Lefamulin (Xenleta) Dose in Adults:

Risk Factor C (Monitor therapy)

Abemaciclib

Abemaciclib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

AmLODIPine

The serum levels of AmLODIPine may rise in response to CYP3A4 Inhibitors (Moderate).

Apixaban

Apixaban's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

BCG Vaccine (Immunization)

Antibiotics may reduce the BCG vaccine's therapeutic effect (Immunization).

Benzhydrocodone

The serum levels of Benzhydrocodone may rise in response to moderate CYP3A4 inhibitors. In particular, there might be an increase in hydrocodone concentration.

Blonanserin

Blonanserin's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Brexpiprazole

Brexpiprazole's serum levels may rise in the presence of moderate CYP3A4 inhibitors. Treatment: If brexpiprazole is used with a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer, the dose should be lowered to 25% of the usual amount.

Cannabidiol

Cannabidiol's serum levels may rise in response to moderate CYP3A4 inhibitors.

Cannabis

Cannabis serum concentrations may rise in response to moderate CYP3A4 inhibitors. Serum concentrations of cannabidiol and tetrahydrocannabinol may rise particularly.

Clofazimine

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Codeine

CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine.

CYP3A4 Inhibitors (Moderate)

Lefamulin serum levels might rise. Management: Keep an eye out for lefamulin side effects when taking mild CYP3A4 inhibitors alongside lefamulin tablets.

CYP3A4 Substrates (High risk with Inhibitors)

The metabolism of CYP3A4 Substrates may be decreased by moderate CYP3A4 Inhibitors (High risk with Inhibitors). Alitretinoin (Systemic), Praziquantel, Trabectedin, and Vinorelbine are exceptions.

Deferasirox

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Dronabinol

Dronabinol's serum levels may rise in response to moderate CYP3A4 inhibitors.

Duvelisib

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Erdafitinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Erdafitinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Erdafitinib

P-glycoprotein/ABCB1 Substrates serum levels can rise.

Estrogen Derivatives

The serum concentration of oestrogen derivatives may rise in response to moderately potent CYP3A4 inhibitors.

Fosnetupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

HYDROcodone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone.

Ifosfamide

The active metabolite(s) of ifosfamide may be present in lower serum concentrations when CYP3A4 Inhibitors (Moderate) are used.

Imatinib

Imatinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Lactobacillus and Estriol

The therapeutic effects of Lactobacillus and Estriol may be reduced by antibiotics.

Larotrectinib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Levamlodipine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine.

Manidipine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine.

Meperidine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine.

Mirodenafil

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil.

Naldemedine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine.

Nalfurafine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine.

Netupitant

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

NiMODipine

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine.

OxyCODONE

CYP3A4 Inhibitors (Moderate) may intensify OxyCODONE's harmful/toxic effects. The serum concentration of OxyCODONE may rise in response to moderately potent CYP3A4 inhibitors. The active metabolite Oxymorphone's serum concentrations could also rise.

Palbociclib

May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).

Pexidartinib

Pexidartinib's serum levels may rise in response to moderate CYP3A4 inhibitors.

Pimecrolimus

The metabolism of pimecrolimus may be decreased by moderate CYP3A4 inhibitors.

QT-prolonging Agents (Highest Risk)

The QTc-prolonging action of QT-prolonging Agents may be enhanced by QT-prolonging Agents (Indeterminate Risk - Avoid) (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Rupatadine

Rupatadine's serum levels may rise in response to moderate CYP3A4 inhibitors.

Ruxolitinib

Ruxolitinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Salmeterol

Salmeterol's serum levels may rise in response to CYP3A4 Inhibitors (Moderate).

Sarilumab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

SAXagliptin

The serum levels of SAXagliptin may rise in response to moderately potent CYP3A4 inhibitors.

Sildenafil

The serum concentration of Sildenafil may rise in response to CYP3A4 Inhibitors (Moderate).

Silodosin

Silodosin's serum levels may rise in response to moderate CYP3A4 inhibitors.

