Addyi

Multifunctional Serotonin Agonists/Antagonists for HSDD

Oral Administration

Administer once per day at bedtime only, to decrease the risk for daytime hypotension, syncope, or accidental injury, and to decrease risks associated with central nervous system (CNS) depression (e.g., sedation).
Do not administer with grapefruit juice.
The patient must avoid alcoholic beverages (1 or 2 standard drinks) for at least 2 hours before their bedtime flibanserin dose due to the increased risk of severe hypotension or syncope. If the patient has 3 or more standard alcoholic drinks in an evening, the flibanserin bedtime dose should be skipped.
Missed Dose: If a bedtime dose is missed, administer next dose at bedtime next day. Do not double up on doses.

Severe

angioedema / Rapid / Incidence not known

Moderate

constipation / Delayed / 1.6-1.6
hypotension / Rapid / 0.2-0.2
orthostatic hypotension / Delayed / Incidence not known

Mild

dizziness / Early / 11.4-11.4
drowsiness / Early / 1.3-11.2
nausea / Early / 10.4-10.4
fatigue / Early / 9.2-9.2
insomnia / Early / 4.9-4.9
xerostomia / Early / 2.4-2.4
anxiety / Delayed / 1.8-1.8
abdominal pain / Early / 1.5-1.5
rash / Early / 1.3-1.3
vertigo / Early / 1.0-1.0
syncope / Early / 0.4-0.4
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known

Ethanol ingestion

Patients receiving flibanserin should be instructed to avoid ethanol ingestion (1 or 2 standard alcoholic drinks) for at least 2 hours before taking their bedtime dose of flibanserin, due to an increased risk of severe hypotension and syncope. Alternatively, the patient may skip the flibanserin dose if alcohol is consumed that evening. Patients who drink 3 or more standard alcoholic drinks must skip their flibanserin bedtime dose. After taking a flibanserin dose at bedtime, advise all patients to not use alcohol until the following day. Clinical studies have demonstrated that the use of flibanserin and alcohol increases the risk of severe hypotension and syncope vs. the use of either agent alone, and coadministration also increases the risk for additive CNS effects, such as sedation. In a dedicated interaction study of the effects of alcohol with flibanserin, systolic and diastolic blood pressure reductions and orthostatic changes were clinically significant and required clinical intervention in some patients. There were no events requiring therapeutic interventions when flibanserin or alcohol were administered alone.

Hepatic disease

Flibanserin is contraindicated for use in patients with any degree of hepatic impairment. The product information of flibanserin contains a boxed warning emphasizing that hepatic impairment (including hepatic disease) significantly increases flibanserin concentrations (4.5-fold compared to patients with normal hepatic function), which can lead to severe hypotension, syncope, and CNS depressive effects. The coadministration of certain medications may significantly inhibit the hepatic metabolism of flibanserin, even when hepatic function is normal. Flibanserin is primarily metabolized by hepatic CYP3A4 and to a lesser extent by CYP2C19. The concomitant use of moderate or strong CYP3A4 inhibitors with flibanserin is contraindicated. If the patient requires a moderate or strong CYP3A4 inhibitor, discontinue flibanserin at least 2 days prior to starting the moderate or strong CYP3A4 inhibitor. In cases where the benefit of initiating a moderate or strong CYP3A4 inhibitor within 2 days of stopping flibanserin clearly outweighs the risk of hypotension and syncope, monitor the patient closely. Discontinue the moderate or strong CYP3A4 inhibitor for 2 weeks before restarting flibanserin. The concomitant use of multiple weak CYP3A4 inhibitors including herbal supplements (e.g., ginkgo, resveratrol) or non-prescription drugs (e.g., cimetidine), or the use of potent CYP2C19 inhibitors, could also lead to clinically relevant increases in flibanserin concentrations that may increase the risk for hypotension and syncope.

Addyi

Rx

Oral serotonin 5-HT1A receptor agonist/serotonin 5-HT2A receptor antagonist
For use in premenopausal women with generalized hypoactive sexual desire disorder (HSDD) not due to identifiable causes; contraindicated with moderate and strong CYP3A4 inhibitors and with hepatic impairment
Boxed warning regarding risk for severe hypotension and syncope under certain conditions; patients must avoid alcohol for at least 2 hours before a dose and to skip a dose if 3 or more standard alcoholic drinks have been consumed

For the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) (also known as female sexual interest/arousal disorder) . Oral dosage Adult Premenopausal Females

100 mg PO once daily at bedtime. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Counsel patients to avoid alcohol for at least 2 hours prior to taking the bedtime dose of flibanserin. Discontinue after 8 weeks if improvement does not occur. LIMITS OF USE: Safety and efficacy are only established in premenopausal females 18 to 56 years of age. Flibanserin is not indicated for the treatment of HSDD in males or postmenopausal women, or to enhance sexual performance.

