Addyi

Addyi (flibanserin) tablets are a prescription medication used to treat women with hypoactive sexual desire disorder (HSDD), a condition of low sexual desire that causes significant distress or interpersonal difficulty. It is approved for use in both premenopausal and postmenopausal women under the age of 65 years who have not had low sexual desire in the past.

Addyi is taken as one tablet once daily at bedtime and is designed to work over time with regular use, rather than on an as-needed basis.

This medicine is not indicated to enhance sexual performance.

Hypoactive sexual desire disorder is when a person has low sexual desire, no matter the type of sexual activity, the situation, or the sexual partner, and this issue is troubling the person. HSDD is also known as low libido, low sex drive, low sexual desire disorder, and is clinically referred to as female sexual interest/arousal disorder (FSIAD).

Clinical trials studied addyi's ability to increase the frequency of satisfying sexual events, increase the intensity of sexual desire, and decrease the associated distress women feel from its loss.

Addyi is FDA-approved for use in women who are:

• premenopausal or postmenopausal, and
• under 65 years of age, and
• diagnosed with acquired, generalized hypoactive sexual desire disorder (HSDD), characterized by low sexual desire that causes marked distress or interpersonal difficulty.

Addyi should not be used when hypoactive sexual desire disorder is caused by:

• A co-existing medical or psychiatric condition,
• Relationship problems, or
• The effects of a medication or other drug substance.

Addyi was granted FDA approval after positive results from clinical trials called BEGONIA, DAISY, and VIOLET.

Addyi is thought to work in the brain to rebalance neurotransmitters involved in sexual desire and response, although its mechanism of action for treating HSDD is not fully understood.

Addyi is a centrally acting serotonin modulator. It acts as a 5-HT1A receptor agonist and 5-HT2A receptor antagonist, which reduces serotonin activity while increasing dopamine and norepinephrine levels in key brain areas, including the prefrontal cortex which is associated with sexual motivation and reward.

Take 1 addyi tablet one time a day 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.

Take addyi exactly as your doctor tells you to take it.

If you drink alcohol, see the "Warnings and Precautions” section.

Tell your doctor if your symptoms of HSDD have not improved after you have taken this medicine for 8 weeks. Your doctor or healthcare provider may discontinue this medicine after 8 weeks if there is no improvement in your symptoms.

The recommended addyi dose is 100 mg administered orally once per day at bedtime.

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 of this medicine, call your doctor.

If initiating addyi following moderate or strong CYP3A4 inhibitor use, start addyi 2 weeks after the last dose of the CYP3A4 inhibitor.

If initiating a moderate or strong CYP3A4 inhibitor following addyi use, start the moderate or strong CYP3A4 inhibitor 2 days after the last dose of addyi.

Interactions

Other drugs may interact with addyi, including prescription and over-the-counter medicines, vitamins, and herbal products. 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.

Oral Contraceptives and Other Weak CYP3A4 Inhibitors: Increases flibanserin exposures and incidence of adverse reactions (6.1, 7)

Strong CYP2C19 Inhibitors: Increases flibanserin exposure, which may increase the risk of hypotension, syncope, and CNS depression (7)

CYP3A4 Inducers: Use of ADDYI not recommended; flibanserin concentrations substantially reduced (7)

Digoxin: Increases digoxin concentrations, which may lead to digoxin toxicity. Increase monitoring of digoxin concentrations.

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

Not all possible drug interactions are listed here.

Boxed warnings

A boxed warning is the most serious warning from the FDA.

Addyi and alcohol. There is a boxed warning for addyi being used with alcohol due to causing severe low blood pressure (hypotension) and fainting (syncope). To lower your risk of low blood pressure and fainting (loss of consciousness) with alcohol, do not drink alcohol close to the time you take your addyi dose.

• Wait at least 2 hours after drinking 1 or 2 standard alcoholic drinks before taking addyi at bedtime.
• Do not take your addyi dose if you have had 3 or more standard alcoholic drinks that evening.

Addyi, drug interactions, and liver impairments. There is also a boxed warning for using addyi with moderate or strong CYP3A4 inhibitors or in patients with hepatic impairment due to causing severe hypotension and syncope. Therefore addyi is contraindicated in these settings.

Other warnings and precautions

Low blood pressure and fainting with addyi alone. Patients with felling dizzy or lightheaded (pre-syncope) should immediately lie down and promptly seek medical help if symptoms do not resolve.

Hypersensitivity Reactions, including anaphylaxis, swelling, itching, or hives: Avoid taking this medicine if you have a know hypersensitivity to the active ingredient flibanserin, or any of the inactive ingredients.

Sleepiness and sedation - central Nervous System (CNS) Depression: This can occur with addyi alone, and also exacerbated by other CNS depressants, and in settings where flibanserin concentrations are increased. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least six hours after each dose and until they know how addyi affects them.

CYP2C19 Poor Metabolizers: Increases flibanserin exposure, which may increase the risk of hypotension, syncope, and CNS depression

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

Pregnancy

Tell your doctor or healthcare professional if you are pregnant or plan to become pregnant. It is not known if addyi will harm your unborn baby.

Breastfeeding

Tell your doctor or healthcare professional if are breastfeeding or plan to breastfeed. It is not known if this medicine passes into your breast milk. You and your doctor should decide if you will take addyi or breastfeed. You should not do both.

Common addyi side effects may include:

• dizziness, drowsiness;
• tiredness;
• nausea;
• dry mouth; or
• trouble sleeping.

Serious 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.

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 the FDA at 1-800-FDA-1088.

• Do not drink alcohol close to the time you take your addyi dose because this increases your risk of severe low blood pressure and fainting (loss of consciousness). If you have consumed one or two standard alcoholic drinks, you should wait at least two hours before taking Addyi at bedtime, or you should skip taking your dose.
• Do not drive, operate machinery, or do things that require clear thinking until at least 6 hours after you take this medicine and until you know how this medicine affects you.
• Do not drink grapefruit juice if you take this medicine. 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 addyi if you:

• Take medicines that are moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors. If you are unsure, check with your doctor or pharmacist.
• Have liver impairment (hepatic impairment).
• With alcohol.

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

Active ingredient: flibanserinInactive ingredients: lactose monohydrate, microcrystalline cellulose, hypromellose, croscarmellose sodium, magnesium stearate, talc, macrogol, and the coloring agents, titanium dioxide and iron oxide.

Sprout Pharmaceuticals, Inc. Raleigh, NC 27609 USA