Cream Flashcards
0.3% cream Indication
Zoryve 0.3% cream is indicated for the topical treatment of plaque psoriasis, including the intertriginous areas, in patients 6 years and older
0.15% cream Indication
is indicated for the topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older
administration
apply to affected areas once daily and rub in completely. wash hands after application, unless cream is for treatment of hands
dosage
0.3% per gram
packaging
60 g tubes
CI
moderate-to-severe liver impairment (Child-Pugh B or C)
Most common AE that led to discontinuation in DERMIS 1, 2
urticaria (0.3%)
Most common AEs (7)
- Diarrhea (3.1%)
- Headache (2.4%)
- Insomnia (1.4%)
- Nausea (1.2%)
- Application site pain (1%)
- URI (1%)
- UTI (1%)
Drug interactions:
co-administration with CYP3A4 INHIBITORS or dual inhibitors that simultaneously affect 3A4 and 1A2
(keto/itra/fluconazole, erythro/clarithromycin, grapefruit juice)
(fluvoxamine, enoxacin are dual)
drugs that are dual inhibitors of CYP3A4 and CYP1A2
- Erythromycin
- Ketoconazole
- Fluvoxamine
- Enoxacin
- Cimetidine
Pharmacokinetics: Zoryve + 3A4/1A2 inhibitor
increase systemic exposure of roflumilast and results in increased AEs
Use in pregnancy?
insufficient data. in animal studies with rats and rabbits, no fetal structural abnormalities at 36- and 31-times the maximium dose
Safe with labor/delivery?
avoid using during labor and delivery; no studies, however animal studies show that disrupted the l/d process in mice
use in lactation?
no data, but roflumilast is detected in milk of lactating rats and is likely to be in human milk.
Pediatric: the safety and effectiveness of Zoryve cream has been established in patients of ___ years of age
6
Geriatric: Use in geriatric?
13% of patients in clinical trials with Zoryve were geriatric and no overall differences in safety or effectiveness were detected
Use in hepatic impairment?
CI in moderate-to-severe liver impairment (Child-Pugh B or C); no dosage adjustment is needed in patients with mild (Child-Pugh A) hepatic impairment
Each gram of the cream contains __ of API?
3 mg
what has been added to adjust pH?
hydrochloric acid
MoA
inhibit PDE4, leading to accumulation of intracellular cAMP. The specific mechanisms by which it exerts therapeutic action is not well defined
active metabolite of Zoryve
Roflumilast N-oxide
Pharmacodynamics
unknown
Absorption
In this study, on average, patients applied 3 to 6.5 g of ZORYVE cream once daily for 15 days. Plasma concentrations of roflumilast and roflumilast N-oxide were quantifiable in all be 2 patients at Day 15. Following application of ZORYVE cream, the plasma versus time profile was relatively flat, generally with a peak-to-trough ratio <2. In adults, the mean ± SD systemic exposure (AUC0-24) was 72.7 ± 53.1 and 628 ± 648 hng/mL for roflumilast and the N-oxide metabolite, respectively. In adolescents, the mean ± SD AUC0-24 was 25.1 ± 24.0 and 140 ± 179 hng/mL for roflumilast and the N-oxide metabolite, respectively
distribution
Plasma protein binding of roflumilast and its N-oxide metabolite is approximately 99% and 97%, respectively
elimination
The plasma clearance after short-term IV infusion of roflumilast is on average about 9.6 L/h. Following topical administration, the half-lives of roflumilast and the N-oxide metabolite were 4.0 and 4.6 days, respectively
Metabolism
Roflumilast is extensively metabolized via Phase I (CYP4500) and Phase II (conjugation) reactions. The N-oxide metabolite is the only major metabolite observed in the plasma of humans. Following oral administration, roflumilast and roflumilast N-oxide account for the majority (87.5%) of the total dose administered in plasma. Roflumilast was not detectable in urine, while roflumilast N-oxide was only a trace metabolite (<1%). Other conjugated metabolites, such as roflumilast N-oxide glucuronide and 4-amino-3,5-dichloropyridine N-oxide were detected in urine
PK: Hepatic Impairment AUC
The AUC of roflumilast and roflumilast N-oxide were increased by 51% and 24%, respectively, in Child-Pugh A patients and 92% and 41%, respectively in Child-Pugh B patient, as compared to age-, weight-, and gender-matched healthy participants
PK: Hepatic impairment Cmax
The Cmax of roflumilast and roflumilast N-oxide were increased by 3% and 26%, respectively, in Child-Pugh A patients and by 26% and 40%, respectively, in Child-Pugh B patients, as compared to healthy participants
renal impariment?
no studies; following oral administration in 12 patients with severe renal impairment, no clinically significant differences in the PK of roflumilast were observed
Roflumilast + erythromycin: Cmax
increased 40%, decreased 34% active metabolite
Roflumilast + erythromycin: AUC
increased 70%, 4% active metabolite
Roflumilast + ketoconazole: Cmax
increased 23%, decreased 38% active metabolite
Roflumilast + ketoconazole: AUC
increased 99%, 3% active metabolite
Roflumilast + fluvoxamine: Cmax
increased 12%, decreased 210% active metabolite
Roflumilast + fluvoxamine: AUC
increased 156%, 52% active metabolite
Roflumilast + enoxacin: Cmax
increased 20%, decreased 14% active metabolite
Roflumilast + enoxacin: AUC
increased 56%, 23% active metabolite
Roflumilast + cimetidine: Cmax
increased 46%, decreased 4% active metabolite
Roflumilast + cimetidine: AUC
Increased 85%, 27% active metabolite
carcinoma?
stastically significant increases in the incidence of undifferentiated carcinomas of the nasal epithelium in hamsters at doses 12-times the MRHD; no evidence at lower doses
effect on sperm?
no effect on human semen parameters or reproductive hormones during the 3-month treatment period and the following 3 month off-treatment period
storage?
20-25 C (68 F to 77F); excursions permitted between 59 F and 86 F
Patient counseling: lactation
advise to use on the smallest area of skin for the shortest duration of timewhile breastfeeding; do not apply directly to nipple/areola to avoid direct exposure
Patient counseling: administration
apply to affected areas 1 time a day. rub the cream in completely until you no longer see it on your skin. wash your hands (unless treating hands)
