Pergoveris - Instructions For Use, Reviews, Price Of Injections, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Pergoveris

Pergoveris: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in the elderly
11. 11. Drug interactions
12. 12. Analogs
13. 13. Terms and conditions of storage
14. 14. Terms of dispensing from pharmacies
15. 15. Reviews
16. 16. Price in pharmacies

Latin name: Pergoveris

ATX code: G03GA05

Active ingredient: follitropin alfa (Follitropin alfa) + lutropin alfa (Lutropin alfa)

Manufacturer: Merck Serono S. A. (Merck Serono SA) (Switzerland); Merck Serono SA, Succursale d'Aubonne (Switzerland)

Description and photo update: 2019-18-11

Prices in pharmacies: from 2010 rubles.

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Pergoveris is a combined follicle-stimulating agent.

Release form and composition

The drug is produced in the form of a lyophilisate for the preparation of a solution for subcutaneous (s / c) administration: the drug is a lyophilized powder or porous mass of white or almost white color, the reconstituted solution is slightly opalescent or transparent, colorless or pale yellow; solvent - a clear, colorless liquid [lyophilizate: 150 + 75 International Units (IU) each in a colorless transparent glass vial with a volume of 3 ml, sealed with a bromobutyl rubber stopper and an aluminum cap with a plastic cap; solvent: 1 ml each in a colorless transparent glass vial with a volume of 3 ml, sealed with a rubber stopper and an aluminum cap with a plastic cap; 1 set each containing 1 bottle of lyophilisate and 1 bottle of solvent in a plastic container closed with a polymer film;in a cardboard box with first opening control 1, 3 or 10 sets and instructions for use of Pergoveris].

1 bottle with lyophilisate contains:

• active substances: follitropin alpha - 150 ME (11 μg), lutropin alpha - 75 ME (3 μg);
• additional components: sodium hydrogen phosphate dihydrate, sucrose, sodium dihydrogen phosphate monohydrate, concentrated phosphoric acid, polysorbate-20, methionine, sodium hydroxide.

Composition for 1 ml of reconstituted solution: follitropin alpha - 150 ME and lutropin alpha - 75 ME.

1 bottle with a solvent contains water for injection in an amount of 1 ml.

Pharmacological properties

Pharmacodynamics

Pergoveris is a combined drug that contains follitropin alpha - a recombinant human follicle-stimulating hormone (r-FSHh) and lutropin alpha - a recombinant human luteinizing hormone (r-LHh). The drug is produced by genetic engineering on a Chinese hamster ovary cell culture.

The main task of follicle-stimulating hormone (FSH) is to initiate folliculogenesis by acting on the granulosa cells of the developing follicle, while luteinizing hormone (LH) is assigned the main role in enhancing the production of estradiol by the mature follicle, inducing follicle maturation and ovulation. Thanks to LH, the onset and development of pregnancy occurs in the early stages, since it supports the normal functioning of the corpus luteum.

During the development of the follicle, FSH in combination with estradiol activates LH receptors on the cytoplasmic membranes of granulosa cells. The effect of LH on theca cells leads to the production of androgens for granulosa cells, where the process of transformation of androgens into estrogens with the participation of the aromatase system takes place. Therefore, in the absence of LH, FSH is able to induce follicular growth, however, estradiol production will be reduced. With insufficient synthesis of the latter, the conditions for the onset of pregnancy will be disrupted, as well as the production of cervical mucus, the growth of the endometrium and the maturation of a fully functioning corpus luteum in response to the introduction of human chorionic gonadotropin (hCG).

In clinical studies, the effectiveness of the combined use of follitropin alpha and lutropin alpha was demonstrated in women against the background of hypogonadotropic hypogonadism.

In patients with anovulation with LH and FSH deficiency, the most important effect of lutropin alfa is to increase the production of estradiol by ovarian follicles, which in turn are stimulated by FSH to grow.

It was found that in patients with hypogonadotropic hypogonadism and serum LH in the blood below 1.2 IU / L, the daily use of a combination of follitropin alfa at a dose of 150 IU and lutropin alfa at a dose of 75 IU provides adequate follicular development and an increase in estradiol synthesis. At the same time, the combination of lutropin alfa at 25 IU and follitropin alpha at 150 IU did not lead to the same effect. Thus, with the introduction of less than 1 bottle of Pergoveris per day, the LH activity may be insufficient to maintain the full development of follicles.