Postmenopausal and Geriatric Adult females†

Safety and efficacy not established; not FDA-approved. 100 mg/day PO at bedtime was effective in one trial. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Counsel patients to avoid alcohol for at least 2 hours prior to taking the bedtime dose of flibanserin. Discontinue after 8 weeks if improvement does not occur.

Hepatic Impairment

Do not use. Contraindicated in patients with any degree of hepatic impairment.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Chlorpheniramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Diphenhydramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Acrivastine; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Adagrasib: (Contraindicated) The concomitant use of flibanserin and strong CYP3A inhibitors such as adagrasib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of adagrasib, start flibanserin at least 2 weeks after the last dose of adagrasib. If initiating adagrasib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating adagrasib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Afatinib: (Moderate) If the concomitant use of flibanserin and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of flibanserin. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and flibanserin is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Aldesleukin, IL-2: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including aldesleukin, IL-2, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Amiodarone: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as amiodarone, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Amobarbital: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as clarithromycin, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Apalutamide: (Major) Coadministration of flibanserin with apalutamide is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased flibanserin exposure by 95%.
Aprepitant, Fosaprepitant: (Contraindicated) The concomitant use of flibanserin and a multi-day regimen of oral aprepitant is contraindicated. If flibanserin treatment is necessary, start the first dose at least 2 weeks after the last dose of aprepitant . If initiating multi-day aprepitant following flibanserin use, start treatment at least 2 days after the last dose of flibanserin. If the benefit of initiating a multi-day course of aprepitant within 2 days of stopping flibanserin clearly outweighs the risk of increased flibanserin exposure, monitor the patient for signs of hypotension and syncope. Flibanserin may be used with a single, 40-mg dose of aprepitant as for post-operative nausea/vomiting (PONV) or with fosaprepitant 150 mg IV for chemotherapy-induced nausea and vomiting (CINV); however, carefully monitor for an increase in flibanserin-related adverse effects. Concomitant use of multiple weak CYP3A4 inhibitors including herbal supplements (e.g., ginkgo, resveratrol) or non-prescription drugs (e.g., cimetidine) could also lead to clinically relevant increases in flibanserin concentrations that may increase the risk of hypotension and syncope. Flibanserin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of flibanserin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Armodafinil: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as modafinil or armodafinil, is not recommended. In addition, modafinil and armodafinil are inhibitors of CYP2C19, a minor metabolic pathway of flibanserin.
Asciminib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including asciminib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Aspirin, ASA; Butalbital; Caffeine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Aspirin, ASA; Omeprazole: (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Atazanavir: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as atazanavir, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Atazanavir; Cobicistat: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as atazanavir, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as cobicistat is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of cobicistat, start flibanserin at least 2 weeks after the last dose of cobicistat. If initiating cobicistat following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating cobicistat therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Avacopan: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including avacopan, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Barbiturates: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Belumosudil: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including belumosudil, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Berotralstat: (Contraindicated) The concomitant use of flibanserin and berotralstat is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of berotralstat, start flibanserin at least 2 weeks after the last dose of berotralstat. If initiating berotralstat following flibanserin use, start berotralstat at least 2 days after the last dose of flibanserin. If concomitant use cannot be avoided, reduce the berotralstat dose to 110 mg PO once daily. Flibanserin is a CYP3A4 substrate and a P-gp inhibitor; and berotralstat is a P-gp substrate and moderate CYP3A4 inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving flibanserin. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving flibanserin. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; flibanserin inhibits P-gp.
Bexarotene: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as bexarotene, is not recommended.
Bicalutamide: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including bicalutamide, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Bosentan: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as bosentan, is not recommended.
Brompheniramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Brompheniramine; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Brompheniramine; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Butabarbital: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Butalbital; Acetaminophen: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Butalbital; Acetaminophen; Caffeine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Butalbital; Aspirin; Caffeine; Codeine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and flibanserin. CNS depressants can potentiate the effects of cannabidiol.
Carbamazepine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and carbamazepine, a strong CYP3A4 inducer, is not recommended.
Carbinoxamine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Cenobamate: (Major) Coadministration of flibanserin with cenobamate is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%. Additionally, additive CNS depression may occur.
Ceritinib: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as ceritinib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of ceritinib, start flibanserin at least 2 weeks after the last dose of ceritinib. If initiating ceritinib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating ceritinib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with flibanserin should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with flibanserin should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlophedianol; Dexbrompheniramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chloramphenicol: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as chloramphenicol, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Chlorcyclizine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Codeine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Dextromethorphan: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Hydrocodone: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Chlorpheniramine; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Cimetidine: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including cimetidine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Ciprofloxacin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as ciprofloxacin, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Clarithromycin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as clarithromycin, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Clemastine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Cobicistat: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as cobicistat is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of cobicistat, start flibanserin at least 2 weeks after the last dose of cobicistat. If initiating cobicistat following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating cobicistat therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Cobimetinib: (Minor) If concurrent use of cobimetinib and flibanserin is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and flibanserin is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
Colchicine: (Major) Avoid concomitant use of colchicine and flibanserin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and flibanserin is a P-gp inhibitor.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including flibanserin, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Conivaptan: (Contraindicated) The concomitant use of flibanserin and conivaptan is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of conivaptan, start flibanserin at least 2 weeks after the last dose of conivaptan. If initiating conivaptan following flibanserin use, start conivaptan at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Contraindicated) The concomitant use of flibanserin and crizotinib is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of crizotinib, start flibanserin at least 2 weeks after the last dose of crizotinib. If initiating crizotinib following flibanserin use, start crizotinib at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor.
