Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Anyone considering the use of nefazodone or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared with placebo in adults aged ≥65 years. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Nefazodone is not approved for use in pediatric patients.
Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 to 300,000 patient-years of nefazodone treatment. The total patient-years is a summation of each patient's duration of exposure expressed in years. For example, 1 patient-year is equal to 2 patients each treated for 6 months, 3 patients each treated for 4 months, etc.
Ordinarily, treatment with nefazodone should not be initiated in individuals with active liver disease or with elevated baseline serum transaminases. There is no evidence that preexisting liver disease increases the likelihood of developing liver failure; however, baseline abnormalities can complicate patient monitoring.
Patients should be advised to be alert for signs and symptoms of liver dysfunction (eg, jaundice, anorexia, GI complaints, malaise) and to report them to their doctor immediately if they occur.
Nefazodone tablets should be discontinued if clinical signs or symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury such as increased serum AST or serum ALT levels ≥3 times the ULN, while on nefazodone tablets should be withdrawn from the drug. These patients should be presumed to be at increased risk for liver injury if nefazodone is reintroduced. Accordingly, such patients should not be considered for re-treatment.
Depression: Oral: Initial: 100 mg twice daily; alternatively, depression treatment guidelines suggest starting doses of 50 to 100 mg/day (APA 2010; Bauer 2013). Based on response and tolerability, gradually increase dose in increments of 100 to 200 mg/day (in 2 divided doses) and intervals ≥1 week to a usual dose of 150 to 600 mg/day in 2 divided doses.
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower taper (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants (APA 2010; Hirsch 2019). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).
Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from a monoamine oxidase inhibitor (MAOI). A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), and the degree of symptom control desired (Hirsch 2018; Ogle 2013; WFSBP [Bauer 2013]).
Switching to or from an MAOI:
Allow 14 days to elapse between discontinuing an MAOI and initiation of nefazodone.
Allow at least 7 days to elapse between discontinuing nefazodone and initiation of an MAOI.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; however, adjustment unlikely since renal impairment does not alter steady state nefazodone plasma concentrations.
There are no dosage adjustments provided in the manufacturer’s labeling; however, use with caution because the AUC of nefazodone and its metabolites are ~25% greater in patients with cirrhosis. Use is contraindicated in patients with liver injury due to previous nefazodone treatment, and ordinarily should not be initiated in patients with active liver disease or elevated baseline serum transaminases.
Depression: Oral: Initial: 50 mg twice daily; gradually increase dose based on response and tolerability
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg
Yes
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ucm100211.pdf, must be dispensed with this medication.
Administer with or without food. Dosing after meals may decrease lightheadedness and postural hypotension, but may also decrease absorption and therefore effectiveness.
Depression: Treatment of depression
Serzone may be confused with selegiline, SEROquel, sertraline
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (36%), drowsiness (16% to 28%), dizziness (10% to 22%), insomnia (11%), agitation
Gastrointestinal: Xerostomia (25%), nausea (22%), constipation (14%)
Neuromuscular & skeletal: Weakness (11%)
1% to 10%:
Cardiovascular: Orthostatic hypotension (4%), vasodilation (4%), peripheral edema (3%), hypotension (2%), bradycardia
Central nervous system: Confusion (2% to 8%), memory impairment (4%), paresthesia (4%), abnormal dreams (3%), lack of concentration (3%), ataxia (2%), chills (2%), psychomotor retardation (2%), hypertonia (1%)
Dermatologic: Pruritus (2%), skin rash (2%)
Endocrine & metabolic: Decreased libido (1%), increased thirst (1%)
Gastrointestinal: Dyspepsia (9%), diarrhea (8%), increased appetite (5%), dysgeusia (2%), vomiting (2%), gastroenteritis
Genitourinary: Urinary frequency (2%), urinary retention (2%), mastalgia (1%), impotence
Hematologic & oncologic: Decreased hematocrit (3%)
Infection: Infection (8%)
Neuromuscular & skeletal: Tremor (2%), arthralgia (1%), neck stiffness (1%)
Ophthalmic: Visual disturbance (7% to 10%), blurred vision (3% to 9%), visual field defect (2%), eye pain
Otic: Tinnitus (2% to 3%)
Respiratory: pharyngitis (6%), cough (3%), flu-like symptoms (3%), bronchitis, dyspnea
Miscellaneous: Fever (2%)
