Addyi

Name: Addyi

Addyi Interactions

Do not drink alcohol while taking flibanserin. Drinking alcohol with this medicine can cause dangerous or unwanted side effects.

Grapefruit and grapefruit juice may interact with flibanserin and lead to unwanted side effects. Avoid the use of grapefruit products while taking flibanserin.

Avoid taking an herbal supplement containing: ginkgo, resveratrol, or St. John's wort.

Flibanserin may impair your thinking or reactions. Avoid driving or operating machinery for at least 6 hours after you take flibanserin, and until you know how this medicine will affect you. Dizziness or low blood pressure can cause falls or other accidents.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Taking this medicine with other drugs that make you sleepy or lower your blood pressure can worsen this effect. Ask your doctor before taking flibanserin with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • cimetidine;
  • gingko biloba;
  • resveratrol; or
  • St. John's wort.

This list is not complete. Other drugs may interact with flibanserin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

What are the side effects of flibanserin?

WARNING

Flibanserin may cause low blood pressure and fainting. Patients should lie down and seek medical help if they experience fainting.

Flibanserin causes drowsiness and reduces alertness. Patients should avoid operating machinery, driving, or performing other dangerous activities for at least 6 hours after taking each dose of flibanserin.

What is the dosage for flibanserin?

Flibanserin is administered once daily by mouth at bedtime. It should be stopped after 8 weeks if there is no improvement in symptoms.

What should I discuss with my healthcare provider before taking flibanserin?

You must not drink alcohol while taking flibanserin. It may cause you to have dangerously low blood pressure.

You should not use flibanserin if you are allergic to it, or if you have:

  • low blood pressure;

  • a history of alcoholism or drug addiction;

  • liver disease;

  • a history of depression or mental illness; or

  • if you currently drink alcohol.

Some medicines can cause unwanted or dangerous effects when used with flibanserin. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • nefazodone;

  • an antibiotic--ciprofloxacin, clarithromycin, erythromycin, telithromycin;

  • antifungal medicine--fluconazole, itraconazole, ketoconazole, posaconazole;

  • antiviral medicine to treat hepatitis C--boceprevir, telaprevir;

  • heart or blood pressure medicine--conivaptan, diltiazem, verapamil; or

  • HIV or AIDS medicine--atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir.

To make sure flibanserin is safe for you, tell your doctor if you have:

  • history of alcoholism or drug addiction.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether flibanserin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Flibanserin is not approved for use by anyone younger than 18 years old.

How should I take flibanserin?

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Take flibanserin only at bedtime.

Flibanserin can lower your blood pressure, which can make you dizzy. If you feel light-headed after taking this medicine, lie down if you are not already in bed.

It may take up to 8 weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

Store at room temperature away from moisture and heat.

What should I avoid while taking flibanserin?

Do not drink alcohol while taking flibanserin. Drinking alcohol with this medicine can cause dangerous or unwanted side effects.

Grapefruit and grapefruit juice may interact with flibanserin and lead to unwanted side effects. Avoid the use of grapefruit products while taking flibanserin.

Avoid taking an herbal supplement containing: ginkgo, resveratrol, or St. John's wort.

Flibanserin may impair your thinking or reactions. Avoid driving or operating machinery for at least 6 hours after you take flibanserin, and until you know how this medicine will affect you. Dizziness or low blood pressure can cause falls or other accidents.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Commonly used brand name(s)

In the U.S.

  • Addyi

Available Dosage Forms:

  • Tablet

Therapeutic Class: Central Nervous System Agent

Proper Use of Addyi

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

The medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Take flibanserin only at bedtime. Taking this medicine at a time other than bedtime may increase risk of low blood pressure, fainting, accidental injury, or sleepiness.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For treatment of hypoactive sexual desire disorder:
      • Adults—100 milligrams (mg) once a day at bedtime.
      • Children—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Uses of Addyi

  • It is used in some women to raise interest in sex.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Addyi?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Addyi - Clinical Pharmacology

Mechanism of Action

The mechanism of action of Addyi in the treatment of premenopausal women with hypoactive sexual desire disorder is not known.

Pharmacodynamics

Receptor Binding:
In vitro, flibanserin demonstrated high affinity for the following serotonin (5-hydroxytryptamine or 5-HT) receptors: agonist activity at 5-HT1A and antagonist activity at 5-HT2A. Flibanserin also has moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors.

