roflumilast (systemic)

Contraindicated in:

Acute bronchospasm;
Moderate or severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

History of depression/suicidal thoughts;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

GI: diarrhea, abdominal pain, ↓appetite, dyspepsia, gastritis, nausea, vomiting

Metab: weight loss

MS: muscle spasm

Neuro: anxiety, depression, dizziness, headache, insomnia, SUICIDAL THOUGHTS/BEHAVIOR, tremor

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 and CYP1A2 inducers, including rifampin, phenobarbital, carbamazepine, and phenytoin, may ↓ levels and effectiveness; avoid concurrent use.
Concurrent use of CYP3A4 inhibitors and dual CYP3A4 and CYP1A2 inhibitors, including erythromycin, ketoconazole, fluvoxamine, and cimetidine, may ↑ levels and risk of toxicity.
Ethinyl estradiol may ↑ levels and risk of toxicity.

Availability ⬆ ⬇

(Generic available)

Tablets: 250 mcg; 500 mcg

Route/Dosage ⬆ ⬇

PO (Adults ): 250 mcg once daily for 4 wk, then ↑ to 500 mcg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Roflumilast and one active metabolite (roflumilast N-oxide) act as selective inhibitors of phosphodiesterase 4, responsible for breaking down 3', 5'-adenosine monophosphate (cAMP). Resulting intracellular accumulation of cAMP in lung tissue.
Reduces cells (neutrophils, eosinophils and total cells) in sputum.

Therapeutic effects:

↓frequency of COPD exacerbations.

Classifications ⬆ ⬇

Therapeutic Classification: copd agents

Pharmacologic Classification: phosphodiesterase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Parent drug and metabolites probably enter breast milk.

Protein Binding: Roflumilast: 99%; roflumilast N-oxide: 97%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 and CYP1A2 isoenzyme. One metabolite, roflumilast N-oxide, is pharmacologically active. Inactive metabolites excreted in urine.

Half-Life: Roflumilast: 17 hr; roflumilast N-oxide: 30 hr.

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 (4–13‡)	24 hr

‡For roflumilast N-oxide.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take roflumilast as directed. Advise patient to read Medication Guide before starting therapy and with each Rx refill; new information may be available.
Inform patient that roflumilast is not a bronchodilator and should not be used for treating sudden breathing problems.
Advise patient to monitor weight regularly. If weight loss occurs, notify health care professional; may require discontinuation of therapy.
Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide, trouble sleeping, new or worse depression, new or worse anxiety, acting on dangerous impulses, or other unusual changes in behavior or mood or signs and symptoms of hypersensitivity reactions occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products without consulting health care professional.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding.

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Indications ⬇

Contraind./Precautions ⬆ ⬇