NDC 65162-042 Eletriptan Hydrobromide

Eletriptan Hydrobromide

NDC Product Code 65162-042

NDC CODE: 65162-042

Proprietary Name: Eletriptan Hydrobromide What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Eletriptan Hydrobromide What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Eletriptan is used to treat migraines. It helps to relieve headache, pain, and other migraine symptoms (including nausea, vomiting, sensitivity to light/sound). Prompt treatment helps you return to your normal routine and may decrease your need for other pain medications. Eletriptan belongs to a class of drugs known as triptans. It affects a certain natural substance (serotonin) that causes narrowing of blood vessels in the brain. It may also relieve pain by affecting certain nerves in the brain. Eletriptan does not prevent future migraines or lessen how often you get migraine attacks.

Product Characteristics

Shape: ROUND (C48348)
6 MM
Score: 1

NDC Code Structure

NDC 65162-042-03

Package Description: 30 TABLET, FILM COATED in 1 BOTTLE

NDC 65162-042-80


NDC Product Information

Eletriptan Hydrobromide with NDC 65162-042 is a a human prescription drug product labeled by Amneal Pharmaceuticals Llc. The generic name of Eletriptan Hydrobromide is eletriptan hydrobromide. The product's dosage form is tablet, film coated and is administered via oral form.

Labeler Name: Amneal Pharmaceuticals Llc

Dosage Form: Tablet, Film Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Eletriptan Hydrobromide Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • FD&C BLUE NO. 2 (UNII: L06K8R7DQK)
  • FD&C YELLOW NO. 5 (UNII: I753WB2F1M)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Serotonin 1b Receptor Agonists - [MoA] (Mechanism of Action)
  • Serotonin 1d Receptor Agonists - [MoA] (Mechanism of Action)
  • Serotonin-1b and Serotonin-1d Receptor Agonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Amneal Pharmaceuticals Llc
Labeler Code: 65162
FDA Application Number: ANDA206787 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 05-30-2018 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Eletriptan Hydrobromide Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

  • Eletriptan hydrobromide tablets are indicated for the acute treatment of migraine with or without aura in adults.Limitations of Use:Use only if a clear diagnosis of migraine has been established. If a patient has no response to the first migraine attack treated with eletriptan hydrobromide tablets, reconsider the diagnosis of migraine before eletriptan hydrobromide tablets are administered to treat any subsequent attacks.
  • Eletriptan hydrobromide tablets are not intended for the prevention of migraine attacks.
  • Safety and effectiveness of eletriptan hydrobromide tablets have not been established for cluster headache.

2 Dosage And Administration

The maximum recommended single dose is 40 mg.In controlled clinical trials, single doses of 20 mg and 40 mg were effective for the acute treatment of migraine in adults. A greater proportion of patients had a response following a 40 mg dose than following a 20 mg dose [see Clinical Studies (14)].If the migraine has not resolved by 2 hours after taking eletriptan hydrobromide tablets, or returns after transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose should not exceed 80 mg.The safety of treating an average of more than 3 migraine attacks in a 30-day period has not been established.

3 Dosage Forms And Strengths

20 mg Tablets: Light yellow to yellow colored, round shaped, biconvex, film-coated tablets, debossed with “AN” on one side and “42” on other side.40 mg Tablets:  Light orange to dark yellow colored, round shaped, biconvex, film-coated tablets, debossed with “AN” on one side and “43” on other side.

4 Contraindications

  • Eletriptan hydrobromide is contraindicated in patients with:Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina [see Warnings and Precautions (5.1)].
  • Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions (5.2)].
  • History of stroke, transient ischemic attack (TIA), or history or current evidence of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions (5.4)].Peripheral vascular disease [see Warnings and Precautions (5.5)].Ischemic bowel disease [see Warnings and Precautions (5.5)].Uncontrolled hypertension [see Warnings and Precautions (5.8)].Recent use (i.e., within 24 hours) of another 5-hydroxytryptamine1 (5-HT1) agonist, ergotamine-containing medication, or ergot-type medication such as dihydroergotamine (DHE) or methysergide [see Drug Interactions (7.1)].
  • Hypersensitivity to eletriptan hydrobromide (angioedema and anaphylaxis seen) [see Warnings and Precautions (5.9)].Recent use (i.e., within at least 72 hours) of the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

5 Warnings And Precautions

Eletriptan hydrobromide should only be used where a clear diagnosis of migraine has been established.