Alcohol Interaction
A randomized, double-blind, single-dose, cross-over, dedicated alcohol interaction study was conducted in 25 healthy subjects (23 men and 2 premenopausal women). In this study, 68%, 16%, 8% and 8% subjects reported a history of drinking 5-6, 7-10, 11-15 and 16-21 drinks per week, respectively.  Subjects received one of the following five treatments [Addyi and alcohol were administered in the morning and the alcohol was consumed in 10 minutes. Addyi is to be only administered at bedtime, see Dosage and Administration (2.1)]:

• 100 mg of Addyi alone • 0.4 g/kg 95% ethanol (equivalent to two 12-ounce cans of beer containing 5% alcohol content, two 5- ounce glasses of wine containing 12% alcohol, or two 1.5-ounce shots of 80 proof spirit in a 70 kg person) • 0.8 g/kg 95% ethanol (equivalent to four 12-ounce cans of beer containing 5% alcohol content, four 5-ounce glasses of wine containing 12% alcohol, or four 1.5-ounce shots of 80 proof spirit in a 70 kg person) • 100 mg of Addyi in combination with 0.4 g/kg 95% ethanol • 100 mg of Addyi in combination with 0.8 g/kg 95% ethanol

Patients who received Addyi with alcohol had a higher incidence of somnolence than patients who received Addyi alone or alcohol alone [see Warnings and Precautions (5.4)]. There were no significant changes in the pharmacokinetics of flibanserin when administered with or without alcohol.

Cardiac Electrophysiology
The effect of Addyi on the QT interval was evaluated in a randomized, double-blind, placebo- and active- (single dose moxifloxacin) controlled crossover study in 56 healthy men and women.  Subjects in the Addyi groups received either 50 mg twice a day (equivalent to the daily recommended dosage) or 100 mg three times a day (3 times the daily recommended dosage) administered for 5 days. The time frame for electrocardiogram (ECG) measurements covered maximum plasma concentrations of flibanserin and relevant metabolites.  In this study, Addyi did not prolong the QT interval to any clinically relevant extent.  The mean increase in heart rate associated with the 100 mg three times a day dose of Addyi compared to placebo ranged from 1.7 to 3.2 beats per minute.

Pharmacokinetics

Flibanserin showed dose-proportional pharmacokinetics for Cmax after single oral doses of 100 mg to 250 mg (the recommended and 2.5 times the recommended dosage, respectively) in healthy female subjects. Steady state was achieved after 3 days of dosing. The extent of exposure (AUC0-∞) with once-daily dosing of 100 mg of flibanserin was increased 1.4-fold as compared to a single dose.

Absorption
Following oral administration of a single 100 mg dose of flibanserin in healthy premenopausal women (N=8), mean (SD) Cmax was 419 (206) ng/mL and mean (SD) AUC0-inf was 1543 (511) ng*hr/mL. Median (range) time to reach Cmax was 0.75 (0.75 to 4.0) hours. Absolute bioavailability of flibanserin following oral dosing is 33%.

Effect of Food
Food increased the extent of absorption and slowed the rate of absorption of a 50 mg dose of flibanserin (one half the recommended dosage). Low-, moderate-, and high-fat meals increased flibanserin AUC0-inf by 1.18-, 1.43-, and 1.56-fold; increased Cmax by 1.02-, 1.13-, and 1.15-fold; and prolonged median Tmax to 1.5, 0.9, 1.8 hours from 0.8 hours under fasted conditions, respectively.

Distribution
Approximately 98% of flibanserin is bound to human serum proteins, mainly to albumin.

Elimination
Metabolism
Flibanserin is primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2C19. Based on in vitro and/or in vivo data, CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 contribute minimally to the metabolism of flibanserin. After a single oral solution dose of 50 mg 14C-radiolabeled flibanserin, 44% of the total 14C-flibanserin related radioactivity was recovered in urine, and 51% was recovered in feces. Flibanserin is extensively metabolized to at least 35 metabolites, most of them occurring in low concentrations in plasma.  Two metabolites could be characterized that showed plasma concentrations similar to that achieved with flibanserin: 6,21-dihydroxy-flibanserin-6,21-disulfate and 6-hydroxy-flibanserin-6-sulfate.  These two metabolites are inactive.

Excretion
Flibanserin has a mean terminal half-life of approximately 11 hours.