<1%, postmarketing, and/or case reports: Abnormal gait, abnormal hepatic function tests, abnormality in thinking, accommodation disturbance, acne vulgaris, ageusia, alopecia, amenorrhea, anemia, angina pectoris, angioedema, angle-closure glaucoma, anorgasmia, apathy, arthritis, asthma, atrioventricular block, attempted suicide, breast hypertrophy, bruise, bursitis, cardiac failure, cellulitis, cerebrovascular accident, colitis, conjunctivitis, convulsions, cystitis, deafness, dehydration, depersonalization, derealization, diplopia, disturbance in attention, dry eye syndrome, dysarthria, eczema, ejaculatory disorder, enlargement of abdomen, epistaxis, eructation, esophagitis, euphoria, facial edema, galactorrhea, gastritis, gingivitis, gout, gynecomastia, halitosis, hallucination, hangover effect, heavy eyelids, hematuria, hemorrhage, hepatic failure, hepatic necrosis, hepatitis, hernia, hiccups, hostility, hyperacusis, hypercholesterolemia, hyperesthesia, hyperkinesia, hypermenorrhea, hypersensitivity reaction, hypertension, hyperventilation, hypoglycemia, hyponatremia, hypotonia, increased lactate dehydrogenase, increased libido, increased serum alt, increased serum ast, increased serum prolactin, keratoconjunctivitis, laryngitis, leukopenia, lymphadenopathy, maculopapular rash, malaise, muscle rigidity, mydriasis, myoclonus, nephrolithiasis, neuralgia, neuroleptic malignant syndrome, nocturia, nocturnal amblyopia, oliguria, oral candidiasis, oral mucosa ulcer, otalgia, pallor, paranoia, pelvic pain, peptic ulcer, periodontal abscess, photophobia, pneumonia, polyuria, priapism, rectal hemorrhage, rhabdomyolysis, seizure, serotonin syndrome (with lovastatin/simvastatin), sialorrhea, skin photosensitivity, stevens-johnson syndrome, stomatitis, suicidal ideation, syncope, tachycardia, tendinopathy, tendinous contracture, tenosynovitis, thrombocytopenia, tonic-clonic seizures, twitching, ulcerative colitis, urinary incontinence, urinary urgency, urticaria, uterine fibroid enlargement, uterine hemorrhage, vaginal hemorrhage, varicose veins, ventricular premature contractions, vertigo, vesicobullous dermatitis, voice disorder, weight loss, xeroderma, yawning
Hypersensitivity to nefazodone, related compounds (phenylpiperazines), or any component of the formulation; liver injury due to previous nefazodone treatment; concurrent use with carbamazepine, cisapride, terfenadine, astemizole, or pimozide; concurrent therapy with triazolam is generally contraindicated (dosage must be reduced by 75% for triazolam; such reductions may not be possible with available dosage forms).
Major psychiatric warnings:
• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Nefazodone is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression occurs.
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is very low relative to other antidepressants (APA 2010).
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). The degree of sedation is moderate relative to other antidepressants (Bauer 2013).
• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).
• Hepatic failure: Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone. The reported rate in the United States is about 1 case of liver failure resulting in death or transplant per 250,000 to 300,000 patient-years of nefazodone treatment, which is 3 to 4 times the estimated background rate of liver failure. There is no evidence that preexisting liver disease increases the likelihood of developing liver failure; however, baseline abnormalities can complicate patient monitoring. The time to liver injury in reported, severe cases ranged from 2 weeks to 6 months; not all cases had a clear prodromal onset of symptoms. Treatment should not ordinarily be initiated in patients with active liver disease or elevated baseline serum transaminases. There is no evidence that periodic monitoring of serum transaminases will prevent serious hepatic injury, but it can be used for early detection in symptomatic patients. Nefazodone tablets should be discontinued if clinical signs or symptoms (such as jaundice, anorexia, GI complaints, malaise, or increased serum AST or ALT levels ≥3 times the ULN) suggest liver failure. Patients who develop symptoms while on nefazodone should not be considered for re-treatment. Doses as low as 100 mg/day have been associated with hepatotoxicity (Stewart 2002).
• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.
• Orthostatic hypotension: May cause orthostatic hypotension (risk is low relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, dehydration, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Sexual dysfunction: Rare reports of priapism have occurred. The incidence of sexual dysfunction with nefazodone is generally lower than with SSRIs (APA 2010; Bauer 2013).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk conduction abnormalities with this agent is very low relative to other antidepressants (APA 2010; Bauer 2013).
• Hepatic impairment: [US Boxed Warning]: Ordinarily, treatment with nefazodone should not be initiated in individuals with active liver disease or with elevated baseline serum transaminases. Use with caution in patients with hepatic impairment.
• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer may be effective for acute treatment of bipolar major depressive episodes, but should be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Nefazodone is not FDA approved for the treatment of bipolar depression.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications that may lower seizure threshold.
Other warnings/precautions:
• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant, but commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).