Siltuximab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Tamsulosin

Tamsulosin's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Tetrahydrocannabinol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.

Ticagrelor

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor.

Tocilizumab

May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).

Tofacitinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tofacitinib.

Trabectedin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin.

Udenafil

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil.

Vilazodone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone.

Vindesin

: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine.

Zuclopenthixol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol.

Risk Factor D (Consider therapy modification)

Acalabrutinib

Acalabrutinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: Lower the dose of acalabrutinib to 100 mg once daily while using a mild CYP3A4 inhibitor. If there is any concurrent use, keep a watchful eye on the patient for both acalabrutinib response and signs of side effects.

ARIPiprazole

The serum levels of ARIPiprazole may rise in the presence of CYP3A4 Inhibitors (Moderate). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph.

Avanafil

Avanafil's serum levels may rise in response to moderate CYP3A4 inhibitor therapy. Management: When used with a mild CYP3A4 inhibitor, the maximum adult dose of avanafil is 50 mg per 24 hours. Additionally, patients taking such a combination should have increased surveillance for signs.

Avapritinib

Avapritinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Avoid using mild CYP3A4 inhibitors while taking avapritinib. Reduce the dose of avapritinib from 300 mg once daily to 100 mg once daily if this combination cannot be avoided.

Brigatinib

Brigatinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: When possible, avoid taking brigatinib at the same time as mild CYP3A4 inhibitors. Reduce the brigatinib dosage by around 40% if such a combination cannot be avoided (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg).

Bromocriptine

The serum levels of bromocriptine may rise in response to moderately potent CYP3A4 inhibitors. Treatment: When used with a mild CYP3A4 inhibitor, the daily dose of bromocriptine should not exceed 1.6 mg.

Budesonide (Topical)

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased.

Cilostazol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4.

Colchicine

Colchicine's serum levels may rise after taking CYP3A4 Inhibitors (Moderate). Management: Increase monitoring for colchicine-related toxicity and decrease colchicine dose as advised when used with a moderate CYP3A4 inhibitor. For information, see the entire monograph. Patients with weakened liver or kidney function should be treated with extreme caution.

CYP3A4 Inducers (Moderate)

Lefamulin serum concentration can drop. Management: Unless the advantages outweigh the hazards, avoid using lefamulin concurrently with mild CYP3A4 inducers.

CYP3A4 Inducers (Strong)

Lefamulin serum concentration can drop. Management: Unless the advantages outweigh the hazards, avoid using lefamulin concurrently with potent CYP3A4 inducers.

Dabrafenib

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).

Dapoxetine

Dapoxetine's serum levels may rise in response to moderate CYP3A4 inhibitors. Treatment: When used with a mild CYP3A4 inhibitor, the daily dose of dapoxetine should be restricted to 30 mg.

Deflazacort

The active metabolite(s) of Deflazacort may be present in higher serum quantities when taking CYP3A4 Inhibitors (Moderate). When taking deflazacort with a strong or moderate CYP3A4 inhibitor, only take one-third of the prescribed dose.

DOXOrubicin (Conventional)

The serum concentration of DOXOrubicin may rise after using moderate amounts of CYP3A4 inhibitors (Conventional). Treatment: Whenever possible, avoid using mild CYP3A4 inhibitors in patients receiving doxorubicin. Pfizer Inc., a U.S. manufacturer, advises against using certain mixtures.

Eletriptan

Eletriptan's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Eletriptan shouldn't be taken within 72 hours of a moderate CYP3A4 inhibitor.

Eliglustat

Eliglustat's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: There are specific situations when use should be avoided. For information, consult the entire medication interaction monograph.

Enzalutamide

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.

Eplerenone

Eplerenone's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). Management: Depending on the indication and foreign labelling, different doses of eplerenone should be used concurrently with mild CYP3A4 inhibitors. For information, consult the entire medication interaction monograph.

Everolimus

CYP3A4 Inhibitors (Moderate) may raise the level of Everolimus in the blood. For the majority of cases, everolimus dose decreases are necessary. For detailed dose modification and monitoring suggestions, consult the full monograph or prescription information.

