Daliresp

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking roflumilast,

• tell your doctor and pharmacist if you are allergic to roflumilast, any other medications, or any of the ingredients in roflumilast tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Tegretol), cimetidine (Tagamet), enoxacin (not available in the U.S.), erythromycin (E.E.S., E-Mycin, Erythrocin), fluvoxamine, ketoconazole (Nizoral), phenobarbital, phenytoin (Dilantin), rifampicin and certain oral contraceptives ('birth control pills'). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have liver disease. Your doctor may tell you not to take roflumilast.
• tell your doctor if you have or have ever had a history of mental health conditions, including depression; thoughts about harming or killing yourself, or planning or trying to do so; extreme worry; or other unusual changes in your behavior or mood. Talk to your doctor about the risks of taking roflumilast.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking Roflumilast, call your doctor.
• you should know that your mental health may change in unexpected ways during treatment with roflumilast. You, your family, or your caregiver should call your doctor right away if you experience any of the following new symptoms or a worsening of these symptoms: difficulty falling asleep or staying asleep; depression; thinking about harming or killing yourself, or planning or trying to do so; extreme worry; agitation; or changes in mood. Be sure that your family or caregiver know these symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.
• you should know that roflumilast can cause weight loss. Your weight should be checked regularly by your doctor and you should also check your weight on a regular basis during treatment with roflumilast. If you notice you are losing weight, call your doctor.

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

Roflumilast is usually taken once per day, with or without food. Follow your doctor's instructions.

Weight loss is a common side effect of roflumilast. While using roflumilast, weigh yourself regularly and tell your doctor if you have any unplanned or unexplained weight loss.

Store at room temperature away from moisture and heat.

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

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Included as part of the "PRECAUTIONS" Section

Human Experience

No case of overdose has been reported in clinical studies with DALIRESP. During the Phase I studies of DALIRESP, the following symptoms were observed at an increased rate after a single oral dose of 2500 mcg and a single dose of 5000 mcg: headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess, and arterial hypotension.

Management Of Overdose

In case of overdose, patients should seek immediate medical help. Appropriate supportive medical care should be provided. Since roflumilast is highly protein bound, hemodialysis is not likely to be an efficient method of drug removal. It is not known whether roflumilast is dialyzable by peritoneal dialysis.

Daliresp is part of the drug class:

• OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES

Serious side effects have been reported with Daliresp. See the "Daliresp Precautions" section.

The most common side effects include:

• diarrhea
• weight loss
• nausea
• headache
• back pain
• flu-like symptoms
• problems sleeping (insomnia)
• dizziness
• decreased appetite

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Daliresp.

Daliresp can cause serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while taking Daliresp.

1. Mental health problems including suicidal thoughts and behavior. Some people taking Daliresp may develop mood or behavior problems including:
   • thoughts of suicide or dying
   • attempt to commit suicide
   • trouble sleeping (insomnia)
   • new or worse anxiety
   • new or worse depression
   • acting on dangerous impulses
   • other unusual changes in your behavior or mood
2. Weight loss. Daliresp can cause weight loss. You should check your weight on a regular basis. You will also need to see your healthcare provider regularly to have your weight checked. If you notice that you are losing weight, call your healthcare provider. Your healthcare provider may ask you to stop taking Daliresp if you lose too much weight.

Do not take Daliresp if you have liver problems. Talk with your healthcare provider before you take Daliresp if you have liver problems.

• Store Daliresp at 68°F to 77°F (20°C to 25°C); excursions permitted to 15° - 30°C (59° - 86°F). 
• Keep Daliresp and all medicines out of the reach of children.

You should not use roflumilast if you are allergic to it, or if you have moderate or severe liver disease.

There are many other drugs that can make roflumilast less effective and should not be used at the same time. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Before you take roflumilast, tell your doctor if you have liver disease or a history of depression, mental illness, or suicidal thoughts or actions.

You may have unusual thoughts or behavior, or thoughts about suicide, while taking this medicine. Tell your doctor if you have new or worsening depression, or suicidal thoughts. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, depression, trouble sleeping, or if you feel impulsive, or you have thoughts about suicide or hurting yourself.