Substrate of CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (strong)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. Risk D: Consider therapy modification
Acalabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. Risk X: Avoid combination
Adagrasib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Adagrasib. Management: Avoid use of adagrasib and strong CYP3A4 inhibitors until adagrasib concentrations have reached stead state (ie, after approximately 8 days of therapy). Risk D: Consider therapy modification
Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. Management: Avoid concomitant use of ado-trastuzumab emtansine and strong CYP3A4 inhibitors when possible. Consider alternatives that do not inhibit CYP3A4 or consider administering after CYP3A4 inhibitor discontinuation. Monitor for toxicities if combined. Risk D: Consider therapy modification
Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Risk X: Avoid combination
Alitretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Almotriptan: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Almotriptan. Management: Limit the initial almotriptan dose to 6.25 mg when combined with nefazodone, and do not exceed 12.5 mg in any 24-hour period. Avoid concomitant use in patients with impaired hepatic or renal function. Monitor for serotonin syndrome. Risk D: Consider therapy modification
Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk C: Monitor therapy
Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
ALPRAZolam: Nefazodone may increase the serum concentration of ALPRAZolam. Management: Consider alternatives to this combination when possible. If combined, consider an alprazolam dose reduction and monitor for increased alprazolam effects and toxicities (eg, sedation, lethargy). Risk D: Consider therapy modification
Amiodarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Amiodarone. Management: Consider alternatives to use of amiodarone and strong CYP3A4 inhibitors. If combined, monitor for increased amiodarone concentrations and toxicities. Risk D: Consider therapy modification
AmLODIPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of AmLODIPine. Risk C: Monitor therapy
Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Apalutamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apalutamide. Risk C: Monitor therapy
Apixaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban. Risk C: Monitor therapy
Aprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required for indications other than major depressive disorder. Dose reductions vary based on formulation, CYP2D6 genotype, and use of CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification
ARIPiprazole Lauroxil: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification
Artemether and Lumefantrine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy
Asciminib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asciminib. Risk C: Monitor therapy
Astemizole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Risk X: Avoid combination
Asunaprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atogepant. Management: The recommended dose of atogepant is 10 mg once daily when coadministered with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Atorvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Avacopan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avacopan. Management: Decrease the avacopan dose to 30 mg once daily during coadministration with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. Risk D: Consider therapy modification
Barnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. Risk X: Avoid combination
Bedaquiline: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with strong CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline, including QTc interval prolongation. Risk D: Consider therapy modification
Benidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. Risk C: Monitor therapy
Betamethasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Nasal). Risk C: Monitor therapy
Betamethasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). Risk C: Monitor therapy
Betamethasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy
Betamethasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Topical). Risk C: Monitor therapy
Blonanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. Risk X: Avoid combination
Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. Risk C: Monitor therapy
Bosentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Risk C: Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Brexanolone: Serotonin Reuptake Inhibitor/Antagonists may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a strong CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. Risk D: Consider therapy modification
Brigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). Risk D: Consider therapy modification
Bromocriptine: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Bromocriptine. Management: Consider alternatives to this combination. If combined, monitor for increased bromocriptine toxicities and consider bromocriptine dose reductions. Additionally, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Bromperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromperidol. Risk C: Monitor therapy
Brotizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brotizolam. Risk C: Monitor therapy
Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). Risk C: Monitor therapy
Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of inhaled budesonide and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Budesonide (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). Management: Avoid the concomitant use of CYP3A4 inhibitors and oral budesonide. If patients receive both budesonide and a strong CYP3A4 inhibitor, they should be closely monitored for signs and symptoms of corticosteroid excess. Risk D: Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Risk X: Avoid combination
BusPIRone: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities, including serotonin syndrome, if combined with nefazodone. Risk D: Consider therapy modification
Cabazitaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. Risk D: Consider therapy modification
Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, decrease cabozantinib capsules (Cometriq) by 40 mg from previous dose or decrease cabozantinib tablets (Cabometyx) by 20 mg from previous dose. Risk D: Consider therapy modification
Calcifediol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. Risk C: Monitor therapy
Calcitriol (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. Risk C: Monitor therapy
Cannabis: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy
Capmatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Capmatinib. Risk C: Monitor therapy
CarBAMazepine: Nefazodone may increase the serum concentration of CarBAMazepine. Also, concentrations of the active CarBAMazepine epoxide metabolite may be reduced. CarBAMazepine may decrease the serum concentration of Nefazodone. Concentrations of active Nefazodone metabolites may also be reduced. Risk X: Avoid combination
Cariprazine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Cariprazine. Specifically, concentrations of didesmethylcariprazine (DDCAR), the primary active metabolite of cariprazine, may increase. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Decrease cariprazine dose 50% (4.5 mg to 1.5 mg or 3 mg; 1.5 mg to 1.5 mg every other day) if starting a strong CYP3A4 inhibitor. If on a strong CYP3A4 inhibitor, start cariprazine at 1.5 mg day 1, 0 mg day 2, then 1.5 mg daily. May increase to 3 mg daily Risk D: Consider therapy modification
Ceritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: Avoid this combination whenever possible. If combined, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
ChlordiazePOXIDE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ChlordiazePOXIDE. Risk C: Monitor therapy
Ciclesonide (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ciclesonide (Oral Inhalation). Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilnidipine. Risk C: Monitor therapy