Cyclizine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Cyclosporine: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as cyclosporine, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Cyproheptadine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dalfopristin; Quinupristin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including dalfopristin; quinupristin, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Danazol: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as danazol, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Darunavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as darunavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. A similar contraindication applies to combination products containing darunavir such as darunavir; cobicistat.
Darunavir; Cobicistat: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as cobicistat is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of cobicistat, start flibanserin at least 2 weeks after the last dose of cobicistat. If initiating cobicistat following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating cobicistat therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope. (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as darunavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. A similar contraindication applies to combination products containing darunavir such as darunavir; cobicistat.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as cobicistat is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of cobicistat, start flibanserin at least 2 weeks after the last dose of cobicistat. If initiating cobicistat following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating cobicistat therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope. (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as darunavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. A similar contraindication applies to combination products containing darunavir such as darunavir; cobicistat.
Delavirdine: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as delavirdine, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as flibanserin, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dexchlorpheniramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Digoxin: (Major) The concomitant use of flibanserin, a P-glycoprotein (P-gp) inhibitor, and digoxin, a P-gp substrate, can increase digoxin concentrations, which may lead to digoxin toxicity. Increased monitoring of digoxin concentrations is recommended during concurrent use. In a controlled cross-over study in 24 healthy men and women, flibanserin 100 mg was administered once daily over 5 days followed by a single dose of 0.5 mg digoxin. Flibanserin increased the digoxin AUC by 2.0-fold and Cmax by 1.5-fold, compared to digoxin alone. Patients should be instructed to contact their healthcare provider if they experience symptoms of digoxin toxicity such as changes in color vision (more yellow color), blurred vision, eyes sensitive to light, light flashes, or halos around bright lights, changes in behavior, chest pain or palpitations, bradycardia, or loss of appetite.
Diltiazem: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as diltiazem, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Dimenhydrinate: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Diphenhydramine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Diphenhydramine; Ibuprofen: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Diphenhydramine; Naproxen: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Diphenhydramine; Phenylephrine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Doxylamine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Doxylamine; Pyridoxine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dronabinol: (Moderate) The concomitant use of flibanserin with CNS depressants, such as dronabinol, THC, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Dronedarone: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as dronedarone, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Duvelisib: (Contraindicated) The concomitant use of flibanserin and duvelisib is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of duvelisib, start flibanserin at least 2 weeks after the last dose of duvelisib. If initiating duvelisib following flibanserin use, start duvelisib at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as efavirenz is not recommended.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as efavirenz is not recommended.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as efavirenz is not recommended.
Elagolix: (Major) Coadministration of elagolix with flibanserin is not recommended due to decreased plasma exposure to flibanserin which may result in decreased efficacy. Flibanserin is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant administration with a moderate CYP3A4 inducer decreased flibanserin exposures by approximately 21%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Coadministration of elagolix with flibanserin is not recommended due to decreased plasma exposure to flibanserin which may result in decreased efficacy. Flibanserin is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant administration with a moderate CYP3A4 inducer decreased flibanserin exposures by approximately 21%.
Elbasvir; Grazoprevir: (Moderate) Administering flibanserin with elbasvir; grazoprevir may result in elevated flibanserin plasma concentrations. Flibanserin is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ivacaftor, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as cobicistat is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of cobicistat, start flibanserin at least 2 weeks after the last dose of cobicistat. If initiating cobicistat following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating cobicistat therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as cobicistat is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of cobicistat, start flibanserin at least 2 weeks after the last dose of cobicistat. If initiating cobicistat following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating cobicistat therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Enzalutamide: (Major) Coadministration of flibanserin with enzalutamide is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased flibanserin exposure by 95%.
Erythromycin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as erythromycin, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and flibanserin for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Eslicarbazepine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as eslicarbazepine, is not recommended.
Esomeprazole: (Moderate) Use of esomeprazole may increase flibanserin concentrations, resulting in severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Esomeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Ethanol: (Major) Advise patients to wait at least 2 hours after consuming 1 or 2 standard alcohol-containing drinks before taking flibanserin at bedtime. Patients who consume 3 or more standard alcohol-containing drinks should skip their flibanserin dose. After taking flibanserin at bedtime, advise patients not to consume alcohol until the following day. Severe hypotension including systolic blood pressure drops of up to 50 mmHg, syncope, and additive CNS depression may occur if flibanserin and alcohol are taken together in close proximity.
Ethotoin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as ethotoin, is not recommended.
Etravirine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as etravirine, is not recommended. In one study, etravirine decreased flibanserin exposure by about 21%.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with flibanserin is necessary; the dose of everolimus may need to be reduced. Also, monitor for potentially increased flibanserin-induced adverse reactions such as hypotension, syncope, somnolence, or other adverse reactions. Everolimus is a weak CYP3A4 inhibitor as well as a P-glycoprotein (P-gp) substrate. Flibanserin is a CYP3A4 substrate as well as a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations. The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors may increase flibanserin concentrations.
Ezetimibe; Simvastatin: (Moderate) In a cross-over study in 12 healthy men and women, the effect of flibanserin 50 mg twice daily for 4 days on the pharmacokinetics of simvastatin 40 mg once daily was evaluated. Flibanserin increased the AUC of simvastatin, a substrate of CYP3A4, by 1.3-fold and the Cmax by 1.2-fold. The AUC and Cmax of simvastatin acid were increased by 1.5-fold and 1.4-fold, respectively.
Fedratinib: (Contraindicated) The concomitant use of flibanserin and fedratinib is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of fedratinib, start flibanserin at least 2 weeks after the last dose of fedratinib. If initiating fedratinib following flibanserin use, start fedratinib at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and flibanserin. Concurrent use may result in additive CNS depression.
Fluconazole: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as fluconazole, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. In a pharmacokinetic drug interaction study of 100 mg flibanserin and 200 mg fluconazole, hypotension

