Calcipotriol

D05A - Antipsoriatics for topical use ATC D05AX52 Small molecule approved 1993 Topical Natural product

JFDA label: Beta-cal Ointment

Mechanism of Action

Agonist of Vitamin D3 receptor — Vitamin D receptor agonist

Target	Action	Gene / class
Vitamin D3 receptor efficacy	AGONIST	VDR

Indications

Approved

Plaque psoriasis

Contraindications

Source: Lexicomp

Hypersensitivity to calcipotriene or any component of the formulation Absolute
patients with acute psoriatic eruptions (scalp solution) Documentation of allergenic cross-reactivity for Vitamin D derivatives is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute
patients with demonstrated hypercalcemia or evidence of vitamin D toxicity Absolute
use on the face (cream, ointment) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Not Known Tingling of skin

Skin and subcutaneous tissue disorders (10)

Not Known Burning sensation of skin · dermatitis · desquamation · erythema · exacerbation of psoriasis · pruritus · skin irritation · skin rash · stinging of the skin · xeroderma

General disorders and administration site conditions (2)

Not Known application site erythema · Application site pain

Dosing

Source: Lexicomp

Plaque psoriasis: Topical: Cream: Apply a thin film to the affected skin twice daily Foam: Apply a thin film to the affected skin or scalp twice daily Ointment: Apply a thin film to the affected skin once or twice daily Solution: Apply to the affected scalp twice daily

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Contact dermatitis

Contact dermatitis, including allergic contact dermatitis, may occur.

Hypercalcemia

May cause transient increases in serum calcium (reversible); if hypercalcemia occurs, discontinue treatment until calcium levels return to normal.

Irritation

Transient irritation of both lesions and surrounding uninvolved skin may occur; discontinue use if irritation occurs. Special populations:

Elderly

Use with caution in elderly patients; severity of skin-related adverse reactions may be increased compared to younger adults. Dosage form specific issues:

Foam, solution

Flammable; keep the foam and the solution away from fire, flame, or smoking during and immediately following application. Other warnings/precautions:

Appropriate use

For external use only; not for ophthalmic, oral, or intravaginal use. Avoid or limit excessive exposure to natural or artificial sunlight, or phototherapy. Thoroughly wash hands after use. The safety and effectiveness in dermatoses other than psoriasis have not been established. Do not use concurrently with products that may alter the pH of the vehicle (eg, topical lactic acid); if the use of multiple topical agents is necessary, apply the various agents at separate times throughout the day (Menter 2009).

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in some animal reproduction studies. If treatment during pregnancy is needed, other agents may be preferred (Hsu 2012; Zeichner 2010).

Lactation

It is not known if calcipotriene is excreted in breast milk. The manufacturer recommends that caution be exercised when administering calcipotriene to nursing women. In general, topical agents should not be applied around the nipple area in nursing women (Zeichner 2010).

Monitoring

Clinical pearl	Serum calcium

Chemistry & Properties

Formula	C27H40O3
Molecular weight	412.61 g/mol
IUPAC name	trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5S)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
CAS	112965-21-6
PubChem CID	5288783
InChIKey	`LWQQLNNNIPYSNX-UROSTWAQSA-N`
logP	5.09 (XLogP 4.3)
Polar surface area	60.69 Å²
H-bond acceptors / donors	3 / 3
Drug-likeness (QED)	0.55
Lipinski violations	1

SMILES

C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)/C=C/[C@@H](O)C4CC4)CC[C@@H]23)C[C@@H](O)C[C@@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.528 h
Volume of distribution	0.357 L/kg
Protein binding	80.1%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—

Receptor binding (top 1)

Target	Action	Affinity
Vitamin D receptor (VDR)	Agonist	pKd 9.3

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (6)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Daivobet Ointment	Ointment 0.5 mg/g, 50 mcg/g	15 g tube pack varies	Khoury Drug Store	8.870
Beta-cal Gel	Gel as Dipropionate 0.05 %, as Monohydrate 0.005 %	30 GM	JERASH PHARMACEUTICALS LTD.CO/JORDAN	9.810
Daivobet Gel	Gel 0.5 mg/g, 50 mcg/g	30 gm pack varies	Khoury Drug Store	10.900
Psoriano Ointment	Ointment 0.5 mg/g (as dipropionate), 50 mcg/g (as monohydrate)	30 GM/1 TUB	SANA PHARMACEUTICAL INDUSTRY/JORDAN	14.000
Beta-cal Ointment	Ointment 50 mcg/g, 0.5 mg/g	30 g tube	JERASH PHARMACEUTICALS LTD.CO/JORDAN	14.730
Daivobet Ointment	Ointment 0.5 mg/g, 50 mcg/g	30 g tube pack varies	Khoury Drug Store	16.890