Auvelity is a brand-name prescription drug. It’s FDA-approved to treat major depressive disorder (MDD) in adults. MDD is also called depression.

For more information, refer to the “Auvelity uses” section below.

Drug details

Auvelity contains the active drugs dextromethorphan and bupropion. Dextromethorphan belongs to a drug class called N-methyl D-aspartate (NMDA) receptor antagonists. Bupropion belongs to a drug class called norepinephrine and dopamine reuptake inhibitors.

Auvelity comes as an extended-release oral tablet. This means the tablet is long acting and releases the drug slowly into your body over time.

Auvelity is available in one strength: 45 milligrams (mg) dextromethorphan/105 mg bupropion.

FDA approval

The Food and Drug Administration (FDA) approved Auvelity in 2022 to treat major depressive disorder.

Effectiveness

For information about the efficacy of Auvelity treatment, see the “Auvelity uses” section below.

Auvelity contains the active drugs dextromethorphan and bupropion. Auvelity is available only as a brand-name medication. It’s not currently available in generic form.

A generic drug is an exact copy of the active drug in a brand-name medication. Generics usually cost less than brand-name drugs.

Here are answers to some frequently asked questions about Auvelity.

Can Auvelity be prescribed to treat anxiety, ADHD, or bipolar disorder?

Auvelity is not currently approved to treat anxiety, attention deficit hyperactivity disorder (ADHD), or bipolar disorder. At this time, the drug is only approved to treat major depressive disorder.

However, doctors may prescribe Auvelity off-label to treat anxiety, ADHD, or bipolar disorder. Off-label drug use is when a drug that’s approved by the Food and Drug Administration (FDA) is prescribed for a purpose other than what it’s approved for.

Talk with your doctor to learn about treatment options for anxiety, ADHD, or bipolar disorder. They can recommend whether Auvelity may be used off-label for these specific conditions.

Is Auvelity an antidepressant?

Yes, Auvelity is an antidepressant.

Auvelity contains two active drugs, one of which is the antidepressant bupropion. Specifically, bupropion is a type of antidepressant called a norepinephrine and dopamine reuptake inhibitor. The other active drug is dextromethorphan, which belongs to a drug class called N-methyl D-aspartate (NMDA) receptor antagonists.

To learn more about how Auvelity works, see the “How Auvelity works” section below. You can also talk with your doctor or pharmacist.

Is Auvelity a controlled substance?

No, Auvelity is not a controlled substance.

The federal government regulates controlled substances. These medications often have a high risk of misuse. (Misuse involves taking a drug in a way that’s different from how a healthcare professional prescribed it.)

Due to the risk of misuse, doctors must follow special rules when prescribing controlled substances. However, Auvelity isn’t known to have these risks.

Auvelity is approved to treat major depressive disorder (MDD) (also called depression). To learn more about this, see the “Auvelity uses” section below.

Auvelity is an antidepressant. It contains the active drugs dextromethorphan and bupropion. Dextromethorphan belongs to a drug class called N-methyl D-aspartate (NMDA) receptor antagonists. Bupropion belongs to an antidepressant drug class called norepinephrine and dopamine reuptake inhibitors.

Auvelity’s mechanism of action (the way it works) for treating depression isn’t completely understood. It’s thought to affect levels of certain brain chemicals that help regulate mood. These chemicals include norepinephrine, dopamine, serotonin, and glutamate. By increasing the levels of these chemicals, Auvelity may help treat depression.

How long does it take to work?

Auvelity starts working right after your first dose. In clinical trials, many people who took Auvelity reported an improvement in their depression symptoms within 1 week of starting the drug.

Auvelity can cause mild or serious side effects. The following lists contain some key side effects that may occur while taking Auvelity. These lists do not include all possible side effects.

For more information about the possible side effects of Auvelity, talk with your doctor or pharmacist. They can give you tips on how to manage any side effects that may concern or bother you.

Note: The Food and Drug Administration (FDA) tracks side effects of drugs it has approved. If you would like to notify the FDA about a side effect you’ve had with Auvelity, you can do so through MedWatch.