or syncope requiring placement supine with legs elevated occurred in 20% of subjects treated with concomitant flibanserin and fluconazole compared to no similar reactions in subjects treated with flibanserin alone or fluconazole alone. One of the subjects experiencing hypotension became unresponsive with a blood pressure of 64/41 mm Hg and required transportation to the hospital emergency department where she required intravenous saline. Due to these adverse reactions, the study was stopped. In this study, the concomitant use of flibanserin and fluconazole increased flibanserin exposure 7-fold. It should be noted that in addition to being a moderate CYP3A4 inhibitor, fluconazole is a potent inhibitor of CYP2C19, a minor metabolic pathway of flibanserin.
Fluoxetine: (Major) The concomitant use of flibanserin and a strong CYP2C19 inhibitor or multiple weak CYP3A4 inhibitors, including fluoxetine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Fluvoxamine: (Contraindicated) The concomitant use of flibanserin and fluvoxamine is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of fluvoxamine, start flibanserin at least 2 weeks after the last dose of fluvoxamine. If initiating fluvoxamine following flibanserin use, start fluvoxamine at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Contraindicated) The concomitant use of flibanserin and fosamprenavir is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of fosamprenavir, start flibanserin at least 2 weeks after the last dose of fosamprenavir. If initiating fosamprenavir following flibanserin use, start fosamprenavir at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenytoin or fosphenytoin, which are strong CYP3A4 inducers, is not recommended.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of flibanserin and gabapentin. Concurrent use may result in additive CNS depression.
Ginkgo, Ginkgo biloba: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ginkgo biloba, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Grapefruit juice: (Contraindicated) Grapefruit juice should be avoided during flibanserin administration. Moderate CYP3A4 inhibitors, such as grapefruit juice, can increase flibanserin concentrations, which can cause severe hypotension and syncope. In a study of 26 healthy female subjects, 240 mL of grapefruit juice increased flibanserin 100 mg single dose exposure (AUC) by 1.4-fold and Cmax 1.1-fold compared to flibanserin 100 mg alone.
Hydroxyzine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Idelalisib: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as idelalisib, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Imatinib: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as imatinib, STI-571, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Indinavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as indinavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Isavuconazonium: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as isavuconazonium, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Isoniazid, INH: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including isoniazid, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and rifampin, a strong CYP3A4 inducer, is not recommended. In a study of 24 healthy female subjects, rifampin 600 mg once daily for 7 days prior to administration of 100 mg flibanserin significantly decreased flibanserin exposure by 95%. (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including isoniazid, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Isoniazid, INH; Rifampin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and rifampin, a strong CYP3A4 inducer, is not recommended. In a study of 24 healthy female subjects, rifampin 600 mg once daily for 7 days prior to administration of 100 mg flibanserin significantly decreased flibanserin exposure by 95%. (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including isoniazid, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Istradefylline: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including istradefylline 40 mg daily, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient. Istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as itraconazole, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Ivacaftor: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ivacaftor, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Ketoconazole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as ketoconazole is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of ketoconazole, start flibanserin at least 2 weeks after the last dose of ketoconazole. If initiating ketoconazole following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating ketoconazole therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope. Coadministration with ketoconazole increased flibanserin exposure by 4.5-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as clarithromycin, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Lapatinib: (Moderate) Monitor for an increase in treatment-related adverse reactions, including hypotension, syncope, and somnolence, if coadministration of lapatinib with flibanserin is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and weak CYP3A4 inhibitor. Flibanserin is a P-gp inhibitor and CYP3A4 substrate. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors. The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including lapatinib, may increase flibanserin concentrations.
Larotrectinib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including larotrectinib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and flibanserin. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) The concomitant use of flibanserin and oral lefamulin is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of oral lefamulin, start flibanserin at least 2 weeks after the last dose of oral lefamulin. If initiating oral lefamulin following flibanserin use, start oral lefamulin at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and flibanserin. Dosage adjustments of lemborexant and flibanserin may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lenacapavir: (Contraindicated) The concomitant use of flibanserin and lenacapavir is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of lenacapavir, start flibanserin at least 2 weeks after the last dose of lenacapavir. If initiating lenacapavir following flibanserin use, start lenacapavir at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Contraindicated) Concurrent use of letermovir and flibanserin is contraindicated. Coadministration may increase flibanserin concentration and risk for adverse events including hypotension and syncope. If initiating flibanserin following use of letermovir, start flibanserin at least 2 weeks after the last dose of letermovir. If initiating letermovir following flibanserin use, start letermovir at least 2 days after the last dose of flibanserin. Flibanserin is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with flibanserin should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levoketoconazole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as ketoconazole is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of ketoconazole, start flibanserin at least 2 weeks after the last dose of ketoconazole. If initiating ketoconazole following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating ketoconazole therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope. Coadministration with ketoconazole increased flibanserin exposure by 4.5-fold.