5.1    Myocardial Ischemia, Myocardial Infarction And Prinzmetal’S Angina

Eletriptan hydrobromide is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of eletriptan hydrobromide. Some of these reactions occurred in patients without known CAD.  Eletriptan hydrobromide may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD.Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving eletriptan hydrobromide. Do not use eletriptan hydrobromide if there is evidence of CAD or coronary artery vasospasm [see Contraindications (4)].  For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first eletriptan hydrobromide dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following administration of eletriptan hydrobromide. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of eletriptan hydrobromide.

5.2    Arrhythmias

Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue eletriptan hydrobromide if these disturbances occur. Eletriptan hydrobromide is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Contraindications (4)].

5.3    Chest, Throat, Neck And/Or Jaw Pain/Tightness/Pressure

Sensations of tightness, pain and pressure in the chest, throat, neck and jaw commonly occur after treatment with eletriptan hydrobromide and are usually non-cardiac in origin.  However, perform a cardiac evaluation if these patients are at high cardiac risk. Eletriptan hydrobromide is contraindicated in patients with CAD or Prinzmetal’s variant angina [see Contraindications (4)].

5.4    Cerebrovascular Events

Cerebral hemorrhage, subarachnoid hemorrhage and stroke have occurred in patients treated with 5-HT1 agonists and some have resulted in fatalities.  In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not.Before treating headaches in patients not previously diagnosed as migraineurs and in migraineurs who present with symptoms atypical of migraine, other potentially serious neurological conditions need to be excluded. Eletriptan hydrobromide is contraindicated in patients with a history of stroke or TIA [see Contraindications (4)].

5.5    Other Vasospasm Reactions

Eletriptan hydrobromide may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea) and Raynaud’s syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT1 agonist, rule out a vasospastic reaction before receiving additional eletriptan hydrobromide doses [see Contraindications (4)].

5.6    Medication Overuse Headache

Overuse of acute migraine drugs (e.g. ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused acute migraine drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.

5.7    Serotonin Syndrome

Serotonin syndrome may occur with eletriptan hydrobromide, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and monoamine oxidase (MAO) inhibitors [see Drug Interactions (7.3)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue eletriptan hydrobromide if serotonin syndrome is suspected.

5.8    Increase In Blood Pressure

Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1 agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with eletriptan hydrobromide. Eletriptan hydrobromide is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].

5.9    Anaphylactic/Anaphylactoid Reactions

There have been reports of anaphylaxis, anaphylactoid and hypersensitivity reactions including angioedema in patients receiving eletriptan hydrobromide. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. Eletriptan hydrobromide is contraindicated in patients with a history of hypersensitivity reaction to eletriptan hydrobromide [see Contraindications (4)].

5.10    Risk Of Allergic Reactions Due To Tartrazine

The 20 mg tablets contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

6 Adverse Reactions

  • The following adverse reactions are described elsewhere in other sections of the prescribing information:Myocardial ischemia and myocardial infarction and Prinzmetal’s angina [see Warnings and Precautions (5.2)]
  • Arrhythmias [see Warnings and Precautions (5.3)]
  • Chest, throat, neck and/or jaw pain/tightness/pressure [see Warnings and Precautions (5.4)]
  • Cerebrovascular events [see Warnings and Precautions (5.4)]
  • Other vasospasm reactions [see Warnings and Precautions (5.5)]
  • Medication overuse headache [see Warnings and Precautions (5.6)]
  • Serotonin syndrome [see Warnings and Precautions (5.7)]
  • Increase in blood pressure [see Warnings and Precautions (5.8)]
  • Hypersensitivity reactions [see Contraindications (4)  and Warnings and Precautions (5.9)]

