ستروتاید
Cetrorelix (Cetrotide)
ستروتاید

نام ژنریک

Cetrorelix acetate

شکل دارویی

اشكال دارويي:


Injection, Powder: 250 mcg, 3 mg

موارد مصرف

موارد و مقدار مصرف


مهار افزايش پيش از موعد هورمون LH در موارد افزايش تحريك تخمدان


بزرگسالان: 3 ميلي‌گرم زير جلدي در ابتدا يا اواسط فاز فوليكولار، زماني كه سطح استراديول سرمي نشان دهنده پاسخ تحريكي مناسب است معمولاً در روز هفتم تحريك (بين روزهاي 5 تا 9). در صورت عدم تجويز HCG ظرف 4 روز بعد از تزريق، روزانه بايد 25/0 ميلي‌گرم از دارو به صورت زير جلدي تا زمان تجويز HCG تزريق شود. يا 25/0 ميلي‌گرم زير جلدي به صورت رژيم چند دوزي كه يا در روز پنجم تحريك (صبح يا عصر) يا روز ششم (صبح) و ادامه آن به صورت يك بار در روز تا زمان تجويز HCG.

موارد منع مصرف

موارد منع مصرف و احتياط


موارد منع مصرف: سابقه حساسيت به سترورليكس،‌ هورمون‌هاي پپتيدي برونزاد،‌ مانيتول، GnRH و آنالوگ‌هاي GnRH و نارسائي شديد كليوي و خانم‌هاي باردار يا مشكوك به بارداري و شيرده.

عوارض جانبی دارو

عوارض جانبي


اعصاب مرکزي: سردرد.


دستگاه گوارش: تهوع.


ادراري ـ تناسلي: سندرم تحريك بيش از حد تخمدان.


مسموميت و درمان


موردي گزارش نشده است. تجويز دوز واحد 120 ميلي‌گرم بدون ايجاد علائم مسموميت توسط بيمار تحمل مي‌شود.

موارد قابل توجه

-

تداخل دارویی

تداخل دارويي


موردي گزارش نشده است.

مکانیزم اثر

تداخل دارويي


موردي گزارش نشده است.

فارماكوكینتیك

فارماكوكينتيك


جذب: دارو متعاقب تجويز زير جلدي سريعاً جذب مي‌شود. حداكثر غلظت خوني دارو در عرض 3-1 ساعت ايجاد مي‌شود.


پخش: دارو 86 درصد به پروتئين‌هاي پلاسما اتصال مي‌يابد.


متابوليسم: در عرض 24 ساعت مقادير كمي از دارو ممكن است در صفرا وارد شود.


دفع: دارو به صورت تغيير نايافته در ادرار و به صورت متابوليت از صفرا دفع مي‌شود.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: آنالوگ هورمون آزاد كننده گنادوتروپين.


طبقه‌بندي درماني: درمان عقيمي.


طبقه‌بندي مصرف در بارداري: رده X


نام‌هاي تجاري: Cetrotide


ملاحظات اختصاصي


1- دارو بايد توسط پزشك باتجربه در درمان ناباروري تجويز شود.


2- وقتي سونوگرافي تعداد كافي از فوليكول با سايز مناسب را نشان داد، به منظور القاء تخمگ‌گذاري بايد از HCG استفاده شود.


3- به منظور كاهش خطر بروز سندرم تحريك بيش از حد تخمدان، در صورت پاسخ بيش از حد تخمدان به درمان از HCG استفاده نشود.


4- پس از توصيه‌هاي لازم دارو توسط خود بيمار نيز مي‌تواند استفاده شود.


5- قبل از شروع دارو درماني احتمال بارداري بايد بررسي شود.


نكات قابل توصيه به بيمار


1- به بيمار توصيه نمائيد شكل داروئي 3 ميلي‌گرم را در دماي اتاق (25 درجه سانتي‌گراد ) و شكل داروئي 25/0 ميلي‌گرم را در يخچال (8-2 درجه سانتي‌گراد ) نگهداري نمايد.


2- به بيمار توصيه نمائيد هرگونه عارضه ناخواسته را گزارش نمايد.


3- بيمار را نسبت به اهميت تبعيت دقيق از رژيم درماني آموزش دهيد.


4- روش تجويز دقيق دارو را به بيمار آموزش دهيد.


5- به بيمار توصيه نمائيد از ناحيه تحتاني شكم جهت تزريق استفاده نمايد. در صورت استفاده از رژيم چند دوزي به منظور كاهش عارضه تحريك موضعي روزانه محل تزريق را تغيير دهد.


6- به بيمار توصيه نمائيد براي هر بار تزريق از سرنگ جداگانه استفاده نمايد.


مصرف در شيردهي: ترشح دارو در شير مشخص نيست. خانم‌ها در ايام شيردهي از دارو استفاده نكنند.


