Version July 2025
Dosage guidance:
Dosage form information: Xenleta tablets and injection have been discontinued in the United States for >1 year.
Pneumonia, community acquired (alternative agent for patients unable to tolerate beta-lactams or fluoroquinolones): Patients without risk factors for Pseudomonas aeruginosa or Enterobacterales (Ref):
Oral: 600 mg every 12 hours (Ref).
IV: 150 mg every 12 hours (Ref).
Duration of therapy: Total duration (which may include oral step-down therapy) is a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
IV:
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): 150 mg every 24 hours.
Oral:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B or C): Use is not recommended (has not been studied).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Diarrhea (12%)
1% to 10%:
Cardiovascular: Atrial fibrillation (<2%), palpitations (<2%), prolonged QT interval on ECG (<2%)
Central nervous system: Insomnia (3%), headache (2%), anxiety (<2%), drowsiness (<2%)
Endocrine & metabolic: Hypokalemia (3%), increased gamma-glutamyl transferase (<2%)
Gastrointestinal: Nausea (3% to 5%), vomiting (3%), abdominal pain (<2%), Clostridioides difficile associated diarrhea (<2%), constipation (<2%), dyspepsia (<2%), epigastric discomfort (<2%), gastritis (<2%), oropharyngeal candidiasis (<2%)
Genitourinary: Urinary retention (<2%), vulvovaginal candidiasis (<2%)
Hematologic & oncologic: Anemia (<2%), thrombocytopenia (<2%)
Hepatic: Increased liver enzymes (≤3), increased serum alanine aminotransferase (≤3), increased serum aspartate aminotransferase (≤3), increased serum alkaline phosphatase (<2%)
Local: Infusion-site pain (≤7%), injection site phlebitis (≤7%), injection site reaction (≤7%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (<2%)
Hypersensitivity to lefamulin, pleuromutilin class drugs, or any component of the formulation.
Additional contraindications: Tablets: Concomitant CYP3A4 substrates that prolong the QT interval (eg, pimozide).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• QT prolongation: Lefamulin may prolong the QT interval in some patients. The magnitude of QT prolongation may increase with increasing lefamulin concentrations or increased rate of infusion of the injection; do not exceed recommended dose or infusion rate. Avoid use in patients with known prolongation of the QT interval or ventricular arrhythmias (including torsades de pointes) and in patients taking concomitant class IA (eg, quinidine, procainamide) or class III (eg, amiodarone, sotalol) antiarrhythmics, or other drugs that prolong the QT interval (eg, antipsychotics, erythromycin, moxifloxacin, pimozide, tricyclic antidepressants). Metabolic disturbances associated with hepatic impairment or renal failure (patients requiring dialysis) may also lead to QT prolongation. If use of lefamulin cannot be avoided in patients predisposed to or with risk factors for QT prolongation, monitor ECG during treatment.
• Superinfection: Use may result in bacterial superinfection, including Clostridioides difficile infection (CDI) and pseudomembranous colitis; CDI has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Lefamulin tablets are not recommended for use in patients with moderate or severe impairment (Child-Pugh class B or C). Reduce dose of lefamulin injection in patients with severe impairment (Child-Pugh class C).
Xenleta tablets and injection have been discontinued in the United States >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as acetate [preservative free]:
Xenleta: 150 mg/15 mL (15 mL [DSC])
Tablet, Oral, as acetate:
Xenleta: 600 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake]
No
Solution (Xenleta Intravenous)
150 mg/15 mL (per mL): $8.20
Tablets (Xenleta Oral)
600 mg (per each): $165.00
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.
IV: Administer by IV infusion over 60 minutes. Note: Injection solution in vials must be further diluted with supplied diluent prior to administration.
Oral: Administer ≥1 hour before a meal or 2 hours after a meal. Swallow tablet whole with 6 to 8 ounces of water; do not crush or divide tablet.
Pneumonia, community-acquired: Treatment of adults with community-acquired bacterial pneumonia caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Lefamulin may be confused with leflunomide.