6.1    Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.Among 4,597 patients who treated the first migraine headache with eletriptan hydrobromide in short-term placebo-controlled trials, the most common adverse reactions reported with treatment with eletriptan hydrobromide were asthenia, nausea, dizziness and somnolence. These reactions appear to be dose-related.In long-term open-label studies where patients were allowed to treat multiple migraine attacks for up to 1 year, 128 (8.3%) out of 1,544 patients discontinued treatment due to adverse reactions.Table 1 lists adverse reactions that occurred in the subset of 5,125 migraineurs who received eletriptan doses of 20 mg, 40 mg and 80 mg or placebo in worldwide placebo-controlled clinical trials.Only adverse reactions that were more frequent in a eletriptan hydrobromide treatment group compared to the placebo group with an incidence greater than or equal to 2% are included in Table 1.Table 1: Adverse Reactions Incidence in Placebo-Controlled Migraine Clinical Trials:  Reactions Reported by > 2% Patients Treated with Eletriptan Hydrobromide and More Than Placebo Adverse Reaction Type Placebo (n=988)Eletriptan Hydrobromide 20 mg (n=431)Eletriptan Hydrobromide 40 mg (n=1774) Eletriptan Hydrobromide80 mg (n=1932)  ATYPICAL SENSATIONS     Paresthesia2%  3% 3% 4% Flushing/feeling of warmth2% 2% 2% 2%  PAIN AND PRESSURE  SENSATIONS     Chest – tightness/pain/pressure1% 1%  2%4%  Abdominal – pain/discomfort/stomach pain/ cramps/pressure1% 1%  2%2%  DIGESTIVE     Dry mouth2% 2% 3% 4%  Dyspepsia1% 1%2% 2%  Dysphagia – throat  tightness/difficulty swallowing0.2% 1% 2% 2%  Nausea5% 4% 5% 8%  NEUROLOGICAL     Dizziness3% 3% 6% 7%  Somnolence4% 3%    6%     7%  Headache3% 4% 3% 4%  OTHER     Asthenia3% 4% 5% 10% The frequency of adverse reactions in clinical trials did not increase when up to 2 doses of eletriptan hydrobromide were taken within 24 hours. The incidence of adverse reactions in controlled clinical trials was not affected by gender, age, or race of the patients. Adverse reaction frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (e.g., SSRIs, beta blockers, calcium channel blockers, tricyclic antidepressants), estrogen replacement therapy or oral contraceptives.

6.2    Postmarketing Experience

The following adverse reaction(s) have been identified during post approval use of eletriptan hydrobromide. 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.Neurological: seizureDigestive: vomiting

7.1    Ergot-Containing Drugs And Other 5-Ht 1B/1D Agonists

​Ergot-containing drugs have been reported to cause prolonged vasospastic reactions.  Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine [DHE] or methysergide) and eletriptan hydrobromide within 24 hours of each other is contraindicated. Concomitant use of other 5-HT1 agonists within 24 hours of eletriptan hydrobromide treatment is contraindicated [see Contraindications (4)].

7.2     Cyp3a4 Inhibitors

Potent CYP3A4 inhibitors significantly increase the exposure of eletriptan hydrobromide.  Eletriptan hydrobromide should not be used within at least 72 hours of treatment with potent CYP3A4 inhibitors [see Contraindications (4) and Clinical Pharmacology (12.3)].

7.3    Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors And Serotonin Syndrome

Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs, SNRIs, TCAs and MAO inhibitors [see Warnings and Precautions (5.7)].

8.1 Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. In reproductive toxicity studies in pregnant animals, oral administration of eletriptan was associated with developmental toxicity (decreased fetal and pup weights and an increased incidence of fetal structural abnormalities) at clinically relevant plasma exposures. Eletriptan hydrobromide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.When pregnant rats were administered eletriptan during the period of organogenesis at doses of 10, 30 or 100 mg/kg/day, fetal weights were decreased and the incidences of vertebral and sternebral variations were increased at 100 mg/kg/day (approximately 12 times the maximum recommended human dose [MRHD] of 80 mg/day on a mg/m2 basis). The 30 and 100 mg/kg/day doses were also maternally toxic, as evidenced by decreased maternal body weight gain during gestation. The no-effect dose for developmental toxicity in rats was 30 mg/kg/day, which is approximately 4 times the MRHD on a mg/m2 basis.When doses of 5, 10, or 50 mg/kg/day were given to pregnant rabbits throughout organogenesis, fetal weights were decreased at 50 mg/kg/day, which is approximately 12 times the MRHD on a mg/m2 basis. The incidences of fused sternebrae and vena cava deviations were increased at all doses. Maternal toxicity was not evident at any dose. A no-effect dose for developmental toxicity in rabbits was not established; the lowest dose tested (5 mg/kg/day) is similar to the MRHD on a mg/m2 basis.

