Addyi

Name: Addyi

Addyi Dosage

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.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Skip the missed dose and take the medicine the following day at bedtime. Do not take flibanserin in the morning, and do not take extra medicine to make up the missed dose.

What else should I know about flibanserin?

What preparations of flibanserin are available?

Tablets: 100 mg

How should I keep flibanserin stored?

Flibanserin should be stored at room temperature between 15 C and 30 C (59 F and 86 F).

Interactions for Addyi

Metabolized principally by CYP3A4 and, to a lesser extent, by CYP2C19.1 CYP 1A2, 2B6, 2C8, 2C9, and 2D6 contribute minimally (<10%) to metabolism.1 10

Inhibits P-glycoprotein (P-gp).1 5 10

Drugs Affecting Hepatic Microsomal Enzymes

Moderate or potent CYP3A4 inhibitors: Substantially increased flibanserin exposure possible; may lead to hypotension and syncope.1 Concomitant use contraindicated.1 18 (See General under Dosage and Administration and also see Hypotension and Syncope with CYP3A4 Inhibitors under Cautions.)

Weak CYP3A4 inhibitors: Possible increased flibanserin exposure with concurrent use of multiple weak CYP3A4 inhibitors; advise patients of increased risk of adverse effects (e.g., hypotension, syncope, CNS depression).1 (See Hypotension and Syncope with CYP3A4 Inhibitors under Cautions.)

CYP3A4 inducers: Substantially decreased flibanserin exposure possible.1 Concomitant use not recommended.1

Potent CYP2C19 inhibitors: Potential increased flibanserin exposure; advise patients of increased risk of adverse effects (e.g., hypotension, syncope, CNS depression).1 18

Substrates of P-glycoprotein Transport

Potential increased exposure to P-gp substrates resulting in possible toxicity; more frequent monitoring of concentrations of P-gp substrates with a narrow therapeutic index recommended.1

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Alcohol

Increased risk of severe hypotension, syncope, and CNS depression1 10 (see Hypotension and Syncope with Alcohol under Cautions)

Pharmacokinetics of flibanserin not substantially altered1 10

Concomitant use contraindicated1

Before prescribing flibanserin, clinician must assess likelihood of patient abstaining from alcohol, taking into account the patient's social and medical history, including current and past drinking behavior1

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased flibanserin exposure1

Concomitant use not recommended1

Antidepressants, SSRIs

Possible increased flibanserin exposure with SSRIs that are potent CYP2C19 inhibitors (e.g., fluvoxamine); may lead to hypotension, syncope, and CNS depression1 18 20

Fluoxetine (weak CYP3A4 inhibitor): Possible increased flibanserin exposure with multiple weak CYP3A4 inhibitors1

Paroxetine: No clinically important effects on flibanserin pharmacokinetics1

Fluoxetine and fluvoxamine: Advise patients of the increased risk for adverse effects1

Antifungals, azole (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)

Possible increased flibanserin exposure with moderate or potent CYP3A4 inhibitors (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole) and/or potent CYP2C19 inhibitors (fluconazole); may lead to hypotension, syncope, and CNS depression1 18 20

Fluconazole: Increased peak concentrations and AUC of flibanserin 2.2- and 7-fold, respectively; hypotension and syncope reported1 10

Itraconazole: Increased peak concentrations and AUC of flibanserin 1.7- and 2.6-fold, respectively1

Ketoconazole: Increased peak concentrations and AUC of flibanserin 1.8- and 4.5-fold, respectively1

Concomitant use contraindicated1

If treatment with an azole antifungal is necessary, discontinue flibanserin ≥2 days prior to initiation of the azole antifungal1

If benefit of initiating azole antifungal therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of the azole antifungal and reinitiation of flibanserin1

Antimycobacterials (rifabutin, rifampin, rifapentine)

Possible decreased flibanserin exposure1

Rifampin: Decreased flibanserin exposure by about 95%1 10

Concomitant use not recommended1

Bupropion

No clinically important effects on bupropion pharmacokinetics1

Ciprofloxacin

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with ciprofloxacin is necessary, discontinue flibanserin ≥2 days prior to initiation of ciprofloxacin1

If benefit of initiating ciprofloxacin therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of ciprofloxacin and reinitiation of flibanserin1

CNS depressants (e.g., benzodiazepines, diphenhydramine, sedatives and hypnotics, opiates)

Possible additive CNS depression1

Advise patients of increased risk for adverse CNS effects1

Conivaptan

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with conivaptan is necessary, discontinue flibanserin ≥2 days prior to initiation of conivaptan1

If benefit of initiating conivaptan therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of conivaptan and reinitiation of flibanserin1

Contraceptives, hormonal

Possible increased flibanserin exposure and increased risk of adverse effects (e.g., nausea, dizziness, somnolence, fatigue)1 5 10