Substrate of CYP3A4 (Major), P-glycoprotein (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Moderate);
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 Inhibitors (Moderate) may increase serum concentration of Abemaciclib. Management: Monitor for increased abemaciclib toxicities if combined with moderate CYP3A4 inhibitors. Consider reducing the abemaciclib dose in 50 mg decrements if necessary. Risk C: Monitor
Acalabrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use. Risk D: Consider Therapy Modification
Acrivastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Acrivastine. Risk C: Monitor
Adagrasib: Lefamulin may increase QTc-prolonging effects of Adagrasib. Lefamulin may increase serum concentration of Adagrasib. Adagrasib may increase serum concentration of Lefamulin. Risk X: Avoid
ALfentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALfentanil. Management: If use of alfentanil and moderate CYP3A4 inhibitors is necessary, consider dosage reduction of alfentanil until stable drug effects are achieved. Frequently monitor patients for respiratory depression and sedation when these agents are combined. Risk D: Consider Therapy Modification
Alfuzosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alfuzosin. Risk C: Monitor
Alitretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Alitretinoin (Systemic). Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider Therapy Modification
AmLODIPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of AmLODIPine. Risk C: Monitor
Apixaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Apixaban. Risk C: Monitor
Aprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
Asciminib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Atogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atogepant. Risk C: Monitor
Atorvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Atorvastatin. Risk C: Monitor
Avacopan: Lefamulin may increase serum concentration of Avacopan. Avacopan may increase serum concentration of Lefamulin. Risk C: Monitor
Avanafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Risk D: Consider Therapy Modification
Avapritinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Avapritinib. Management: Avoid use of moderate CYP3A4 inhibitors with avapritinib. If this combination cannot be avoided, reduce the avapritinib dose to 100 mg daily for the treatment of GIST or to 50 mg daily for the treatment of advanced systemic mastocytosis. Risk D: Consider Therapy Modification
Axitinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Axitinib. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
Barnidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Barnidipine. Risk C: Monitor
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Benidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benidipine. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Risk C: Monitor
Blonanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bortezomib. Risk C: Monitor
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bosutinib. Risk X: Avoid
Brexpiprazole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer. Risk C: Monitor
Brigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider Therapy Modification
Bromocriptine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations. Risk D: Consider Therapy Modification
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Oral Inhalation). Risk C: Monitor
Budesonide (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and CYP3A4 inhibitors, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider Therapy Modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Budesonide (Topical). Risk X: Avoid
Buprenorphine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of BusPIRone. Risk C: Monitor
Cabozantinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cabozantinib. Risk C: Monitor
Cannabis: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor
Capivasertib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Capivasertib. Management: If capivasertib is combined with moderate CYP3A4 inhibitors, reduce the capivasertib dose to 320 mg twice daily for 4 days, followed by 3 days off. Monitor patients closely for adverse reactions. Risk D: Consider Therapy Modification
Cariprazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cariprazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Cariprazine. Management: Cariprazine dose adjustments are recommended and depend upon whether a patient is initiating a moderate CYP3A4 inhibitor or cariprazine, as well as cariprazine indication. See full mono for details. Some non-US labels contraindicate this combination. Risk D: Consider Therapy Modification
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Clindamycin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Cobimetinib. Management: Avoid this combination when possible. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose from 60 mg to 20 mg daily. Avoid concomitant use in patients already receiving reduced cobimetinib doses. Risk D: Consider Therapy Modification
Codeine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Colchicine. Management: Avoidance, dose reduction, or increased monitoring for colchicine toxicity may be needed and will depend on brand, indication for colchicine use, renal/hepatic function, and use of a P-gp inhibitor. See full monograph for details. Risk D: Consider Therapy Modification
Conivaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Conivaptan. Risk C: Monitor
Copanlisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Copanlisib. Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
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
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Lefamulin. Management: Monitor for lefamulin adverse effects during coadministration of lefamulin tablets with moderate CYP3A4 inhibitors. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Risk X: Avoid
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4. Risk D: Consider Therapy Modification
Daridorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Darifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Darifenacin. Risk C: Monitor
Deflazacort: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DexAMETHasone (Systemic). Risk C: Monitor
DiazePAM: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor
Diazoxide Choline: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Diazoxide Choline. Risk C: Monitor
Dienogest: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Dienogest. Risk C: Monitor