8.3 Nursing Mothers

Eletriptan is excreted in human milk. Caution should be exercised when eletriptan hydrobromide is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.The efficacy of eletriptan hydrobromide tablets (40 mg) in patients 11 to 17 was not established in a randomized, placebo-controlled trial of 274 adolescent migraineurs [see Clinical Studies (14)]. Adverse reactions observed were similar in nature to those reported in clinical trials in adults. Postmarketing experience with other triptans includes a limited number of reports that describe pediatric patients who have experienced clinically serious adverse reactions that are similar in nature to those reported rarely in adults. Long-term safety of eletriptan was studied in 76 adolescent patients who received treatment for up to one year.  A similar profile of adverse reactions to that of adults was observed. The long-term safety of eletriptan in pediatric patients has not been established.

8.5 Geriatric Use

Blood pressure was increased to a greater extent in elderly subjects than in young subjects.  The pharmacokinetic disposition of eletriptan in the elderly is similar to that seen in younger adults [see Clinical Pharmacology (12.3)]. In clinical trials, there were no apparent differences in efficacy or the incidence of adverse reactions between patients under 65 years of age and those 65 and above.

8.6    Hepatic Impairment

The effect of severe hepatic impairment on eletriptan hydrobromide metabolism has not been evaluated. Eletriptan hydrobromide is not recommended for use in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

10 Overdosage

The elimination half-life of eletriptan is about 4 hours [see Clinical Pharmacology (12.3)], therefore monitoring of patients after overdose with eletriptan should continue for at least 20 hours or longer while symptoms or signs persist.There is no specific antidote to eletriptan.It is unknown what effect hemodialysis or peritoneal dialysis has on the serum concentration of eletriptan.

11 Description

Eletriptan hydrobromide tablets contain eletriptan hydrobromide monohydrate, which is a selective 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist. Eletriptan hydrobromide monohydrate is chemically designated as3-((( R )-1-Methyl Pyrrolidin-2yl)methyl)-5-(2-phenylsulphonyl) ethyl)-1H-indole hydrobromide monohydrate and it has the following chemical structure:The molecular formula is C22H26N2O2S . HBr.H2O, representing a molecular weight of 481.45 g/mol. Eletriptan hydrobromide monohydrate is an off-white to light brown color powder and freely soluble in methanol.Each eletriptan hydrobromide tablet for oral administration contains 25.17 or 50.34 mg of eletriptan hydrobromide monohydrate equivalent to 20 mg or 40 mg of eletriptan, respectively.  Each tablet also contains the inactive ingredients croscarmellose sodium, FD&C blue #2 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, titanium dioxide and triacetin. Additionally 20 mg tablets contains FD&C yellow #5 aluminum lake and 40 mg tablet contains D&C yellow #10 aluminum lake and FD&C yellow #6 aluminum lake.

12.1 Mechanism Of Action

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors.Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system.  The therapeutic activity of eletriptan hydrobromide for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

