OTEZLA XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OTEZLA XR (OTEZLA XR).
Phosphodiesterase 4 (PDE4) inhibitor; increases intracellular cAMP levels, reducing pro-inflammatory cytokine production and modulating immune response.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP1A2 and CYP2A6. |
| Excretion | Renal 58% (primarily as inactive metabolites), fecal 39% (as unchanged drug and metabolites), biliary excretion contributes minimally. Total clearance is approximately 8.5 L/h. |
| Half-life | Terminal elimination half-life is 6-9 hours in healthy subjects; in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), half-life increases to 15-20 hours, necessitating dose reduction. |
| Protein binding | Approximately 68-75% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd/F is approximately 87 L (1.2 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral: Approximately 73% (fasting) with extended-release formulation; high-fat meal reduces Cmax by 34% and AUC by 6%, but clinical significance is minimal. |
| Onset of Action | Oral: Clinical improvement in psoriatic arthritis may be observed as early as 2 weeks, with maximal effect by 16-24 weeks. For psoriasis, onset at 2-4 weeks. |
| Duration of Action | Duration of clinical effect persists for the dosing interval (twice daily); sustained efficacy requires continuous dosing. After discontinuation, symptoms may recur within weeks to months. |
30 mg orally twice daily after an initial 5-day titration: 10 mg AM on day 1, 10 mg AM and 10 mg PM on day 2, 10 mg AM and 20 mg PM on day 3, 20 mg AM and 20 mg PM on day 4, and 30 mg AM and 30 mg PM on day 5 and thereafter.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For severe renal impairment (eGFR <30 mL/min/1.73 m²): 30 mg orally once daily, not recommended for end-stage renal disease (ESRD). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use with caution due to higher risk of infections and renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OTEZLA XR (OTEZLA XR).
| Breastfeeding | No data are available on the presence of apremilast in human milk, effects on the breastfed infant, or effects on milk production. Apremilast was excreted in the milk of lactating mice at concentrations approximately 2.7 times the maternal plasma concentration. The M/P ratio in mice was 2.7. Caution should be exercised when administered to a nursing woman, as there is potential for serious adverse reactions in the breastfed infant. |
| Teratogenic Risk | Apremilast is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, apremilast caused developmental toxicity in mice and monkeys at exposures greater than 1.2 times the maximum recommended human dose (MRHD) of 60 mg per day. In mice, decreased fetal body weight and increased incidence of skeletal variations were observed. In monkeys, increased fetal loss and reduced fetal body weight occurred. Use during pregnancy only if potential benefit justifies potential risk to the fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to apremilast or any component of the formulation","Patients with moderate to severe renal impairment (CrCl <50 mL/min) for OTEZLA XR formulation (dose adjustment required for immediate-release, but contraindicated for XR)"]
| Precautions | ["Depression and suicidal ideation: Monitor patients for psychiatric symptoms; weigh risks vs benefits","Weight loss: Monitor weight regularly; consider discontinuation if unexplained or clinically significant","Drug interactions: Strong CYP3A4 inducers (e.g., rifampin) may decrease exposure; strong CYP3A4 inhibitors (e.g., ketoconazole) may increase exposure","Diarrhea, nausea, vomiting: Manage with dose reduction or interruption"] |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring is mandated for apremilast use. However, given the lack of human data, routine prenatal monitoring as per standard obstetric care is recommended. For patients with psoriatic arthritis or psoriasis, standard disease activity monitoring should be continued. If used during pregnancy, consider ultrasound to assess fetal growth and development. |
| Fertility Effects | Based on animal studies, apremilast may impair fertility. In male mice, decreased fertility and sperm count were observed at doses equivalent to 1.7 times the MRHD. In female mice, increased estrous cycle length and decreased fertility occurred at doses 1.2 times the MRHD. Reversibility of these effects is unknown. Human data are lacking; therefore, counsel patients of reproductive potential about potential fertility impairment. |