Crinone^® (Gel) Instructions for Use

Marketing Authorization Holder

Merck LLC (Russia)

Manufactured By

Dendron Brands Limited (United Kingdom)

Labeled By

MAROPACK, AG (Switzerland)

Packaging and Quality Control Release

CENTRAL PHARMA (CONTRACT PACING), Ltd. (United Kingdom)

ATC Code

G03DA04 (Progesterone)

Active Substance

Progesterone (Rec.INN registered by WHO)

Dosage Form

Crinone®

Vaginal gel 90 mg/1 dose: applicators 6 or 15 pcs.

Dosage Form, Packaging, and Composition

Vaginal gel white or almost white, homogeneous, with a specific odor.

* The amounts are indicated per 1.125 g of gel, i.e., per 1 dose, which is released from the applicator during its use. To ensure the declared dosage, the actual amount of gel in the applicator is 1.45 g.

Excipients: glycerol, liquid paraffin, hydrogenated palm oil glycerides, carbomer 974P, sorbic acid, polycarbophil, sodium hydroxide, purified water.

1 dose (1.125 g) – disposable polyethylene vaginal applicators (1) – laminated foil bags (6) – cardboard boxes.
1 dose (1.125 g) – disposable polyethylene vaginal applicators (1) – laminated foil bags (15) – cardboard boxes.

Clinical-Pharmacological Group

Gestagen

Pharmacotherapeutic Group

Sex hormones and modulators of the genital system; gestagens; pregn-4-ene derivatives

Pharmacological Action

A hormone identical to the natural hormone of the corpus luteum of the ovary. By binding to receptors on the surface of target organ cells, it penetrates the nucleus where, by activating DNA, it stimulates RNA synthesis.

It promotes the transition of the uterine mucosa from the proliferation phase, induced by the follicular hormone estradiol, to the secretory phase. After fertilization, it promotes the transition to the state necessary for the development of the fertilized egg. It reduces the excitability and contractility of the uterine and fallopian tube muscles. It promotes the formation of normal endometrium. It stimulates the development of the terminal elements of the mammary gland and induces lactation.

By stimulating protein lipase, it increases fat reserves and increases glucose utilization. By increasing the concentration of basal and stimulated insulin, it promotes the accumulation of glycogen in the liver, increases the production of pituitary gonadotropic hormones; reduces azotemia, increases nitrogen excretion in the urine.

Pharmacokinetics

After vaginal administration, the C_max of progesterone is reached on average after 6 hours and is 11 ng/ml. Progesterone intensively binds to plasma proteins, especially albumin (approximately 80%) and corticosteroid-binding globulin (approximately 17%). It undergoes intensive biotransformation in the liver. The intravaginal route of administration significantly reduces the “first-pass” effect through the liver. It is mainly excreted by the kidneys in the form of 3-α, 5-β-pregnanediol.

Indications

Luteal phase support as part of assisted reproductive technology programs; secondary amenorrhea, dysfunctional uterine bleeding due to progesterone deficiency; hormone replacement therapy in postmenopause (in combination with HRT drugs containing estrogen).

ICD codes

Dosage Regimen

Administer vaginally using the provided single-use applicator. The daily dose is 90 mg per application, equivalent to one full applicator.

For luteal phase support in assisted reproductive technology: apply once daily. Start therapy on the day of embryo transfer and continue for 10-12 weeks of gestation if pregnancy is confirmed.

For secondary amenorrhea: apply every other day. The total course is six applications. Expect withdrawal bleeding within 3-5 days after the last dose.

For dysfunctional uterine bleeding due to progesterone deficiency: apply once daily for 10-12 consecutive days.

For hormone replacement therapy in postmenopausal women receiving estrogens: apply every other day for 12-14 days per 28-day cycle.

Insert the applicator deeply into the vagina while lying down. The gel adheres to the vaginal mucosa, allowing for sustained release. Dispose of the used applicator after a single use.

If a dose is missed, administer as soon as remembered. Do not double the next dose to make up for a missed one.

Adverse Reactions

Allergic reactions skin itching, rash, urticaria, anaphylactoid reactions.

Nervous system disorders headache, drowsiness.

Digestive system disorders abdominal pain.

Reproductive system and breast disorders breast tenderness, intermenstrual bleeding, vaginal itching and burning, irritation of the vaginal mucosa at the application site.

Contraindications

Deep vein thrombosis, thrombophlebitis; thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke); vaginal bleeding/spotting of unknown origin; established or suspected malignant neoplasms of the breast and genital organs; incomplete abortion; breastfeeding period.

With caution

Cardiovascular diseases, arterial hypertension, liver function disorders, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, photosensitivity; II and III trimesters of pregnancy.

Use in Pregnancy and Lactation

Can be used in the first trimester of pregnancy as part of assisted reproductive technologies. Use in the second and third trimesters of pregnancy is not recommended.

Progesterone is excreted in breast milk, therefore use is contraindicated during breastfeeding.

Use in Hepatic Impairment

Contraindicated in severe liver diseases (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor syndrome, malignant liver tumors) currently or in history.

Use with caution in mild to moderate liver function impairment.

Use in Renal Impairment

Use the drug with caution in chronic renal failure.

Pediatric Use

Contraindicated for use under 18 years of age (efficacy and safety have not been established).

Geriatric Use

Efficacy and safety in elderly patients (over 65 years) have not been established. There are no indications for use in old age.

Special Precautions

Not used for contraception.

Before starting treatment, it is necessary to perform an examination of the mammary glands and pelvic organs, including a Pap test. With long-term use, regular gynecological examinations should be performed to exclude the development of endometrial hyperplasia.

Use is not indicated for threatened abortion. In case of diagnosed missed abortion, use should be discontinued. To prevent the possibility of threatened abortion when using this product, hCG concentration should be determined and ultrasound performed.

Due to the risk of thromboembolic complications, progesterone use should be discontinued in case of occurrence of: visual disturbances, such as vision loss, exophthalmos, double vision, vascular lesions of the retina; migraine; venous thromboembolism or thrombotic complications, regardless of their location.

If there is a history of thrombophlebitis, the patient should be under close observation.

Effect on ability to drive vehicles and machinery

During treatment, caution should be exercised when driving vehicles, operating machinery, or engaging in activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

Concomitant use of other intravaginally administered medicinal products should be avoided to prevent impairment of progesterone release and absorption.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.