Mild side effects

Below is a partial list of mild side effects of Auvelity. To learn about other mild side effects, talk with your doctor or pharmacist, or view Auvelity’s prescribing information.

Mild side effects of Auvelity can include:

Most of these side effects may go away within a few days to a couple of weeks. However, if they become more severe or don’t go away, talk with your doctor or pharmacist.

* For more information about allergic reaction and Auvelity, see “Allergic reaction” below.

Serious side effects

Serious side effects from Auvelity aren’t common, but they can occur. Call your doctor right away if you have serious side effects. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include:

  • Mental health effects. Examples include:
    • delusions (untrue thoughts or beliefs)
    • confusion
    • trouble concentrating
  • Seizures. Symptoms can include:
    • rapid blinking
    • changes in smell or taste
    • jerking, twitching, or shaking movements
    • staring into space
    • loss of consciousness
  • High blood pressure, which may not cause symptoms unless it’s severe. Symptoms of severely high blood pressure can include:
    • headache
    • chest pain
    • shortness of breath
  • Risk of suicidal thoughts and behaviors in certain people.*
  • Severe allergic reaction.†

* Auvelity has a boxed warning for this side effect. This is a serious warning from the FDA. To learn more, see the “Auvelity precautions” section below.
† For details about allergic reaction and Auvelity, see “Allergic reaction” below.

Suicide prevention

If you know someone at immediate risk of self-harm, suicide, or hurting another person:

  • Ask the tough question: “Are you considering suicide?”
  • Listen to the person without judgment.
  • Call 911 or the local emergency number, or text TALK to 741741 to communicate with a trained crisis counselor.
  • Stay with the person until professional help arrives.
  • Try to remove any weapons, medications, or other potentially harmful objects.

If you or someone you know is having thoughts of suicide, a prevention hotline can help. The 988 Suicide and Crisis Lifeline is available 24 hours a day at 988. During a crisis, people who are hard of hearing can use their preferred relay service or dial 711 then 988.

Click here for more links and local resources.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Auvelity. This side effect wasn’t reported in clinical trials of Auvelity but has occurred with other forms of dextromethorphan and bupropion. (These are the active drugs in Auvelity.)

Symptoms of a mild allergic reaction can include:

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

  • swelling under your skin, typically in your eyelids, lips, hands, or feet
  • swelling of your tongue, mouth, or throat
  • trouble breathing

Call your doctor right away if you have an allergic reaction to Auvelity, as the reaction could become severe. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency.

Other drugs are available that can treat your condition. Some may be a better fit for you than others. If you’re interested in finding an alternative to Auvelity, talk with your doctor. They can tell you about other medications that may work well for you.

Note: Some of the drugs listed here are used off-label to treat these specific conditions. Off-label drug use is when a drug that’s approved by the Food and Drug Administration (FDA) is prescribed for a purpose other than what it’s approved for.

Alternatives for major depressive disorder

Examples of other drugs that may be used to treat major depressive disorder include:

  • other antidepressants, including:
    • selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and sertraline (Zoloft)
    • serotonin-norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor XR)

The Food and Drug Administration (FDA) approves prescription drugs such as Auvelity to treat certain conditions.

Auvelity for major depressive disorder

Auvelity is FDA-approved to treat major depressive disorder (MDD) in adults.

Major depressive disorder explained

MDD is also called depression. With MDD, you have intense and long-lasting feelings of sadness that can affect your daily life.

Symptoms of MDD can include:

  • loss of appetite
  • weight changes
  • sleep problems, such as sleepiness or insomnia
  • mood changes
  • trouble concentrating

You can learn more about MDD by visiting our depression hub.

Effectiveness for major depressive disorder

Clinical trials have shown Auvelity to be effective for treating MDD. For information about how the drug performed in clinical trials, see Auvelity’s prescribing information.

Auvelity and children

Auvrlity is not FDA-approved for use in children. Clinical trials of the drug only included adults. It’s unknown whether Auvelity is safe or effective for children.