Pharmacokinetics of oral contraceptive components (ethinyl estradiol and levonorgestrel; weak CYP3A4 inhibitor) not substantially affected1

Advise patients of the increased risk of adverse effects, particularly when used with other weak CYP3A4 inhibitors1

Digoxin

Increased AUC and peak concentrations of digoxin (a P-gp substrate) by 2- and 1.5-fold, respectively; digoxin toxicity possible1

More frequent monitoring of digoxin concentrations recommended1

Diltiazem

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with diltiazem is necessary, discontinue flibanserin ≥2 days prior to initiation of diltiazem1

If benefit of initiating diltiazem therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of diltiazem and reinitiation of flibanserin1

Etravirine

Etravirine (moderate CYP3A4 inducer) decreased flibanserin exposure by about 21%1 10

Concomitant use not recommended1

Gingko

Possible increased flibanserin exposure with multiple weak CYP3A4 inhibitors1

Advise patients of the increased risk for adverse effects1

Grapefruit

Grapefruit juice (moderate CYP3A4 inhibitor) increased flibanserin AUC and peak concentrations by 1.4- and 1.1-fold, respectively; concomitant use may lead to hypotension and syncope1

Concomitant use contraindicated; advise patients to avoid grapefruit during flibanserin therapy1

Histamine H2-receptor antagonists (cimetidine, ranitidine)

Possible increased flibanserin exposure with multiple weak CYP3A4 inhibitors1

Advise patients of the increased risk for adverse effects1

HIV protease inhibitors (PIs) (atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir)

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with the HIV PI is necessary, discontinue flibanserin ≥2 days prior to initiation of the HIV PI1

If benefit of initiating HIV PI therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of the HIV PI and reinitiation of flibanserin1

Macrolides (clarithromycin, erythromycin, telithromycin)

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with the macrolide is necessary, discontinue flibanserin ≥2 days prior to initiation of the macrolide antibiotic1

If benefit of initiating macrolide therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of the macrolide and reinitiation of flibanserin1

Nefazodone

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with nefazodone is necessary, discontinue flibanserin ≥2 days prior to initiation of nefazodone1

If benefit of initiating nefazodone therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of nefazodone and reinitiation of flibanserin1

Proton-pump inhibitors (PPIs)

Possible increased flibanserin exposure with PPIs that are potent CYP2C19 inhibitors1

Advise patients of the increased risk for adverse effects1

Resveratrol

Possible increased flibanserin exposure with multiple weak CYP3A4 inhibitors1

Advise patients of the increased risk for adverse effects1

Simvastatin

AUC and peak concentrations of simvastatin (CYP3A4 substrate) increased by 1.3- and 1.2-fold, respectively, and AUC and peak concentrations of simvastatin acid increased by 1.5- and 1.4-fold, respectively1 10

Sirolimus

Possible increased sirolimus (P-gp substrate) exposure and risk of toxicity1

St. John's wort (Hypericum perforatum)

Possible decreased flibanserin exposure1

Concomitant use not recommended1

Verapamil

Possible increased flibanserin exposure; may lead to hypotension and syncope1

Concomitant use contraindicated1

If treatment with verapamil is necessary, discontinue flibanserin ≥2 days prior to initiation of verapamil1

If benefit of initiating verapamil therapy within 2 days of flibanserin discontinuance clearly outweighs risk of hypotension and syncope, monitor for hypotension and syncope1

Allow ≥2 weeks to elapse between discontinuance of verapamil and reinitiation of flibanserin1

What are some things I need to know or do while I take Addyi?

  • Tell all of your health care providers that you take Addyi (flibanserin). This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert for at least 6 hours after taking this medicine. Avoid these tasks or actions until you feel fully awake.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Avoid grapefruit and grapefruit juice.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Only take Addyi at bedtime. Taking this medicine at any other time of day may raise the chance of low blood pressure, passing out, accidental injury, and feeling sleepy. Talk with your doctor.
  • This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Addyi with your other drugs.
  • This medicine is not approved for use in children. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • 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.

This information should not be used to decide whether or not to take Addyi or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Addyi. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Indications and Usage for Addyi

Addyi® (flibanserin) tablets are indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

• A co-existing medical or psychiatric condition, • Problems within the relationship, or • The effects of a medication or other drug substance.

Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner.

Limitations of Use

• Addyi is not indicated for the treatment of HSDD in postmenopausal women or in men. • Addyi is not indicated to enhance sexual performance.

Use in specific populations

Pregnancy

Risk Summary
There are no studies of Addyi in pregnant women to inform whether there is a drug-associated risk in humans. In animals, fetal toxicity only occurred in the presence of significant maternal toxicity including reductions in weight gain and sedation. Adverse reproductive and developmental effects consisted of decreased fetal weight, structural anomalies and increases in fetal loss at exposures greater than 15 times exposures achieved with the recommended human dosage [see Data]. Animal studies cannot rule out the potential for fetal harm.

