fezolinetant (Rx)

Brand and Other Names:Veozah

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 45mg

Menopausal Vasomotor Symptoms

Indicated for treatment of moderate-to-severe vasomotor symptoms (VMS) caused by menopause

45 mg PO qDay

Dosage Modifications

Renal impairment

  • Mild or moderate (eGFR 30-89 mL/min/1.73 m2): No dose adjustment required
  • Severe (eGFR 15-29 mL/min/1.73 m2 or end-stage renal disease [ESRD]): Contraindicated

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): Increased systemic exposure observed; no recommendations listed in prescribing information
  • Severe (Child-Pugh C): Not studied
  • Cirrhosis: Contraindicated

Dosing Considerations

Monitoring

  • Before initiating
    • Perform baseline bloodwork for hepatic function and injury (including ALT, AST, and serum bilirubin [total and direct])
    • May initiate fezolinetant if baseline hepatic transaminases <2x ULN and total bilirubin is normal
    • Do not start fezolinetant if ALT or AST ≥2x ULN or if total bilirubin elevated (eg, ≥2x ULN)
  • During treatment
    • Perform follow-up bloodwork at 3, 6, and 9 months after initiating and when symptoms (eg, nausea, vomiting, jaundice) suggest liver injury

Not indicated

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Interactions

Interaction Checker

and fezolinetant

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            Contraindicated (26)

            • caffeine

              caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • cannabidiol

              cannabidiol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • cimetidine

              cimetidine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • ciprofloxacin

              ciprofloxacin will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • conjugated estrogens

              conjugated estrogens will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • disulfiram

              disulfiram will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • estradiol

              estradiol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • estrogens conjugated synthetic

              estrogens conjugated synthetic will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • fexinidazole

              fexinidazole will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • fluvoxamine

              fluvoxamine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • givosiran

              givosiran will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • interferon alfa 2b

              interferon alfa 2b will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • leniolisib

              leniolisib will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • mestranol

              mestranol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • methoxsalen

              methoxsalen will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • mexiletine

              mexiletine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • peginterferon alfa 2a

              peginterferon alfa 2a will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • peginterferon alfa 2b

              peginterferon alfa 2b will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • propafenone

              propafenone will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • propranolol

              propranolol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • rucaparib

              rucaparib will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • stiripentol

              stiripentol will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • verapamil

              verapamil will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • viloxazine

              viloxazine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • zileuton

              zileuton will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            Serious - Use Alternative (0)

              Monitor Closely (0)

                Minor (0)

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                  Adverse Effects

                  1-10%

                  Abdominal pain (4.3%)

                  Diarrhea (3.9%)

                  Insomnia (3.9%)

                  Back pain (3%)

                  Hot flush (2.5%)

                  Elevated hepatic transaminase (2.3%)

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                  Warnings

                  Contraindications

                  Known cirrhosis

                  Severe renal impairment or ESRD

                  Coadministration with CYP1A2 inhibitors

                  Cautions

                  Hepatic transaminase elevation

                  • ALT and AST >3x ULN observed during clinical trials
                  • Transaminase levels returned to pretreatment levels (or close to these) without sequelae with dose continuation, and upon dose interruption, or discontinuation
                  • Women with cirrhosis were not studied
                  • Obtain baseline bloodwork before initiating and at 3, 6, and 9 months, or if symptoms suggestive of liver injury (eg, nausea, vomiting, jaundice) occur after starting fezolinetant
                  • May initiate fezolinetant if baseline hepatic transaminases <2x ULN and total bilirubin is normal
                  • Do not start fezolinetant if ALT or AST ≥2x ULN or if total bilirubin elevated (eg, ≥2x ULN)

                  Drug interaction overview

                  • CYP1A2 substrate
                  • CYP1A2 inhibitors
                    • Contraindicated
                    • Peak plasma concentration and AUC of fezolinetant are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
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                  Pregnancy & Lactation

                  Pregnancy

                  There are no data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

                  Animal studies

                  • In a pre- and post-natal development animal study, delayed parturition and embryo-lethality occurred at high doses above the human therapeutic dose in rats
                  • Additionally, in male offspring, delayed male reproductive maturation was observed, characterized by incomplete preputial separation, which affected male fertility at doses above the human therapeutic dose in rats

                  Lactation

                  Data are not available on presence in human milk, effects on breastfed children, or effects on milk production

                  Unknown if present in human milk

                  Animal studies

                  • Following administration of radiolabeled fezolinetant to lactating rats, concentration in milk was higher than that in plasma at all time points
                  • This indicated that fezolinetant-derived components transferred to tissues in infant rats via breast milk

                  Pregnancy Categories

                  A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                  B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                  C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                  D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                  X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                  NA: Information not available.

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                  Pharmacology

                  Mechanism of Action

                  Nonhormonal selective neurokinin 3 (NK3) receptor antagonist

                  Blocks neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron to modulate neuronal activity in the hypothalamus, and thereby reduces frequency and severity of vasomotor symptoms

                  Absorption

                  Peak plasma time: 1.5 hr

                  Steady-state was reached after 2 once daily doses, with minimal fezolinetant accumulation

                  Distribution

                  Protein bound: 51%

                  Vd: 189 L

                  Blood-to-plasma ratio: 0.9

                  Metabolism

                  Primarily metabolized by CYP1A2 and to lesser extent by CYP2C9 and CYP2C19

                  Major metabolite is ES259564 (~20-fold less potent than parent compound)

                  Elimination

                  Half-life: 9.6hr

                  Clearance: 10.8 L/hr

                  Excretion: Urine 76.9% (1.1% unchanged); feces 14.7% (0.1% unchanged)

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                  Administration

                  Oral Administration

                  May take with or without food

                  Administer at approximately the same time each day

                  Swallow tablet whole with liquids; do not cut, crush, or chew

                  Missed dose

                  • If dose is missed or not taken at usual time, administer as soon as possible, unless <12 hr before next scheduled dose
                  • Return to regular schedule the next day

                  Storage

                  Store at 20-25ºC (68-77ºF) with excursions permitted from 15-30ºC (59-86ºF)

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                  Images

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                  Patient Handout

                  A Patient Handout is not currently available for this monograph.
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                  Formulary

                  FormularyPatient Discounts

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                  The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                  Tier Description
                  1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                  2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                  3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                  4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  NC NOT COVERED – Drugs that are not covered by the plan.
                  Code Definition
                  PA Prior Authorization
                  Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                  QL Quantity Limits
                  Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                  ST Step Therapy
                  Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                  OR Other Restrictions
                  Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                  Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.