1.1 Acute Treatment of Migraine

NURTEC ODT is indicated for the acute treatment of migraine with or without aura in adults.

1.2 Preventive Treatment of Episodic Migraine

NURTEC ODT is indicated for the preventive treatment of episodic migraine in adults.

2.1 Recommended Dosing for Acute Treatment of Migraine

The recommended dose of NURTEC ODT is 75 mg taken orally, as needed.

The maximum dose in a 24-hour period is 75 mg. The safety of using more than 18 doses in a 30-day period has not been established.

2.2 Recommended Dosing for Preventive Treatment of Episodic Migraine

The recommended dosage of NURTEC ODT is 75 mg taken orally every other day.

2.3 Administration Information

Instruct the patient on the following administration instructions:

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Use dry hands when opening the blister pack.

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Peel back the foil covering of one blister and gently remove the orally disintegrating tablet (ODT). Do not push the ODT through the foil.

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As soon as the blister is opened, remove the ODT and place on the tongue; alternatively, the ODT may be placed under the tongue.

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The ODT will disintegrate in saliva so that it can be swallowed without additional liquid.

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Take the ODT immediately after opening the blister pack. Do not store the ODT outside the blister pack for future use.

2.4 Concomitant Administration with Strong or Moderate CYP3A4 Inhibitors

Avoid concomitant administration of NURTEC ODT with strong inhibitors of CYP3A4. Avoid another dose of NURTEC ODT within 48 hours when it is concomitantly administered with moderate inhibitors of CYP3A4 [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

2.5 Concomitant Administration with Strong or Moderate CYP3A Inducers

Avoid concomitant administration of NURTEC ODT with strong or moderate inducers of CYP3A, which may lead to loss of efficacy of NURTEC ODT [see Drug Interactions (7.2), Clinical Pharmacology (12.3)].

2.6 Concomitant Administration with Potent Inhibitors of P-gp

Avoid another dose of NURTEC ODT within 48 hours when it is concomitantly administered with potent inhibitors of P-gp [see Drug Interactions (7.3), Clinical Pharmacology (12.3)].

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including dyspnea and rash, have occurred with NURTEC ODT in clinical studies. Hypersensitivity reactions can occur days after administration, and delayed serious hypersensitivity has occurred. If a hypersensitivity reaction occurs, discontinue NURTEC ODT and initiate appropriate therapy [see Contraindications (4)].

5.2 Hypertension

Development of hypertension and worsening of pre-existing hypertension have been reported following the use of CGRP antagonists, including NURTEC ODT, in the postmarketing setting.

Some of the patients who developed new-onset hypertension had risk factors for hypertension. There were cases requiring initiation of pharmacological treatment for hypertension and, in some cases, hospitalization. Hypertension may occur at any time during treatment, but was most frequently reported within 7 days of therapy initiation. NURTEC ODT was discontinued in many of the reported cases.

Monitor patients treated with NURTEC ODT for new-onset hypertension or worsening of pre-existing hypertension, and consider whether discontinuation of NURTEC ODT is warranted if evaluation fails to establish an alternative etiology or blood pressure is inadequately controlled.

5.3 Raynaud’s Phenomenon

Development of Raynaud’s phenomenon and recurrence or worsening of pre-existing Raynaud’s phenomenon have been reported in the postmarketing setting following the use of CGRP antagonists, including NURTEC ODT.

In reported cases with small molecule CGRP antagonists, symptom onset occurred a median of 1.5 days following dosing. Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms.

NURTEC ODT should be discontinued if signs or symptoms of Raynaud’s phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve. Patients with a history of Raynaud’s phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of NURTEC ODT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Vascular Disorders: Hypertension [see Warnings and Precautions (5.2)], Raynaud’s phenomenon [see Warnings and Precautions (5.3)].

7.1 CYP3A4 Inhibitors

Concomitant administration of NURTEC ODT with strong inhibitors of CYP3A4 results in a significant increase in rimegepant exposure. Avoid concomitant administration of NURTEC ODT with strong inhibitors of CYP3A4 [see Clinical Pharmacology (12.3)].

Concomitant administration of NURTEC ODT with moderate inhibitors of CYP3A4 may result in increased exposure of rimegepant. Avoid another dose of NURTEC ODT within 48 hours when it is concomitantly administered with moderate inhibitors of CYP3A4 [see Clinical Pharmacology (12.3)].

