crisaborole ointment

(Crisaborole Ointment) 2% w/w

Product Specifications

Innoyator Each gram contains

Crisaborole. . . . . . . . . . 20 mg

DESCRIPTION

Crisaborole is described chemically as 5-(4-cyanophenoxy) -1,3-dihydro-1-hydroxy-[2,1]-benzoxaborole. The empirical formula is CuHBNO, and the molecular weight is 251.1 g/mol.

CLINICAL PARTICULARS

Therapeutic indications

Crisabo (crisaborole) is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 3 months of age and older.

Posology and method of administration

Apply a thin layer of Crisabo (crisaborole) twice daily to affected areas. Once clinical effect is achieved, consider reducing application to once daily.
Method of administration
Crisabo (crisaborole) is for topical use only and not for ophthalmic, oral, or intravaginal use.

Contraindication

Crisaborole ointment is contraindicated in patients with known hypersensitivity to crisaborole or any component of the formulation.

WARNINGS AND PRECAUTIONS

Available data indicate that local skin reactions, such as burning or stinging, may be more likely to occur on sensitive skin areas (such as the face and neck).

Hypersensitivity Reactions

Hypersensitivity reactions, including contact urticaria, have occurred in patients treated with Crisaborole ointment. Hypersensitivity should be suspected in the event of severe pruritus, swelling and erythema at the application site or at a distant site. If signs and symptoms of hypersensitivity occur, discontinue crisaborole ointment immediately and initiate appropriate therapy.

Excipients with known effect

This medicine contains 90 mg propylene glycol in each gram of ointment.

USE IN SPECIFIC POPULATIONS

Pregnancy

Available data from case reports with crisaborole ointment use in pregnant women are insufficient to inform a drug- associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, there were no adverse developmental effects observed with oral administration of crisaborole in pregnant rats and rabbits during organogenesis at doses up to 3 and 2 times, respectively, the maximum recommended human dose (MRHD). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes.

Lactation

There is no information available on the presence of crisaborole in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production after topical application of crisaborole ointment to women. who are breastfeeding. Crisaborole ointment is systemically absorbed. The lack of clinical data during lactation precludes a clear determination of the risk of crisaborole ointment to a breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for crisaborole ointment and any potential adverse effects on the breastfed infant from crisaborole ointment or from the
underlying maternal condition.

Pediatric Use

The safety and effectiveness of crisabotole ointment have been established in pediatric patients ages 3 months and older for topical treatment of mild to moderate atopic dermatitis. The safety and effectiveness of crisaborole ointment in pediatric patients below the age of 3 months have not been established.

Geriatric Use

Clinical studies of crisaborole ointment did not include whether they respond differently from younger subjects. sufficient numbers of subjects age 65 and over to determine However, dosage adjustment is not expected to be necessary in this patient population.

Hepatic impairment

Clinical studies in subjects with hepatic impairment have not been conducted. However, dosage adjustment is not expected to be necessary in subjects with mild to moderate hepatic impairment.

Renal impairment

Clinical studies in subjects with renal impairment have not been conducted. However, dosage adjustment is not expected to be necessary in this patient population.

Fertility

Reproduction studies in male or female rats using oral administration of crisaborole revealed no effects on fertility. Adverse Reactions
Application site pain reported by 21% of crisaborole ointment treated subjects in clinical trials, including application site pain, e.g., burning or stinging (4.4%), Generally, application site pain was noted early in the treatment period and was transient in nature, resolving spontaneously.

Adverse reactions are ranked under headings of frequency. with the most frequent first, using the following convention: very common (2 1/10); common (2 1/100 to < 1/10); uncommon (2 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Uncommon

Hypersensitivity, Urticaria contact

Common: Application site reactions (e.g., application site pain, application site pruritus, application site dermatitis, application site erythema, application site irritation, application site urticaria)

Post-marketing Experience

Skin and Subcutaneous: allergic contact dermatitis Interaction with other medicinal products and other forms of interaction
Neither crisaborole nor its two main metabolites are expected to cause drug interactions by induction or inhibition of cytochrome P450 (CYP) enzymes based on in vitro and in vivo data,
Based on in vitro data, concomitant administration of Crisaborole ointment and CYP3A4 inhibitors (e.g. itraconazole, erythromycin, clarithromycin, ritonavir) or CYP1A2 inhibitors (e.g.. ciprofloxacin, fluvoxamine) can increase systemic
ketoconazole,
crisaborole concentrations.
is not
Crisaborole ointment has not been evaluated in combination with other cutaneous medicinal products used to treat mild to moderate atopic dermatitis and co- recommended. Emollients may be used on other areas application on the same skin areas of skin not affected by atopic dermatitis; co-application of emollients with crisaborole ointment on the same
skin areas is not recommended.