Cilostazol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Decrease the dose of cilostazol to 50 mg twice daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Cinacalcet: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. Risk C: Monitor therapy
Cisapride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cisapride. Risk X: Avoid combination
Clarithromycin: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clarithromycin. Risk C: Monitor therapy
Clindamycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
ClonazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of ClonazePAM. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobicistat. Risk C: Monitor therapy
Cobimetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. Risk X: Avoid combination
Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Risk D: Consider therapy modification
Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan. Risk X: Avoid combination
Copanlisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. Risk D: Consider therapy modification
Cortisone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cortisone. Risk C: Monitor therapy
Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors whenever possible. If combined use cannot be avoided, crizotinib dose reductions are required, which vary according to indication. See full interaction monograph for details. Risk D: Consider therapy modification
Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of CycloSPORINE (Systemic). Management: Monitor cyclosporine serum concentrations and clinical cyclosporine closely with concurrent use of any strong CYP3A4 inhibitor. Cyclosporine dose reductions and/or prolongation of the dosing interval will likely be required. Risk D: Consider therapy modification
Cyproterone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cyproterone. Risk C: Monitor therapy
Dabrafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. Management: Consider alternatives to any strong CYP3A4 inhibitor for patients being treated with dabrafenib. If such a combination cannot be avoided, monitor closely for evidence of dabrafenib-related adverse effects. Risk D: Consider therapy modification
Daclatasvir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Dapoxetine: Nefazodone may enhance the serotonergic effect of Dapoxetine. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Dapoxetine. Management: Do not use nefazodone with dapoxetine or within 7 days of dapoxetine discontinuation. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination
Daridorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daridorexant. Risk X: Avoid combination
Darifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Darifenacin. Management: Limit the darifenacin dose to no more than 7.5 mg daily if combined with strong CYP3A4 inhibitors. Monitor patients for increased darifenacin toxicities (eg, dry mouth, constipation, headache, CNS effects) when these agents are combined. Risk D: Consider therapy modification
Darunavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Darunavir. Risk C: Monitor therapy
Dasatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: This combination should be avoided if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. For patients taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Risk D: Consider therapy modification
Deflazacort: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification
Delamanid: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Risk D: Consider therapy modification
DexAMETHasone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Systemic). Risk C: Monitor therapy
Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
DiazePAM: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
Digoxin: Nefazodone may increase the serum concentration of Digoxin. Risk C: Monitor therapy
DilTIAZem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DilTIAZem. Risk C: Monitor therapy
Disopyramide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Disopyramide. Risk C: Monitor therapy
DOCEtaxel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. Risk D: Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Domperidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Risk X: Avoid combination
Doxazosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Doxazosin. Risk C: Monitor therapy
Doxercalciferol: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Dronabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Risk X: Avoid combination
Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. Risk C: Monitor therapy
Duvelisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. Monitor closely for evidence of altered response to treatment. Risk D: Consider therapy modification
Dydrogesterone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Ebastine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ebastine. Risk C: Monitor therapy
Efonidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Efonidipine. Risk C: Monitor therapy
Elagolix: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. Risk D: Consider therapy modification
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Elagolix, Estradiol, and Norethindrone may decrease the serum concentration of CYP3A4 Inhibitors (Strong). Specifically, concentrations of strong CYP3A4 inhibitors that are also CYP3A4 substrates may be decreased. Risk X: Avoid combination
Elbasvir and Grazoprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elbasvir and Grazoprevir. Management: Consider alternatives to this combination when possible. If combined, monitor for increased elbasvir/grazoprevir toxicities, including ALT elevations. Risk D: Consider therapy modification
Eletriptan: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Eletriptan. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Management: When combined with strong CYP3A4 inhibitors, administer two elexacaftor/tezacaftor/ivacaftor tablets (100 mg/50 mg/75 mg) in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor (150 mg) alone should be administered. Risk D: Consider therapy modification
Eliglustat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce eliglustat dose to 84 mg daily in CYP2D6 EMs when used with strong CYP3A4 inhibitors. Use of strong CYP3A4 inhibitors is contraindicated in CYP2D6 IMs, PMs, or in CYP2D6 EMs who are also taking strong or moderate CYP2D6 inhibitors. Risk D: Consider therapy modification
Encorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Encorafenib. Management: Avoid use of encorafenib and strong CYP3A4 inhibitors when possible. If combined, decrease encorafenib from 450 mg to 150 mg; or from 300 mg, 225 mg, or 150 mg to 75 mg. Once the CYP3A4 inhibitor is discontinued for 3 to 5 half-lives, resume prior dose. Risk D: Consider therapy modification
Entrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Entrectinib. Management: Avoid strong CYP3A4 inhibitors during treatment with entrectinib when possible. If combined in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters, reduce dose to 100 mg/day. Avoid if BSA is less than 1.5 square meters. Risk D: Consider therapy modification
Enzalutamide: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. Risk X: Avoid combination
Erdafitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Nefazodone may enhance the serotonergic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination
Erlotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of erlotinib-associated adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification
Erythromycin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased erythromycin effects and toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Estrogen Derivatives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Risk D: Consider therapy modification
Etizolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Risk C: Monitor therapy
Etravirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etravirine. Risk C: Monitor therapy
Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Management: Consider avoiding use of strong CYP3A4 inhibitors with everolimus. If combined, closely monitor for increased everolimus serum concentrations and toxicities. Everolimus dose reductions will likely be required. Risk D: Consider therapy modification
Evogliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. Risk C: Monitor therapy
Fedratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. Risk D: Consider therapy modification
Felodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Felodipine. Management: Consider using lower felodipine doses when combined with strong CYP3A4 inhibitors. Monitor patients for increased felodipine effects and toxicities (eg, hypotension, edema) when combined. Risk D: Consider therapy modification
Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
FentaNYL: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of FentaNYL. Management: Consider reducing fentanyl dose. Monitor for signs and symptoms of respiratory depression, sedation, and serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia) when these agents are combined. Risk D: Consider therapy modification
Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Limit fesoterodine doses to 4 mg daily in patients who are also receiving strong CYP3A4 inhibitors. This combination is not recommended in pediatric patients weighing 25 kg up to 35 kg. Risk D: Consider therapy modification
Fexinidazole: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Fexinidazole. Management: Avoid use of fexinidazole and strong CYP3A4 inhibitors when possible. If combined, monitor for reduced fexinidazole efficacy. Risk D: Consider therapy modification
Finerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Finerenone. Risk X: Avoid combination
Flibanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with strong CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Risk X: Avoid combination
Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). Risk X: Avoid combination
Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Consider alternatives to this combination if possible. Coadministration of fluticasone propionate and strong CYP3A4 inhibitors is not recommended. If combined, monitor patients for systemic corticosteroid adverse effects (eg, adrenal suppression). Risk D: Consider therapy modification
Fluticasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Topical). Risk C: Monitor therapy
Fosamprenavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. Risk X: Avoid combination
Fostamatinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy
Galantamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy
Gefitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy
Gilteritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gilteritinib. Management: Consider alternatives to the use of a strong CYP3A4 inhibitor with gilteritinib. If the combination cannot be avoided, monitor more closely for evidence of gilteritinib toxicities. Risk D: Consider therapy modification
Glasdegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. Risk D: Consider therapy modification
GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the extended-release guanfacine dose 50% when combined with a strong CYP3A4 inhibitor. Monitor for increased guanfacine toxicities when these agents are combined. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for halofantrine toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Haloperidol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrexafungerp. Management: Decrease the ibrexafungerp dose to 150 mg every 12 hours for 2 doses in patients receiving strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Ibrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. Risk X: Avoid combination
Idelalisib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Idelalisib. Management: Use alternative therapies that are not strong CYP3A4 inhibitors whenever possible. If unable to use alternative drugs, monitor patients more frequently for idelalisib toxicities. Risk D: Consider therapy modification
Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Imatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. Risk C: Monitor therapy
Imidafenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. Risk C: Monitor therapy
Indinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Indinavir. Risk C: Monitor therapy
Infigratinib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Infigratinib. Risk X: Avoid combination
Irinotecan Products: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider therapy modification
Isavuconazonium Sulfate: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Risk X: Avoid combination
Isradipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. Risk D: Consider therapy modification
Itraconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Itraconazole. Risk C: Monitor therapy
Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full drug interaction monograph content for age- and weight-specific recommendations. Risk D: Consider therapy modification
Ivosidenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily and monitor for increased ivosidenib toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. Management: Avoid use of ixabepilone and strong CYP3A4 inhibitors when possible. If combined, reduce the ixabepilone dose to 20 mg/m2. The previous ixabepilone dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ketamine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy
Lacidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacidipine. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: Avoid use of lapatinib and strong CYP3A4 inhibitors when possible. If combined, a reduced lapatinib dose of 500 mg daily should be considered. The previous lapatinib dose can be resumed 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Larotrectinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor's half-life. Risk D: Consider therapy modification
Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Lefamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. Risk X: Avoid combination
Lemborexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. Risk X: Avoid combination
Leuprolide and Norethindrone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Leuprolide and Norethindrone. Specifically, concentrations of norethindrone may increase. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levobupivacaine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levoketoconazole. Risk X: Avoid combination
Levomilnacipran: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Levomilnacipran. Management: Limit the levomilnacipran dose to 80 mg daily and monitor patients for increased levomilnacipran effects/toxicities, including serotonin syndrome, if combined with nefazodone. Risk D: Consider therapy modification
Lidocaine (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Linezolid: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination
Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lopinavir. Risk C: Monitor therapy
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Lorlatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. Risk D: Consider therapy modification
Lovastatin: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Lovastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Lumacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumacaftor and Ivacaftor. Management: When initiating or resuming lumacaftor/ivacaftor after a therapy interruption of 7 days or more, reduce the lumacaftor/ivacaftor dose to 1 tablet daily or 1 packet of oral granules every other day for the first week, and then resume the standard dose. Risk D: Consider therapy modification
Lumateperone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. Management: Limit the lumateperone dose to 10.5 mg once daily when used with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurbinectedin. Risk X: Avoid combination
Macitentan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. Risk X: Avoid combination
Manidipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce maraviroc to 150mg twice/day in adult and pediatrics weighing 40kg or more. See full interaction monograph for dose adjustments in pediatrics weighing 10 to less than 40kg. Do not use if CrCl less than 30mL/min or in those weighing less than 10 kg. Risk D: Consider therapy modification
Mavacamten: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mefloquine. Risk C: Monitor therapy