Despite the fact that the effectiveness of monotherapy of r-FSHH with the use of assisted reproductive technologies (ART) has been recorded, the available results of clinical studies indicate the advantages of additional use of r-LHH in women with an inadequate response to r-FSHh monotherapy. The additional use of r-LHH aims to increase the sensitivity of the ovaries to r-FSHh, to activate the production of estradiol by the preovulatory follicle and, as a consequence, to the growth of the endometrium, as well as to support the later luteinization of follicles, which ensures the normalization of the progesterone content in the luteal phase.

Pharmacokinetics

When used in combination, follitropin alpha and lutropin alpha retain the same pharmacokinetic characteristics as when these substances are administered separately.

Follitropin alpha

After intravenous (intravenous) injection, the active substance is distributed in extracellular fluids, while the initial half-life of the hormone (T _1/2) from the body is on average 2 hours, and the final T _1/2 is approximately 24 hours. The values of total clearance and the volume of distribution (Vss) are 0.6 l / h and 10 l, respectively. One eighth of the administered dose of follitropin alfa is excreted by the kidneys.

After subcutaneous injection, the bioavailability of the active substance of Pergoveris is on average 70%. Repeated injections lead to a threefold cumulation of the hormone in the blood when compared with a single injection. Stationary equilibrium concentration (Css) in blood is reached within 3-4 days. Follitropin alfa against the background of suppressed secretion of endogenous gonadotropins showed effective stimulation of follicular development and steroidogenesis, despite the inaccessibly low LH content for quantitative measurement.

Lutropin alpha

After intravenous injection, lutropin alfa is intensively distributed with an initial T _{1/2 of} approximately 1 hour, and is eliminated with a final T _1/2 equal to an average of 10-12 hours. Equilibrium Vss varies from 10 to 14 liters. The active substance is characterized by a linear pharmacokinetic profile, which is confirmed by the direct proportional dependence of the area under the concentration-time curve (AUC) on the administered dose. The total clearance of lutropin alfa is approximately 2 L / h, while less than 5% of the dose is excreted in the urine. In the body, the substance is retained for an average of 5 hours.

After subcutaneous injection, the hormone quickly penetrates into organs and tissues, its absolute bioavailability is about 60%, while the final T _{1/2 is} slightly lengthened. With a single administration of Pergoveris, the pharmacokinetics of the substance is comparable to that after repeated administrations, the accumulation coefficient is minimal.

With the combined use of lutropin alfa with follitropin alfa, no pharmacokinetic interaction was detected.

Indications for use

• activation of the growth and maturation of follicles in women with severe LH and FSH deficiency;
• suboptimal (insufficient) response in patients with previously performed controlled ovarian stimulation (CBS), characterized by a small number of preovulatory follicles / oocytes obtained (less than 7), or the use of high doses of FSH (3000 IU and more per cycle), or age (from 35 years and older), both individually and in combination - during the ART program: gamete / zygote transplantation into the fallopian tubes (GIFT / ZIFT), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI).

Contraindications

• bulky neoplasms or ovarian cysts not associated with polycystic ovary syndrome (PCOS);
• tumors of the pituitary gland and / or hypothalamus;
• ovarian, uterine, or breast cancer;
• gynecological bleeding of unknown etiology, including uterine;
• fibroid tumors of the uterus incompatible with pregnancy;
• congenital malformations of the female genital organs incompatible with pregnancy;
• primary ovarian failure;
• pregnancy and lactation;
• hypersensitivity to any of the constituents of Pergoveris or a combination thereof.

Pergoveris, instructions for use: method and dosage

A solution prepared from Pergoveris lyophilisate is intended exclusively for injection under the skin.

Hormonal therapy must be started and carried out only under the supervision of a physician who has the appropriate specialization and experience in infertility treatment.

The lyophilisate should be diluted with the supplied solvent immediately before the injection, the prepared solution for subcutaneous administration is used once.

After the injection, the remainder of the not injected drug, as well as empty vials and used syringes, must be disposed of immediately.