DilTIAZem: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DilTIAZem. Risk C: Monitor
DOCEtaxel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOCEtaxel. Risk C: Monitor
Domperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Domperidone. Risk X: Avoid
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of DroNABinol. Risk C: Monitor
Ebastine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ebastine. Risk C: Monitor
Elacestrant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elacestrant. Risk X: Avoid
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Elbasvir and Grazoprevir. Risk C: Monitor
Eletriptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eletriptan. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: May increase serum concentration of Lefamulin. Lefamulin may increase serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: Consider alternatives to this combination when possible. If combined, monitor for increased lefamulin toxicities and decrease the elexacaftor/tezacaftor/ivacaftor dose. See full monograph for details. Risk D: Consider Therapy Modification
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with moderate CYP3A4 inhibitors. Avoid use of moderate CYP3A4 inhibitors in CYP2D6 IMs or PMs. Use in CYP2D6 EMs or IMs also taking strong or moderate CYP2D6 inhibitors is contraindicated. Risk D: Consider Therapy Modification
Encorafenib: May decrease serum concentration of Lefamulin. Lefamulin may increase serum concentration of Encorafenib. Risk X: Avoid
Ensartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ensartinib. Risk X: Avoid
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eplerenone. Management: If coadministered with moderate CYP3A4 inhibitors, the max dose of eplerenone is 25 mg daily if used for heart failure; if used for hypertension initiate eplerenone 25 mg daily, titrate to max 25 mg twice daily. Risk D: Consider Therapy Modification
Erdafitinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider Therapy Modification
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor
Erlotinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Erlotinib. Risk C: Monitor
Eszopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Eszopiclone. Risk C: Monitor
Everolimus: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Everolimus. Risk C: Monitor
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Fedratinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fedratinib. Risk C: Monitor
Felodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Felodipine. Risk C: Monitor
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase serum concentration of FentaNYL. Management: Consider fentanyl dose reductions when combined with a moderate CYP3A4 inhibitor. Monitor for respiratory depression and sedation. Upon discontinuation of a CYP3A4 inhibitor, consider a fentanyl dose increase; monitor for signs and symptoms of withdrawal. Risk D: Consider Therapy Modification
Fexinidazole: Lefamulin may decrease active metabolite exposure of Fexinidazole. Fexinidazole may decrease serum concentration of Lefamulin. Management: In general, avoid concomitant use of lefamulin and fexinidazole. If concomitant use is deemed necessary, monitor for reduced efficacy of both lefamulin and fexinidazole. Risk D: Consider Therapy Modification
Finerenone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid
Fluticasone (Nasal): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Nasal). Risk C: Monitor
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor
Fosamprenavir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Fosaprepitant. 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: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Gepirone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepirone. Management: Reduce the gepirone dose by 50% if combined with moderate CYP3A4 inhibitors. Monitor for QTc interval prolongation with combined use. Risk D: Consider Therapy Modification
Gepotidacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Gepotidacin. Risk C: Monitor
Glasdegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Glasdegib. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Lefamulin. Risk C: Monitor
GuanFACINE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a moderate CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider Therapy Modification
HYDROcodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of HYDROcodone. Risk C: Monitor
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Risk D: Consider Therapy Modification
Ifosfamide: CYP3A4 Inhibitors (Moderate) may increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Iloperidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Iloperidone. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Irinotecan Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Irinotecan Products. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. Risk C: Monitor
Isradipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Isradipine. Risk C: Monitor
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: Lefamulin may increase serum concentration of Ivacaftor. Ivacaftor may increase serum concentration of Lefamulin. Management: Consider alternatives to this combination when possible. If combined, monitor for increased lefamulin toxicities and decrease the ivacaftor dose. See full monograph for details. Risk D: Consider Therapy Modification
Ixabepilone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Larotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Larotrectinib. Risk C: Monitor
Lasmiditan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Lemborexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lemborexant. Risk X: Avoid
Leniolisib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Leniolisib. Risk C: Monitor
Lercanidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lercanidipine. Risk C: Monitor
Levacetylleucine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levamlodipine. Risk C: Monitor
Levomethadone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomethadone. Risk C: Monitor
Levomilnacipran: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Levomilnacipran. Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lidocaine (Systemic). CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Lidocaine (Systemic). Specifically, concentrations of monoethylglycinexylidide (MEGX) may be increased. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lomitapide. Risk X: Avoid
Lovastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lovastatin. Risk C: Monitor