Specific Populations
Hepatic Impairment
Single 50 mg oral doses of flibanserin were administered to 10 patients with mild hepatic impairment (Child-Pugh score of 6 points), 4 patients with moderate hepatic impairment (Child-Pugh score of 8-9 points), and 14 healthy subjects matched by age, weight, and gender. Systemic flibanserin exposure (AUC0-inf) increased 4.5-fold in patients with mild hepatic impairment, compared to subjects with normal hepatic function, and t1/2 was longer (26 hours compared to 10 hours in matching healthy controls). Due to the small number of patients (n=4) with moderate hepatic impairment enrolled in the study, it is not possible to make conclusions about the quantitative effect of moderate hepatic impairment on flibanserin exposure. Addyi is contraindicated in patients with hepatic impairment [see Warnings and Precautions (5.6)].

Renal Impairment
Single 50 mg oral doses of flibanserin were administered to 7 patients with mild to moderate renal impairment (GFR 30 to 80 mL/min), 9 patients with severe renal impairment (GFR <30 mL/min, not on dialysis), and 16 healthy subjects matched by age, weight, and gender. Flibanserin exposure (AUC0-inf) increased 1.1-fold in patients with mild to moderate renal impairment and 1.2-fold in patients with severe renal impairment, compared to the healthy control subjects.

Race/Ethnicity
A cross-study comparison between healthy Japanese women and Caucasian women with HSDD showed that flibanserin exposure was approximately 1.4-fold higher in Japanese women. When the mean flibanserin exposure in Japanese women was adjusted for weight, the AUCtau,ss in Japanese women was 2246 ng*hr/mL, which is comparable to 2080 ng*hr/mL in Caucasian women. The similarity in weight-adjusted AUCtau,ss suggests that weight, not race, is the factor contributing to the observed difference in flibanserin exposure between Japanese and Caucasian women.

Age
No formal study has been conducted to study the effect of age on flibanserin exposures.

Drug Interaction Studies

Drugs that Increase Flibanserin Exposure
The effects of other drugs on the pharmacokinetics of flibanserin are presented in Table 4 as change relative to flibanserin administered alone (test/reference).

Moderate CYP3A4/Moderate CYP2C9/Strong CYP2C19 Inhibitor (Fluconazole)
In a study of 15 healthy female subjects, a fluconazole 400 mg loading dose followed by 200 mg administered once daily for 5 days increased flibanserin 100 mg single dose exposure (AUC0-inf) 7-fold and Cmax 2.2-fold compared to flibanserin 100 mg alone. Three of 15 subjects (20%) experienced hypotension or syncope from concomitant use of fluconazole and flibanserin; therefore, the study was stopped early [see Warnings and Precautions (5.3), Adverse Reactions (6.1) and Drug Interactions (7)].

Strong CYP3A4 Inhibitor (Ketoconazole)
In a study of 24 healthy female subjects, ketoconazole 400 mg administered once daily for 5 days following a light breakfast increased flibanserin 50 mg single-dose exposure (AUC0-inf) 4.5-fold and Cmax 1.8-fold compared to flibanserin 50 mg alone [see Warnings and Precautions (5.3), Adverse Reactions (6.1) and Drug Interactions (7)].

Strong CYP3A4 Inhibitor (Itraconazole)
In a study of 12 healthy male and female subjects, itraconazole 200 mg administered once daily for 4 days following a loading dose of 400 mg increased flibanserin 50 mg single dose exposure (AUC0-inf) 2.6-fold and Cmax 1.7-fold when flibanserin was given 2 hours after itraconazole on Day 5, compared to exposures with flibanserin 50 mg alone. The 200 mg itraconazole dose does not maximally inhibit the CYP3A4 enzyme [see Drug Interactions (7)].

Moderate CYP3A4 Inhibitor (Grapefruit Juice)
In a study of 26 healthy female subjects, grapefruit juice (240 mL) increased flibanserin 100 mg single dose exposure (AUC0-inf) by 1.4-fold and Cmax 1.1-fold compared to flibanserin 100 mg alone [see Warnings and Precautions (5.3), Adverse Reactions (6.1) and Drug Interactions (7)].

Weak CYP3A4 Inhibitor (Oral Contraceptives)
In a meta-analysis of 17 oral contraceptive users and 91 non-users in Phase 1 studies, the oral contraceptive users had a 1.4-fold higher flibanserin AUC and 1.3‑fold higher Cmax compared to the non-users [see Adverse Reactions (6.1) and Drug Interactions (7)].