FentaNYL

The serum levels of FentaNYL may rise in response to CYP3A4 Inhibitors (Moderate). Management: After starting this combination, keep a watchful eye on the patients for a few days and alter the fentanyl dosage as necessary.

GuanFACINE

CYP3A4 Inhibitors (Moderate) may raise the level of GuanFACINE in the serum. When starting this combo, cut the guanfacine dose in half.

Ibrutinib

Ibrutinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: While paired with mild CYP3A4 inhibitors, reduce ibrutinib dosage to 280 mg per day when treating B-cell malignancies. When treating graft versus host disease, keep a close eye on the patients and adjust the ibrutinib dosage as necessary based on side effects.

Ivacaftor

Ivacaftor's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: For product-specific advice, read the full monograph. Ivacaftor dose reductions may be necessary. When taking ivacaftor/lumacaftor with a mild CYP3A4 inhibitor, there is no need to change the dosage.

Lorlatinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.

Lurasidone

Lurasidone's serum levels may rise in response to moderate CYP3A4 inhibitors. Treatment: According to the US labelling for lurasidone, the dose should be cut in half and used with a mild CYP3A4 inhibitor. Some non-US labelling advises starting with 20 mg/day of lurasidone and limiting the dosage to 40 mg/day; avoid grapefruit concomitantly.

Mitotane

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.

Olaparib

Olaparib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: If at all feasible, refrain from administering mild CYP3A4 inhibitors to patients receiving olaparib. Olaparib dosage should be decreased to 150 mg twice daily if such concomitant use cannot be avoided.

P-glycoprotein/ABCB1 Inducers

Lefamulin serum concentration can drop. Management: Unless the advantages outweigh the hazards, avoid using lefamulin concurrently with P-glycoprotein/ABCB1 inducers.

P-glycoprotein/ABCB1 Inhibitors

Lefamulin serum levels might rise. Avoid taking lefamulin tablets at the same time as P-glycoprotein/ABCB1 inhibitors. Watch for any negative effects of lefamulin if concurrent use is necessary.

Ranolazine

Ranolazine's serum levels may rise after taking CYP3A4 Inhibitors (Moderate). Treatment: In patients receiving mild CYP3A4 inhibitors concurrently, the adult ranolazine dose should be restricted to no more than 500 mg twice daily (e.g., diltiazem, verapamil, erythromycin, etc.).

Sirolimus

The serum concentration of Sirolimus may rise after taking CYP3A4 Inhibitors (Moderate). Management: If sirolimus is taken with a mild CYP3A4 inhibitor, keep an eye out for elevated serum concentrations. Lower starting dosages of sirolimus or dose reductions of sirolimus will probably be needed.

Sodium Picosulfate

Antibiotics may reduce Sodium Picosulfate's therapeutic impact. Management: If a patient previously used or is currently using an antibiotic, think about utilising an alternative product for bowel cleansing prior to a colonoscopy.

Sonidegib

Sonidegib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: Whenever possible, refrain from taking moderate CYP3A4 inhibitors and sonidegib concurrently. Limit the use of CYP3A4 inhibitors to less than 14 days when concurrent usage cannot be avoided, and keep an eye out for sonidegib toxicity (particularly musculoskeletal adverse reactions).

Stiripentol

Suvorexant

Suvorexant's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: Suvorexant is administered at a dose of 5 mg per day to patients who are on a mild CYP3A4 inhibitor.

Tezacaftor

Tezacaftor's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: Tezacaftor/ivacaftor or elexacaftor/tezacaftor/ivacaftor should be administered in the morning, every other day, when used with mild CYP3A4 inhibitors. Ivacaftor should be administered by itself in the morning on alternate days.

Tolvaptan

Tolvaptan's serum levels may rise in response to CYP3A4 Inhibitors (Moderate). Management: When used with a mild CYP3A4 inhibitor, jynarque dosage must be adjusted. For more detailed advice, consult the complete interaction monograph or labelling. Samsca use should generally be avoided when moderate CYP3A4 inhibitors are present.