Stimulation of follicular growth and maturation in women with severe LH and FSH deficiency

It is recommended to start treatment with the introduction of the contents of 1 bottle of Pergoveris once a day (150 IU r-FSHh + 75 IU r-LHh). Since patients in this group are characterized by amenorrhea and a low level of endogenous estrogen secretion, treatment can be started any day.

The course is set individually after assessing the growth / size of the follicle during ultrasound (ultrasound monitoring) and takes into account the content of estrogen in the blood serum. If an increase in the dose of r-FSHch is required, it is recommended to increase it at intervals of 7-14 days by 37.5-75 IU of follitropin alfa. The resulting Pergoveris solution can be mixed with follitropin alfa and administered in one injection. It is allowed to increase the duration of stimulation within one of the treatment cycles up to 5 weeks.

When an optimal response is achieved, HCG is administered 1 time at a dose of 5000-10,000 IU or p-HCG at a dose of 250 μg 24–48 hours after the last injection of Pergoveris. Sexual intercourse is recommended on the day of HCG injection and the next day after injection. Alternatively, the method of intrauterine insemination (IUI) is allowed.

It may be necessary to support the luteal phase, since too low luteotropic activity (LHH / HCG) after ovulation can provoke premature corpus luteum failure. In the event of an excessive ovarian response to stimulation, therapy should be suspended and the administration of hCG delayed. Treatment can be resumed in the next cycle, starting the administration of r-FSHH with a dose lower than in the previous cycle.

Suboptimal response in patients with previously performed CBS in ART programs

It is recommended to start therapy with the introduction of r-FSHH once a day at a dose of 300 IU for 5-7 days. Starting from 6-8 days of CBS, injections of r-FSHh should be replaced by daily administration of the contents of 2 vials of Pergoveris - 300 IU r-FSHh + 150 IU r-LHh. An alternative therapy regimen can be the use of the drug in a similar daily dose, starting from the first day of CBS, carried out after desensitization of the pituitary gland.

Treatment should be continued until the required level of follicle development, as determined by the serum estrogen content in the blood and ultrasound data, adjusting the dose of r-FSHCH taking into account the severity of the effect. When increasing the dose of r-FSHCH, it is necessary to keep in mind that its maximum daily dose should not exceed 450 IU.

When an adequate level of follicular development is achieved, hCG is required in order to induce final follicular maturation and prepare for a puncture for oocyte retrieval.

With a significant increase in the ovaries on the last day of therapy, HCG administration should be abandoned to reduce the risk of ovarian hyperstimulation syndrome (OHSS). If an excessive ovarian response is observed, the course of therapy should be suspended, and hCG injections should be canceled. In the next cycle, treatment can be resumed by starting the use of Pergoveris with a lower dose than in the previous cycle.

Recommendations for self-administration of the drug

Self-administration of Pergoveris injections is allowed only in patients who are highly motivated and well trained, who must be under the constant supervision of a physician with appropriate training. The first injection of the drug should be done under the direct supervision of a healthcare professional.

The procedure for performing the manipulation:

1. Wash the hands; it is imperative that hands and all items required for use are as clean as possible.
2. Prepare a clean surface and place the following items on it: a bottle with a drug, a bottle with a solvent, a syringe, a needle for solution preparation and a needle for subcutaneous administration, two tampons soaked in an antiseptic, a container for disposal.
3. Connect the needle designed to dissolve the lyophilisate with the syringe; release the solvent bottle from the protective cap and draw air into the syringe up to the 1 ml mark. Then, piercing the rubber cap, insert a needle into the solvent bottle, push the syringe plunger, letting all the air into the bottle. Turn the bottle upside down and carefully draw all of the solvent into the syringe. Without touching the needle, carefully place the filled syringe on the work surface.
4. Remove the snap-on cap from the lyophilisate vial. Pierce the rubber cap of the vial with a syringe needle and slowly inject the solvent from the syringe into the vial. For better dissolution, stir the contents of the bottle in a circular motion, but do not shake the bottle. After dissolving the drug, which usually occurs immediately, check the transparency and purity of the prepared solution, and also make sure that there are no particles in it. With the bottle turned upside down, slowly draw the solution back into the syringe. Remove the needle from the bottle.
5. Replace the needle for preparing the solution with a thin needle for subcutaneous injection, then remove all air bubbles from the syringe. If individual bubbles are visible in the cylinder, you need to hold the syringe with the needle up and lightly tap on it so that all the air is collected in the upper part. It is required to continue pressing the piston until all bubbles disappear.
6. Immediately after that, introduce the resulting solution. The doctor must first instruct in which part of the body should be injected: into the abdomen or the front of the thigh. For the injection, it is necessary to collect the skin in a small fold and insert the needle into it at an angle of 45–90 ° in one motion. Slowly press the plunger until the entire dose is injected, then gently remove the needle and wipe the injection site with an antiseptic swab in a circular motion. Immediately place all used items and the remainder of the solution that has not been introduced into the disposal container.
7. If the next injection of Pergoveris was missed, you should not enter a double dose. In this case, it is necessary to consult a doctor, and a specialist consultation is also required in case of accidental administration of a dose exceeding the recommended one.