The Auvelity dosage your doctor prescribes will depend on several factors. These include:

  • how well your body breaks down Auvelity
  • other medical conditions you may have

Typically, your doctor will start you on a low dosage. Then they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Drug forms and strengths

Auvelity comes as an extended-release oral tablet. This means the tablet is long-acting and releases the drug slowly into your body over time.

Auvelity comes in one strength: 45 milligrams (mg) dextromethorphan/105 mg bupropion.

Dosage for major depressive disorder

The usual starting dosage of Auvelity for major depressive disorder (MDD) is one tablet once per day. After 3 days, your doctor may increase your dosage to one tablet twice per day. You’ll take each dose at least 8 hours apart.

Your doctor may recommend a different dosage depending on other factors, such as whether you have kidney disease. Talk with your doctor about the dosage that’s right for you.

What if I miss a dose?

If you miss a dose of Auvelity, skip your missed dose and take your next dose at the usual time. Do not take any extra doses to make up for a missed dose. Doing so can increase your risk for side effects. (For information on side effects, see the “Auvelity side effects” section above.)

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm or using a timer. You could also download a reminder app on your phone.

Will I need to use this drug long term?

Auvelity is meant to be a long-term treatment. If you and your doctor determine that Auvelity is safe and effective for you, you’ll likely take it long term.

It’s best to limit or avoid alcohol while taking Auvelity. This is because mental health changes have been reported in people who drank alcohol while taking bupropion (one of the active drugs in Auvelity). In addition, bupropion could make your body more sensitive to the effects of alcohol.

Also, drinking large amounts of alcohol can increase your risk of seizures as a side effect of Auvelity. Your risk of seizures can also increase if you’ve recently stopped drinking alcohol. For this reason, before starting Auvelity, it’s important to tell your doctor if you’ve suddenly stopped drinking alcohol.

If you have questions about limiting or avoiding alcohol while taking Auvelity, talk with your doctor.

Auvelity can interact with several other medications.

Different interactions can cause different effects. For instance, some interactions can interfere with how well a drug works. Other interactions can increase side effects or make them more severe. Drug-condition interactions can also cause certain effects. For information about these interactions, see the “Auvelity precautions” section below.

Auvelity and other medications

Below is a list of medications that can interact with Auvelity. This list does not contain all drugs that may interact with Auvelity.

Before taking Auvelity, talk with your doctor and pharmacist. Tell them about all prescription, over-the-counter, and other drugs you take. Also, tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

Doctors typically will not prescribe Auvelity with the following medications:

  • Monoamine oxidase inhibitors (MAOIs). These drugs are used to treat certain blood disorders, certain infections, and depression. Taking Auvelity with MAOIs could increase the risk of severely high blood pressure and serotonin syndrome. Examples of these medications include:
    • methylene blue (Provayblue)
    • linezolid (Zyvox)
    • phenelzine (Nardil)
    • selegiline (Emsam)
    • isocarboxazid (Marplan)

Other medications that may interact with Auvelity include the following:

  • Antidepressants. These drugs are used to treat depression and certain other mental health conditions. Taking Auvelity with antidepressants could increase the risk of side effects from either drug. Examples of these drugs include:
    • selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and paroxetine (Paxil)
    • serotonin-norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor XR) and atomoxetine (Straterra)
  • Corticosteroids. These drugs are used to treat inflammation. Taking Auvelity with corticosteroids could increase the risk of seizures with Auvelity. Examples of these drugs include:
    • prednisolone (Orapred ODT, Prelone)
  • Antipsychotics. These medications are used to treat mental health conditions. Taking Auvelity with antipsychotics could increase the risk of seizures as a side effect of either drug. Examples of these medications include:
    • aripiprazole (Abilify, Abilify Maintena, others)
  • Certain dopamine agonists. These drugs are used to treat Parkinson’s disease. Taking Auvelity with these medications could increase the risk of side effects from either drug. Examples of these medications include:
    • levodopa
  • The heart rhythm drug quinidine. Quinidine is used to treat an abnormal heart rhythm. Taking Auvelity with this drug could increase the risk of side effects from Auvelity.
  • The xanthine drug theophylline (Theo-24). Theophylline is used to treat asthma. Taking Auvelity with this medication could increase the risk of seizures as a side effect of either drug.
  • The cardiac glycoside drug digoxin (Lanoxin). Digoxin is used to treat certain heart conditions, such as abnormal heart rhythm and heart failure. Taking Auvelity with this medication could make digoxin less effective than usual.
  • The antiseizure drug carbamazepine (Epitol, Tegretol, others). Carbamazepine is used to treat seizures. Taking Auvelity with this medication could make Auvelity less effective than usual.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Auvelity and herbs and supplements