Lumateperone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lumateperone. Management: Limit the lumateperone dose to 21 mg once daily when used with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification
Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, reduce the lurbinectedin dose by 50%. Risk D: Consider Therapy Modification
Macitentan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Macitentan. Risk C: Monitor
Manidipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Manidipine. Risk C: Monitor
Maraviroc: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Maraviroc. Risk C: Monitor
Mavacamten: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a moderate CYP3A4 inhibitor, and reduce the mavacamten dose by one dose level if initiating a moderate CYP3A4 inhibitor. Avoid initiating moderate CYP3A4 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification
Meperidine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Meperidine. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of MethylPREDNISolone. Risk C: Monitor
Methysergide: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Methysergide. Risk X: Avoid
Midazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Midazolam. Management: Avoid concomitant use of nasal midazolam and moderate CYP3A4 inhibitors. Consider alternatives to use with oral midazolam whenever possible and consider using lower midazolam doses. Monitor patients for sedation and respiratory depression if combined. Risk D: Consider Therapy Modification
Mirodenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mirodenafil. Risk C: Monitor
Mitapivat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Mitapivat. Management: When coadministered with moderate CYP3A4 inhibitors, doses of mitapivat should not exceed 20 mg twice daily. Additionally, patients should be monitored for changes in hemoglobin response and increased mitapivat adverse effects. Risk D: Consider Therapy Modification
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Naldemedine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naldemedine. Risk C: Monitor
Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nalfurafine. Risk C: Monitor
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Naloxegol. Management: The use of naloxegol and moderate CYP3A4 inhibitors should be avoided. If concurrent use is unavoidable, reduce naloxegol dose to 12.5 mg once daily and monitor for signs of opiate withdrawal (eg, hyperhidrosis, chills, diarrhea, anxiety, irritability). Risk D: Consider Therapy Modification
NIFEdipine (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NIFEdipine. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of NiMODipine. Risk C: Monitor
Nirogacestat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nisoldipine. Risk X: Avoid
Nitrendipine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Nitrendipine. Risk C: Monitor
Olaparib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 150 mg twice daily and the dose of olaparib capsules should be reduced to 200 mg twice daily. Risk D: Consider Therapy Modification
Oliceridine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
Omaveloxolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Omaveloxolone. Management: Avoid this combination if possible. If coadministration is required, decrease the omaveloxolone dose to 100 mg daily and monitor closely for adverse reactions. If adverse reactions occur, decrease omaveloxolone to 50 mg daily. Risk D: Consider Therapy Modification
OxyCODONE: CYP3A4 Inhibitors (Moderate) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor
P-glycoprotein/ABCB1 Inducers: May decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider Therapy Modification
PACLitaxel (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Palbociclib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palbociclib. Risk C: Monitor
Palovarotene: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Palovarotene. Management: Avoid concomitant use of palovarotene and moderate CYP3A4 inhibitors when possible. If combined, decrease palovarotene dose by 50% as described in the full interaction monograph. Monitor for palovarotene toxicities when combined. Risk D: Consider Therapy Modification
Panobinostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Panobinostat. Risk C: Monitor
Pemigatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the moderate inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider Therapy Modification
Pexidartinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider Therapy Modification
Pimavanserin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pimavanserin. Risk C: Monitor
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease metabolism of Pimecrolimus. Risk C: Monitor
PONATinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of PONATinib. Risk C: Monitor
Pralsetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Prazepam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Prazepam. Risk C: Monitor
Praziquantel: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Praziquantel. Risk C: Monitor
Pretomanid: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Primaquine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging CYP3A4 Substrates: Lefamulin may increase QTc-prolonging effects of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ranolazine. Management: Limit the ranolazine dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors. Monitor for increased ranolazine effects and toxicities during concomitant use. Risk D: Consider Therapy Modification
Red Yeast Rice: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Red Yeast Rice. Risk C: Monitor
Regorafenib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Regorafenib. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Regorafenib. Risk C: Monitor
Repotrectinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Repotrectinib. Risk X: Avoid
Rimegepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rimegepant. Management: If taking rimegepant for the acute treatment of migraine, avoid a second dose of rimegepant within 48 hours when used concomitantly with moderate CYP3A4 inhibitors. No dose adjustment needed if using rimegepant for prevention of episodic migraine. Risk D: Consider Therapy Modification
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Risk C: Monitor
Roflumilast-Containing Products: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Roflumilast-Containing Products. Risk C: Monitor