12.3 Pharmacokinetics

Absorption: Eletriptan is well absorbed after oral administration with peak plasma levels occurring approximately 1.5 hours after dosing to healthy subjects. In patients with moderate to severe migraine the median Tmax is 2 hours. The mean absolute bioavailability of eletriptan is approximately 50%. The oral pharmacokinetics are slightly more than dose-proportional over the clinical dose range. The AUC and Cmax of eletriptan are increased by approximately 20% to 30% following oral administration with a high fat meal. Eletriptan hydrobromide can be taken with or without food.Distribution: The volume of distribution of eletriptan following IV administration is 138L. Plasma protein binding is moderate and approximately 85%.Metabolism: The N-demethylated metabolite of eletriptan is the only known active metabolite. This metabolite causes vasoconstriction similar to eletriptan in animal models. Though the half-life of the metabolite is estimated to be about 13 hours, the plasma concentration of the N-demethylated metabolite is 10% to 20% of parent drug and is unlikely to contribute significantly to the overall effect of the parent compound.In vitro studies indicate that eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4 [see Contraindications (4) and Drug Interactions (7.2)].Elimination: The terminal elimination half-life of eletriptan is approximately 4 hours. Mean renal clearance (CLR) following oral administration is approximately 3.9 L/h.  Non-renal clearance accounts for about 90% of the total clearance.Special PopulationsAge: The pharmacokinetics of eletriptan are generally unaffected by age. Blood pressure was increased to a greater extent in elderly subjects than in young subjects [see Use in Specific Populations (8.5)]. The pharmacokinetic disposition of eletriptan in the elderly is similar to that seen in younger adults.There is a statistically significant increased half-life (from about 4.4 hours to 5.7 hours) between elderly (65 to 93 years of age) and younger adult subjects (18 to 45 years of age) [see Use in Specific Populations (8.5)].Gender: The pharmacokinetics of eletriptan are unaffected by gender.Race: A comparison of pharmacokinetic studies run in western countries with those run in Japan has indicated an approximate 35% reduction in the exposure of eletriptan in Japanese male volunteers compared to western males. Population pharmacokinetic analysis of two clinical studies indicates no evidence of pharmacokinetic differences between Caucasians and non-Caucasian patients.Menstrual Cycle: In a study of 16 healthy females, the pharmacokinetics of eletriptan remained consistent throughout the phases of the menstrual cycle.Renal Impairment: There was no significant change in clearance observed in subjects with mild, moderate or severe renal impairment, though blood pressure elevations were observed in this population [see Warnings and Precautions (5.8)].Hepatic Impairment: Subjects with mild or moderate hepatic impairment demonstrated an increase in both AUC (34%) and half-life. The Cmax was increased by 18%. No dose adjustment is necessary in subjects with mild or moderate hepatic impairment. The effects of severe hepatic impairment on eletriptan metabolism have not been evaluated [see Use in Specific Populations (8.6)].Drug Interaction StudiesCYP3A4 inhibitors: In vitro studies have shown that eletriptan is metabolized by the CYP3A4 enzyme. A clinical study demonstrated about a 3-fold increase in Cmax and about a 6-fold increase in the AUC of eletriptan when combined with ketoconazole.  The half-life increased from 5 hours to 8 hours and the Tmax increased from 2.8 hours to 5.4 hours. Another clinical study demonstrated about a 2-fold increase in Cmax and about a 4-fold increase in AUC when erythromycin was co-administered with eletriptan.  It has also been shown that co-administration of verapamil and eletriptan yields about a 2-fold increase in Cmax and about a 3-fold increase in AUC of eletriptan and that co-administration of fluconazole and eletriptan yields about a 1.4-fold increase in Cmax and about a 2-fold increase in AUC of eletriptan.Eletriptan hydrobromide is contraindicated within at least 72 hours of treatment with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir and nelfinavir. Eletriptan hydrobromide should not be used within 72 hours with drugs that have demonstrated potent CYP3A4 inhibition [see Contraindications (4)].Propranolol: The Cmax and AUC of eletriptan were increased by 10% and 33%, respectively, in the presence of propranolol.  No interactive increases in blood pressure were observed. No dosage adjustment appears to be needed for patients taking propranolol.The effect of eletriptan on other drugs: The effect of eletriptan on enzymes other than cytochrome P450 has not been investigated.  In vitro human liver microsome studies suggest that eletriptan has little potential to inhibit CYP1A2, 2C9, 2E1 and 3A4 at concentrations up to 100 µM. While eletriptan has an effect on CYP2D6 at high concentration, this effect should not interfere with metabolism of other drugs when eletriptan is used at recommended doses. There is no in vitro or in vivo evidence that clinical doses of eletriptan will induce drug metabolizing enzymes. Therefore, eletriptan is unlikely to cause clinically important drug interactions mediated by these enzymes.

13.1  Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisEletriptan was administered to rats and mice in the diet for 104 weeks. In rats, the incidence of testicular interstitial cell adenomas was increased at the high dose of 75 mg/kg/day, but not at 15 mg/kg/day, a dose associated with plasma exposures (AUC) approximately 2 times that in humans at the MRHD of 80 mg/day.   In mice, the incidence of hepatocellular adenomas was increased at the high dose of 400 mg/kg/day, but not a dose of 90 mg/kg/day, associated with plasma AUC approximately 7 times that in humans at the MRHD.MutagenesisEletriptan was negative in in vitro (bacteria reverse mutation (Ames), mammalian cell gene mutation (CHO/HGPRT), chromosomal aberration assay in human lymphocytes) and in vivo (mouse micronucleus) assays.Impairment of FertilityIn a fertility and early embryonic development study, eletriptan (50, 100, or 200 mg/kg/day) was orally administered to male and female rats prior to and throughout mating and continuing in females to implantation. Plasma exposures (AUC) were 4, 8 and 16 times in males and 7, 14 and 28 times in females, respectively, that in humans at the MRHD. Dose-related decreases in the number of corpora lutea, implants and viable fetuses per dam were observed at all doses. Prolongation of the estrus cycle was observed at the highest dose tested. Male fertility parameters were not affected.