Crisaborole ointment has no or negligible influence on the Effects on ability to drive and use machines
ability to drive and use machines.

OVERDOSAGE

Overdose following cutaneous administration is unlikely. If too much of the ointment has been applied; the excess can be wiped off. In cases of accidental ophthalmic, oral mucosa, or intravaginal exposure, the ointment should be thoroughly wiped off and/or rinsed with water.

CLINICAL PHARMACOLOGY

Mechanism of Action

Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor. PDE-4 inhibition results in increased intracellular cyclic adenosine monophosphate (CAMP) levels. The specific mechanism(s) by which crisaborole exerts its therapeutic action for the treatment of atopic dermatitis is not well
defined.

Pharmacodynamics

Cardiac Electrophotog
At therapeutic doses, crisaborcle ointment is not expected to prolong QTc to any clinically relevant extent
Pharmacokinetics

Absorption

The PK of arisabordle ointment were investigated in 33 pediatric subjects 26 17 years of age with mild to moderate atopic dermatitis and a mean & SO body surface area (BSA) involvement of 49 20% (range 27% to 92%). In this study. subjects applied approximately 3 mg/cm2 of crisaborole ointment (dose range was approximately 6 g to 30 g per application) twice daily for 8 days. Plasma concentrations were quantifiable in all the subjects.

The mean ± SD maximum plasma concentration (Cmax) and area under the concentration time curve from 0 to 12 hours post dose (AUCO-12) for crisatorole on Day 8 were 127: 196 ng/mL and 949 1240 ng him, respectively. Systemic concentrations of crisaborcie were at steady state by Day 8. Based on the ratios of AUCO-12 between Day 8 and Day 1, the mean accumulation factor for crisaborole was 1.9. The PK of crisaborgie ointment were investigated in 13 subjects 4 months to less than 24 months of age. The mean SD Cmax and AUCO-12 for crisaborole were 188: 100 ng/ml and 1164 550 ng ml, respectively

Distribution

Based on
I vitro study, crisaborole is 97% bound to human plasma proteins

Elimination

Metabolisin

Crisaborole is substantially metabolized into inactive metabolites. The major metabolite 5-(4-cyanophenoxy)-2- hydroxyl benzylalcohol (metabolite 1) is formed via hydrolysis: this metabolite is further metabolized into downstream metabolites, among which 5-(4
formed via oxidation, is also a major metabolite cyanophenoxy)-2-hydroxyf benzoic acid (metabolite 2), Excretion
Renal excretion of metabolites is the major route of
elimination.

toxicity,

Preclinical data from studies conducted in vitro or in vivo by Carcinogenesis, Mutagenesis, Impairment of Fertility the oral and dermal roules of administration reveal no of safety pharmacology, repeated-dose special hazard for humans based on conventional studies genotoxicity, juvenile toxicity, or toxicity to reproduction and development.

A drug-related increased incidence of benign (combined) was noted in crisaborole-treated female rats at granular cell tumours in the uterus with cervix and vagina oral doses approximately 2 times the mean human systemic exposure in maximum use conditions. The clinical relevance of this finding is unknown, however given the tumour type and benign status in a single species and single sex, the relevance to humans is considered to be
low.
HOW SUPPLIED Crisabo Ointment 2% w/w:

STORAGE

Do not store above 30°C.
Pack of 10 gram
The expiration date refers to the product correctly stored at the required condition.

INSTRUCTIONS

Keep away from heat, light and moisture.
Keep all medicines out of the reach of children.
To be sold on the prescription of a registered medical practitioner only.
DO NOT USE IN THE EYES.
FOR EXTERNAL USE ONLY.