Rupatadine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Rupatadine. Risk C: Monitor
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Salmeterol. Risk C: Monitor
SAXagliptin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SAXagliptin. Risk C: Monitor
Selpercatinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 80 mg twice/day, or from 160 mg twice/day to 120 mg twice/day. Risk D: Consider Therapy Modification
Selumetinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider Therapy Modification
Sertindole: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sertindole. Risk X: Avoid
Sildenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sildenafil. Risk C: Monitor
Silodosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Silodosin. Risk C: Monitor
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Conventional). Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a moderate CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Solifenacin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider Therapy Modification
Sparsentan: May increase serum concentration of Lefamulin. Lefamulin may increase serum concentration of Sparsentan. Specifically, the use of oral lefamulin may increase sparsentan concentrations. Risk X: Avoid
SUFentanil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of SUFentanil. Risk C: Monitor
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider Therapy Modification
Suzetrigine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Suzetrigine. Management: Reduce suzetrigine dose as follows: initiate with 100 mg for 1 dose; then 12 hours after first dose, give 50 mg every 12 hours for doses 2, 3, and 4; then 50 mg every 24 hours for dose 5 and thereafter. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
Tadalafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tadalafil. Risk C: Monitor
Tamsulosin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Taurursodiol: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Tazemetostat: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tazemetostat. Management: Avoid when possible. If combined, reduce tazemetostat dose from 800 mg twice daily to 400 mg twice daily, from 600 mg twice daily to 400 mg in AM and 200 mg in PM, or from 400 mg twice daily to 200 mg twice daily. Risk D: Consider Therapy Modification
Temsirolimus: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: Lefamulin may increase serum concentration of Tezacaftor and Ivacaftor. Tezacaftor and Ivacaftor may increase serum concentration of Lefamulin. Management: Consider alternatives to this combination when possible. If combined, monitor for increased lefamulin toxicities and decrease the tezacaftor/ivacaftor dose. See full monograph for details. Risk D: Consider Therapy Modification
Thiotepa: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Thiotepa. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Thiotepa. Risk C: Monitor
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ticagrelor. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor
Tilidine: CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Tilidine. CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tilidine. Risk C: Monitor
Tofacitinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tofacitinib. Risk C: Monitor
Tolterodine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolterodine. Risk C: Monitor
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tolvaptan. Management: Avoid this combination with Samsca brand of tolvaptan. Reduce dose for Jynarque brand: 90 mg AM and 30 mg PM, reduce to 45 mg AM and 15 mg PM; 60 mg AM and 30 mg PM, reduce to 30 mg AM and 15 mg PM; 45 mg AM and 15 mg PM, reduce to 15 mg AM and PM. Risk D: Consider Therapy Modification
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Trabectedin. Risk C: Monitor
TraMADol: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraMADol. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of TraZODone. Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Tretinoin (Systemic). Risk C: Monitor
Triamcinolone (Systemic): CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Ubrogepant: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and avoid a second dose for 24 hours when used with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Udenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Udenafil. Risk C: Monitor
Valbenazine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Vamorolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vamorolone. Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Management: Age- and weight-specific dose reductions of vanzacaftor, tezacaftor, and deutivacaftor are recommended. Please see full Interact monograph or labeling for details. Risk D: Consider Therapy Modification
Vardenafil: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider Therapy Modification
Venetoclax: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with moderate CYP3A4 inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Venetoclax: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Avoid concomitant use of venetoclax and oral p-glycoprotein (P-gp) substrates if possible. If combined use is unavoidable, administer the P-gp substrate at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider Therapy Modification
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vilazodone. Risk C: Monitor
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
VinBLAStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinBLAStine. Risk C: Monitor
VinCRIStine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of VinCRIStine. Risk C: Monitor
Vindesine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vindesine. Risk C: Monitor
Vinflunine: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vinflunine. CYP3A4 Inhibitors (Moderate) may increase active metabolite exposure of Vinflunine. Risk C: Monitor
Voclosporin: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Voclosporin. Management: Decrease the voclosporin dose to 15.8 mg in the morning and 7.9 mg in the evening when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Vorapaxar. Risk C: Monitor
Xanomeline: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Zanubrutinib: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zopiclone. Risk C: Monitor
Zuranolone: CYP3A4 Inhibitors (Moderate) may increase serum concentration of Zuranolone. Risk C: Monitor
Administration with a high-fat, high-calorie breakfast slightly reduced bioavailability. Management: Administer ≥1 hour before a meal or 2 hours after a meal.