Side effects

Possible side reactions from the patient's systems and organs that develop during therapy with Pergoveris:

• nervous system: very often - headache; often - drowsiness;
• immune system: extremely rarely - systemic allergic reactions of varying severity, such as rash, facial edema, redness of the skin, urticaria, fever, arthralgia, difficulty breathing, generalized edema, anaphylaxis;
• heart and blood vessels: extremely rarely - thromboembolism, in most cases due to severe OHSS;
• Gastrointestinal tract: often - nausea, vomiting, flatulence, abdominal pain, abdominal colic, diarrhea;
• respiratory system: extremely rarely - in patients with bronchial asthma, aggravation of the course or exacerbation of this disease;
• local reactions: very often - varying degrees of severity of the reaction at the injection site (redness, swelling, pain, bruising);
• genitals and mammary gland: very often - ovarian cysts; often - OHSS in a mild form, accompanied by nausea, vomiting, pain in the lower abdomen, weight gain, ovarian enlargement, including as a result of the formation of cysts; OHSS of moderate severity, in which shortness of breath, ascites, pleural effusion, oliguria, fluid accumulation in the pericardial cavity may also be noted; pelvic pain, pain in the area of the mammary glands; infrequently - a severe form of OHSS in which severe forms of ascites, acute respiratory distress syndrome (ARDS) and pulmonary thromboembolism (extremely rare) may occur; rarely - torsion of the ovarian cyst, as a complication of OHSS.

When using r-FSHC, the following adverse events may develop: rarely - multiple pregnancy, ovarian apoplexy, ectopic pregnancy (if there is a history of fallopian tube diseases).

All adverse reactions that occur when using Pergoveris should be reported immediately to your doctor.

Overdose

Overdose cases of Pergoveris are unknown. Presumably, in this condition, OHSS and other undesirable effects may occur (see the "Side Effects" section).

special instructions

Pergoveris includes the active substances of gonadotropins that can cause side effects of varying severity, so it should be prescribed only by a doctor with the appropriate qualifications, who is well acquainted with the problems of infertility and methods of its treatment.

Before starting the course of therapy, the infertile couple should undergo examinations in order to exclude hypothalamic-pituitary neoplasms, hyperprolactinemia, adrenal insufficiency, hypothyroidism. In the course of treatment, it is required to regularly monitor the development of follicles based on the results of ultrasound, and, if possible, simultaneously determine the serum level of estradiol in the blood.

For patients with porphyria, as well as in the presence of porphyria in relatives, careful medical supervision is necessary during therapy. If the condition worsens or the first signs of this disease develop, it may be necessary to stop treatment.

Pergoveris in 1 dose contains 30 mg of sucrose, which should be taken into account by patients with diabetes mellitus.

Against the background of ovarian stimulation, the threat of ovarian hyperstimulation is aggravated due to the possibility of an excessively high estrogenic response and multiple development of follicles. As a result, it is necessary to use Pergoveris in the minimum effective doses.

In contrast to uncomplicated ovarian enlargement, OHSS may develop clinical symptoms with increasing severity. For severe OHSS, the following symptoms are most characteristic: a significant increase in the size of the ovaries, pain and a feeling of fullness in the abdomen, shortness of breath, weight gain, oliguria, nausea, diarrhea, and vomiting. It is also possible the appearance of disorders such as hypovolemia, electrolyte imbalance, hemoconcentration, ascites, hemoperitoneum, pleural effusion, thromboembolic disorders, ARDS. In extremely rare cases, complications such as ovarian torsion, pulmonary embolism, ischemic stroke or myocardial infarction can be recorded.