Strong CYP2D6 Inhibitor (Paroxetine)
Paroxetine is a strong CYP2D6 inhibitor. In a study of 19 healthy male and female subjects, flibanserin exposure decreased by approximately 4% when flibanserin 50 mg twice daily was given with paroxetine compared to flibanserin alone. Paroxetine was dosed at 20 mg once daily for 3 days followed by 40 mg once daily for 7 days.

Drugs that Decrease Flibanserin Exposure
Strong CYP3A4 Inducer (Rifampin)
In a study of 24 healthy female subjects, rifampin 600 mg given once daily for 7 days prior to administration of 100 mg flibanserin significantly decreased flibanserin exposure by 95% [see Drug Interactions (7)].

Moderate CYP3A4 Inducer (Etravirine)
Steady state etravirine, a moderate CYP3A4 inducer, decreased flibanserin exposures by approximately 21% [see Drug Interactions (7)].

Table 4 Drugs That Increase Flibanserin Exposure
* itraconazole dose was not optimal for maximal inhibition of CYP3A4 enzyme.

Coadministered Drug(s) and Dose(s)

Dose of Addyi

n

Geometric Mean Ratio (90% Confidence Interval) of Pharmacokinetic Parameters of Flibanserin with/without Coadministered Drug
No Effect =1.00

Cmax

AUC0-inf

Fluconazole 200 mg

100 mg

15

2.2 (1.8 – 2.8)

7.0 (6.0 – 8.2)

Ketoconazole 400 mg

50 mg

24

1.8 (1.7 – 2.1)

4.5 (4.0 – 5.1)

Itraconazole 200 mg*

50 mg

12

1.7 (1.4 – 2.0)

2.6 (2.1 – 3.0)

Oral Contraceptives

50 mg

39

1.3 (1.1 – 1.6)

1.4 (1.2 – 1.7)

Paroxetine 40 mg

50 mg twice daily

19

1.0 (0.9 – 1.2)

1.0 (0.9 – 1.0)

Effects of Flibanserin on Other Drugs
The effects of flibanserin on the pharmacokinetics of other drugs are presented in Table 5 as change relative to the other drug administered alone (test/reference).

Digoxin and P-glycoprotein Substrates
A single center, open-label, randomized, two-way crossover study in 24 healthy men and women evaluated the effect of flibanserin on the pharmacokinetics of digoxin. Flibanserin 100 mg was administered once daily over 5 days followed by a single dose of 0.5 mg digoxin, a P-gp substrate. Flibanserin increased digoxin AUC0-inf by 2.0-fold and Cmax by 1.5-fold, compared to digoxin alone [see Drug Interactions (7)].

Drugs Metabolized by CYP3A4 (Simvastatin)
An open-label, randomized, crossover study in 12 healthy men and women evaluated the effect of flibanserin 50 mg twice daily for 4 days on the pharmacokinetics of simvastatin 40 mg once daily. Flibanserin increased the AUC0-inf of simvastatin, a substrate of CYP3A4, 1.3‑fold and Cmax by 1.2-fold. Flibanserin co-administered with simvastatin increased simvastatin acid AUC0-inf by 1.5-fold and Cmax by 1.4-fold.

Oral Contraceptives
A study in 24 healthy women evaluated the effect of 100 mg flibanserin once daily for 2 weeks on the pharmacokinetics of a single-dose of ethinyl estradiol (EE) 30 mcg/levonorgestrel (LNG) 150 mcg. Flibanserin increased the EE AUC0-inf by 1.09-fold and the EE Cmax by 1.1-fold.  Flibanserin decreased the LNG AUC0-inf by 1.06-fold and did not change the LNG Cmax. [see Adverse Events (6.1), Drug Interactions (7)].

Drugs Metabolized by CYP2B6 (Bupropion)
An open-label, randomized, two-period crossover study in 28 healthy women evaluated the effect of flibanserin on the pharmacokinetics of bupropion.  Flibanserin 50 mg twice daily was administered for 2 days followed by 100 mg once daily for 13 days. Bupropion 150 mg twice daily was given for 8 days beginning on Day 6 of flibanserin treatment. Flibanserin did not change bupropion  AUCt,ss (1.0-fold change) and Cmax (1.0-fold change) but hydroxybupropion AUCt,ss decreased by 9% and Cmax by 11%.