In the general population (not taking Addyi), the estimated background risk of major birth defects is 2% to 4% of live births, and the estimated background risk of miscarriage of clinically recognized pregnancies is 15% to 20%.

Data
Animal Data
Pregnant rats were administered flibanserin at doses of 0, 20, 80 and 400 mg/kg/day (3, 15 and 41 times clinical exposures at the recommended human dose based on AUC) during organogenesis. The highest dose was associated with significant maternal toxicity as evidenced by severe clinical signs and marked reductions in weight gain during dosing. In the litters of high-dose dams, there were decreased fetal weights, decreased ossification of the forelimbs and increased number of lumbar ribs, and two fetuses with anophthalmia secondary to severe maternal toxicity. The no adverse effect level for embryofetal toxicity was 80 mg/kg/day (15 times clinical exposure based on AUC).

Pregnant rabbits were administered flibanserin at doses of 0, 20, 40 and 80 mg/kg/day (4, 8 and 16 times the clinical exposure at the recommended human dose) during organogenesis. Marked decreases in maternal body weight gain (>75%), abortion and complete litter resorption were observed at 40 and 80 mg/kg/day indicating significant maternal toxicity at these doses. Increases in resorptions and decreased fetal weights were observed at ≥ 40 mg/kg/day. No treatment-related teratogenic effects were observed in fetuses at any dose level. The no adverse effect level for maternal and embryofetal effects was 20 mg/kg/day (3-4 times clinical exposure based on AUC).

Pregnant rats were administered flibanserin at doses of 0, 20, 80 and 200 mg/kg/day (3, 15 and ~ 20 times clinical exposures at the recommended human dose) from day 6 of pregnancy until day 21 of lactation to assess for effects on peri- and postnatal development. The highest dose was associated with clinical signs of toxicity in pregnant and lactating rats. All doses resulted in sedation and decreases in body weight gain during pregnancy. Flibanserin prolonged gestation in some dams in all dose groups and decreased implantations, number of fetuses and fetal weights at 200 mg/kg/day. Dosing dams with 200 mg/kg also decreased pup weight gain and viability during the lactation period and delayed opening of the vagina and auditory canals. Flibanserin had no effects on learning, reflexes, fertility or reproductive capacity of the F1 generation. The no adverse effect level for maternal toxicity and peri/postnatal effects was 20 mg/kg/day [see Nonclinical Toxicology (13.1)].

Lactation

Risk Summary
Flibanserin is excreted in rat milk. It is unknown whether flibanserin is present in human milk, whether Addyi has effects on the breastfed infant, or whether Addyi affects milk production. Because of the potential for serious adverse reactions including sedation in a breastfed infant, breastfeeding is not recommended during treatment with Addyi.

Pediatric Use

Addyi is not indicated for use in pediatric patients.

Geriatric Use

Addyi is not indicated for use in geriatric patients. Safety and effectiveness have not been established in geriatric patients.

Hepatic Impairment

Addyi is contraindicated for use in patients with any degree of hepatic impairment. Flibanserin exposure increased 4.5-fold in patients with hepatic impairment, compared to those with normal hepatic function, increasing the risk of hypotension, syncope, and CNS depression [see Boxed Warning, Contraindications (4),Warnings and Precautions  (5.6), and Clinical Pharmacology (12.3)].

CYP2C19 Poor Metabolizers

CYP2C19 poor metabolizers had increased flibanserin exposures compared to CYP2C19 extensive metabolizers.  Additionally, syncope occurred in a subject who was a CYP2C19 poor metabolizer [see Adverse Reactions (6.1) and Clinical Pharmacology (12.5)].  Therefore, increase monitoring for adverse reactions (e.g., hypotension) in patients who are CYP2C19 poor metabolizers.  The frequencies of poor CYP2C19 metabolizers are approximately 2–5% among Caucasians and Africans and approximately 2–15% among Asians.

How Supplied/Storage and Handling

Addyi is available as a 100 mg oval, pink, film-coated tablet debossed on one side with “f100” and blank on the other side.  Available in bottles of 30 tablets.  (NDC 58604-214-30)

Storage
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP controlled room temperature].

Before taking this medicine

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

You should not use Addyi if you are allergic to flibanserin, 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 Addyi. 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 Addyi is safe for you, tell your doctor if you have:

  • history of alcoholism or drug addiction.

It is not known whether flibanserin 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.

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

What happens if I miss a dose?

Skip the missed dose and take the medicine the following day at bedtime. Do not take Addyi in the morning, and do not take extra medicine to make up the missed dose.

Addyi side effects

Get emergency medical help if you have signs of an allergic reaction to Addyi: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe drowsiness; or

  • a light-headed feeling, like you might pass out.

Common Addyi side effects may include:

  • dizziness, drowsiness;

  • tiredness;

  • nausea;

  • dry mouth; or

  • sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

(web3)