Meperidine: Nefazodone may enhance the serotonergic effect of Meperidine. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Meperidine. Management: Consider reducing meperidine dose. Monitor for signs and symptoms of respiratory depression, sedation, and serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia) when these agents are combined. Risk D: Consider therapy modification
Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methylene Blue: Nefazodone may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midazolam. Management: Avoid use of nasal midazolam and strong CYP3A4 inhibitors whenever possible, and consider alternatives to use with other routes of midazolam (oral, IV, IM). If combined, consider lower midazolam doses and monitor for increased midazolam toxicities. Risk D: Consider therapy modification
Midostaurin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and strong CYP3A4 inhibitors if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Risk D: Consider therapy modification
MiFEPRIStone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of MiFEPRIStone. Management: For treatment of hyperglycemia in Cushing's syndrome, start mifepristone at 300 mg/day, may titrate to a maximum of 900 mg/day. If starting a strong CYP3A4 inhibitor and taking > 300 mg/day mifepristone, decrease the mifepristone dose by 300 mg/day. Risk D: Consider therapy modification
Mirodenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. Risk D: Consider therapy modification
Mirtazapine: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Mirtazapine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and for increased mirtazapine toxicities when these agents are combined. Risk C: Monitor therapy
Mirvetuximab Soravtansine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirvetuximab Soravtansine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mitapivat. Risk X: Avoid combination
Mobocertinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mobocertinib. Risk X: Avoid combination
Mometasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Nasal). Risk C: Monitor therapy
Mometasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Oral Inhalation). Risk C: Monitor therapy
Mometasone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mometasone (Topical). Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination
Naldemedine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Nalfurafine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. Risk C: Monitor therapy
Naloxegol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. Risk X: Avoid combination
Nelfinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nelfinavir. Risk C: Monitor therapy
Neratinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. Risk X: Avoid combination
NiCARdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NIFEdipine. Management: Consider alternatives to this combination when possible. If combined, initiate nifedipine at the lowest dose available and monitor patients closely for increased nifedipine effects and toxicities (eg, hypotension, edema). Risk D: Consider therapy modification
Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Risk D: Consider therapy modification
Nilvadipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. Risk X: Avoid combination
Nirmatrelvir and Ritonavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor therapy
Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrendipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nitrendipine. Risk C: Monitor therapy
Olaparib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib tablets should be reduced to 100 mg twice daily and the dose of olaparib capsules should be reduced to 150 mg twice daily. Risk D: Consider therapy modification
Olmutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for increased opioid effects, including fatal respiratory depression, when these agents are combined and consider opioid dose reductions until stable drug effects are achieved. Additionally, monitor for serotonin syndrome/serotonin toxicity. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Orelabrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Orelabrutinib. Risk X: Avoid combination
Osilodrostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Osilodrostat. Management: Reduce osilodrostat dose by 50% during coadministration with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Ospemifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. Risk C: Monitor therapy
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Oxybutynin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. Risk C: Monitor therapy
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. Management: Avoid concurrent use of strong CYP3A4 inhibitors with palbociclib when possible. If the use of a strong CYP3A4 inhibitor cannot be avoided, decrease the palbociclib dose to 75 mg/day. Risk D: Consider therapy modification
Palovarotene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palovarotene. Risk X: Avoid combination
Panobinostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. Monitor patient response to therapy closely for evidence of more severe adverse effects related to panobinostat therapy. Risk D: Consider therapy modification
Parecoxib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. Specifically, serum concentrations of the active moiety valdecoxib may be increased. Risk C: Monitor therapy
Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. Risk C: Monitor therapy
PAZOPanib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PAZOPanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib dose to 400 mg. Further dose reductions may also be required if adverse reactions occur. Risk D: Consider therapy modification
Pemigatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pemigatinib. Management: If combined use cannot be avoided, reduce the pemigatinib dose from 13.5 mg daily to 9 mg daily, or from 9 mg daily to 4.5 mg daily. Resume prior pemigatinib dose after stopping the strong inhibitor once 3 half-lives of the inhibitor has passed. Risk D: Consider therapy modification
Pexidartinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg per day to 200 mg once daily Risk D: Consider therapy modification
Pimavanserin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Piperaquine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Risk C: Monitor therapy
Polatuzumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. Risk C: Monitor therapy
PONATinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Avoid concomitant use if possible. If combined, reduce ponatinib dose as follows: If taking 45 mg, reduce to 30 mg; if taking 30 mg, reduce to 15 mg; if taking 15 mg, reduce to 10 mg. If taking 10 mg, avoid concomitant use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Pralsetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pralsetinib. Risk X: Avoid combination
Prazepam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Prazepam. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Praziquantel. Risk C: Monitor therapy
PrednisoLONE (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE. Risk C: Monitor therapy
Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
QUEtiapine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of original dose after starting a strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Risk D: Consider therapy modification
QuiNIDine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Quinidine (Non-Therapeutic). Risk C: Monitor therapy
QuiNINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of QuiNINE. Risk C: Monitor therapy
Radotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. Risk X: Avoid combination
Ramelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Rasagiline: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination
Reboxetine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. Risk C: Monitor therapy
Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Risk X: Avoid combination
Regorafenib: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. Risk X: Avoid combination