Table 5 Effects of Flibanserin on Exposure of Other Drugs

Coadministered Drug(s) and Dose(s)

 Dose of Addyi

n

Geometric Mean Ratio (90% Confidence Interval) of Pharmacokinetic Parameters of Coadministered Drug with/without Flibanserin
No Effect =1.00

Cmax

AUC0-inf

Simvastatin 40 mg

50 mg twice daily

12

1.7 (1.4 – 2.0)

2.6  (2.1 – 3.1)

Digoxin 0.5 mg

100 mg

24

1.5 (1.3 – 1.6)

2.0 (1.5 – 2.5)

Ethinyl estradiol 30 mcg/
Levonorgestrel 150 mcg

100 mg

 24

1.1 (1.0 – 1.1)
1.0 (0.9 – 1.0)

1.1  (1.0 – 1.2)
1.0 (0.9  – 1.1)

Bupropion 150 mg

100 mg

28

1.0 (0.9 – 1.1)

1.0 (1.0 – 1.1)

Pharmacogenomics

Patients who are poor metabolizers of CYP2D6, CYP2C9 or CYP2C19 are deficient in CYP2D6, CYP2C9 or CYP2C19 enzyme activity, respectively.  Extensive metabolizers have normal functioning CYP enzymes.

CYP2C19 Poor Metabolizers
A study comparing flibanserin exposure in CYP2C19 poor metabolizers to CYP2C19 extensive metabolizers was conducted in lieu of a drug interaction study with Addyi and a strong CYP2C19 inhibitor.  In 9 women who were poor metabolizers of CYP2C19, Cmax and AUC0-inf of flibanserin 100 mg once daily increased 1.5-fold (1.1-2.1) and 1.3-fold (0.9-2.1), compared to exposures among 8 extensive metabolizers of CYP2C19. Flibanserin half-life was increased from 11.1 hours in the extensive metabolizers of CYP2C19 to 13.5 hours in the poor metabolizers of CYP2C19 [see Adverse Reactions (6.1) and Use in Specific Populations (8.7)].

The frequencies of poor metabolizers of CYP2C19 are approximately 2–5% among Caucasians and Africans and approximately 2–15% among Asians.

CYP2D6 Poor Metabolizers
A study comparing flibanserin exposure in CYP2D6 poor metabolizers to CYP2D6 extensive metabolizers was conducted in addition to a drug interaction study with paroxetine, a strong CYP2D6 inhibitor. In 12 poor metabolizers of CYP2D6, steady state Cmax and AUC of flibanserin 50 mg twice daily was decreased by 4% and increased by 18%, respectively, compared to exposures among 19 extensive metabolizers, intermediate metabolizers and ultra rapid metabolizers of CYP2D6.

CYP2C9 Poor Metabolizers
A study comparing flibanserin exposure in CYP2C9 poor metabolizers to CYP2C9 extensive metabolizers was conducted in lieu of a drug interaction study with Addyi and a strong CYP2C9 inhibitor. In 8 women who were poor metabolizers of CYP2C9, Cmax and AUC0-inf of flibanserin 100 mg once daily decreased 23% and 18%, compared to exposures among 8 extensive metabolizers of CYP2C9.

Patient Counseling Information

See FDA-Approved Patient Labeling (Medication Guide).

Hypotension and Syncope

Inform patients that Addyi can cause severe hypotension and syncope, particularly with alcohol or with moderate or strong CYP3A4 inhibitors. Inform patients that alcohol use and moderate or strong CYP3A4 inhibitors are contraindicated. Counsel patients about the importance of abstaining from alcohol and to ask about drug interactions before starting a new prescription or non-prescription medication or using other products that contain CYP3A4 inhibitors (e.g., grapefruit juice or St. John’s Wort). Advise patients who experience pre-syncope or lightheadedness to lie down and to call for help if symptoms persist [see Contraindications (4), Warnings and Precautions (5.1,5.3)].

Addyi is available only through a restricted program called the Addyi REMS Program. Patients can only obtain Addyi from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain Addyi.

CNS Depression
Advise patients that Addyi can cause CNS depression, such as somnolence and sedation, and that the risk is increased with other CNS depressants and with certain drug interactions (e.g., hypnotics, benzodiazepines, opioids). The risk is also increased if Addyi is taken during waking hours. Advise patients to avoid engaging in activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after the Addyi dose and until they know how Addyi affects them [see Warnings and Precautions (5.4)].