Lofexidine: (Major) Monitor for excessive hypotension and sedation during coadministration of lofexidine and flibanserin. Lofexidine can potentiate the effects of CNS depressants.
Lonafarnib: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as lonafarnib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of lonafarnib, start flibanserin at least 2 weeks after the last dose of lonafarnib. If initiating lonafarnib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating lonafarnib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with flibanserin. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and flibanserin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with flibanserin. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and flibanserin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as ritonavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Lorlatinib: (Major) Coadministration of flibanserin with lorlatinib is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%.
Lumacaftor; Ivacaftor: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ivacaftor, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and flibanserin. Concurrent use may result in additive CNS depression.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and flibanserin as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); flibanserin is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Maribavir: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including maribavir, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Mavacamten: (Major) Avoid concomitant use of flibanserin and mavacamten due to the potential for decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased flibanserin exposure by approximately 21%.
Meclizine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Methohexital: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Mifepristone: (Contraindicated) The concomitant use of flibanserin and strong CYP3A inhibitors such as mifepristone is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of mifepristone, start flibanserin at least 2 weeks after the last dose of mifepristone. If initiating mifepristone following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating mifepristone therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Mirtazapine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as mirtazapine, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Mitotane: (Major) The concomitant use of mitotane with flibanserin is not recommended due to the potential for decreased efficacy of flibanserin. Mitotane is a strong CYP3A4 inducer and flibanserin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of flibanserin. In a study of 24 healthy female subjects, another strong CYP3A inducer, rifampin (600 mg daily for 7 days), given prior to flibanserin significantly decreased flibanserin exposure by 95%.
Modafinil: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as modafinil or armodafinil, is not recommended. In addition, modafinil and armodafinil are inhibitors of CYP2C19, a minor metabolic pathway of flibanserin.
Nabilone: (Contraindicated) The concomitant use of flibanserin with CNS depressants, such as nabilone, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Nafcillin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as nafcillin, is not recommended.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and flibanserin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and flibanserin is a P-gp inhibitor.
Naproxen; Esomeprazole: (Moderate) Use of esomeprazole may increase flibanserin concentrations, resulting in severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Esomeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Nefazodone: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as nefazodone, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Nelfinavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as nelfinavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Netupitant, Fosnetupitant; Palonosetron: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as netupitant; palonosetron, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Niacin; Simvastatin: (Moderate) In a cross-over study in 12 healthy men and women, the effect of flibanserin 50 mg twice daily for 4 days on the pharmacokinetics of simvastatin 40 mg once daily was evaluated. Flibanserin increased the AUC of simvastatin, a substrate of CYP3A4, by 1.3-fold and the Cmax by 1.2-fold. The AUC and Cmax of simvastatin acid were increased by 1.5-fold and 1.4-fold, respectively.
Nicardipine: (Moderate) Concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including nicardipine, may significantly increase flibanserin concentrations and the risk of hypotension and syncope. Discuss the use of multiple weak CYP3A4 inhibitors with the patient when using flibanserin.
Nilotinib: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as nilotinib, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and flibanserin is contraindicated due to the potential for hypotension, syncope, and CNS depression. Consider temporary discontinuation of flibanserin during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion; if not feasible, consider alternative COVID-19 therapy. Coadministration may increase flibanserin exposure resulting in increased toxicity. Flibanserin is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor. (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as ritonavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Olanzapine; Fluoxetine: (Major) The concomitant use of flibanserin and a strong CYP2C19 inhibitor or multiple weak CYP3A4 inhibitors, including fluoxetine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Omeprazole: (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Omeprazole; Amoxicillin; Rifabutin: (Major) Coadministration of flibanserin with rifabutin is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%. (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Omeprazole; Sodium Bicarbonate: (Moderate) Use of omeprazole may increase flibanserin concentrations, potentially increasing the risk for severe hypotension, syncope, and/or CNS depression. Monitor for flibanserin-induced adverse reactions; consider if a different PPI would be a better choice for the patient. Omeprazole is a CYP2C19 inhibitor, and has been noted to cause clinically important drug interactions with certain CYP2C19 substrates. Flibanserin is a CYP2C19 substrate. Interactions may be especially significant for patients who are also known CYP2C19 poor metabolizers.
