May increase adverse/toxic effects of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease serum concentration of Dapsone (Systemic). Management: Consider alternatives to this combination when possible. Monitor for decreased dapsone efficacy if combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Daridorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Daridorexant. Risk X: Avoid
Darunavir: May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Darunavir. Management: Consider alternatives. If combined, monitor for reduced darunavir efficacy and possible development of resistance. Additionally, lumacaftor/ivacaftor dose reductions may be needed with this combination. See full interaction monograph for details. Risk D: Consider Therapy Modification
Dasabuvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasabuvir. Risk X: Avoid
Dasatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasatinib. Management: Avoid concurrent use of dasatinib with strong CYP3A4 inducers when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider Therapy Modification
Deflazacort: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid
Delamanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Delamanid. Risk X: Avoid
Deuruxolitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Deuruxolitinib. Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of DexAMETHasone (Systemic). Management: Avoid coadministration of dexamethasone and strong CYP3A4 inducers. If concomitant use cannot be avoided, consider dexamethasone dose increases. Risk D: Consider Therapy Modification
DiazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of DiazePAM. Risk C: Monitor
Dienogest: CYP3A4 Inducers (Strong) may decrease serum concentration of Dienogest. Risk C: Monitor
Digitoxin: CYP3A4 Inducers (Strong) may decrease serum concentration of Digitoxin. Risk C: Monitor
Digoxin: Lumacaftor and Ivacaftor may decrease serum concentration of Digoxin. Lumacaftor and Ivacaftor may increase serum concentration of Digoxin. Risk C: Monitor
DilTIAZem: CYP3A4 Inducers (Strong) may decrease serum concentration of DilTIAZem. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased diltiazem efficacy. Risk D: Consider Therapy Modification
Disopyramide: CYP3A4 Inducers (Strong) may decrease serum concentration of Disopyramide. Risk C: Monitor
DOCEtaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of DOCEtaxel. Risk C: Monitor
Domperidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Domperidone. Risk C: Monitor
Doravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Doravirine. Risk X: Avoid
Doxercalciferol: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inducers (Strong) may decrease serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dronedarone. Risk X: Avoid
Duvelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Duvelisib. Risk X: Avoid
Dydrogesterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dydrogesterone. Risk C: Monitor
Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ebastine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ebastine. Risk C: Monitor
Efavirenz: CYP3A4 Inducers (Strong) may decrease serum concentration of Efavirenz. Risk C: Monitor
Elacestrant: CYP3A4 Inducers (Strong) may decrease serum concentration of Elacestrant. Risk X: Avoid
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Elagolix, Estradiol, and Norethindrone. Risk C: Monitor
Elagolix: CYP3A4 Inducers (Strong) may decrease serum concentration of Elagolix. Risk C: Monitor
Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid
Eliglustat: CYP3A4 Inducers (Strong) may decrease serum concentration of Eliglustat. Risk X: Avoid
Encorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Encorafenib. Risk X: Avoid
Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor
Ensartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Entrectinib. Risk X: Avoid
Eplerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eplerenone. Risk C: Monitor
Eravacycline: CYP3A4 Inducers (Strong) may decrease serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Erdafitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erdafitinib. Risk X: Avoid
Erlotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification
Erythromycin (Systemic): Lumacaftor and Ivacaftor may decrease serum concentration of Erythromycin (Systemic). Risk X: Avoid
Escitalopram: CYP3A4 Inducers (Strong) may decrease serum concentration of Escitalopram. Risk C: Monitor
Esketamine (Injection): CYP3A4 Inducers (Strong) may decrease serum concentration of Esketamine (Injection). Risk C: Monitor
Estazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Estazolam. Risk C: Monitor
Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
Eszopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eszopiclone. Risk C: Monitor
Ethosuximide: CYP3A4 Inducers (Strong) may decrease serum concentration of Ethosuximide. Risk C: Monitor
Etizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Etizolam. Risk C: Monitor
Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Risk D: Consider Therapy Modification
Etoposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Risk D: Consider Therapy Modification
Etoricoxib: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoricoxib. Risk C: Monitor
Etravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Etravirine. Risk X: Avoid
Everolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Everolimus. Management: Concomitant use of everolimus and strong CYP3A4 inducers is generally not recommended. However, if combined, monitor for decreased everolimus concentrations and effects, and adjust everolimus dose as needed. Risk D: Consider Therapy Modification
Evogliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Evogliptin. Risk C: Monitor
Exemestane: CYP3A4 Inducers (Strong) may decrease serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider Therapy Modification
Fedratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fedratinib. Risk X: Avoid
Felbamate: CYP3A4 Inducers (Strong) may decrease serum concentration of Felbamate. Risk C: Monitor
Felodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Felodipine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced felodipine efficacy and the need for felodipine dose increases. Risk D: Consider Therapy Modification
Fenfluramine: CYP3A4 Inducers (Strong) may decrease serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider Therapy Modification
FentaNYL: CYP3A4 Inducers (Strong) may decrease serum concentration of FentaNYL. Risk C: Monitor
Fesoterodine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fesoterodine. Risk C: Monitor
Fexinidazole: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid
Finerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Finerenone. Risk X: Avoid
Flibanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Flibanserin. Risk X: Avoid
Fludrocortisone: CYP3A4 Inducers (Strong) may decrease serum concentration of Fludrocortisone. Risk C: Monitor
Fosamprenavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosnetupitant. Risk X: Avoid
Fostamatinib: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostamatinib. Risk X: Avoid
Fostemsavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostemsavir. Risk X: Avoid
Fruquintinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fruquintinib. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Futibatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Futibatinib. Risk C: Monitor
Ganaxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and strong CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification
Gefitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider Therapy Modification
Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Gemigliptin. Risk X: Avoid
Gepirone: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepirone. Risk X: Avoid
Gepotidacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepotidacin. Risk X: Avoid
Gilteritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Gilteritinib. Risk C: Monitor
Glasdegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Glasdegib. Risk X: Avoid
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Lumacaftor and Ivacaftor. Specifically, grapefruit juice may increase ivacaftor concentrations during the first week of therapy. Management: Advise patients to avoid grapefruit products during the first week of treatment with lumacaftor/ivacaftor. Risk D: Consider Therapy Modification
GuanFACINE: CYP3A4 Inducers (Strong) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification
Haloperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Haloperidol. Risk C: Monitor
Hormonal Contraceptives: CYP3A4 Inducers (Strong) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification
HYDROcodone: CYP3A4 Inducers (Strong) may decrease serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid
Ibrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrutinib. Risk X: Avoid
Ibuprofen: Lumacaftor and Ivacaftor may decrease serum concentration of Ibuprofen. Risk C: Monitor
Idelalisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Idelalisib. Risk X: Avoid
Ifosfamide: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Imatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Imatinib. Management: Avoid use of imatinib and strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Doses up to 1200 mg/day (600 mg twice daily) have been used. Risk D: Consider Therapy Modification
Indinavir: Lumacaftor and Ivacaftor may decrease serum concentration of Indinavir. Indinavir may increase serum concentration of Lumacaftor and Ivacaftor. Management: Consider alternatives. If combined, monitor for reduced indinavir efficacy and possible development of resistance. Additionally, lumacaftor/ivacaftor dose reductions may be needed with this combination. See full interaction monograph for details. Risk D: Consider Therapy Modification
Inhibitors of the Proton Pump (PPIs and PCABs): Lumacaftor and Ivacaftor may decrease serum concentration of Inhibitors of the Proton Pump (PPIs and PCABs). Risk C: Monitor
Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Irinotecan Products. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid
Isradipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inducers (Strong) may decrease serum concentration of Istradefylline. Risk X: Avoid
Itraconazole: May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Itraconazole. Risk X: Avoid
Ivabradine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivacaftor. Risk X: Avoid
Ivosidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivosidenib. Risk X: Avoid
Ixabepilone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider Therapy Modification
Ixazomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixazomib. Risk X: Avoid
Ketamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ketamine. Risk C: Monitor
Ketoconazole (Systemic): May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Ketoconazole (Systemic). Management: Consider alternatives to this combination. If combined, monitor for reduced ketoconazole serum concentrations and efficacy. If lumacaftor/ivacaftor is initiated in patients taking ketoconazole, lumacaftor/ivacaftor dose reductions are needed. Risk D: Consider Therapy Modification
Lacidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lacidipine. Risk C: Monitor
Lapatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk D: Consider Therapy Modification
Larotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inducers with larotrectinib. If this combination cannot be avoided, double the larotrectinib dose. Reduced to previous dose after stopping the inducer after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification
Lazertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lazertinib. Risk X: Avoid
Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lefamulin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Lemborexant. Risk X: Avoid
Lenacapavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Lenacapavir. Risk X: Avoid
Leniolisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lercanidipine. Risk C: Monitor
Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor
Levamlodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Levamlodipine. Risk C: Monitor
Levoketoconazole: May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Levoketoconazole. Risk X: Avoid
Levomethadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Levomethadone. Risk C: Monitor
Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may decrease therapeutic effects of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease serum concentration of Levonorgestrel (IUD). Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Lidocaine (Systemic). Risk C: Monitor
LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider Therapy Modification
Lonafarnib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lonafarnib. Risk X: Avoid
Lopinavir: Lumacaftor and Ivacaftor may decrease serum concentration of Lopinavir. Lopinavir may increase serum concentration of Lumacaftor and Ivacaftor. Management: Consider alternatives. If combined, monitor for reduced lopinavir efficacy and possible development of resistance. Additionally, lumacaftor/ivacaftor dose reductions may be needed with this combination. See full interaction monograph for details. Risk D: Consider Therapy Modification
Lorlatinib: CYP3A4 Inducers (Strong) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Strong) may decrease serum concentration of Lorlatinib. Risk X: Avoid
Lovastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumateperone. Risk X: Avoid
Lurasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurasidone. Risk X: Avoid
Lurbinectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurbinectedin. Risk X: Avoid
Macimorelin: CYP3A4 Inducers (Strong) may decrease serum concentration of Macimorelin. Risk X: Avoid
Macitentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Macitentan. Risk X: Avoid
Manidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Risk D: Consider Therapy Modification
Maraviroc: CYP3A4 Inducers (Strong) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification
Maribavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Maribavir. Risk X: Avoid
Mavacamten: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavacamten. Risk X: Avoid
Mavorixafor: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavorixafor. Risk X: Avoid
Mefloquine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mefloquine. Risk C: Monitor
Meperidine: CYP3A4 Inducers (Strong) may decrease serum concentration of Meperidine. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor
Methadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Methadone. Risk C: Monitor
Methylergonovine: CYP3A4 Inducers (Strong) may decrease serum concentration of Methylergonovine. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Risk D: Consider Therapy Modification
Mianserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Mianserin. Risk C: Monitor
Midazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Midazolam. Risk C: Monitor
Midostaurin: CYP3A4 Inducers (Strong) may decrease serum concentration of Midostaurin. Risk X: Avoid
MiFEPRIStone: Lumacaftor and Ivacaftor may decrease serum concentration of MiFEPRIStone. MiFEPRIStone may increase serum concentration of Lumacaftor and Ivacaftor. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced; follow-up assessment is required if combined. Lumacaftor/ivacaftor dose adjustments may be needed; see full mono. Risk D: Consider Therapy Modification
Mirabegron: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirabegron. Risk C: Monitor
Mirodenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Risk D: Consider Therapy Modification
Mirtazapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirtazapine. Risk C: Monitor
Mitapivat: CYP3A4 Inducers (Strong) may decrease serum concentration of Mitapivat. Risk X: Avoid
Mobocertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid
Montelukast: Lumacaftor and Ivacaftor may decrease serum concentration of Montelukast. Risk C: Monitor
Naldemedine: CYP3A4 Inducers (Strong) may decrease serum concentration of Naldemedine. Risk X: Avoid
Naloxegol: CYP3A4 Inducers (Strong) may decrease serum concentration of Naloxegol. Risk X: Avoid
Nateglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Nateglinide. Risk C: Monitor
Nelfinavir: May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Nelfinavir. Management: Consider alternatives. If combined, monitor for reduced nelfinavir efficacy and possible development of resistance. Additionally, lumacaftor/ivacaftor dose reductions may be needed with this combination. See full interaction monograph for details. Risk D: Consider Therapy Modification
Neratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Neratinib. Risk X: Avoid
Netupitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Netupitant. Risk X: Avoid
Nevirapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nevirapine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced nevirapine efficacy. Risk D: Consider Therapy Modification
NiCARdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiCARdipine. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine. Management: Avoid coadministration of nifedipine with strong CYP3A4 inducers when possible and if combined, monitor patients closely for clinical signs of diminished nifedipine response. Risk D: Consider Therapy Modification
Nilotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilotinib. Risk X: Avoid
Nilvadipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiMODipine. Risk X: Avoid
Nintedanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Nintedanib. Risk C: Monitor
Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid
Nirogacestat: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nisoldipine. Risk X: Avoid
Nitrazepam: CYP3A4 Inducers (Strong) may decrease serum concentration of Nitrazepam. Risk C: Monitor
Olaparib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olaparib. Risk X: Avoid
Oliceridine: CYP3A4 Inducers (Strong) may decrease serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olmutinib. Risk C: Monitor
Olutasidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olutasidenib. Risk X: Avoid
Omaveloxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Omaveloxolone. Risk X: Avoid
Ondansetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Ondansetron. Risk C: Monitor
Osilodrostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Osilodrostat. Risk C: Monitor
Osimertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification
OXcarbazepine: CYP3A4 Inducers (Strong) may decrease serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor
OxyCODONE: CYP3A4 Inducers (Strong) may decrease serum concentration of OxyCODONE. Risk C: Monitor
P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers): Lumacaftor and Ivacaftor may increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pacritinib. Risk X: Avoid
Palbociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Palbociclib. Risk X: Avoid
Paliperidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and strong CYP3A4 inducers. If coadministration is required consider use of paliperidone extended-release tablets, monitor for reduced effects, and increase the dose as needed. Risk D: Consider Therapy Modification
Palovarotene: CYP3A4 Inducers (Strong) may decrease serum concentration of Palovarotene. Risk X: Avoid
Panobinostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Panobinostat. Risk X: Avoid
PAZOPanib: CYP3A4 Inducers (Strong) may decrease serum concentration of PAZOPanib. Risk X: Avoid
Pemigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pemigatinib. Risk X: Avoid
Perampanel: CYP3A4 Inducers (Strong) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
Perazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Perazine. Risk C: Monitor
Pexidartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pexidartinib. Risk X: Avoid
Phenobarbital-Primidone: May decrease serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor
Pimavanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Pimavanserin. Risk X: Avoid
Piperaquine: CYP3A4 Inducers (Strong) may decrease serum concentration of Piperaquine. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pirtobrutinib. Risk X: Avoid
Pitolisant: CYP3A4 Inducers (Strong) may decrease serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider Therapy Modification
Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor
PONATinib: CYP3A4 Inducers (Strong) may decrease serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider Therapy Modification
Posaconazole: Lumacaftor and Ivacaftor may decrease serum concentration of Posaconazole. Posaconazole may increase serum concentration of Lumacaftor and Ivacaftor. Management: Consider alternatives to this combination. If combined, monitor for reduced posaconazole serum concentrations and efficacy. If lumacaftor/ivacaftor is initiated in patients taking posaconazole, lumacaftor/ivacaftor dose reductions are needed. Risk D: Consider Therapy Modification
Pralsetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider Therapy Modification
Praziquantel: CYP3A4 Inducers (Strong) may decrease serum concentration of Praziquantel. Risk X: Avoid
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inducers (Strong) may decrease serum concentration of PredniSONE. Risk C: Monitor
Pretomanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Pretomanid. Risk X: Avoid
Propafenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Propafenone. Risk C: Monitor
Pyrimethamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Pyrimethamine. Risk C: Monitor
QUEtiapine: CYP3A4 Inducers (Strong) may decrease serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7 to 14 days of discontinuing the inducer. Risk D: Consider Therapy Modification
QuiNIDine: CYP3A4 Inducers (Strong) may decrease serum concentration of QuiNIDine. Risk C: Monitor
QuiNINE: CYP3A4 Inducers (Strong) may decrease serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced quinine efficacy and treatment failure. Risk D: Consider Therapy Modification
Quizartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Quizartinib. Risk X: Avoid
Radotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Risk D: Consider Therapy Modification
Ramelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Ramelteon. Risk C: Monitor
RaNITIdine: Lumacaftor and Ivacaftor may decrease serum concentration of RaNITIdine. Lumacaftor and Ivacaftor may increase serum concentration of RaNITIdine. Risk C: Monitor
Ranolazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ranolazine. Risk X: Avoid
Reboxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Reboxetine. Risk C: Monitor
Regorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Regorafenib. Risk X: Avoid
Repaglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Repotrectinib. Risk X: Avoid
Revumenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Revumenib. Risk X: Avoid
Ribociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ribociclib. Risk X: Avoid
Rifabutin: May decrease serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk C: Monitor
Rilpivirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid
Rimegepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rimegepant. Risk X: Avoid
Riociguat: CYP3A4 Inducers (Strong) may decrease serum concentration of Riociguat. Risk C: Monitor
Ripretinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ripretinib. Risk X: Avoid
RisperiDONE: CYP3A4 Inducers (Strong) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
Ritlecitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritlecitinib. Risk X: Avoid
Ritonavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritonavir. Risk X: Avoid
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease serum concentration of Rivaroxaban. Management: Consider alternatives to use of rivaroxaban with strong CYP3A4 inducers. Use of a strong CYP3A4 inducer with rivaroxaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification
Roflumilast (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Roflumilast (Systemic). Risk X: Avoid
Rolapitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rolapitant. Risk X: Avoid
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease serum concentration of RomiDEPsin. Risk X: Avoid
Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ruxolitinib (Systemic). Risk C: Monitor
Samidorphan: CYP3A4 Inducers (Strong) may decrease serum concentration of Samidorphan. Risk X: Avoid
Saquinavir: May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Saquinavir. Management: Consider alternatives. If combined, monitor for reduced saquinavir efficacy and possible development of resistance. Additionally, lumacaftor/ivacaftor dose reductions may be needed with this combination. See full interaction monograph for details. Risk D: Consider Therapy Modification
SAXagliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of SAXagliptin. Risk C: Monitor
Selpercatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selpercatinib. Risk X: Avoid
Selumetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selumetinib. Risk X: Avoid
Sertindole: CYP3A4 Inducers (Strong) may decrease serum concentration of Sertindole. Risk C: Monitor
Sertraline: CYP3A4 Inducers (Strong) may decrease serum concentration of Sertraline. Risk C: Monitor
Sildenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Sildenafil. Risk C: Monitor
Simeprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Conventional). Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Solifenacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sonidegib. Risk X: Avoid
SORAfenib: CYP3A4 Inducers (Strong) may decrease serum concentration of SORAfenib. Risk X: Avoid
Sotorasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sotorasib. Risk X: Avoid
Sparsentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Sparsentan. Risk X: Avoid
St John's Wort: May decrease serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid
Stiripentol: CYP3A4 Inducers (Strong) may decrease serum concentration of Stiripentol. Management: Avoid concomitant use of stiripentol and strong CYP3A4 inducers when possible. If combined, monitor for reduced stiripentol efficacy and increase the stiripentol dose as needed. Risk D: Consider Therapy Modification
SUFentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of SUFentanil. Management: If a strong CYP3A4 inducer is initiated in a patient on sufentanil, consider a sufentanil dose increase and monitor for decreased sufentanil effects and opioid withdrawal symptoms. Risk D: Consider Therapy Modification
SUNItinib: CYP3A4 Inducers (Strong) may decrease serum concentration of SUNItinib. Management: Avoid when possible. If combined, increase sunitinib dose to a max of 87.5 mg daily when treating GIST or RCC. Increase sunitinib dose to a max of 62.5 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider Therapy Modification
Suvorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Suvorexant. Risk C: Monitor
Suzetrigine: CYP3A4 Inducers (Strong) may decrease serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose increases will likely be needed during concomitant use with strong CYP3A4 inducers. Monitor more closely and frequently for decreased tacrolimus concentrations and effects when combined. Risk D: Consider Therapy Modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Tadalafil. Management: Erectile dysfunction or benign prostatic hypertrophy: monitor for decreased effectiveness - no standard dose adjustment is recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Tamoxifen. Risk X: Avoid
Tasimelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Tasimelteon. Risk X: Avoid
Tazemetostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Tazemetostat. Risk X: Avoid
Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Teniposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Teniposide. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider Therapy Modification
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid
Thiotepa: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Strong) may decrease serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider Therapy Modification
TiaGABine: CYP3A4 Inducers (Strong) may decrease serum concentration of TiaGABine. Risk C: Monitor