اثر بر آزمايشهاي تشخيصي


ممكن است باعث افزايش سطح GGT, AST, ALT و آلكالين فسفاتاز مي‌شود.

Cetrorelix (Cetrotide)

Cetrotide®
(cetrorelix acetate) for Injection 0.25 mg and 3 mg

FOR SUBCUTANEOUS USE ONLY

DRUG DESCRIPTION

Cetrotide® (cetrorelix acetate for injection) is a synthetic decapeptide with gonadotropin- releasing hormone (GnRH) antagonistic activity. Cetrorelix acetate is an analog of native GnRH with substitutions of amino acids at positions 1, 2, 3, 6, and 10. The molecular formula is Acetyl-D-3-(2´-naphtyl)-alanine-D-4-chlorophenylalanine-D-3-(3´-pyridyl)- alanine-L-serine-L-tyrosine-D-citruline-L-leucine-L-arginine-L-proline-D-alanine-amide, and the molecular weight is 1431.06, calculated as the anhydrous free base. The structural formula is as follows:

Cetrotide® (cetrorelix acetate) structural formula illustration

(Ac-0-Nal 1 -D-Cpa2-D-Pal3-Ser4-Tyr5-D < it6-Leu7-Arg8-Pro9-D-Ala 10-NH2)

Cetrotide® (cetrorelix acetate for injection) 0.25 mg or 3 mg is a sterile lyophilized powder intended for subcutaneous injection after reconstitution with Sterile Water for Injection, USP (pH 5-8), that comes supplied in either a 1.0 mL (for 0.25 mg vial) or 3.0 mL (for 3 mg vial) pre-filled syringe. Each vial of Cetrotide® (cetrorelix) 0.25 mg (multiple dose regimen) contains 0.26-0.27 mg cetrorelix acetate, equivalent to 0.25 mg cetrorelix, and 54.80 mg mannitol. Each vial of Cetrotide (cetrorelix) ® 3 mg (single dose regimen) contains 3.12-3.24 mg cetrorelix acetate, equivalent to 3 mg cetrorelix, and 164.40 mg mannitol.

What are the possible side effects of cetrorelix (Cetrotide)?

Stop using cetrorelix and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Approximately 3.5 % of female patients treated with cetrorelix have developed ovarian hyperstimulation syndrome (OHSS). Symptoms of OHSS include severe pelvic pain, swelling of the hands or legs, abdominal pain and swelling, shortness of breath, weight gain, low urine output, diarrhea, and nausea or vomiting. OHSS can be fatal. Notify your doctor immediately or seek emergency medical...

Read All Potential Side Effects and See Pictures of Cetrotide »

What are the precautions when taking cetrorelix (Cetrotide)?

Before using cetrorelix, tell your doctor or pharmacist if you are allergic to it; or to other hormones (e.g., GnRH); or if you have any other allergies. This product may contain inactive ingredients (such as mannitol), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of severe allergic reactions, kidney disease.

This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Breast-feeding while using this drug is not recommended because it may harm the nursing infant. Consult your doctor...

Read All Potential Precautions of Cetrotide »

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Cetrotide® (cetrorelix acetate for injection) is indicated for the inhibition of premature LH surges in women undergoing controlled ovarian stimulation.

DOSAGE AND ADMINISTRATION

Ovarian stimulation therapy with gonadotropins (FSH, hMG) is started on cycle Day 2 or 3. The dose of gonadotropins should be adjusted according to individual response. Cetrotide® (cetrorelix acetate for injection) may be administered subcutaneously either once daily (0.25 mg dose) or once (3 mg dose) during the early- to mid-follicular phase.

In the single dose regimen, 3 mg of Cetrotide® (cetrorelix) is administered when the serum estradiol level is indicative of an appropriate stimulation response, usually on stimulation day 7 (range day 5-9). If hCG has not been administered within four days after injection of Cetrotide® (cetrorelix) 3 mg, Cetrotide® (cetrorelix) 0.25 mg should be administered once daily until the day of hCG administration.

In the multiple dose regimen, 0.25 mg of Cetrotide® (cetrorelix) is administered on either stimulation day 5 (morning or evening) or day 6 (morning) and continued daily until the day of hCG administration.

When assessment by ultrasound shows a sufficient number of follicles of adequate size, hCG is administered to induce ovulation and final maturation of the oocytes. No hCG should be administered if the ovaries show an excessive response to the treatment with gonadotropins to reduce the chance of developing ovarian hyperstimulation syndrome (OHSS).

Administration

Cetrotide® (cetrorelix) 0.25 mg and 3 mg can be administered by the patient herself after appropriate instructions by her doctor.