Opiate Agonists: (Moderate) Concomitant use of opioid agonists with flibanserin may cause excessive sedation and somnolence. Limit the use of opioid pain medication with flibanserin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opiate Agonists-Antagonists: (Moderate) The concomitant use of flibanserin with CNS depressants, such as mixed opiate agonists/antagonists or their combinations (e.g., buprenorphine; naloxone), may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Oral Contraceptives: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including oral contraceptives, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient. In one study of 24 healthy women, the effect of 100 mg flibanserin once daily for 2 weeks on the pharmacokinetics of a single dose of ethinyl estradiol 30 mcg/levonorgestrel 150 mcg was evaluated. Flibanserin increased the AUC and Cmax of ethinyl estradiol by 1.09-fold and 1.1-fold, respectively. Flibanserin decreased the levonorgestrel AUC by 1.06-fold. During pre-marketing evaluation of flibanserin, patients who reported using oral contraceptives had a greater incidence of CNS effects than flibenserin-treated patients who did not report oral contraceptive use, including dizziness (13.4% vs. 9.9%), somnolence (12.3% vs. 10.6%), and fatigue (11.4% vs. 7.5%).
Osilodrostat: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including osilodrostat, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Oxcarbazepine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as oxcarbazepine, is not recommended.
Pacritinib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including pacritinib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Palbociclib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including palbociclib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Pazopanib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including pazopanib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Pentobarbital: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Pexidartinib: (Major) Coadministration of flibanserin with pexidartinib is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%.
Phenobarbital: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Phenothiazines: (Moderate) The concomitant use of flibanserin with CNS depressants, such as phenothiazines, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Phentermine; Topiramate: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as topiramate is not recommended.
Phenytoin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenytoin or fosphenytoin, which are strong CYP3A4 inducers, is not recommended.
Pirtobrutinib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including pirtobrutinib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Posaconazole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as posaconazole, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Pralsetinib: (Major) Avoid concomitant use of flibanserin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and flibanserin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of flibanserin and pregabalin. Concurrent use may result in additive CNS depression.
Primidone: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and flibanserin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and flibanserin is a P-gp inhibitor.
Pseudoephedrine; Triprolidine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Pyrilamine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Quinine: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as quinine, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Ranitidine: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ranitidine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Ranolazine: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ranolazine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Relugolix: (Major) Avoid concomitant use of relugolix and oral flibanserin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer flibanserin at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and flibanserin is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral flibanserin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer flibanserin at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and flibanserin is a P-gp inhibitor.
Ribociclib: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as ribociclib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of ribociclib, start flibanserin at least 2 weeks after the last dose of ribociclib. If initiating ribociclib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating ribociclib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Ribociclib; Letrozole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as ribociclib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of ribociclib, start flibanserin at least 2 weeks after the last dose of ribociclib. If initiating ribociclib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating ribociclib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Rifabutin: (Major) Coadministration of flibanserin with rifabutin is not recommended due to decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%.
Rifampin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and rifampin, a strong CYP3A4 inducer, is not recommended. In a study of 24 healthy female subjects, rifampin 600 mg once daily for 7 days prior to administration of 100 mg flibanserin significantly decreased flibanserin exposure by 95%.
Rifapentine: (Major) Avoid coadministration of flibanserin with rifapentine as concurrent use may decrease flibanserin exposure. Flibanserin is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased flibanserin exposure by 95%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with flibanserin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and flibanserin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with flibanserin; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and flibanserin is a P-gp inhibitor.
Ritlecitinib: (Contraindicated) The concomitant use of flibanserin and ritlecitinib is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of ritlecitinib, start flibanserin at least 2 weeks after the last dose of ritlecitinib. If initiating ritlecitinib following flibanserin use, start ritlecitinib at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as ritonavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Rucaparib: (Moderate) Monitor for hypotension, syncope, somnolence, or other flibanserin-related adverse reactions if coadministration with multiple weak CYP3A4 inhibitors, including rucaparib, is necessary. Flibanserin is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor. Concomitant use of flibanserin and multiple weak CYP3A4 inhibitors may increase flibanserin plasma concentrations.
Saquinavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as saquinavir boosted with ritonavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Secobarbital: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and phenobarbital or other barbiturates, which are strong CYP3A4 inducers, is not recommended.
Sedating H1-blockers: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Selpercatinib: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including selpercatinib, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Simvastatin: (Moderate) In a cross-over study in 12 healthy men and women, the effect of flibanserin 50 mg twice daily for 4 days on the pharmacokinetics of simvastatin 40 mg once daily was evaluated. Flibanserin increased the AUC of simvastatin, a substrate of CYP3A4, by 1.3-fold and the Cmax by 1.2-fold. The AUC and Cmax of simvastatin acid were increased by 1.5-fold and 1.4-fold, respectively.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of flibanserin. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and flibanserin is a P-gp inhibitor.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with flibanserin. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); flibanserin is an inhibitor of P-gp.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with flibanserin. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); flibanserin is an inhibitor of P-gp.
Sotorasib: (Major) Avoid concomitant use of flibanserin and sotorasib due to the potential for decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased flibanserin exposure by approximately 21%.
Spironolactone: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including spironolactone, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including spironolactone, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
St. John's Wort, Hypericum perforatum: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and St. John's Wort, Hypericum perforatum, a strong CYP3A4 inducer, is not recommended.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and flibanserin. CNS depressants can potentiate the effects of stiripentol.
Streptogramins: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including dalfopristin; quinupristin, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with flibanserin is necessary. Talazoparib is a P-gp substrate and flibanserin is a P-gp inhibitor.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with flibanserin is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and flibanserin is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Tenofovir Alafenamide: (Minor) Caution is advised when administering tenofovir alafenamide concurrently with flibanserin, as coadministration may result in elevated tenofovir alafenamide plasma concentrations. Inhibitors of the drug transporter P-glycoprotein (P-gp), such as flibanserin, may increase absorption of tenofovir alafenamide, a P-gp substrate. If these medications are administered together, monitor for tenofovir-associated adverse reactions. Of note, when tenofovir alafenamide is administered as part of a cobicistat-containing product, its availability is increased by cobicistat and a further increase of tenofovir alafenamide concentrations is not expected upon coadministration of an additional P-gp inhibitor.
Tezacaftor; Ivacaftor: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ivacaftor, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Ticagrelor: (Major) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ticagrelor, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Tipranavir: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as tipranavir, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Topiramate: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as topiramate is not recommended.
Topotecan: (Major) Avoid coadministration of flibanserin with oral topotecan due to increased topotecan exposure; flibanserin may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and flibanserin is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Trandolapril; Verapamil: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as verapamil, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Trazodone: (Moderate) The concomitant use of flibanserin with CNS depressants, such as trazodone, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Triprolidine: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Trofinetide: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including trofinetide, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Tucatinib: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as tucatinib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of tucatinib, start flibanserin at least 2 weeks after the last dose of tucatinib. If initiating tucatinib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating tucatinib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with flibanserin. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; flibanserin is a P-gp inhibitor.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with flibanserin due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of flibanserin. Venetoclax is a P-glycoprotein (P-gp) substrate; flibanserin is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verapamil: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as verapamil, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Viloxazine: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including viloxazine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Vonoprazan; Amoxicillin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including vonoprazan, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as clarithromycin, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin. (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including vonoprazan, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Voriconazole: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as voriconazole, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Voxelotor: (Contraindicated) The concomitant use of flibanserin and voxelotor is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of voxelotor, start flibanserin at least 2 weeks after the last dose of voxelotor. If initiating voxelotor following flibanserin use, start voxelotor at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zafirlukast: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including zafirlukast, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.