Call your doctor at once if you have rapid and unintended weight loss.

• Advair Diskus
• Advair HFA
• Atrovent HFA
• Azmacort
• Bevespi Aerosphere
• Combivent
• Incruse Ellipta
• Prolastin
• Qvar

• Spiriva Respimat
• Stiolto Respimat
• Utibron Neohaler
• Ventolin HFA
• Ventolin Solution
• Ventolin Syrup
• Xolegel
• Zyban

Read the Daliresp User Reviews »

© Daliresp Patient Information is supplied by Cerner Multum, Inc. and Daliresp Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Metabolized by CYP3A4 and CYP1A2 to roflumilast N-oxide;1 6 roflumilast N-oxide metabolized mainly by CYP3A4, to a lesser extent by CYP2C19 and extrahepatic CYP1A, and glucuronidated.6

Roflumilast and roflumilast N-oxide do not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.1

Roflumilast does not induce CYP isoenzymes 1A2, 2A6, 2C9, 2C19, or 3A4/5 and is a weak inducer of CYP2B6.1

Roflumilast and roflumilast N-oxide do not inhibit the P-glycoprotein transport system.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inducers: Decrease systemic exposure and may reduce the therapeutic efficacy of roflumilast.1 Concomitant use not recommended.1

CYP3A4 inhibitors or inhibitors of both CYP3A4 and CYP1A2: May result in increased systemic exposure to roflumilast and increased adverse effects.1 Carefully weigh risk of concurrent use against benefit.1

Specific Drugs

Absorption

Bioavailability

Roflumilast: Absolute bioavailability is approximately 80%.1 Peak plasma concentrations attained in approximately 1 hour (range: 0.5–2 hours).1 Steady-state plasma concentrations attained after approximately 4 days.1

Roflumilast N-oxide: Peak concentrations attained in approximately 8 hours (range: 4–13 hours).1 Steady-state plasma concentrations attained after approximately 6 days.1

Food

Roflumilast: No effect on total drug absorption.1 Time to peak plasma concentrations delayed by 1 hour and peak plasma concentrations reduced by approximately 40%.1

Roflumilast N-oxide: Peak plasma concentrations and time to peak plasma concentrations unaffected.1

Special Populations

Mild hepatic impairment (Child-Pugh class A): Following roflumilast 250 mcg once daily for 14 days, AUCs of roflumilast and roflumilast N-oxide were 51 and 24% higher, respectively, and peak plasma concentrations were 3 and 26% higher, respectively, compared with values for healthy individuals matched for age, weight, and gender.1 (See Hepatic Impairment under Dosage and Administration.)

Moderate hepatic impairment (Child-Pugh class B): Following roflumilast 250 mcg once daily for 14 days, AUCs of roflumilast and roflumilast N-oxide were 92 and 41% higher, respectively, and peak plasma concentrations were 26 and 40% higher, respectively, compared with values for healthy individuals matched for age, weight, and gender.1 (See Hepatic Impairment under Dosage and Administration.)

Severe renal impairment: Following single 500-mcg dose of roflumilast, AUCs of roflumilast and roflumilast N-oxide were reduced by 21 and 7%, respectively, and peak plasma concentrations were reduced by 16 and 12%, respectively.1

Geriatric patients: AUCs of roflumilast and roflumilast N-oxide were 27 and 19% higher, respectively, and peak plasma concentrations were 16 and 13% higher, respectively, in geriatric individuals (>65 years of age) compared with younger adults (18–45 years of age).1 (See Geriatric Use under Cautions.)

Gender: AUCs of roflumilast and roflumilast N-oxide were 39 and 33% higher, respectively, in healthy women compared with healthy men.1 (See Special Populations under Dosage and Administration.)

Race: In African-American, Hispanic, and Japanese individuals, AUCs were 16, 41, and 15% higher, respectively, for roflumilast and 43, 27, and 16% higher, respectively, for roflumilast N-oxide compared with white individuals.1 In African-American, Hispanic, and Japanese individuals, peak plasma concentrations were 8, 21, and 5% higher, respectively, for roflumilast and 43, 27, and 17% higher, respectively, for roflumilast N-oxide compared with white individuals.1 (See Special Populations under Dosage and Administration.)