Nursing Mothers
Advise patients not to breastfeed if they are taking Addyi [see Use in Specific Populations (8.2)].

Bedtime Dosing
Advise patients to take only one tablet at bedtime and not to take Addyi at any other time of day [see Dosage and Administration (2)].

Distributed by:
Sprout Pharmaceuticals a division of
Valeant Pharmaceuticals North America LLC
Bridgewater, NJ 08807 USA

Addyi tablets are covered by U.S. Patents Nos. 7,151,103; 7,420,057; 7,183,410; and 8,227,471

®/™ are trademarks of Valeant Pharmaceuticals International, Inc. or its affiliates.
All other product/brand names are trademarks of their respective owners.

© Valeant Pharmaceuticals North America LLC
ALL RIGHTS RESERVED
9513300

Medication Guide

Addyi® (add-ee)
(flibanserin)Tablets

Read this Medication Guide before you start taking Addyi® and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor.

What is the most important information I should know about Addyi?
Your risk of SEVERE LOW BLOOD PRESSURE AND FAINTING (LOSS OF CONSCIOUSNESS) is increased if you take Addyi and:

• drink alcohol. Do not drink alcohol if you take Addyi. • take certain prescription medicines, over-the-counter medicines, or herbal supplements. Do not take or start taking any prescription medicines, over-the-counter medicines, or herbal supplements while taking Addyi until you have talked with your doctor. Your doctor will tell you if it is safe to take other medicines or herbal supplements while you are taking Addyi. • have liver problems. Do not take Addyi if you have liver problems.

If you take Addyi and you feel lightheaded or dizzy, lie down right away. Get emergency medical help or ask someone to get emergency medical help for you if the symptoms do not go away or if you faint (lose consciousness). If you faint (lose consciousness), tell your doctor as soon as you can.

Addyi is only available through the Addyi risk evaluation and mitigation strategy (REMS) Program because of the increased risk of severe low blood pressure and fainting (loss of consciousness) with alcohol use. You can only get Addyi from pharmacies that are enrolled in the Addyi REMS Program. For more information about the Program and a list of pharmacies that are enrolled in the Addyi REMS Program, go to www.AddyiREMS.com or call 1-844-PINK-PILL (1-844-746-5745).

What is Addyi?

Addyi is a prescription medicine used to treat hypoactive (low) sexual desire disorder (HSDD) in women who have not gone through menopause, who have not had problems with low sexual desire in the past, and who have low sexual desire no matter the type of sexual activity, the situation, or the sexual partner. Women with HSDD have low sexual desire that is troubling to them. Their low sexual desire is not due to:

• a medical or mental health problem • problems in the relationship • medicine or other drug use

Addyi is not for use for the treatment of HSDD in women who have gone through menopause or in men.
Addyi is not for use to improve sexual performance.
Addyi is not for use in children.

Who should not take Addyi?
Do not take Addyi if you:

• drink alcohol • take certain other medicines. Taking Addyi with certain other medicines can increase the amount of Addyi in your blood and cause severe low blood pressure, fainting (loss of consciousness), and sleepiness.
Do not take Addyi if you are taking any of the following medicines: • certain medicines used to treat HIV-1 infection, such as: • amprenavir • atazanavir (REYATAZ) • fosamprenavir (LEXIVA) • ritonavir (NORVIR) • saquinavir (INVIRASE) • nelfinavir (VIRACEPT) • indinavir (CRIXIVAN) • certain medicines that you take by mouth used to treat fungal infections, such as: • fluconazole (DIFLUCAN) • ketoconazole • itraconazole (ONMEL, SPORANOX) • posaconazole (NOXAFIL) • certain antibiotics, including: • ciprofloxacin (CIPRO, CIPRO XR) • erythromycin (ERY-TAB,ERYC,PCE) • telithromycin (KETEK) • clarithromycin (BIAXIN) • certain medicines used to treat Hepatitis C infection, such as: • boceprevir (VICTRELIS) • telaprevir • certain medicines used to treat high blood pressure, chest pain (angina), or other heart problems, such as: • diltiazem (CARDIZEM®,CARDIZEM CD, CARDIZEM LA, CARTIA XT, DILT CD, DILTZAC, TAZTIA XT, Tiazac) • verapamil (CALAN, CALAN SR, COVERA-HS, Verelan, Verelan PM) • conivaptan (Vaprisol) • nefazodone: a medicine used to treat depression
Ask your doctor or pharmacist if you are not sure if you take any of the medicines listed above.
These are examples of the medicines that you should not take if you are taking Addyi. Tell your doctor about all of the medicines you take before you start taking Addyi.
• have liver problems