Addyi Oral Tab: 100mg

Adults

Premenopausal adult females: 100 mg/day PO.

Geriatric

Safety and efficacy have not been established.

Adolescents

Not indicated.

Children

Not indicated.

Infants

Not indicated.

Neonates

Not indicated.

Flibanserin is an agent with dual actions primarily on serotonin, the drug is a serotonin 5-HT1A receptor agonist and a serotonin 5-HT2A receptor antagonist. In vitro, flibanserin demonstrated high affinity for agonist activity at 5-HT1A and antagonist activity at 5-HT2A. Flibanserin also has moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors. The mechanism of action of flibanserin in the treatment of premenopausal women with hypoactive sexual desire disorder (HSDD) is not known; however, many neurotransmitters affect sexual response in women, and modulation of some of these neurotransmitters by flibanserin may contribute to its mechanism of action and efficacy. In studies with flibanserin alone and in combination with moxifloxacin (a drug known to prolong the QT interval) prolongation of the QT interval did not occur to a clinically relevant extent.

Flibanserin is administered orally. The drug is 98% bound to plasma proteins, primarily albumin. Flibanserin is extensively metabolized in the liver, primarily via CYP3A4 and to a lesser extent by CYP2C19. There are at least 35 metabolites, most of which are present in low concentrations in the plasma. Two inactive metabolites, 6,21-dihydroxy-flibanserin-6,21-disulfate and 6-hydroxy-flibanserin-6-sulfate, have plasma concentrations that are similar to flibanserin. The half-life of flibanserin is about 11 hours. Approximately 44% of a dose is excreted in the urine and 51% is excreted in feces.
 
Affected cytochrome P450 (CYP450) enzymes and drug transporters: CYP3A4, CYP2C19, P-glycoprotein (P-gp)
Flibanserin is primarily metabolized by CYP3A4, and to a lesser extent, by CYP2C19. Drugs which inhibit or induce CYP3A4 may have a significant effect on flibanserin exposure. Concurrent use of flibanserin with moderate to strong CYP3A4 inhibitors is contraindicated. Patients using potent CYP2C19 inhibitors, or, persons with poor metabolizer (PM) status for CYP2C19, may also have increased flibanserin exposure, which may increase the risk of hypotension, syncope, or CNS depression. Poor CYP2C9 metabolizers may have decreased flibanserin exposures. Increased AUC and decreased Cmax values were seen in poor metabolizers of CYP2D6. Flibanserin inhibits P-glycoprotein (P-gp) and thus drugs with narrow therapeutic index that are transported by P-gp (e.g., digoxin, sirolimus) require monitoring. Isoenzymes including CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 are minimally involved in the metabolism of flibanserin.

Oral Route

Following single-dose oral administration of 100 mg, the median time to reach the maximum concentration (Cmax) was 0.75 hours with a range of 0.75 hours to 4 hours. The absolute bioavailability is 33%. Steady-state is achieved after 3 days of dosing. Under fasting conditions, the Tmax occurs in 0.8 hours. Daily dosing of 100 mg of flibanserin increased the extent of exposure by 1.4-fold compared to single-dose administration.
 
Food increased the extent of absorption and slowed the rate of absorption of a 50-mg dose of flibanserin (1/2 the recommended adult dosage). Low-, moderate-, and high-fat meals increased flibanserin exposure (AUC) by 1.18-, 1.43-, and 1.56-fold; increased Cmax by 1.02-, 1.13-, and 1.15-fold; and prolonged median Tmax to 1.5, 0.9, 1.8 hours, respectively. However, the manufacturer makes no recommendations regarding dosing with food or specific types of food, outside of administration with grapefruit juice. In a study of 26 healthy female subjects, grapefruit juice (240 mL) increased flibanserin 100 mg single dose exposure (AUC) by 1.4-fold and Cmax 1.1-fold compared to flibanserin 100 mg alone, so flibanserin should not be taken with grapefruit juice.

Pregnancy

There are no studies of flibanserin during human pregnancy to inform whether there is a drug-associated risk in humans. In animals, fetal toxicity only occurred in the presence of significant maternal toxicity including reductions in weight gain and sedation. Adverse reproductive and developmental effects consisted of decreased fetal weight, structural anomalies and increases in fetal loss at exposures greater than 15 times exposures achieved with the recommended human dosage. Animal studies cannot rule out the potential for fetal harm.

Breast-feeding is not recommended during treatment with flibanserin, due to the potential for serious adverse reactions, including sedation, in a breastfed infant. It is unknown whether flibanserin is present in human milk, whether the drug has effects on the breastfed infant, or whether the drug can affect milk production.