Directions for using Cetrotide® (cetrorelix) 0.25 mg and 3 mg with the enclosed needles and pre-filled syringe:

  1. Wash hands thoroughly with soap and water.
  2. Flip off the plastic cover of the vial and wipe the aluminum ring and the rubber stopper with an alcohol swab.
  3. Twist the injection needle with the yellow mark (20 gauge) on the pre-filled syringe.
  4. Push the needle through the center of the rubber stopper of the vial and slowly inject the solvent into the vial.
  5. Leaving the syringe in the vial, gently swirl the vial until the solution is clear and without residues. Avoid forming bubbles.
  6. Draw the total contents of the vial into the syringe. If necessary, invert the vial and pull back the needle as far as needed to withdraw the entire contents of the vial.
  7. Replace the needle with the yellow mark by the injection needle with the grey mark (27 gauge).
  8. Invert the syringe and push the plunger until all air bubbles have been expelled.
  9. Choose an injection site in the lower abdominal area, preferably around, but staying at least one inch away from the navel. If you are on a multiple dose (0.25 mg) regimen, choose a different injection site each day to minimize local irritation. Use the second alcohol swab to clean the skin at the injection site and allow alcohol to dry. Gently pinch up the skin surrounding the site of injection.
  10. Inject the prescribed dose as directed by your doctor, nurse or pharmacist.
  11. Use the syringe and needles only once. Dispose of the syringe and needles properly after use. If available, use a medical waste container for disposal.

HOW SUPPLIED

Cetrotide® (cetrorelix acetate for injection) 0.25 mg is available in a carton of one packaged tray (NDC 44087-1225-1).

Each packaged tray contains: one glass vial containing 0.26 - 0.27 mg cetrorelix acetate (corresponding to 0.25 mg cetrorelix), one pre-filled glass syringe with 1 mL of Sterile Water for Injection, USP (pH 5-8), one 20 gauge needle (yellow), one 27 gauge needle (grey), and two alcohol swabs.

Cetrotide® (cetrorelix acetate for injection) 3 mg is available in a carton of one packaged tray (NDC 44087-1203-1). Each packaged tray contains: one glass vial containing 3.12 - 3.24 mg cetrorelix acetate (corresponding to 3 mg cetrorelix), one pre-filled glass syringe with 3 mL of Sterile Water for Injection, USP (pH 5-8), one 20 gauge needle (yellow), one 27 gauge needle (grey), and two alcohol swabs.

Storage

Cetrotide® (cetrorelix) 3 mg: Store at 25?C (77?F); excursions permitted to 15-30?C (59-86?F) [see USP Controlled Room Temperature]. Store the packaged tray in the outer carton.

Cetrotide® (cetrorelix) 0.25 mg: Store refrigerated, 2-8?C (36-46?F). Store the packaged tray in the outer carton.

Manufactured for: EMD Serono, Inc., Rockland, MA 02370, USA. April 2008. FDA Rev date: 4/4/2008

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The safety of Cetrotide® (cetrorelix acetate for injection) in 949 patients undergoing controlled ovarian stimulation in clinical studies was evaluated. Women were between 19 and 40 years of age (mean: 32). 94.0 % of them were Caucasian. Cetrotide® (cetrorelix) was given in doses ranging from 0.1 mg to 5 mg as either a single or multiple dose.

Table 3 shows systemic adverse events, reported in clinical studies without regard to causality, from the beginning of Cetrotide® (cetrorelix) treatment until confirmation of pregnancy by ultrasound at an incidence ≥ 1% in Cetrotide® (cetrorelix) treated subjects undergoing COS.

Table 3: Adverse Events in ≥ 1%


(WHO preferred term)
Cetrotide* N=949
% (n)
Ovarian Hyperstirnulation Syndrome# 3.5(33)
Nausea 1,3(12)
Headache 1.1 (10)
# Intensity moderate or severe, or WHO Grade II or III, respectively

Local site reactions (e.g. redness, erythema, bruising, itching, swelling, and pruritus) were reported. Usually, they were of a transient nature, mild intensity and short duration. During post-marketing surveillance, rare cases of hypersensitivity reactions including anaphylactoid reactions have been reported.

Two stillbirths were reported in Phase 3 studies of Cetrotide® (cetrorelix) .

Congenital Anomalies

Clinical follow-up studies of 316 newborns of women administered Cetrotide® (cetrorelix) were reviewed. One infant of a set of twin neonates was found to have anencephaly at birth and died after four days. The other twin was normal. Developmental findings from ongoing baby follow-up included a child with a ventricular septal defect and another child with bilateral congenital glaucoma.

Four pregnancies that resulted in therapeutic abortion in Phase 2 and Phase 3 controlled ovarian stimulation studies had major anomalies (diaphragmatic hernia, trisomy 21, Klinefelter syndrome, polymalformation, and trisomy 18). In three of these four cases, intracytoplasmic sperm injection (ICSI) was the fertilization method employed; in the fourth case, in vitro fertilization (IVF) was the method employed.

The minor congenital anomalies reported include: supernumerary nipple, bilateral strabismus, imperforate hymen, congenital nevi, hemangiomata, and QT syndrome.