There aren’t any herbs or supplements that have been specifically reported to interact with Auvelity. However, you should still check with your doctor or pharmacist before using any of these products while taking Auvelity.

Auvelity and foods

There aren’t any foods that have been specifically reported to interact with Auvelity. If you have any questions about eating certain foods with Auvelity, talk with your doctor.

Auvelity and lab tests

Bupropion (one of the active drugs in Auvelity) may interact with certain drug tests for amphetamines. Examples of amphetamines include amphetamine/dextroamphetamine (Adderall, Adderall XR) and dextroamphetamine (Dexedrine, Xelstrym).

With this interaction, bupropion may cause a false-positive result for amphetamines in the urine. This means the urine drug test may show a positive result for amphetamines even though bupropion is not an amphetamine.

Before you have a urine drug test for amphetamines, tell the healthcare professional giving the test that you’re taking Auvelity. They can give you a different type of amphetamine drug test that is not affected by bupropion.

As with all medications, the cost of Auvelity can vary. The actual price you’ll pay depends on your insurance plan, your location, and the pharmacy you use.

Keep in mind that you may be able to get a 90-day supply of Auvelity. If approved by your insurance company, getting a 90-day supply of the drug could reduce your number of trips to the pharmacy and help lower the cost. If you’re interested in this option, check with your doctor, pharmacist, or insurance company.

Before approving coverage for Auvelity, your insurance company may require you to get prior authorization. This means that your doctor and insurance company will need to communicate about your prescription before the insurance company will cover the drug. The insurance company will review the prior authorization request and decide if the drug will be covered.

If you’re not sure if you’ll need to get prior authorization for Auvelity, contact your insurance company.

Financial and insurance assistance

If you need financial support to pay for Auvelity, or if you need help understanding your insurance coverage, help is available.

To learn more about saving money on prescriptions, check out this article.

Mail-order pharmacies

Auvelity may be available through a mail-order pharmacy. Using this service may help lower the drug’s cost and allow you to get your medication without leaving home.

If recommended by your doctor, you may be able to receive a 90-day supply of Auvelity, so there’s less concern about running out of the medication. If you’re interested in this option, check with your doctor, pharmacist, or insurance company. Some Medicare plans may help cover the cost of mail-order medications.

If you don’t have insurance, you can ask your doctor or pharmacist about online pharmacy options.

Generic version

Auvelity is not available in a generic form. A generic drug is an exact copy of the active drug in a brand-name medication. Generics tend to cost less than brand-name drugs.

You should take Auvelity according to the instructions your doctor gives you.

Auvelity comes as a tablet that you swallow.

When to take

You’ll likely take Auvelity twice per day. You should take each dose at least 8 hours apart.

If possible, try to take your doses around the same time each day. Taking the medication around the same time of day helps keep a steady level of the drug in your body. This helps Auvelity work effectively.

To help make sure that you do not miss a dose, try using a medication reminder. This can include setting an alarm or using a timer. You could also download a reminder app on your phone.

Accessible labels and containers

If your prescription label is hard to read, talk with your doctor or pharmacist. Some pharmacies offer labels that have large print, braille, or a code you scan with a smartphone to convert text to speech. If your local pharmacy doesn’t have these options, your doctor or pharmacist may be able to direct you to one that does.