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ticagrelor. Risk X: Avoid
Tipranavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Tipranavir. Risk C: Monitor
Tivozanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tivozanib. Risk X: Avoid
Tofacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tofacitinib. Risk X: Avoid
Tolvaptan: CYP3A4 Inducers (Strong) may decrease serum concentration of Tolvaptan. Risk X: Avoid
Toremifene: CYP3A4 Inducers (Strong) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Toremifene. Risk X: Avoid
Trabectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Trabectedin. Risk X: Avoid
TraMADol: CYP3A4 Inducers (Strong) may decrease serum concentration of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inducers (Strong) may decrease serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Tretinoin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inducers when possible. If combined, monitor for reduced tretinoin concentrations and efficacy. Risk D: Consider Therapy Modification
Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Triazolam. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced triazolam efficacy. Substantial triazolam dose increases will likely be required. Risk D: Consider Therapy Modification
Tropisetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Tropisetron. Risk C: Monitor
Tucatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tucatinib. Risk X: Avoid
Ubrogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Ubrogepant. Risk X: Avoid
Udenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Udenafil. Risk C: Monitor
Ulipristal: CYP3A4 Inducers (Strong) may decrease serum concentration of Ulipristal. Risk X: Avoid
Upadacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Upadacitinib. Risk X: Avoid
Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Valbenazine. Risk X: Avoid
Vandetanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Vandetanib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Vandetanib. Risk X: Avoid
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid
Velpatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Velpatasvir. Risk X: Avoid
Vemurafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Vemurafenib. Management: Avoid coadministration of vemurafenib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after discontinuation of strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Venetoclax: CYP3A4 Inducers (Strong) may decrease serum concentration of Venetoclax. Risk X: Avoid
Verapamil: CYP3A4 Inducers (Strong) may decrease serum concentration of Verapamil. Management: Consider alternatives to this combination. If combined, monitor for reduced verapamil efficacy. Verapamil dose increases may be necessary. Risk D: Consider Therapy Modification
Vilazodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1 to 2 weeks after inducer discontinuation. Risk D: Consider Therapy Modification
VinCRIStine: CYP3A4 Inducers (Strong) may decrease serum concentration of VinCRIStine. Risk X: Avoid
Vinflunine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinflunine. Risk X: Avoid
Vinorelbine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinorelbine. Risk C: Monitor
Voclosporin: CYP3A4 Inducers (Strong) may decrease serum concentration of Voclosporin. Risk X: Avoid
Vonoprazan: CYP3A4 Inducers (Strong) may decrease serum concentration of Vonoprazan. Risk X: Avoid
Vorapaxar: CYP3A4 Inducers (Strong) may decrease serum concentration of Vorapaxar. Risk X: Avoid
Voriconazole: May increase serum concentration of Lumacaftor and Ivacaftor. Lumacaftor and Ivacaftor may decrease serum concentration of Voriconazole. Management: Consider alternatives to this combination. If combined, monitor for reduced voriconazole serum concentrations and efficacy. If lumacaftor/ivacaftor is initiated in patients taking voriconazole, lumacaftor/ivacaftor dose reductions are needed. Risk D: Consider Therapy Modification
Vortioxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Risk D: Consider Therapy Modification
Voxelotor: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification
Voxilaprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxilaprevir. Risk X: Avoid
Zaleplon: CYP3A4 Inducers (Strong) may decrease serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zaleplon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Risk D: Consider Therapy Modification
Zanubrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Zanubrutinib. Risk X: Avoid
Ziprasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ziprasidone. Risk C: Monitor
Zolpidem: CYP3A4 Inducers (Strong) may decrease serum concentration of Zolpidem. Risk C: Monitor
Zonisamide: CYP3A4 Inducers (Strong) may decrease serum concentration of Zonisamide. Risk C: Monitor
Zopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zopiclone. Risk C: Monitor
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuclopenthixol. Risk C: Monitor
Zuranolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuranolone. Risk X: Avoid
Food increases exposure to lumacaftor and ivacaftor. Ivacaftor serum concentrations may be increased when taken with grapefruit. Management: Administer with fat-containing food; avoid grapefruit during the first week of therapy.
Fertility and contraception should be reassessed prior to starting variant-specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy (Southern 2023). Fertility may improve with use of CFTR therapy and an increase in unintentional pregnancies has been observed. Contraception advice is recommended for patients who do not wish to become pregnant (Gramegna 2024; Southern 2023).