The causal relationship between the reported anomalies and Cetrotide® (cetrorelix) is unknown. Multiple factors, genetic and others (including, but not limited to ICSI, IVF, gonadotropins, and progesterone) make causal attribution difficult to study.

Read the Cetrotide (cetrorelix) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No formal drug interaction studies have been performed with Cetrotide® (cetrorelix) .

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Cetrotide® (cetrorelix acetate for injection) should be prescribed by physicians who are experienced in fertility treatment. Before starting treatment with Cetrotide (cetrorelix) ®, pregnancy must be excluded (see CONTRAINDICATIONS and PRECAUTIONS).

PRECAUTIONS

General

Cases of hypersensitivity reactions, including anaphylactoid reactions with the first dose, have been reported during post-marketing surveillance (see ADVERSE REACTIONS). A severe anaphylactic reaction associated with cough, rash, and hypotension, was observed in one patient after seven months of treatment with Cetrotide® (cetrorelix) (10 mg/day) in a study for an indication unrelated to infertility.

Special care should be taken in women with signs and symptoms of active allergic conditions or known history of allergic predisposition. Treatment with Cetrotide® (cetrorelix) is not advised in women with severe allergic conditions.

Laboratory Tests

After the exclusion of preexisting conditions, enzyme elevations (ALT, AST, GGT, alkaline phosphatase) were found in 1-2% of patients receiving Cetrotide® (cetrorelix) during controlled ovarian stimulation. The elevations ranged up to three times the upper limit of normal. The clinical significance of these findings was not determined.

During stimulation with human menopausal gonadotropin, Cetrotide® (cetrorelix) had no notable effects on hormone levels aside from inhibition of LH surges.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenicity studies in animals have not been performed with cetrorelix acetate. Cetrorelix acetate was not genotoxic in vitro (Ames test, HPRT test, chromosome aberration test) or in vivo (chromosome aberration test, mouse micronucleus test). Cetrorelix acetate induced polyploidy in CHL-Chinese hamster lung fibroblasts, but not in V79-Chinese hamster lung fibroblasts, cultured peripheral human lymphocytes or in an in vitro micronucleus test in the CHL-cell line. Treatment with 0.46 mg/kg cetrorelix acetate for 4 weeks resulted in complete infertility in female rats which was reversed 8 weeks after cessation of treatment.

Pregnancy Category X

(see CONTRAINDICATIONS)

Cetrotide® (cetrorelix) is contraindicated in pregnant women.

When administered to rats for the first seven days of pregnancy, cetrorelix acetate did not affect the development of the implanted conceptus at doses up to 38 µg/kg(approximately 1 times the recommended human therapeutic dose based on body surface area). However, a dose of 139 µg/kg (approximately 4 times the human dose) resulted in a resorption rate and a post-implantation loss of 100%.

When administered from day 6 to near term to pregnant rats and rabbits, very early resorptions and total implantation losses were seen in rats at doses from 4.6 µg/kg (0.2 times the human dose) and in rabbits at doses from 6.8 µg/kg (0.4 times the human dose). In animals that maintained their pregnancy, there was no increase in the incidence of fetal abnormalities.

The fetal resorption observed in animals is a logical consequence of the alteration in hormonal levels affected by the antigonadotrophic properties of Cetrotide® (cetrorelix) , which could result in fetal loss in humans as well. Therefore, this drug should not be used in pregnant women.

Nursing Mothers

It is not known whether Cetrotide® (cetrorelix) is excreted in human milk. Because many drugs are excreted in human milk, and because the effects of Cetrotide® (cetrorelix) on lactation and/or the breast-fed child have not been determined, Cetrotide® (cetrorelix) should not be used by nursing mothers.

Geriatric Use

Cetrotide® (cetrorelix) is not intended to be used in subjects aged 65 and over.

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There have been no reports of over-dosage with Cetrotide® (cetrorelix) 0.25 mg or 3 mg in humans. Single doses up to 120 mg Cetrotide® (cetrorelix) have been well tolerated in patients treated for other indications without signs of over-dosage.

CONTRAINDICATIONS

Cetrotide® (cetrorelix acetate for injection) is contraindicated under the following conditions:

  1. Hypersensitivity to cetrorelix acetate, extrinsic peptide hormones or mannitol.
  2. Known hypersensitivity to GnRH or any other GnRH analogs.
  3. Known or suspected pregnancy, and lactation (see PRECAUTIONS).
  4. Severe renal impairment

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

GnRH induces the production and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the gonadotrophic cells of the anterior pituitary. Due to a positive estradiol (E2) feedback at midcycle, GnRH liberation is enhanced resulting in an LH-surge. This LH-surge induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization as indicated by rising progesterone levels. Cetrotide® (cetrorelix) competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner. The onset of LH suppression is approximately one hour with the 3 mg dose and two hours with the 0.25 mg dose. This suppression is maintained by continuous treatment and there is a more pronounced effect on LH than on FSH. An initial release of endogenous gonadotropins has not been detected with Cetrotide® (cetrorelix) , which is consistent with an antagonist effect. The effects of Cetrotide® (cetrorelix) on LH and FSH are reversible after discontinuation of treatment. In women, Cetrotide® (cetrorelix) delays the LH-surge, and consequently ovulation, in a dose- dependent fashion. FSH levels are not affected at the doses used during controlled ovarian stimulation. Following a single 3 mg dose of Cetrotide® (cetrorelix) , duration of action of at least 4 days has been established. A dose of Cetrotide® (cetrorelix) 0.25 mg every 24 hours has been shown to maintain the effect.