If you have trouble opening medication bottles, ask your pharmacist if they can put Auvelity in an easy-open container. They also may be able to recommend tools that can make it simpler to open lids.

Taking Auvelity with food

You can take Auvelity with or without food.

Can Auvelity be crushed, split, or chewed?

Auvelity tablets should not be crushed, split, or chewed.* You should swallow the tablets whole.

If you have trouble swallowing Auvelity tablets, talk with your doctor or pharmacist.

* Auvelity comes in an extended-release tablet. This means the tablet is long-acting and releases the drug slowly into your body over time. Crushing, splitting, or chewing the tablet can affect how the drug works in your body.

Auvelity is not safe to use in pregnancy.

Animal studies have shown harm to offspring born to animals given dextromethorphan during pregnancy. (Dextromethorphan is one of the active drugs in Auvelity.) However, animal studies do not always predict what happens in humans.

If you’re pregnant or planning a pregnancy, talk with your doctor before taking Auvelity. They can recommend treatment options other than Auvelity for your condition.

The National Pregnancy Registry for Antidepressants is collecting information on the safety of Auvelity when used during pregnancy. (Pregnancy registries collect information about the effects of a medication when used during pregnancy.) To learn more, talk with your doctor or visit the registry website.

Auvelity is not safe to take during pregnancy. If you’re sexually active and you or your partner can become pregnant, talk with your doctor about your birth control needs while you’re using Auvelity.

For more information about taking Auvelity during pregnancy, see the “Auvelity and pregnancy” section above.

It’s recommended that you avoid breastfeeding while taking Auvelity.

Bupropion (one of the active drugs in Auvelity) passes into breast milk. However, it is unknown whether the bupropion may cause side effects in a breastfed child. And it’s not known whether dextromethorphan (the other active drug in Auvelity) can pass into breast milk.

If you’re breastfeeding or considering it, talk with your doctor before taking Auvelity. They can recommend other ways to feed your child.

This drug comes with several precautions. These are considered drug-condition interactions.

FDA warning: Risk of suicidal thoughts and behaviors in certain people

This drug has a boxed warning. This is the most serious warning from the Food and Drug Administration (FDA). A boxed warning alerts doctors and patients about drug effects that may be dangerous.

Medications used to treat depression may increase the risk of suicidal thoughts and behaviors in certain people. This risk affects children and adults ages 24 years or younger. Auvelity is approved to treat depression in adults. However, the drug isn’t approved for use in people younger than age 18 years.

There were no reports of suicidal thoughts and behaviors in clinical trials of Auvelity. However, there were reports of these side effects with another form of bupropion (one of the active drugs in Auvelity) after it became available on prescription. It is unknown whether Auvelity increases the risk of suicidal thoughts or behaviors.

While you’re taking Auvelity, watch for the following:

  • mood changes, such as agitation (feeling annoyed or restless)
  • panic attacks
  • feeling hopeless or sad
  • thoughts of death or harming yourself
  • isolating yourself from others
  • increased use of drugs or alcohol

Keep in mind that depression, which Auvelity is used to treat, can also increase the risk of suicidal thoughts and behaviors. Therefore, it may be hard to tell if these symptoms are related to Auvelity or the condition you’re using the drug to treat.

Tell your doctor right away if you have symptoms of suicidal thoughts or behaviors while taking Auvelity. They may adjust your treatment plan or prescribe a different medication for you.

If you have thoughts of harming yourself, call 911 or your local emergency number immediately.