What should I tell my doctor before taking Addyi?
Before you take Addyi, tell your doctor about all of your medical conditions, including if you:

• drink alcohol, use drugs or have a history of alcohol or drug abuse • have ever had depression or other mental health problems • have low blood pressure or a medical condition that can cause low blood pressure • are pregnant or plan to become pregnant. It is not known if Addyi will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if Addyi passes into your breast milk. You and your doctor should decide if you will take Addyi or breastfeed. You should not do both.

Tell your doctor about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Addyi can affect the way other medicines work, and other medicines can affect the way Addyi works, and can cause serious side effects. Know the medicines and herbal supplements you take. Keep a list of them to show your doctor or pharmacist each time you get a new medicine.

How should I take Addyi?

• Take Addyi exactly as your doctor tells you to take it. • Take 1 Addyi tablet one time a day at bedtime. • Take Addyi only at bedtime. Taking Addyi at a time other than bedtime can increase your risk of low blood pressure, fainting (loss of consciousness), accidental injury, and sleepiness. • If you miss a dose of Addyi, skip your missed dose. Take your next dose at bedtime the next day. Do not take Addyi the next morning or double your next dose. If you take too much Addyi, call your doctor. • Tell your doctor if your symptoms of HSDD have not improved after you have taken Addyi for 8 weeks.

What should I avoid while taking Addyi?

• Do not drive, operate machinery, or do things that require clear thinking until at least 6 hours after you take Addyi and until you know how Addyi affects you. • Do not drink grapefruit juice if you take Addyi. Drinking grapefruit juice during your treatment with Addyi increases your risk of severe low blood pressure and fainting (loss of consciousness). • You should not take the herbal supplements St. John’s Wort, ginkgo, or resveratrol or certain over-the-counter medicines such as cimetidine until you talk to your doctor. Taking Addyi with these herbal supplements and over-the-counter medicine may increase your risk of low blood pressure, fainting (loss of consciousness), and sleepiness.

What are the possible side effects of Addyi?
Addyi can cause serious side effects, including:

• See “What is the most important information I should know about Addyi?” • Sleepiness is a common side effect of Addyi and can be serious. Taking Addyi can increase your risk of sleepiness if taken during waking hours, if you drink alcohol, or take certain medicines or herbal supplements. • Low blood pressure and fainting (loss of consciousness) can happen when you take Addyi even if you do not drink alcohol or take other medicines or herbal supplements. Your risk of low blood pressure and fainting (loss of consciousness) is increased if Addyi is taken during waking hours, if you drink alcohol, or if you take certain medicines or herbal supplements.

The most common side effects of Addyi include:

• dizziness • nausea • tiredness • difficulty falling asleep or staying asleep • dry mouth

These are not all of the possible side effects of Addyi.
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 Addyi?

• Store Addyi at room temperature between 68°F to 77°F (20°C to 25°C).

Keep Addyi and all medicines out of the reach of children.

General information about the safe and effective use of Addyi
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Addyi for a condition for which it was not prescribed. Do not give Addyi to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about Addyi that is written for health professionals.

What are the ingredients in Addyi?
Active ingredient: flibanserin
Inactive ingredients: lactose monohydrate, microcrystalline cellulose, hypromellose, croscarmellose sodium, magnesium stearate, talc, macrogol, and the coloring agents, titanium dioxide and iron oxide.


Sprout Pharmaceuticals, a division of
Valeant Pharmaceuticals North America LLC
Bridgewater, NJ 08807 USA

© Valeant Pharmaceuticals North America LLC
ALL RIGHTS RESERVED
®/™ are trademarks of Valeant Pharmaceuticals International, Inc. or its affiliates.
All other product/brand names are trademarks of their respective owners.
For more information go to www.Addyi.com or call 1‑844-PINK-PILL (1-844-746-5745).

This Medication Guide has been approved by the U.S. Food and Drug Administration.
9513300

Issued: 6/2016

Important information

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

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