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for 2 days after the last dose.
Based on data from animal reproduction studies, in utero exposure to lefamulin may cause fetal harm.
Data collection to monitor pregnancy and infant outcomes following exposure to lefamulin is ongoing. Health care providers are encouraged to enroll females exposed to lefamulin during pregnancy in the pregnancy pharmacovigilance program (1-855-5NABRIVA).
It is not known if lefamulin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 days after the last lefamulin dose. Lactating women should express and discard milk during this time.
Take tablet ≥1 hour before a meal or 2 hours after a meal.
Hepatic function; ECG in patients predisposed to or with risk factors for QT prolongation; pregnancy status in females of reproductive potential.
Lefamulin is a pleuromutilin that inhibits bacterial protein synthesis through interactions (hydrogen bonds, hydrophobic interactions, and Van der Waals forces) with the A- and P- sites of the peptidyl transferase center in domain V of the 23s ribosomal RNA of the 50S subunit. The binding pocket of the bacterial ribosome closes around the mutilin core for an induced fit that prevents correct positioning of transfer RNA.
Distribution: Vdss: IV: 86.1 L (range: 34.2 to 153 L).
Protein binding: 94.8% to 97.1%.
Metabolism: Primarily CYP3A4.
Bioavailability: Oral: 25%; administration with food slightly decreases bioavailability.
Half-life elimination: ~8 hours (range: 3 to 20 hours); 17.5 hours in patients with severe hepatic impairment after IV administration.
Time to peak: Oral: 0.88 to 2 hours.
Excretion:
IV: Feces: 77.3% (4.2% to 9.1% unchanged); urine: 15.5% (9.6% to 14.1% unchanged).
Oral: Feces: 88.5% (7.8% to 24.8% unchanged); urine: 5.3% (percentage unchanged not determined).
Hepatic function impairment: Half-life is prolonged in patients with severe impairment (17.5 hours vs 11.5 hours in subjects with normal hepatic function). Protein binding is reduced in hepatic impairment, leading to increased concentrations of unbound lefamulin (increased 3-fold in subjects with severe impairment).
Anti-infective considerations:
Parameters associated with efficacy: Time and concentration dependent; associated with free area under the curve (fAUC24)/minimum inhibitory concentration (MIC) (Bhavnani 2019; Wicha 2019a; Wicha 2019b).
Organism specific, community-acquired pneumonia:
S. pneumoniae: Goal: fAUC24/MIC 1.37 (1-log kill) (Bhavnani 2019; Wicha 2019b).
S. aureus: Goal: fAUC24/MIC 2.13 (1-log kill) (Bhavnani 2019; Wicha 2019b).
Expected drug exposure in adults with community-acquired pneumonia:
Cmax (peak):
IV (150 mg):
Single dose: 3.5 mg/L.
Steady state: 3.6 mg/L.
Oral (600 mg):
Single dose: 2.24 mg/L.
Steady state: 2.24 mg/L.
AUC0-24h:
IV (150 mg):
Single dose: 27 mg•hour/L.
Steady state: 28.6 mg•hour/L.
Oral (600 mg):
Single dose: 30.7 mg•hour/L.
Steady state: 32.7 mg•hour/L.
Postantibiotic effect: Bacterial killing continues after lefamulin concentration falls below the MIC of targeted pathogen; time of postantibiotic effect varies based on organism:
S. aureus: ~1 to 1.5 hours (Wicha 2019a).
S. pneumoniae: ~3 to 3.5 hours (Wicha 2019a).