Repaglinide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Retapamulin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: The use of retapamulin with strong CYP3A4 inhibitors is not recommended in patients less than 2 years old. No action is required in other populations. Risk C: Monitor therapy
Ribociclib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ribociclib. Management: Avoid use of ribociclib with strong CYP3A4 inhibitors when possible; if combined use cannot be avoided, reduce ribociclib dose to 400 mg once daily. Risk D: Consider therapy modification
Rifabutin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rifabutin. Risk C: Monitor therapy
Rilpivirine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. Risk C: Monitor therapy
Rimegepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rimegepant. Risk X: Avoid combination
Riociguat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Riociguat. Risk C: Monitor therapy
Ripretinib: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ripretinib. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ripretinib. Risk C: Monitor therapy
RisperiDONE: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritonavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ritonavir. Risk C: Monitor therapy
Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. For clarithromycin, refer to more specific clarithromycin-rivaroxaban monograph recommendations. Risk C: Monitor therapy
Roflumilast-Containing Products: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Rupatadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. Risk X: Avoid combination
Ruxolitinib (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider therapy modification
Ruxolitinib (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib (Topical). Risk X: Avoid combination
Safinamide: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Risk X: Avoid combination
Saquinavir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
SAXagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Nefazodone may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Selegiline: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination
Selpercatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Selpercatinib. Management: Avoid combination if possible. If use is necessary, reduce selpercatinib dose as follows: from 120 mg twice/day to 40 mg twice/day, or from 160 mg twice/day to 80 mg twice/day. Risk D: Consider therapy modification
Selumetinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Selumetinib. Management: Avoid concomitant use when possible. If combined, selumetinib dose reductions are recommended and vary based on body surface area and selumetinib dose. For details, see the full drug interaction monograph or selumetinib prescribing information. Risk D: Consider therapy modification
Serotonergic Agents (High Risk, Miscellaneous): Nefazodone may enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: Nefazodone may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Sertindole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sertindole. Risk X: Avoid combination
Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary arterial hypertension (PAH) should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, consider using a lower starting dose of 25 mg and monitor patients for sildenafil toxicities. Risk D: Consider therapy modification
Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. Risk X: Avoid combination
Simeprevir: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Risk X: Avoid combination
Sirolimus (Conventional): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with strong CYP3A4 inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Concomitant use of sirolimus and voriconazole or posaconazole is contraindicated. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sirolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sirolimus (Topical). Risk C: Monitor therapy
Solifenacin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Solifenacin. Management: Limit adult solifenacin doses to 5 mg daily and limit doses in pediatric patients to the recommended weight-based starting dose (and do not increase the dose) when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Sonidegib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. Risk X: Avoid combination
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Management: Avoid when possible. If combined, decrease sunitinib dose to a minimum of 37.5 mg daily when treating GIST or RCC. Decrease sunitinib dose to a minimum of 25 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider therapy modification
Suvorexant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. Risk X: Avoid combination
Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tacrolimus (Systemic). Management: Reduce tacrolimus dose to one-third of the original dose if starting posaconazole or voriconazole. Coadministration with nelfinavir is not generally recommended. Tacrolimus dose reductions or prolongation of dosing interval will likely be required. Risk D: Consider therapy modification
Tacrolimus (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tacrolimus (Topical). Risk C: Monitor therapy
Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Avoid this combination in patients taking tadalafil for pulmonary arterial hypertension. In patients taking tadalafil for ED or BPH, max tadalafil dose is 2.5 mg if taking daily or 10 mg no more frequently than every 72 hours if used as needed. Risk D: Consider therapy modification
Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk X: Avoid combination
Tasimelteon: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tazemetostat. Risk X: Avoid combination
Telithromycin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Telithromycin. Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be increased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors. If coadministration is unavoidable, decrease temsirolimus dose to 12.5 mg per week. Resume previous temsirolimus dose 1 week after discontinuation of the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Terfenadine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Risk X: Avoid combination
Tetrahydrocannabinol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor and Ivacaftor. Management: If combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. Tezacaftor/ivacaftor dose depends on age and weight; see full Lexi-Interact monograph for details. Risk D: Consider therapy modification
Thiotepa: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Avoid coadministration of thiotepa and strong CYP3A4 inhibitors. If concomitant use cannot be avoided, monitor for thiotepa adverse effects and decreased efficacy. Risk D: Consider therapy modification
Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination
Tisotumab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tisotumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Risk C: Monitor therapy
Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full Lexi Interact monograph for details. Risk D: Consider therapy modification
Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended dose of tolterodine is 2 mg per day (1 mg twice daily for immediate-release tablets or 2 mg daily for extended-release capsules) when used together with a strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Toremifene: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Risk D: Consider therapy modification
Trabectedin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. Risk X: Avoid combination
TraMADol: Nefazodone may enhance the adverse/toxic effect of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Nefazodone may increase the serum concentration of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes), seizures, and tramadol adverse effects when these agents are combined. Risk C: Monitor therapy
TraZODone: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects such as sedation, QTc prolongation, and signs and symptoms of serotonin syndrome/serotonin toxicity when these agents are combined. Risk D: Consider therapy modification
Tretinoin (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tretinoin (Systemic). Risk C: Monitor therapy