Smoking: Pharmacokinetics of roflumilast and roflumilast N-oxide were similar in smokers and nonsmokers.1

Distribution

Extent

Low penetration across blood-brain barrier.1

Roflumilast and/or its metabolites distributed into milk in rats.1 Distribution likely into human milk.1

Plasma Protein Binding

Roflumilast: Approximately 99%.1

Roflumilast N-oxide: Approximately 97%.1

Elimination

Metabolism

Extensively metabolized via CYP and conjugation reactions; metabolized mainly by CYP3A4 and 1A2 to roflumilast N-oxide.1 6 Roflumilast N-oxide metabolized mainly by CYP3A4, to a lesser extent by CYP2C19 and extrahepatic CYP1A, and glucuronidated.6

Roflumilast and roflumilast N-oxide together account for most (87.5%) of the administered dose present in plasma.1

N-oxide metabolite is the only major metabolite detected in human plasma.1 6 While potency of roflumilast is 3 times that of roflumilast N-oxide with respect to PDE4 inhibition, AUC of roflumilast N-oxide is about 10 times that of roflumilast.1 6 N-oxide metabolite appears to account for about 90% of the biologic action of roflumilast.6

Elimination Route

Roflumilast not detected in urine; trace amount (<1%) of roflumilast N-oxide detected in urine.1 Other conjugated metabolites detected in urine.1 About 70% of radioactivity recovered in urine following IV or oral administration of radiolabeled roflumilast.1

Half-life

Roflumilast: Approximately 17 hours.1

Roflumilast N-oxide: Approximately 30 hours.1

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

This medicine is used to prevent acute flare-ups of COPD. It is not used to stop a flare-up that has already started. You should use an inhaled medicine for the acute flare-ups that will work quickly to help you breathe better. If you do not have an inhaled medicine for acute COPD flare-ups, or if you have any questions about this, check with your doctor.

This medicine may cause some people to be agitated or display other abnormal behaviors, such as feeling sad or hopeless, getting upset easily, having trouble sleeping, or feeling nervous or hostile. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these side effects, tell your doctor right away.

This medicine may cause you to lose weight. Your doctor may need to check your weight on a regular basis while you are using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Unexplained weight loss

• Chills
• cough
• diarrhea
• discouragement
• fear or nervousness
• feeling sad or empty
• fever
• general feeling of discomfort or illness
• headache
• irritability
• joint pain
• loss of appetite
• loss of interest or pleasure
• muscle aches and pains
• nausea
• runny nose
• shivering
• sleeplessness
• sore throat
• sweating
• thoughts of killing oneself or changes in behavior
• tiredness
• trouble concentrating
• trouble sleeping
• unable to sleep
• unusual tiredness or weakness
• vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• back pain
• bladder pain
• bloody or cloudy urine
• burning feeling in the chest or stomach
• decreased appetite
• difficult, burning, or painful urination
• dizziness
• frequent urge to urinate
• indigestion
• lower back or side pain
• muscle spasm
• pain or tenderness around the eyes and cheekbones
• shakiness in the legs, arms, hands, or feet
• shortness of breath or troubled breathing
• sneezing
• stomach upset
• stuffy or runny nose
• sweating
• tenderness in the stomach area
• tightness of the chest or wheezing
• trembling or shaking of the hands or feet

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take Daliresp. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may cause weight loss. You will need to have your weight checked while taking this medicine. Talk with your 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 Daliresp while you are pregnant.

Daliresp® is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

Limitations of Use

Daliresp is not a bronchodilator and is not indicated for the relief of acute bronchospasm.

Human Experience

No case of overdose has been reported in clinical studies with Daliresp. During the Phase I studies of Daliresp, the following symptoms were observed at an increased rate after a single oral dose of 2500 mcg and a single dose of 5000 mcg: headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess, and arterial hypotension.

Management of Overdose

In case of overdose, patients should seek immediate medical help. Appropriate supportive medical care should be provided. Since roflumilast is highly protein bound, hemodialysis is not likely to be an efficient method of drug removal. It is not known whether roflumilast is dialyzable by peritoneal dialysis.