If hCG was not prescribed for the purpose of inducing ovulation, then an excessive ovarian reaction very rarely leads to the development of significant hyperstimulation. As a result, in case of an excessive response of the ovaries to stimulation, hCG is not administered, and patients are advised to refrain from coitus or use barrier methods of contraception for at least 4 days.

Since OHSS can progress rapidly (from one to several days) to a severe form, patients after using hCG should be monitored for at least 14 days. The risk of developing OHSS during anovulation is exacerbated by estradiol levels above 900 pg / ml (3300 pmol / ml) and the presence of more than 3 follicles with a diameter of at least 14 mm. Regular ultrasound and assessment of serum estradiol, as well as strict adherence to prescribed dosages, minimizes the threat of OHSS and multiple pregnancies.

With the onset of pregnancy, an increase in the severity of OHSS and an increase in its duration are possible. In most cases, the development of this complication occurs after the end of hormone therapy and reaches a maximum 7-10 days after that. OHSS passes spontaneously, usually with the onset of menstruation.

In patients with polycystic ovary syndrome, the threat of OHSS is exacerbated.

With the induction of ovulation, the frequency of multiple pregnancies and childbirth is higher compared to those in the case of natural fertilization. With multiple births, twins are the most common option. To minimize the risk of this effect, it is necessary to carefully monitor the ovarian response. The threat of multiple pregnancies in the case of ART is associated mainly with the patient's age, the number of transferred embryos and their viability.

Against the background of recent or current thromboembolic diseases, as well as with the existing risk of their development, treatment with gonadotropins can aggravate this risk or cause complications in the course of these diseases. Before starting the course of drug therapy in patients belonging to this group, it is necessary to assess the expected benefits of treatment and the potential risk. However, it is important to take into account that the pregnancy itself increases the threat of thromboembolic complications.

In the presence of a history of diseases of the fallopian tubes, the risk of ectopic pregnancy increases. The likelihood of developing the latter after using ART is 2–5%, compared with 1–1.5% in the general population.

Influence on the ability to drive vehicles and complex mechanisms

The effect of Pergoveris on the ability to drive a car or use complex mechanisms has not been studied.

Application during pregnancy and lactation

During pregnancy and during breastfeeding, the use of Pergoveris is contraindicated.

Use in the elderly

Pergoveris is not prescribed for elderly patients.

Drug interactions

There are no reports of incompatibility of the follicle-stimulating drug with other drugs / preparations.

Do not mix Pergoveris solution in one syringe with any other agent, with the exception of follitropin alfa.

Analogs

Pergoveris analogs are: Gonal-F, Follitrop, Luveris, etc.

Terms and conditions of storage

Store out of the reach of children, protected from light penetration, at a temperature not exceeding 25 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Pergoveris

As a rule, reviews of Pergoveris indicate the high efficacy of the drug when used to enhance the growth and maturation of follicles in women with severe LH and FSH deficiency, as well as in case of insufficient response during a previously performed CBS.

However, many patients point to a number of side effects associated with therapy. For example, a feeling of fullness in the ovarian region and an increase in the abdomen, which most often developed after the evening injections and intensified towards the night so much that they had to sleep on their backs. Periodic headache, breast enlargement, and in isolated cases morning fainting when getting out of bed are also noted.

Pergoveris is recommended to be used only as directed by an experienced fertility specialist and under his supervision. Regardless of the results of IVF, 2-3 months after the completion of the course, it is advised to do an ultrasound of the pelvic organs in order to make sure that ovarian stimulation did not cause any complications.

Price for Pergoveris in pharmacies

The price of Pergoveris, a lyophilisate for the preparation of a solution for subcutaneous administration (150 IU r-FSHch + 75 IU r-LHh) may be: 2650–2900 rubles. for 1 bottle, volume 3 ml + solvent.

Pergoveris: prices in online pharmacies

Drug name Price Pharmacy

Pergoveris 150 IU + 75 IU lyophilisate for the preparation of a solution for subcutaneous administration 3 ml 1 pc. 2010 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!