14 Clinical Studies

The efficacy of eletriptan hydrobromide in the acute treatment of migraines was evaluated in eight randomized, double-blind placebo-controlled studies.  All eight studies used 40 mg. Seven studies evaluated an 80 mg dose and two studies included a 20 mg dose.In all eight studies, randomized patients treated their headaches as outpatients. Seven studies enrolled adults and one study enrolled adolescents (age 11 to 17). Patients treated in the seven adult studies were predominantly female (85%) and Caucasian (94%) with a mean age of 40 years (range 18 to 78).  In all studies, patients were instructed to treat a moderate to severe headache.  Headache response, defined as a reduction in headache severity from moderate or severe pain to mild or no pain, was assessed up to 2 hours after dosing. Associated symptoms such as nausea, vomiting, photophobia and phonophobia were also assessed.Maintenance of response was assessed for up to 24 hours post dose. In the adult studies, a second dose of eletriptan hydrobromide or other medication was allowed 2 to 24 hours after the initial treatment for both persistent and recurrent headaches. The incidence and time to use of these additional treatments were also recorded.In the seven adult studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater among patients receiving eletriptan hydrobromide at all doses compared to those who received placebo. The two-hour response rates from these controlled clinical studies are summarized in Table 2.Table 2: Percentage of Patients with Headache Response (Mild or No Headache) 2 Hours Following Treatment Placebo Eletriptan Hydrobromide20 mg Eletriptan Hydrobromide40 mg Eletriptan Hydrobromide80 mg Study 123.8%(n=126)54.3%*(n=129) 65%*(n=117) 77.1%*(n=118)  Study 219%(n=232) NA 61.6%*(n=430) 64.6%*(n=446)  Study 321.7%(n=276) 47.3%*(n=273) 61.9%*(n=281) 58.6%*(n=290)  Study 439.5%(n=86) NA 62.3%*(n=175) 70%*(n=170) Study 520.6%(n=102) NA 53.9%*(n=206) 67.9%*(n=209)  Study 6 31.3%(n=80)NA 63.9%*(n=169) 66.9%*(n=160)  Study 729.5%(n=122) NA 57.5%*(n=492)  NA * p value < 0.05 vs. placeboNA - Not ApplicableComparisons of the performance of different drugs based upon results obtained in different clinical trials are never reliable.  Because studies are generally conducted at different times, with different samples of patients, by different investigators, employing different criteria and/or different interpretations of the same criteria, under different conditions (dose, dosing regimen, etc.), quantitative estimates of treatment response and the timing of response may be expected to vary considerably from study to study.The estimated probability of achieving an initial headache response within 2 hours following treatment is depicted in Figure 1.Figure 1: Estimated Probability of Initial Headache Response Within 2 Hours*

16     How Supplied/Storage And Handling

Eletriptan hydrobromide tablets, 20 mg are light yellow to yellow colored, round shaped, biconvex, film-coated tablets, debossed with “AN” on one side and “42” on other side.They are available as follows:Carton of 6 tablets:                       NDC 65162-042-80(Packages of 6 unit doses, 1 card of 6 tablets each)Eletriptan hydrobromide tablets, 40 mg are light orange to dark yellow colored, round shaped, biconvex, film coated tablets, debossed with “AN” on one side and “43” on other side.They are available as follows:Carton of 6 tablets:                         NDC 65162-043-80(Packages of 6 unit doses, 1 card of 6  tablets each)Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

