by immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.melphalanMonitor Closely (1)roflumilast will increase the level or effect of melphalan by immunosuppressive effects; risk of infection. Use Caution/Monitor. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects.mitotaneMonitor Closely (1)mitotane decreases levels of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.modafinilMonitor Closely (1)modafinil will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Concomitant therapy may reduce therapeutic effectiveness.nafcillinContraindicated (1)nafcillin will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessnevirapineContraindicated (1)nevirapine will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessomeprazoleMonitor Closely (1)omeprazole will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Concomitant therapy may reduce therapeutic effectiveness.oxaliplatinMonitor Closely (1)roflumilast and oxaliplatin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Use of oxaliplatin with concomitant immunosuppressants or with impaired immune systems may increased risk for serious infections.oxcarbazepineContraindicated (1)oxcarbazepine will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenesspentobarbitalContraindicated (1)pentobarbital will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessphenobarbitalContraindicated (2)phenobarbital will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness phenobarbital will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessphenytoinContraindicated (1)phenytoin will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessprimidoneContraindicated (2)primidone will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness primidone will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessprocarbazineMonitor Closely (1)roflumilast will increase the level or effect of procarbazine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifabutinContraindicated (1)rifabutin will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessrifampinContraindicated (2)rifampin will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness rifampin will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessrifapentineContraindicated (1)rifapentine will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessriociguatMonitor Closely (1)riociguat, roflumilast. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Riociguat is contraindicated with specific PDE-5 inhibitors (eg sildenafil, tadalafil, vardenafil) and nonspecific PDE-5 inhibitors (eg theophylline, dipyridamole) due to risk of hypotension; data are limited with other PDE inhibitors (eg, milrinone, cilostazol, roflumilast).ritonavirMonitor Closely (1)ritonavir will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Concomitant therapy may reduce therapeutic effectiveness.Serious - Use Alternative (1)ritonavir will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.secobarbitalSerious - Use Alternative (1)secobarbital will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.St John's WortContraindicated (1)St John's Wort will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectivenessstiripentolMonitor Closely (1)stiripentol, roflumilast. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.zafirlukastMonitor Closely (1)zafirlukast increases levels of roflumilast by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration with dual inhibitors of CYP3A4 and CYP1A2 may increase systemic exposure and result in increased adverse reactions. 1-10% Diarrhea (9.5%) Weight loss (7.5%) Nausea (4.7%) Headache (4.4%) Back pain (3.2%) Insomnia (2.4%) Decreased appetite (2.1%) Dizziness (2.1%) 1-10% Abdominal pain (1-2%) Anxiety (1-2%) Depression (1-2%) Dyspepsia (1-2%) Gastritis (1-2%) Muscle spasms (1-2%) Rhinitis (1-2%) Sinusitis (1-2%) Tremor (1-2%) Urinary tract infection (1-2%) Vomiting (1-2%) Frequency Not Defined Suicidality Postmarketing Reports Hypersensitivity reactions including angioedema, urticaria, rash Gynecomastia Contraindications Hypersensitivity Moderate-to-severe liver impairment (Child-Pugh class B or C) Cautions Not indicated for relief of acute bronchospasm; drug is not bronchodilator Psychiatric events, including suicidality, reported (monitor for emergence or worsening of insomnia, mood disturbance, or anxiety) Monitor for clinically significant weight loss; this may be reversible upon discontinuance Drug interaction overview Strong CYP3A4 inducers may reduce therapeutic effectiveness of roflumilast; coadministration not recommended CYP P450 enzyme inhibitors CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously may increase roflumilast systemic exposure and increase risk for adverse effects Pregnancy Data are not available regarding use in pregnant women Lactation Probable that roflumilast, its metabolites, or both are excreted into milk; avoid usePregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Selective phosphodiesterase (PDE)-4 inhibitor; PDE-4 inhibition leads to accumulation of intracellular cyclic adenosine monophosphate (cAMP) in lung tissue and is thought to be underlying mechanism of action Absorption 80% absorbed Peak plasma time: 1 hr (range, 0.5-2 hr); active metabolite, 8 hr Distribution Protein bound: 99% Vd: 2.9 L/kg Metabolism Extensively metabolized via phase I (CYP450) and phase II (conjugation) reactions; N-oxide metabolite is only major metabolite observed in human plasma; together, roflumilast and roflumilast N-oxide account for 87.5% of total dose administered in plasma Biotransformation of roflumilast to N-oxide metabolite is mediated by CYP1A2 and CYP3A4 Elimination Half-life: Roflumilast, 17 hr; N-oxide metabolite, 30 hr Clearance: 9.6 L/hr Excretion: Urine (70%) Oral Administration May take with or without food May titrate dose from 250 mcg/day to 500 mcg/day (therapeutic dose) over 4 weeks to improve tolerability (see Dosing) BRAND FORM. UNIT PRICE PILL IMAGE roflumilast oral- 500 mcg tabletroflumilast oral- 500 mcg tabletroflumilast oral- 500 mcg tabletroflumilast oral- 250 mcg tabletroflumilast oral- 500 mcg tabletDaliresp oral- 500 mcg tabletDaliresp oral- 250 mcg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationroflumilast oral ROFLUMILAST - ORAL (roe-FLUE-mi-last) COMMON BRAND NAME(S): Daliresp USES: Roflumilast is used to control and prevent symptoms (wheezing and shortness of breath) caused by ongoing lung disease (chronic obstructive pulmonary disease-COPD which includes bronchitis). It should be used along with other medications (bronchodilators such as salmeterol, ipratropium) to treat COPD. It works by reducing the irritation and swelling of the airways. Controlling symptoms of breathing problems can decrease time lost from work or school.This medication must be used regularly to be effective. It does not work right away and should not be used to relieve sudden shortness of breath or wheezing. If sudden breathing problems occur, use your quick-relief inhaler (such as albuterol, also called salbutamol in some countries) as prescribed. HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet from your pharmacist before you start taking roflumilast and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily.Use this medication regularly in order to get the most benefit from it. This medication works best if used at evenly spaced intervals. To help you remember, use it at the same time each day. Do not increase your dose, use this medication more frequently, or stop using it without first consulting your doctor.Tell your doctor if your condition does not improve or if it worsens. SIDE EFFECTS: Diarrhea, weight loss, stomach/abdominal pain, nausea, loss of appetite, headache, or dizziness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Check your weight regularly while taking this medication. Tell your doctor right away of any unusual or extreme weight loss.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as nervousness, depression, thoughts of suicide), trouble sleeping, shaking (tremors), fast/irregular heartbeat.A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may