Triazolam

Triazolam's serum levels may rise in response to moderately potent CYP3A4 inhibitors. Treatment: If patients are using moderate CYP3A4 inhibitors concurrently, triazolam dosage reduction may be an option.

Typhoid Vaccine

The Typhoid Vaccine's therapeutic benefits may be reduced by antibiotics. The only strain impacted is the live attenuated Ty21a strain. Treatment: Patients receiving systemic antibacterial drugs should refrain from receiving the live attenuated typhoid vaccination (Ty21a). It is recommended to wait at least 3 days following the last dose of antibacterial medication before administering this vaccine.

Ubrogepant

The serum levels of Ubrogepant may rise in response to CYP3A4 Inhibitors (Moderate). When used with mild CYP3A4 inhibitors, administer a 50 mg dose of ubrogepant as the initial dose and wait 24 hours before administering a second dose.

Venetoclax

Venetoclax's serum levels may rise in response to moderate CYP3A4 inhibitors. Management: In patients who need these combinations, lower the dose of venetoclax by at least 50%.

Zanubrutinib

Zanubrutinib's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: When taking zanubrutinib with a mild CYP3A4 inhibitor, reduce the dose to 80 mg twice daily. For further information, see the prescribing information, since additional dose modifications may be necessary for zanubrutinib toxicity.

Zopiclone

Zopiclone's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Management: If taken with a mild CYP3A4 inhibitor, the first adult dose of zopiclone shouldn't be more than 3.75 mg. If these medications are taken together, patients should be kept an eye out for any zopiclone toxicity symptoms.

Risk Factor X (Avoid combination)

Aprepitant

Aprepitant's serum levels may rise in response to moderate CYP3A4 inhibitors.

Asunaprevir

Asunaprevir's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

BCG (Intravesical)

The therapeutic benefit of BCG may be reduced by antibiotics (Intravesical).

Bosutinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib.

Budesonide (Systemic)

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic).

Cholera Vaccine

The curative power of the cholera vaccine may be diminished by antibiotics. Avoid administering the cholera vaccine to individuals taking systemic antibiotics and within 14 days after taking oral or parenteral antibiotics.

Cobimetinib

The serum levels of Cobimetinib may rise in response to CYP3A4 Inhibitors (Moderate). Management: Avoid using mild CYP3A4 inhibitors and cobimetinib together. The cobimetinib dose should be decreased to 20 mg per day if concurrent short-term (14 days or less) use cannot be avoided.

Conivaptan

May raise the serum level of CYP3A4 substrates (High risk with Inhibitors).

CYP3A4 Inhibitors (Strong)

Lefamulin serum levels could become more elevated. Management: Steer clear of combining the usage of lefamulin pills with potent CYP3A4 inhibitors.

Domperidone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.

Flibanserin

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin.

Fosaprepitant

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant.

Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Idelalisib

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

Ivabradine

Ivabradine's serum levels may rise in response to moderate CYP3A4 inhibitors.

Lasmiditan

P-glycoprotein/ABCB1 Substrates serum levels can rise.

Lemborexant

Lemborexant's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Lomitapide

Lomitapide's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Lumateperone

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone.

Naloxegol

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol.

Neratinib

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib.

Pimozide

CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide.

QT-prolonging CYP3A4 Substrates

Lefamulin may intensify the CYP3A4 substrates' ability to prolong QTc. Management: Avoid taking lefamulin pills with CYP3A4 substrates that prolong QT. The prescribing label for lefamulin states that this combination is not recommended.

Simeprevir

Simeprevir's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate).

Ulipristal

Ulipristal's serum levels may rise when taken with CYP3A4 Inhibitors (Moderate). Treatment: This is specific to the use of ulipristal for indications or symptoms of uterine fibroids (Canadian indication). When ulipristal is administered to patients as an emergency contraception, they should be watched closely for ulipristal toxicity.