Pharmacokinetics

The pharmacokinetic parameters of single and multiple doses of Cetrotide* (cetrorelix acetate for injection) in adult healthy female subjects are summarized in Table 1.

Table 1: Pharmacokinetic parameters of Cetrotide® (cetrorelix) following 3 mg single or 0.25 mg single and multiple (daily for 14 days) subcutaneous (sc) administration.

  Single dose
3 mg
Single dose
0.25 mg
Multiple dose
0.25 mg
No. of subjects 12 12 12
tmax* [h] 1.5
(0.5-2)
1.0
(0.5-1.5)
1.0
(0,5-2)
t½* [h] 62.8
(38.2-108)
5.0
(2.4-48.8)
20.6
(4.1-179.3)
Cmax[ng/ml] 28.5
(22,5-36.2)
4.97
(4.17-5,92)
6,42
(5.18-7.96)
AUC [ng·h/ml] 536
(451-636)
31.4
(23.4-42.0)
44.5
(36.7-54,2)
CL [ml/min·kg] 1.28a    
VZ [l/kg] 1.16a
Geometric mean (95%CIin), arithmetic mean, or * median (min-max)
tmax Time to reach observed maximum plasma concentration
t½ Elimination half-life
Cmax Maximum plasma concentration; multiple dose Css,max
AUC Area under the curve; single dose AUC0-inf multiple aose AUCt
CL Total plasma clearance
Vz Volume of distribution
a Based on iv administration (n=6, separate study 0013)

Absorption

Cetrotide® (cetrorelix) is rapidly absorbed following subcutaneous injection, maximal plasma concentrations being achieved approximately one to two hours after administration. The mean absolute bioavailability of Cetrotide® (cetrorelix) following subcutaneous administration to healthy female subjects is 85%.

Distribution

The volume of distribution of Cetrotide® (cetrorelix) following a single intravenous dose of 3 mg is about 1 l/kg. In vitroprotein binding to human plasma is 86%.

Cetrotide® (cetrorelix) concentrations in follicular fluid and plasma were similar on the day of oocyte pick-up in patients undergoing controlled ovarian stimulation. Following subcutaneous administration of Cetrotide® 0.25 mg and 3 mg, plasma concentrations of cetrorelix were below or in the range of the lower limit of quantitation on the day of oocyte pick-up and embryo transfer.

Metabolism

After subcutaneous administration of 10 mg Cetrotide® (cetrorelix) to females and males, Cetrotide® (cetrorelix) and small amounts of (1-9), (1-7), (1-6), and (1-4) peptides were found in bile samples over 24 hours.

In in vitro studies, Cetrotide® (cetrorelix) was stable against phase I- and phase II-metabolism. Cetrotide® (cetrorelix) was transformed by peptidases, and the (1-4) peptide was the predominant metabolite.

Excretion

Following subcutaneous administration of 10 mg cetrorelix to males and females, only unchanged cetrorelix was detected in urine. In 24 hours, cetrorelix and small amounts of the (1-9), (1-7), (1-6), and (1-4) peptides were found in bile samples. 2-4% of the dose was eliminated in the urine as unchanged cetrorelix, while 5-10% was eliminated as cetrorelix and the four metabolites in bile. Therefore, only 7-14% of the total dose was recovered as unchanged cetrorelix and metabolites in urine and bile up to 24 hours. The remaining portion of the dose may not have been recovered since bile and urine were not collected for a longer period of time.

Special Populations

Pharmacokinetic investigations have not been performed either in subjects with impaired renal or liver function, or in the elderly, or in children (see PRECAUTIONS).

Pharmacokinetic differences in different races have not been determined.

There is no evidence of differences in pharmacokinetic parameters for Cetrotide® (cetrorelix) between healthy subjects and patients undergoing controlled ovarian stimulation.

Drug-Drug Interactions

No formal drug-drug interaction studies have been performed with Cetrotide® (see PRECAUTIONS).

Clinical Studies

Seven hundred thirty two (732) patients were treated with Cetrotide® (cetrorelix acetate for injection) in five (two Phase 2 dose-finding and three Phase 3) clinical trials. The clinical trial population consisted of Caucasians (95.5%) and Black, Asian, Arabian and others (4.5%). Women were between 19 and 40 years of age (mean: 32). The studies excluded subjects with polycystic ovary syndrome (PCOS), subjects with low or no ovarian reserve, and subjects with stage III-IV endometriosis.