Hormonal contraceptives, regardless of route of administration, may be less effective during lumacaftor/ivacaftor therapy.
Lumacaftor and ivacaftor cross the placenta (Trimble 2018).
In one case report, cord blood concentrations of ivacaftor at delivery were similar to, and lumacaftor concentrations were greater than maternal plasma concentrations following maternal use of ivacaftor/lumacaftor during pregnancy (Trimble 2018).
Data related to the safety of variant-specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy during pregnancy are limited (Southern 2023). Outcome data specific to this dual therapy combination are limited to case reports (Mainz 2019; Trimble 2018).
Monitoring of newborns exposed to CFTR therapy during pregnancy should include genetic testing, LFTs, and ophthalmic exams (Gramegna 2024). In addition, exposed infants may have a false negative immunoreactive trypsinogen test for cystic fibrosis during the newborn baby screen (Castellani 2023; Southern 2023).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of CFTR therapy may be altered (Qiu 2020). Available data are limited (based on a study conducted with ivacaftor in combination with elexacaftor and tezacaftor) and show high interpatient variability. Dose adjustments based on routine clinical monitoring and therapeutic drug monitoring may be needed (Christina 2024). Increased monitoring during pregnancy is recommended (Gramegna 2024).
Patients taking variant-specific CFTR therapy prior to pregnancy may have an acute deterioration of health if treatment is discontinued once pregnant. Continuing or discontinuing therapy during pregnancy should be based on a shared decision-making process (Gramegna 2024).
Lumacaftor and ivacaftor are present in breast milk (Trimble 2018).
In one case report, ivacaftor and lumacaftor were detectable in breast milk and infant plasma following maternal use of ivacaftor/lumacaftor during pregnancy and while breastfeeding (Trimble 2018).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Safety data related to the use of variant-specific cystic fibrosis transmembrane conductance regulator (CFTR) therapy while breastfeeding are limited (Southern 2023). Monitoring of liver function and ophthalmic exams are recommended in infants exposed to CFTR therapy via breast milk (Southern 2023).
Take with fat-containing food (eg, eggs, avocados, nuts, peanut butter, cheese pizza, whole-milk dairy products); avoid grapefruit during the first week of therapy.
CF mutation test (prior to therapy if genotype is unknown); blood pressure periodically (during therapy); ophthalmological examinations (baseline and follow-up in pediatric patients); ALT, AST, and bilirubin (baseline, every 3 months for the first year of therapy, and annually thereafter; increased monitoring may be necessary in patients with a history of elevated hepatic transaminases or bilirubin); signs and symptoms of respiratory effects (in patients with a percent predicted FEV1 <40)
Lumacaftor improves the conformational stability of F508del-CFTR, resulting in increased processing and trafficking of mature protein to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface.
Note: In pediatric patients, exposure (AUC) was comparable to adult data.
Absorption:
Ivacaftor: Variable; increased (by ~3-fold) when administered with fatty foods as compared with fasting
Lumacaftor: Variable; increased (by ~2-fold) when administered with fatty foods as compared with fasting
Distribution: Vd:
Ivacaftor: 353 ± 122 L
Lumacaftor: 86 ± 69.8 L
Protein binding:
Ivacaftor: ~99%; primarily to alpha1-acid glycoprotein and albumin
Lumacaftor: ~99%; primarily to albumin
Metabolism:
Ivacaftor: Hepatic; extensive via CYP3A; forms 2 major metabolites (M1 [active; 1/6 potency] and M6 [inactive])
Lumacaftor: Not extensively metabolized; undergoes oxidation and glucuronidation
Half-life elimination:
Ivacaftor: 9.34 ± 3.81 hours (when administered with lumacaftor in healthy subjects)
Lumacaftor: 25.2 ± 9.94 hours (in patients with CF)
Time to peak (fed state):
Ivacaftor: Median: ~4 hours (2 to 6 hours)
Lumacaftor: Median: ~4 hours (2 to 9 hours)
Excretion:
Ivacaftor: Feces (88%); urine (6.6% as unchanged drug)
Lumacaftor: Feces (51% as unchanged drug); urine (8.6%; 0.18% of administered dose as unchanged drug)
Hepatic function impairment: 50% higher AUC and ~30% higher Cmax in patients with moderate hepatic impairment