This page describes pharmacological agents that may have legal restrictions, side effects, and drug interactions in your jurisdiction. Information is for educational research only — consult a clinician before considering any compound.
Surface here is educational only; do not use without medical supervision. Our editorial verdict is SKIP-FOR-NOW — current cost / risk / redundancy puts it below the line.
Roflumilast
Roflumilast is the FDA-approved oral PDE4 inhibitor for severe COPD (Daliresp, 2011) and the topical FDA-approved PDE4 inhibitor for…
Aliases (5)
Overview
What is Roflumilast?
Roflumilast (Daliresp, Daxas) is an oral selective phosphodiesterase 4 (PDE4) inhibitor, FDA-approved for severe COPD with chronic bronchitis to reduce exacerbations. It is also used topically (Zoryve) for plaque psoriasis and seborrheic dermatitis.
Key Benefits
Reduces COPD exacerbations and improves lung function in severe disease, and clears plaque psoriasis topically. Investigated as a cognitive enhancer in low doses (subtherapeutic for COPD) where it may improve working memory via increased hippocampal cAMP/CREB.
Mechanism of Action
Selective inhibitor of PDE4 (phosphodiesterase 4), preventing cAMP hydrolysis and elevating intracellular cAMP. This downregulates pro-inflammatory cytokine release from macrophages and neutrophils and increases CREB phosphorylation in neurons (relevant to cognitive effects).
Pharmacokinetics
▸Brand options5 known
Status"Rx (US, EU, Japan). Oral: FDA-approved 2011 for severe COPD with chronic bronchitis. Topical (Zoryve, Arcutis): FDA-approved 2022 for plaque psoriasis (different formulation, much lower systemic exposure). Not scheduled."
Peptide Interactions
same mechanism (PDE4 inhibition); redundant and additive emetic risk. Pick one. BPN14770 is the cleaner pick if the PDE4 mechanism is wanted.
same class concern; cumulative GI and area-postrema cAMP load
non-selective PDE inhibitors, additive cAMP elevation
directly stimulates adenylyl cyclase (cAMP from production side); roflumilast blocks degradation (cAMP from breakdown side). Combined cAMP elevation could am…
raise roflumilast plasma levels; amplifies AEs. Fluvoxamine roughly doubles roflumilast exposure.
modest exposure increase; caution in chronic combination.
substantially raise exposure; avoid.
Roflumilast is contraindicated in moderate-to-severe hepatic impairment (Child-Pugh B/C).
, [semax](semax.md), [n-acetyl-semax-amidate](n-acetyl-semax-amidate.md), [adamax](adamax.md) — no documented interaction; orthogonal mechanisms.
Quality Indicators
Pharmacy-dispensed, intact packaging
Prescription tablets in original sealed packaging from a licensed pharmacy.
Generic vs branded
Generics are usually fine but bioavailability can vary slightly; track if you switch.
Unbranded blister or counterfeit risk
Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.
What to Expect
- Day 1PK-driven acute peak per administration. Verify dose tolerated.
- Week 1Steady-state reached for most daily-dosed pharma.
- Week 2-4Therapeutic effect established; titration window if needed.
- Long-termPeriodic monitoring per drug class (labs, BP, ECG as applicable).
Side Effects & Safety 9
Side Effects
- 1Diarrhea — ~10% (vs ~3% placebo); often the first AE to appear, usually within first 4 weeks, usually attenuates but doesn't disappear
- 2Nausea — ~5-16% (varies by trial); first 1-2 weeks worst; food helps marginally
- 3Headache — ~4-5%
- 4Weight loss — ~12% experience clinically meaningful loss; median ~2 kg over 1 year (mechanism-related, not solely GI)
- 5Decreased appetite — closely tied to weight loss
- 6Insomnia — particularly if dosed PM
- 7Anxiety / nervousness
- 8Depression / low mood — small but real signal; patients with prior depression history should not initiate without medical oversight
- 9Back pain, dizziness
When to Stop
- Suicidal ideation / behavior — flagged as warning in some labels; not a black-box in US Daliresp label but real-world signal is non-zero. Roflumilast's psychiatric AEs may be amplified in patients with prior mood disorder
- Severe diarrhea / dehydration
- Hypersensitivity reactions (uncommon with oral; topical Zoryve has rare local reactions)
- Hepatic effects — rare ALT elevations; LFT monitoring not formally required but worth checking at baseline + 3 months in chronic use
- First 4 weeks: Worst window for GI tolerance. If diarrhea persists past 4 weeks at the maintenance dose, the molecule is unlikely to settle further.
- First 12 weeks: Mood/psychiatric watch period. Any new low mood, suicidal thoughts, sleep disturbance — stop and re-assess.
- Indefinite: Weight monitoring monthly. >2 kg weight loss is clinically meaningful and reason to stop or reduce.
- Pregnancy: Avoid (animal teratogenicity at high doses; not relevant to the user but flag for completeness).
References
Van Duinen et al. 2018 — Acute administration of roflumilast enhances immediate recall of verbal word memory in healthy young adults (Neurobiology of Learning and Memory)
the first clean human cognitive RCT for roflumilast; episodic memory benefit, inverted-U
View StudyGilleen et al. 2018 — An experimental study of the symptomatic effect of the PDE4 inhibitor roflumilast in cognitive impairment associated with schizophrenia (Translational Psychiatry / Schizophrenia Research)
schizophrenia adjunct cognitive RCT
View StudyDaliresp (roflumilast) FDA label
original FDA approval label, COPD indication
View StudyDaliresp (roflumilast) updated FDA label
current label including AE language
View StudyZoryve (topical roflumilast) FDA label / Arcutis press
2022 FDA approval for plaque psoriasis; later expansions
View StudyCalverley et al. 2009 — Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials (Lancet) M2-124, M2-125
pivotal Phase 3 COPD trials
View StudyMartinez et al. 2015 — Effect of roflumilast on exacerbations in patients with severe COPD: REACT trial (Lancet)
REACT exacerbation reduction trial
View StudyRobichaud et al. 2002 — Deletion of phosphodiesterase 4D in mice shortens alpha2-adrenoceptor-mediated anaesthesia (J Clin Invest)
PDE4D as the emetic isoform; foundational rationale for subtype-selective design
View StudyPage & Spina 2012 — Selective PDE inhibitors as novel treatments for respiratory diseases (review)
class pharmacology review
View StudyKeshavarzian et al. — PDE4 inhibitors and CNS effects (review)
CNS pharmacology of PDE4 class
View StudyPMC review — Roflumilast pharmacology and clinical use (2019)
comprehensive mechanism + trial review
View StudyBPN14770 (zatolmilast) compound file
companion file; cleaner allosteric PDE4D NAM expression of this mechanism
View StudyHow was your experience with this compound?
Anonymous · one vote per session · results below at 5+ votes.
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