Triamcinolone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Nasal). Risk C: Monitor therapy
Triamcinolone (Ophthalmic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Ophthalmic). Risk C: Monitor therapy
Triamcinolone (Systemic): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Systemic). Management: Consider alternatives to this combination when possible. If combined, monitor for increased corticosteroid adverse effects during coadministration of triamcinolone and strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Triamcinolone (Topical): CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triamcinolone (Topical). Risk C: Monitor therapy
Triazolam: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. Risk X: Avoid combination
Tricyclic Antidepressants: May enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. Risk X: Avoid combination
Udenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. Risk X: Avoid combination
Ulipristal: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Risk C: Monitor therapy
Upadacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. Management: For ulcerative colitis use upadacitinib 30 mg/day for 8 weeks for induction, then 15 mg/day for maintenance. For rheumatoid arthritis, psoriatic arthritis, or atopic dermatitis use upadacitinib 15 mg/day. Monitor for upadacitinib toxicities. Risk D: Consider therapy modification
Valbenazine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification
Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with strong CYP3A4 inhibitors when possible. If concomitant use is unavoidable, consider a vemurafenib dose reduction if clinically indicated. Risk D: Consider therapy modification
Venetoclax: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: Coadministration is contraindicated during venetoclax initiation and ramp-up in CLL/SLL patients. Reduced venetoclax doses are required during ramp-up for patients with AML, and all maintenance therapy. See full Lexi Interact monograph for details. Risk D: Consider therapy modification
Verapamil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Verapamil. Risk C: Monitor therapy
Vilanterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilanterol. Risk C: Monitor therapy
Vilazodone: Nefazodone may enhance the serotonergic effect of Vilazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Vilazodone. Management: Limit maximum vilazodone dose to 20 mg daily and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider therapy modification
VinBLAStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinBLAStine. Risk C: Monitor therapy
VinCRIStine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine. Management: Seek alternatives to this combination when possible. If combined, monitor closely for vincristine toxicities (eg, neurotoxicity, gastrointestinal toxicity, myelosuppression). Risk D: Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vindesine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. Risk C: Monitor therapy
Vinflunine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Vinflunine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. Risk X: Avoid combination
Vinorelbine: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinorelbine. Risk C: Monitor therapy
Voclosporin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voclosporin. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. Risk X: Avoid combination
Voriconazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Zanubrutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider therapy modification
Ziprasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ziprasidone. Risk C: Monitor therapy
Zolpidem: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. Risk C: Monitor therapy
Zopiclone: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: If coadministered with strong CYP3A4 inhibitors, initiate zopiclone at 3.75 mg in adults, with a maximum dose of 5 mg. Monitor for zopiclone toxicity (eg, drowsiness, confusion, lethargy, ataxia, respiratory depression). Risk D: Consider therapy modification
Nefazodone absorption may be delayed and bioavailability may be decreased if taken with food. Management: Administering after meals may decrease lightheadedness and postural hypotension, but may also decrease absorption and therefore effectiveness.
Adverse effects were observed in some animal reproduction studies.
The ACOG recommends that therapy with antidepressants during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. Consideration should be given to using agents with safety data in pregnancy. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).
Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.
Nefazodone and its active metabolites are present in breast milk (Dodd 1999; Dodd 2000; Yapp 2000).
The relative infant dose (RID) of nefazodone is 4.7% when calculated using a trough breast milk concentration from a case report and compared to a weight-adjusted maternal dose of 150 mg/day.
In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).
The RID of nefazodone was calculated using a milk concentration of 687 ng/mL, providing an estimated daily infant dose via breast milk of 0.1 mg/kg/day. This milk concentration was obtained following maternal administration of nefazodone 50 mg in the morning and 100 mg in the evening. It should be noted that this milk concentration was obtained prior to the maternal dose (a trough, not peak, level) and the RID does not include the active metabolites. Although the study was conducted in only two women, maternal dose did not appear to influence milk concentrations (Dodd 1999).
Information related to the use of nefazodone in breastfeeding women is limited. Drowsiness, lethargy, poor feeding, and failure to maintain body temperature have been reported in a premature breastfeeding infant. Adverse events were not observed in case reports of two older infants (Dodd 2000; Yapp 2000). Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015).
The manufacturer recommends that caution be exercised when administering nefazodone to breastfeeding women. When first initiating an antidepressant in a breastfeeding woman, agents other than nefazodone are preferred. Women successfully treated with nefazodone during pregnancy may continue use while breastfeeding if there are no other contraindications (Berle 2011).
Liver function tests (baseline and periodic; if AST/ALT increase ≥3 times ULN, the drug should be discontinued and not reintroduced); mental status, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks, or other unusual changes in behavior
Inhibits neuronal reuptake of serotonin and norepinephrine; also blocks 5-HT2 and alpha1 receptors; has no significant affinity for alpha2, beta-adrenergic, 5-HT1A, cholinergic, dopaminergic, or benzodiazepine receptors
Onset of action: Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).
Absorption: Rapid; well absorbed; food delays absorption by ~20%.
Distribution: Vd: 0.22 to 0.87 L/kg.
Protein binding: >99%.
Metabolism: Hepatic by n-dealkylation and aliphatic and aromatic hydroxylation to at least three metabolites: Triazoledione, hydroxynefazodone (active), and m-chlorophenylpiperazine (mCPP; active).
Bioavailability: 20% (variable); food decreases bioavailability by ~20%; AUC increased by 25% in patients with cirrhosis of the liver.
Half-life elimination: Note: Active metabolites persist longer in all populations.
Children: 4.1 hours.
Adolescents: 3.9 hours.
Adults: Parent drug: 2 to 4 hours; Active metabolites: 1.4 to 8 hours.
Time to peak, serum: Note: Prolonged in presence of food.
Children and Adolescents: 0.5 to 1 hour.
Adults: 1 hour.
Excretion: Primarily urine (~55%; as metabolites); feces (~20% to 30%).
Older adult: Cmax and AUC for nefazodone and hydroxynefazodone were twice as high in patients >65 years of age after single doses and 10% to 20% higher after multiple doses.
Sex: Nefazodone has a higher Cmax and AUC in women after single doses, but no difference after multiple doses.
Tablets (Nefazodone HCl Oral)
50 mg (per each): $4.69
100 mg (per each): $4.80
150 mg (per each): $4.89
200 mg (per each): $4.98
250 mg (per each): $5.07
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