Two dose regimens were investigated in these clinical trials, either a single dose per treatment cycle or multiple dosing. In the Phase 2 studies, a single dose of 3 mg was established as the minimal effective dose for the inhibition of premature LH surges with a protection period of at least 4 days. When Cetrotide® (cetrorelix) is administered in a multidose regimen, 0.25 mg was established as the minimal effective dose. The extent and duration of LH-suppression is dose dependent.

In the Phase 3 program, efficacy of the single 3 mg dose regimen of Cetrotide® (cetrorelix) and the multiple 0.25 mg dose regimen of Cetrotide® (cetrorelix) was established separately in two adequate and well controlled clinical studies utilizing active comparators. A third non-comparative clinical study evaluated only the multiple 0.25 mg dose regimen of Cetrotide® (cetrorelix) . The ovarian stimulation treatment with recombinant FSH or human menopausal gonadotropin (hMG) was initiated on day 2 or 3 of a normal menstrual cycle. The dose of gonadotropins was administered according to the individual patient's disposition and response.

In the single dose regimen study, Cetrotide® (cetrorelix) 3 mg was administered on the day of controlled ovarian stimulation when adequate estradiol levels (400 pg/ml) were obtained, usually on day 7 (range day 5-12). If hCG was not given within 4 days of the 3 mg dose of Cetrotide® (cetrorelix) , then 0.25 mg of Cetrotide® (cetrorelix) was administered daily beginning 96 hours after the 3 mg injection until and including the day of hCG administration.

In the two multiple dose regimen studies, Cetrotide® (cetrorelix) 0.25 mg was started on day 5 or 6 of COS. Both gonadotropins and Cetrotide® (cetrorelix) were continued daily (multiple dose regimen) until the injection of human chorionic gonadotropin (hCG).

Oocyte pick-up (OPU) followed by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) as well as embryo transfer (ET) were subsequently performed. The results for Cetrotide® (cetrorelix) are summarized below in Table 2.

Table 2: Results of Phase 3 Clinical Studies with Cetrotide* (cetrorelix acetate for injection) 3 mg in a single dose (sd) regimen and 0.25 mg in a multiple dose (md) regimen.

Parameter Cetrotide 3 mg
(5d, active comparator study)
Cetrotide* 0.25 mg
(md, active comparator study)
Cetrotide* 0.25 mg
(md, non- comparative study)
No. of subjects 115 159 303
hCG administered [%] 98.3 96.2 96.0
Oocyte pick-up [%] 95.3 94.3 93.1
LH-surge[%](LH ≥ 10 U/L and Pa ≥ 1 ng/mL)b 0.0 1.9 1.0
Serum E2 [pg/ml] at day hCGc,d 1125
(470-2952)
1064
(341-2531)
1185
(311-3676)
Serum LH [U/L] atday hCGc,d 1.0
(0.5-2.5)
1.5
(0.5-7.6)
1.1
(0.5-3.5)
No. of follicles ≥ 11 mm at day hCGe 11.2*5.5 10.8*5.2 10.4±4.5
No. of oocytes: IVFe
ICSIe
9.2±5.2
10.0±4.2
7.6±4.3
10.1±5.6
S.5±5.1
9.3±5.9
Fertilization rate: IVFe
ICSIe
0.4E±0.33
0.66±0.29
0.62±0.26
0.63±0.29
0.60±0.26
0.61 ±0.25
No. of embryos transferrede 2.6±0.9 2.1±0.6 2.7±1.0
Clinical pregnane/ rate [%]
  per attempt
  per subject with ET

22.6
26.3

20.8
24.1

19.8
23.3
a frcgesterone
b Following initiation of Cetrotide (cetrorelix) therapy
c Morning valuesd
d Median with 5th - 95th percentiles
e Mean ± standard deviation

In addition to IVF and ICSI, one pregnancy was obtained after intrauterine insemination. In the five Phase 2 and Phase 3 clinical trials, 184 pregnancies have been reported out of a total of 732 patients (including 21 pregnancies following the replacement of frozen- thawed embryos).

In the 3 mg regimen, 9 patients received an additional dose of 0.25 mg of Cetrotide® (cetrorelix) and two other patients received two additional doses of 0.25 mg Cetrotide® (cetrorelix) . The median number of days of Cetrotide® (cetrorelix) multiple dose treatment was 5 (range 1-15) in both studies. No drug related allergic reactions were reported from these clinical studies.

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Prior to therapy with Cetrotide® (cetrorelix acetate for injection), patients should be informed of the duration of treatment and monitoring procedures that will be required. The risk of possible adverse reactions should be discussed (see ADVERSE REACTIONS).