17 Patient Counseling Information

See FDA Approved Patient Labeling (Patient Information) Myocardial Ischemia and/or Infarction, Prinzmetal’s Angina, Other Vasospastic Reactions and Cerebrovascular EventsInform patients that eletriptan hydrobromide may cause serious cardiovascular adverse reactions such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular reactions can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech and instruct them to ask for medical advice when observing any indicative sign or symptoms. Instruct patients to seek medical advice if they have symptoms of other vasospastic reactions [see Warnings and Precautions (5.1,  5.2,  5.4,  5.5  and 5.8)].Anaphylactic/Anaphylactoid ReactionsInform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving eletriptan hydrobromide.   Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens [see Contraindications (4)].Medication Overuse HeadacheInform patients that use of drugs to treat acute migraines for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6)].Serotonin SyndromeInform patients about the risk of serotonin syndrome with the use of eletriptan hydrobromide or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7)  and Drug Interactions (7.3)]. PregnancyInform patients that eletriptan hydrobromide should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1)]. Nursing MothersInform patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.3)].Manufactured by:Amneal Pharmaceuticals Pvt. Ltd.Ahmedabad 382220, INDIADistributed by:Amneal Pharmaceuticals LLCBridgewater, NJ 08807 Rev. 07-2017-00

