Roflumilast

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Respiratory system -> Nasal preparations

Breast Feeding; Lactation; Milk, Human; Phosphodiesterase 4 Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Warning

H315 (91.1%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 45 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In preregistration studies, roflumilast was not associated with serum enzyme elevations or with episodes of clinically apparent liver injury. Since approval of roflumilast, there have been no published reports of hepatotoxicity, and the product label does not mention liver injury as an adverse event.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Roflumilast

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

R03DX07

R - Respiratory system

D - Dermatologicals

QD - Dermatologicals

QR - Respiratory system

Roflumilast and its active metabolite, roflumilast N-oxide, increase cyclic adenosine-3′, 5′-monophosphate (cAMP) in affected cells by inhibiting PDE4. They are highly selective for PDE4 and are effectively inactive against PDEs 1, 2, 3, 5, and 7.

Roflumilast and its active metabolite (roflumilast N-oxide) are inhibitors of PDE4. Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic 3′,5′-adenosine monophosphate (cyclic AMP) metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP. The specific mechanism(s) by which roflumilast exerts its therapeutic action is not well defined.

Roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans, by CYP3A4 and CYP1A2. The N-oxide metabolite is less potent than its parent drug in regards to PDE4 inhibition, but its plasma AUC is approximately 10-fold greater.

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ROFLUMILAST

Established Pharmacologic Class [EPC] - Phosphodiesterase 4 Inhibitor

Mechanisms of Action [MoA] - Phosphodiesterase 4 Inhibitors

Roflumilast is a Phosphodiesterase 4 Inhibitor. The mechanism of action of roflumilast is as a Phosphodiesterase 4 Inhibitor.

ROFLUMILAST

After a 500mcg dose, the bioavailability of roflumilast is about 80%. In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours, while in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged. Applied topically, the mean systemic exposure for roflumilast and its N-oxide metabolite in adults was 72.7 ± 53.1 and 628 ± 648 h∙ng/mL, respectively. The mean systemic exposure for roflumilast and its N-oxide metabolite in adolescents was 25.1 ± 24.0 and 140 ± 179 h∙ng/mL, respectively.

Roflumilast is excreted 70% in the urine as roflumilast N-oxide.

Following a single oral dose of 500 mcg, the volume of distribution of roflumilast is approximately 2.9 L/kg.

Plasma clearance of roflumilast following short-term intravenous infusion is approximately 9.6 L/h.