Cetrotide® (cetrorelix) should not be prescribed if a patient is pregnant.

If Cetrotide® (cetrorelix) is prescribed to patients for self-administration, information for proper use is given in the Patient Leaflet (see below).

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Prior to therapy with Cetrotide® (cetrorelix acetate for injection), patients should be informed of the duration of treatment and monitoring procedures that will be required. The risk of possible adverse reactions should be discussed (see ADVERSE REACTIONS).

Cetrotide® (cetrorelix) should not be prescribed if a patient is pregnant.

If Cetrotide® (cetrorelix) is prescribed to patients for self-administration, information for proper use is given in the Patient Leaflet (see below).

Last reviewed on RxList: 5/14/2008
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Cetrotide Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

CETRORELIX - INJECTION

(SE-troe-REL-ix)

COMMON BRAND NAME(S): Cetrotide

USES: Cetrorelix is used in women having certain fertility treatments (controlled ovarian stimulation). This medication prevents eggs from being released too early (premature ovulation) by blocking the hormone (gonadotropin-releasing hormone-GnRH) that causes eggs to be released from the ovaries. This gives the eggs time to develop properly.

This medication is usually used with another hormone (human chorionic gonadotropin-hCG) to help you become pregnant. HCG is used to cause the growth and release of a mature egg (ovulation).

This medication must not be used if you are already pregnant. Your doctor may order a pregnancy test before your first dose.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before starting this medication and each time you get a refill. You will be trained by a health care professional on how to properly use this medication. Learn and understand all preparation and usage instructions.

Follow all instructions for proper mixing with the correct fluid provided with this medication. Before using, check the solution visually for particles or discoloration. If either is present, do not use the liquid. Use the solution immediately after the medication is mixed. Discard any unused solution. If you have questions regarding the use of this medication, consult your pharmacist.

Wash hands with soap and water before using this medication. Before injecting each dose, clean the injection site with rubbing alcohol. If you are injecting daily, it is important to change the location of the injection site every day to avoid discomfort and problem areas under the skin.

Inject this medication under the skin in your lower abdomen, at least 1 inch (2.5 centimeters) away from your navel, as directed by your doctor. Your doctor may direct you to inject a single dose or to inject a smaller dose once daily for several days. The timing of your injection, your dosage, and your length of treatment is based on your medical condition and response to treatment. When an ultrasound shows that you are ready, a second medication (hCG) is usually injected to cause the eggs to mature and release (ovulation).

Be sure to keep all medical appointments so your doctor can closely monitor your response to determine the dosage that is right for you and the time you should use the next medication.

Use this medication exactly as directed by your doctor in order to get the most benefit from it. If your doctor has directed you to inject this medication more than once, use it at the same time each day.

Learn how to store and discard needles and medical supplies safely. Consult your pharmacist.

Disclaimer

Cetrotide Consumer (continued)

SIDE EFFECTS: Nausea, headache, and pain/bruising/redness/swelling/itching at the injection site may occur. If any of these effects persist or worsen, tell your doctor promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe pain/swelling/cramping in the abdomen.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice any other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Cetrotide (cetrorelix) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using cetrorelix, tell your doctor or pharmacist if you are allergic to it; or to other hormones (e.g., GnRH); or if you have any other allergies. This product may contain inactive ingredients (such as mannitol), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of severe allergic reactions, kidney disease.

This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Breast-feeding while using this drug is not recommended because it may harm the nursing infant. Consult your doctor before breast-feeding.

Disclaimer

Cetrotide Consumer (continued)

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., ultrasound) may be performed to monitor your progress.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule. Do not double the dose to catch up.

STORAGE: Store the 3-milligram strength at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted.

Store the 0.25-milligram strength in the refrigerator at 36-46 degrees F (2-8 degrees C). Protect from light.

Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised April 2012. Copyright(c) 2012 First Databank, Inc.

Cetrotide Patient Information Including Side Effects

Brand Names: Cetrotide

Generic Name: cetrorelix (injectable) (Pronunciation: SE troe REL ix)

What is cetrorelix (Cetrotide)?

Cetrorelix blocks the effects of the naturally occurring gonadotropin-releasing hormone (GnRH). GnRH controls the release of another hormone, luteinizing hormone (LH), which induces ovulation (release of an egg from the ovary) during the menstrual cycle. During hormone treatment for ovarian stimulation, premature ovulation may lead to eggs that are not suitable for fertilization. Cetrorelix blocks this undesirable premature ovulation.

Cetrorelix is used to prevent premature ovulation during controlled ovarian stimulation.

Cetrorelix may also be used for purposes other than those listed in this medication guide.

What are the possible side effects of cetrorelix (Cetrotide)?