Patient Information

  • Eletriptan Hydrobromide (EL-e-TRIP-tan HYE-droe-BROE-mide) TabletsPlease read this information before you start taking eletriptan hydrobromide and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.What is the most important information I should know about eletriptan hydrobromide?Eletriptan hydrobromide can cause serious side effects, including:Heart attack and other heart problems. Heart problems may lead to death.Stop taking eletriptan hydrobromide and get emergency medical help right away if you have any of the following symptoms of a heart attack:discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes backchest pain or chest discomfort that feels like an uncomfortable heavy pressure, squeezing, fullness, or painpain or discomfort in your arms, back, neck, jaw, or stomachshortness of breath with or without chest discomfortbreaking out in a cold sweatnausea or vomitingfeeling lightheadedEletriptan hydrobromide is not for people with risk factors for heart disease unless a heart exam is done and shows no problem. You have a higher risk for heart disease if you:have high blood pressurehave high cholesterol levelssmokeare overweighthave diabeteshave a family history of heart diseaseare a female who has gone through menopauseare a male over age 40Serotonin syndrome. Serotonin syndrome is a serious and life-threatening problem that can happen in people taking eletriptan hydrobromide, especially if eletriptan hydrobromide is taken with anti-depressant medicines called selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs).Ask your doctor or pharmacist for a list of these medicines if you are not sure.Call your doctor right away if you have any of the following symptoms of serotonin syndrome:mental changes such as seeing things that are not there (hallucinations), agitation, or comafast heartbeatchanges in blood pressurehigh body temperaturetight musclestrouble walkingnausea, vomiting, or diarrheaWhat are eletriptan hydrobromide tablets?Eletriptan hydrobromide tablets are a prescription medicine used to treat acute migraine headaches with or without aura in adults.Eletriptan hydrobromide tablets are for people who have been diagnosed with migraine headaches.Eletriptan hydrobromide is not used to prevent or decrease the number of migraine headaches you have. It is not known if eletriptan hydrobromide is safe and effective to treat cluster headaches. It is not known if eletriptan hydrobromide is safe and effective in children.Who should not take eletriptan hydrobromide?Do not take eletriptan hydrobromide if you:have heart problems or a history of heart problemshave or have had a stroke or problems with your blood circulationhave hemiplegic or basilar migraines. If you are not sure if you have these types of migraines, ask your doctorhave narrowing of the blood vessels in your legs, arms, stomach, or kidney (peripheral vascular disease)have ischemic bowel diseasehave uncontrolled high blood pressurehave taken any of the following medicines in the last 24 hours:other “triptans” or triptan combination products such as:almotriptan (Axert®)frovatriptan (Frova™)naratriptan (Amerge®)rizatriptan (Maxalt®)sumatriptan (Imitrex®)sumatriptan and naproxen sodium, (Treximet™)zolmitriptan (Zomig®)ergotamines such as:Bellergal-S®Ergomar®Cafergot®Wigraine®dihydroergotamines such as:D.H.E. 45® or Migranal® or methysergide (Sansert®)have taken the following medicines within the last 72 hours:ketoconazole (Nizoral®)clarithromycin (Biaxin®)itraconazole (Sporanox®)ritonavir (Norvir®)nefazodone (Serzone®)nelfinavir (Viracept®)troleandomycin (TAO®)are allergic to eletriptan or any of the ingredients in eletriptan hydrobromide tablets. See the end of this leaflet for a complete list of ingredients in eletriptan hydrobromide tablets.What should I tell my doctor before taking eletriptan hydrobromide?Before you take eletriptan hydrobromide, tell your doctor if you:have heart problems or family history of heart problems or strokehave high blood pressurehave high cholesterolhave diabetessmokeare overweightare a female who has gone through menopausehave kidney problemshave liver problemsare pregnant or plan to become pregnant. It is not known if eletriptan hydrobromide will harm your unborn baby.are breastfeeding or plan to breastfeed. Eletriptan hydrobromide passes into your breast milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you take eletriptan hydrobromide. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Your doctor will decide if you can take eletriptan hydrobromide with your other medicines. Eletriptan hydrobromide and other medicines may affect each other causing side effects.Especially tell your doctor if you take anti-depressant medicines called:selective serotonin reuptake inhibitors (SSRIs)serotonin norepinephrine reuptake inhibitors (SNRIs)Ask your doctor or pharmacist for a list of these medicines if you are not sure.Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.How should I take eletriptan hydrobromide?Take eletriptan hydrobromide exactly as your doctor tells you to take it.Your doctor will tell you how much eletriptan hydrobromide to take and when to take it.Your doctor may change your dose if needed. Do not change your dose without first talking to your doctor.Take 1 eletriptan hydrobromide tablet as soon as you feel a migraine coming on.If you do not get any relief after your first eletriptan hydrobromide tablet, do not take a second tablet without first talking with your doctor.If your headache comes back or you only get some relief from your headache, you can take a second tablet 2 hours after the first tablet.Do not take more than a total of 80 mg of eletriptan hydrobromide tablets in a 24-hour period.If you take too much eletriptan hydrobromide, call your doctor or go to the nearest hospital emergency room right away.You should write down when you have headaches and when you take eletriptan hydrobromide so you can talk to your doctor about how well eletriptan hydrobromide is working for you.What should I avoid while taking eletriptan hydrobromide?Eletriptan hydrobromide can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.What are the possible side effects of eletriptan hydrobromide?Eletriptan hydrobromide may cause serious side effects. See “What is the most important information I should know about eletriptan hydrobromide?”These serious side effects include:changes in color or sensation in your fingers and toes (Raynaud’s syndrome)stomach and intestinal problems (gastrointestinal and colonic ischemic events). Symptoms of gastrointestinal and colonic ischemic events include:sudden or severe stomach painstomach pain after mealsweight lossnausea or vomitingconstipation or diarrheabloody diarrheafeverproblems with blood circulation to your legs and feet (peripheral vascular ischemia). Symptoms of peripheral vascular ischemia include:cramping and pain in your legs or hipsfeeling of heaviness or tightness in your leg musclesburning or aching pain in your feet or toes while restingnumbness, tingling, or weakness in your legscold feeling or color changes in 1 or both legs or feetmedication overuse headaches. Some people who take too many eletriptan hydrobromide may have worse headaches (medication overuse headache). If your headaches get worse, your doctor may decide to stop your treatment with eletriptan hydrobromide.The most common side effects of eletriptan hydrobromide include:dizzinessnauseaweaknesstirednessdrowsinessTell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of eletriptan hydrobromide. For more information, ask your doctor or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store eletriptan hydrobromide?Store eletriptan hydrobromide at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F).General information about the safe and effective use of eletriptan hydrobromideMedicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use eletriptan hydrobromide for a condition for which it was not prescribed. Do not give eletriptan hydrobromide to other people, even if they have the same symptoms you have. It may harm them.This Patient Information summarizes the most important information about eletriptan hydrobromide. If you would like more information about eletriptan hydrobromide, talk with your doctor. You can ask your doctor or pharmacist for information on eletriptan hydrobromide that is written for health professionals.For more information, call 1-877-835-5472 or go to www.amneal.com.What are the ingredients in eletriptan hydrobromide tablets?Active ingredient: eletriptan hydrobromide monohydrateInactive ingredients: croscarmellose sodium, FD&C blue #2 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, titanium dioxide and triacetin. Additionally 20 mg tablets contains FD&C yellow #5 aluminum lake and 40 mg tablet contains D&C yellow #10 aluminum lake and FD&C yellow #6 aluminum lake.*The brands listed are the trademarks of their respective owners.Manufactured by:Amneal Pharmaceuticals Pvt. Ltd.Ahmedabad 382220, INDIA Distributed by:Amneal Pharmaceuticals LLCBridgewater, NJ 08807Rev. 07-2017-00

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