7.2 CYP3A Inducers

Concomitant administration of NURTEC ODT with strong or moderate inducers of CYP3A can result in a significant reduction in rimegepant exposure, which may lead to loss of efficacy of NURTEC ODT. Avoid concomitant administration of NURTEC ODT with strong or moderate inducers of CYP3A [see Clinical Pharmacology (12.3)].

7.3 P-gp Inhibitors

Concomitant administration of NURTEC ODT with potent inhibitors of P-gp (e.g., amiodarone, cyclosporine, lapatinib, quinidine, ranolazine) may result in increased exposure of rimegepant. Avoid another dose of NURTEC ODT within 48 hours when it is concomitantly administered with potent inhibitors of P-gp [see Clinical Pharmacology (12.3)].

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

In pharmacokinetic studies, no clinically significant pharmacokinetic differences were observed between elderly and younger subjects. Clinical studies of NURTEC ODT did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

8.6 Hepatic Impairment

No dosage adjustment of NURTEC ODT is required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Plasma concentrations of rimegepant were significantly higher in subjects with severe (Child-Pugh C) hepatic impairment. Avoid use of NURTEC ODT in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

8.7 Renal Impairment

No dosage adjustment of NURTEC ODT is required in patients with mild, moderate, or severe renal impairment. NURTEC ODT has not been studied in patients with end-stage renal disease and in patients on dialysis. Avoid use of NURTEC ODT in patients with end-stage renal disease (CLcr < 15 mL/min) [see Clinical Pharmacology (12.3)].

12.1 Mechanism of Action

Rimegepant is a calcitonin gene-related peptide receptor antagonist.

12.2 Pharmacodynamics

The relationship between pharmacodynamic activity and the mechanism(s) by which rimegepant exerts its clinical effects is unknown.

No clinically relevant differences in resting blood pressure were observed when rimegepant was concomitantly administered with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) compared with sumatriptan alone to healthy volunteers.

12.3 Pharmacokinetics

12.5 Pharmacogenomics

CYP2C9 activity is reduced in individuals with genetic variants such as the CYP2C9*2 and CYP2C9*3 alleles. Rimegepant Cmax and AUC0-inf were similar in CYP2C9 intermediate metabolizers (i.e., *1/*2, *2/*2, *1/*3, n=43) as compared to normal metabolizers (i.e., *1/*1, N=72). Adequate PK data are not available from CYP2C9 poor metabolizers (i.e., *2/*3). Since the contribution of CYP2C9 to rimegepant metabolism is considered minor, CYP2C9 polymorphism is not expected to significantly affect its exposure.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14.1 Acute Treatment of Migraine

The efficacy of NURTEC ODT for the acute treatment of migraine with and without aura in adults was demonstrated in a randomized, double-blind, placebo-controlled trial: Study 1 (NCT03461757). Patients in the study were randomized to receive 75 mg of NURTEC ODT (N=732) or placebo (N=734). Patients were instructed to treat a migraine of moderate to severe headache pain intensity. Rescue medication (i.e., NSAIDs, acetaminophen, and/or an antiemetic) was allowed 2 hours after the initial treatment. Other forms of rescue medication such as triptans were not allowed within 48 hours of initial treatment. Approximately 14% of patients were taking preventive medications for migraine at baseline. None of the patients in Study 1 were on concomitant preventive medication that act on the CGRP pathway.

The primary efficacy analyses were conducted in patients who treated a migraine with moderate to severe pain. NURTEC ODT 75 mg demonstrated an effect on pain freedom and most bothersome symptom (MBS) freedom at two hours after dosing, compared to placebo. Pain freedom was defined as a reduction of moderate or severe headache pain to no headache pain, and MBS freedom was defined as the absence of the self-identified MBS (i.e., photophobia, phonophobia, or nausea). Among patients who selected an MBS, the most commonly selected symptom was photophobia (54%), followed by nausea (28%), and phonophobia (15%).

In Study 1, the percentage of patients achieving headache pain freedom and MBS freedom two hours after a single dose was statistically significantly greater in patients who received NURTEC ODT compared to those who received placebo (Table 1).

Figure 1 presents the percentage of patients achieving migraine pain freedom within 2 hours following treatment in Study 1.

Figure 1: Percentage of Patients Achieving Pain Freedom within 2 Hours in Study 1

Figure 2 presents the percentage of patients achieving MBS freedom within 2 hours in Study 1.