Stop using cetrorelix and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Approximately 3.5 % of female patients treated with cetrorelix have developed ovarian hyperstimulation syndrome (OHSS). Symptoms of OHSS include severe pelvic pain, swelling of the hands or legs, abdominal pain and swelling, shortness of breath, weight gain, low urine output, diarrhea, and nausea or vomiting. OHSS can be fatal. Notify your doctor immediately or seek emergency medical attention if you develop any of these symptoms.

Other side effects may also occur. Notify your doctor if you experience

  • nausea;
  • headache; or
  • redness, bruising, itching, or swelling at the injection site.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to FDA at 1-800-FDA-1088.

Read the Cetrotide (cetrorelix) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about cetrorelix (Cetrotide)?

Talk to your doctor before using cetrorelix if you have kidney disease or any renal (kidney) problems. Cetrorelix should not be used in patients with severe renal impairment.

Side Effects Centers

Cetrotide Patient Information including How Should I Take

What should I discuss with my healthcare provider before using cetrorelix (Cetrotide)?

Do not use cetrorelix without first talking to your doctor if you have ever had an allergic reaction to gonadotropin-releasing hormone (Lupron, Antagon, Goserelin, Naferelin, Synarel, Zoladex), mannitol, or a medicine similar to cetrorelix.

It is not known whether cetrorelix passes into breast milk. Do not use cetrorelix without first talking to your doctor if you are breast-feeding a baby.

Talk to your doctor before using cetrorelix if you have kidney disease or any renal (kidney) problems. Cetrorelix should not be used in patients with severe renal impairment.

How should I use cetrorelix (Cetrotide)?

Use cetrorelix exactly as directed by your doctor. If you do not understand these directions, ask your doctor, nurse, or pharmacist to explain them to you.

Cetrorelix is intended for subcutaneous (under the skin) administration. If you are administering this medication at home, your doctor will give you detailed instructions on how to mix the solution and administer the injection. Do not inject cetrorelix if you are not sure how.

Cetrorelix may be prescribed for use as a single dose (3 mg), or for use once a day (0.25 mg). Your doctor will determine which treatment regimen is best for you. Follow your doctor's instructions.

Wash your hands well with soap and water before preparing and administering this medication.

To prepare the injection:

  • On a clean surface, lay out everything that you need. Flip off the plastic cover of the vial. Wipe the aluminum ring and the rubber stopper with an alcohol wipe. Take the injection needle with the yellow mark and remove the wrapping. Take the pre-filled syringe (filled with sterile water for injection) and remove the cover. Put the needle on the pre-filled syringe and remove the cover. Push the needle through the center of the rubber stopper of the vial. Inject the water into the vial by slowly pushing the plunger of the syringe. Leave the syringe on the vial. Gently shake the vial until the solution is clear and without residue. Avoid forming bubbles during dissolution.
  • Withdraw the entire contents of the vial into the syringe. If liquid is left in the vial, invert the vial, pull back the needle until the opening of the needle is just inside the stopper. If you look from the side through the gap in the stopper, you can control the movement of the needle and the liquid. It is important to withdraw the entire contents of the vial. Detach the syringe from the needle and lay down the syringe.
  • Take the injection needle with the grey mark and remove its wrapping. Put the needle on the syringe and remove the cover of the needle. Invert the syringe and push the plunger until all air bubbles have been pushed out. Do not touch the needle or allow the needle to touch any surface.

To administer the injection:

  • Choose an injection site at the lower abdominal wall, preferably around the belly button. If you are on a multiple dose (0.25 mg) regimen, choose a different injection site each day to minimize local irritation. Take the second alcohol wipe and clean the skin at the injection site. Inject the prescribed dose as directed by your doctor or healthcare provider.

Use the solution immediately after it is mixed. Throw away any medicine that is left over.

Never reuse a needle or syringe. Dispose of all needles and syringes in an appropriate, puncture-resistant disposal container.

Store the 3 mg cetrorelix product at room temperature, away from direct light, moisture, and heat. Keep the packaged tray in the outer carton to protect it from light.

Store the 0.25 mg cetrorelix product in the refrigerator in the original outer carton , to protect it from light and moisture.

Side Effects Centers

Cetrotide Patient Information including If I Miss a Dose

What happens if I miss a dose (Cetrotide)?

Contact your doctor if you miss a dose of cetrorelix. Do not use a double dose of this medication without first talking to your doctor.

What happens if I overdose (Cetrotide)?

An overdose of cetrorelix is unlikely to threaten life. If an overdose of cetrorelix is suspected, notify your doctor immediately to check whether an adjustment of the further ovarian stimulation procedure is required. If you cannot contact your doctor, call an emergency room or poison control center for advice.

What should I avoid while using cetrorelix (Cetrotide)?

There are no restrictions on food, beverages, or activity during therapy with cetrorelix unless otherwise directed by your doctor.

What other drugs will affect cetrorelix (Cetrotide)?

It is not known whether other medications will interact with cetrorelix. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

Where can I get more information?

Your pharmacist can provide more information about cetrorelix.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 4.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

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