Other precautions

Before taking Auvelity, talk with your doctor about your health history. Auvelity may not be right for you if you have certain medical conditions or other factors affecting your health. These include:

  • Stopping use of alcohol or treatment with certain drugs. Before taking Auvelity, tell your doctor if you’ve recently stopped consuming alcohol. Also, tell them if you’ve recently stopped taking barbiturates, epilepsy drugs, or benzodiazepines. Suddenly stopping the use of alcohol or these medications can increase your risk of seizures as a side effect of Auvelity. Your doctor can recommend whether it’s safe to take Auvelity.
  • High blood pressure. Before starting Auvelity treatment, tell your doctor if you have high blood pressure. The drug may cause high blood pressure as a side effect, which could increase your blood pressure even further. Your doctor can tell you whether it’s safe to take Auvelity if you have high blood pressure.
  • Past or current eating disorder. Before taking Auvelity, tell your doctor if you have an eating disorder or had one in the past. Examples include anorexia and bulimia. Past or current eating disorders can increase your risk for seizures as a side effect of Auvelity. Your doctor can tell you whether it’s safe to take this medication.
  • Seizure disorder. Before taking Auvelity, tell your doctor if you have a seizure disorder such as epilepsy. Auvelity may cause seizures as a side effect. And your risk for seizures may be higher if you already have a seizure disorder. Your doctor may advise you to take a medication other than Auvelity.
  • Narrow eye angles. Before taking Auvelity, tell your doctor if you have narrow eye angles. Auvelity may dilate your pupils, which could lead to closed-angle glaucoma in people with narrow eye angles. Closed-angle glaucoma is a medical emergency. It can cause vision loss and severe eye pain. Before starting Auvelity treatment, your doctor may suggest you have an eye exam to check for narrow angles.
  • Mental health conditions. Before taking Auvelity, tell your doctor if you have any mental health conditions such as bipolar disorder. The drug may cause certain mental health side effects. For example, Auvelity may cause hypomania or mania (moments of high excitement and energy, often related to bipolar disorder). Your risk for mental health side effects may be higher if you already have a mental health condition. Your doctor can recommend whether Auvelity is the right treatment option for you.
  • Liver or kidney problems. If you have liver or kidney problems, talk with your doctor before taking Auvelity. In some cases, they may adjust your dosage of Auvelity to make sure it’s safe for you to take the drug. Or, they may prescribe a drug other than Auvelity for your condition.
  • Allergic reaction. If you’ve had an allergic reaction to Auvelity or any of its ingredients, your doctor will likely not prescribe Auvelity. Ask your doctor what other medications may be better options for you.
  • Pregnancy. It’s not safe to take Auvelity while pregnant. For more information, see the “Auvelity and pregnancy” section above.
  • Breastfeeding. It’s recommended to avoid breastfeeding while taking Auvelity. For more information, see the “Auvelity and breastfeeding” section above.

Note: For more information about the potential negative effects of Auvelity, see the “Auvelity side effects” section above.

Using more than the recommended dosage of Auvelity can lead to serious side effects. Do not use more Auvelity than your doctor recommends. (For information on the recommended dosages of Auvelity, see the “Auvelity dosage” section above.)

Overdose symptoms

Symptoms of an overdose can include:

What to do in case of overdose

If you think you’ve taken too much of this drug, call your doctor. You can also call the American Association of Poison Control Centers at 800-222-1222 or use its online tool. However, if your symptoms are severe, call 911 or your local emergency number, or go to the nearest emergency room right away.

When you get Auvelity from the pharmacy, the pharmacist will add an expiration date to the label on the bottle. This date is typically 1 year from the date they dispensed the medication.

The expiration date helps guarantee that the medication is effective during this time. The current stance of the Food and Drug Administration (FDA) is to avoid using expired medications. If you have unused medication that has passed the expiration date, talk with your pharmacist about whether you can still use it.

Storage

How long a medication remains good to use can depend on many factors, including how and where you store the medication.

Auvelity tablets should be stored in their original container. You should store the tablets at a temperature between 20°C to 25°C (68°F to 77°F). You can store the drug at a temperature of 15°C to 30°C (59°F to 86°F) for short periods, such as when traveling. Avoid storing this medication in areas where it could get damp or wet, such as bathrooms.

Disposal

If you no longer need to take Auvelity and have leftover medication, it’s important to dispose of it safely. This helps prevent others, including children and pets, from taking the drug by accident. It also helps keep the drug from harming the environment.

This article provides several useful tips on medication disposal. You can also ask your pharmacist for information about how to dispose of your medication.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.