Figure 2: Percentage of Patients Achieving MBS Freedom within 2 Hours in Study 1

In Study 1, statistically significant effects of NURTEC ODT compared to placebo were demonstrated for the additional efficacy endpoints of pain relief at 2 hours, sustained pain freedom 2-48 hours, use of rescue medication within 24 hours, and the percentage of patients reporting normal function at two hours after dosing (Table 2). Pain relief was defined as a reduction in migraine pain from moderate or severe severity to mild or none. The measurement of the percentage of patients reporting normal function at two hours after dosing was derived from a single item questionnaire, asking patients to select one response on a 4-point scale; normal function, mild impairment, severe impairment, or required bedrest.

The incidence of photophobia and phonophobia was reduced following administration of NURTEC ODT 75 mg as compared to placebo.

14.2 Preventive Treatment of Episodic Migraine

The efficacy of NURTEC ODT for the preventive treatment of episodic migraine in adults was demonstrated in one randomized, double-blind, placebo-controlled trial of a different oral dosage form of rimegepant (Study 2; NCT03732638).

Study 2 enrolled adult patients with at least a 1-year history of migraine (with or without aura). Patients experienced an average of 10.9 headache days during the 28-day observational period, which included an average of 10.2 migraine days, prior to randomization into the trial. Patients were randomized to receive every other day dosing of rimegepant 75 mg (N=373) or placebo (N=374) for 12 weeks. Patients were allowed to use acute headache treatments (i.e., triptans, NSAIDs, acetaminophen, antiemetics, muscle relaxants, and aspirin) as needed. Approximately 10% of patients were taking one preventive medication for migraine at baseline. The use of a concomitant medication that acts on the CGRP pathway was not permitted for either the acute or preventive treatment of migraine.

The study excluded patients with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke, or transient ischemic attack within six months of screening.

The primary efficacy endpoint for Study 2 was the change from baseline in the mean number of monthly migraine days (MMDs) during Weeks 9 through 12 of the double-blind treatment phase.

The percentage of patients who achieved at least a 50% reduction from baseline in moderate to severe MMDs during Weeks 9 through 12 of the double-blind treatment phase compared to placebo was also evaluated. Rimegepant 75 mg dosed every other day demonstrated statistically significant improvements for these efficacy endpoints compared to placebo, as summarized in Table 3.

Figure 3: Change from Baseline in Monthly Migraine Days in Study 2a

aLeast-square means and 95% confidence intervals are presented.

Figure 4: Distribution of Change from Baseline in Mean Monthly Migraine Days at Month 3 by Treatment Group in Study 2a

aFigure excludes patients with missing data.

16.1 How Supplied

NURTEC ODT 75 mg orally disintegrating tablets are white to off-white, circular, debossed with the symbol , and supplied in cartons containing a blister pack of 8 orally disintegrating tablets. Each ODT contains 75 mg rimegepant.

NDC: 72618-3000-2

16.2 Storage and Handling

Store NURTEC ODT at controlled room temperature, 20°C to 25°C (68°F to 77°F); with excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].

Handling of Orally Disintegrating Tablets Packaging

Instruct patients not to remove the blister from the outer aluminum pouch until ready to use the orally disintegrating tablet inside [see Dosage and Administration (2.3)].

Hypersensitivity Reactions

Inform patients about the signs and symptoms of hypersensitivity reactions and that these reactions can occur days after administration of NURTEC ODT. Advise patients to contact their healthcare provider immediately if signs or symptoms of hypersensitivity reactions occur [see Warnings and Precautions (5.1)].

Hypertension

Inform patients that hypertension can develop or pre-existing hypertension can worsen with NURTEC ODT, and that they should contact their healthcare provider if they experience elevation in their blood pressure [see Warnings and Precautions (5.2)].

Raynaud’s Phenomenon

Inform patients that Raynaud’s phenomenon can develop or worsen with NURTEC ODT. Advise patients to discontinue NURTEC ODT and contact their healthcare provider if they experience signs or symptoms of Raynaud’s phenomenon [see Warnings and Precautions (5.3)].

Pregnancy Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to NURTEC ODT during pregnancy. Encourage participation and advise patients about how they may enroll in the registry [see Use in Specific Populations (8.1)].

This product’s labeling may have been updated. For the most recent Prescribing Information, please visit www.pfizer.com.