Cetrotide

Cetrotide is part of the drug class:

• Anti gonadotropin releasing hormones

Serious side effects have been reported with Cetrotide. See the “Cetrotide Precautions” section.

Common side effects of Cetrotide include the following:

• ovarian hyperstimulation syndrome
• pain and/or bruising at the site of injection
• headache
• nausea

This is not a complete list of Cetrotide side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Cetrotide, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Cetrotide falls into category X. In animal studies, pregnant animals were given this medication and had some babies born with problems. Cetrotide can cause harm to the unborn baby and can even result in loss of the baby. There are no situations where the benefits of the medication for the mother outweigh the risks of harm to the baby. These medicines should never be used by pregnant women.

General

• Should be prescribed by clinicians experienced in infertility treatment.1

• Prior to use of cetrorelix, initiate controlled ovarian stimulation (COS) therapy with gonadotropins (FSH or hMG) usually on day 2 or 3 of the menstrual cycle.1 2 3 4 b Individualize dosage of gonadotropins based on the patient’s ovarian response to allow sufficient follicular development.1 2 3 4

• Initiate therapy with cetrorelix on days 5–7 of COS therapy and continue COS therapy until sufficient follicular growth is verified (e.g., ultrasound).1 2 3 4

• When ultrasound assessement shows sufficient follicular maturation, discontinue COS therapy and cetrorelix and administer hCG to complete final follicular maturation and induce ovulation.1 4 Perform oocyte retrieval, followed by in vitro fertilization or intracytoplasmic sperm injection, with subsequent attempts at implantation and pregnancy.1 2 3 4

• Do not administer hCG if the ovaries show an excessive response to treatment with gonadotropins because of an increased risk of ovarian hyperstimulation syndrome.1

Administration

Sub-Q Administration

Administer by sub-Q injection either once as a single dose or once daily in multiple smaller doses in early- to mid-follicular phase of the menstrual cycle.1

For the single-dose regimen, administer by sub-Q injection once on the day of COS when the serum estradiol concentration is indicative of an appropriate stimulation response (400 pg/mL), usually on stimulation day 7 (range: day 5–9).1 2

For the multiple-dose regimen, administer by sub-Q injection on day 5 (morning or evening) or on the morning of day 6 of COS and continue daily until an adequate follicular response is achieved.1 3 4 5

Administer using 27-gauge needle (provided by manufacturer) into lower abdominal area, preferably around, but ≥2.54 cm (1 inch) from the umbilicus.b With multiple doses, rotate injection sites to minimize local irritation.b

Reconstitute vial containing 0.25 or 3 mg of cetrorelix acetate sterile lyophilized powder with 1 or 3 mL, respectively, of sterile water for injection using the prefilled syringe and 20-gauge needle (provided by manufacturer).1 b

Gently agitate vial until powder is completely dissolved;1 b avoid formation of bubbles.1 b Withdraw entire contents of the vial into the syringe, then replace 20-gauge needle with 27-gauge needle (provided by manufacturer) for administration.1 b

Reconstituted solutions contain no preservatives;1 prepare solutions immediately before use.b

Dosage

Available as cetrorelix acetate; dosage expressed in terms of cetrorelix.1 5

Adults

3 mg once as a single dose in combination with COS therapy; initiate usually on day 7 of COS therapy (range: day 5–9).1 2 (See General and also Administration, under Dosage and Administration.)

If hCG is not administered within 4 days of initial cetrorelix injection (i.e., insufficient follicular maturation), administer supplemental cetrorelix dosage of 0.25 mg once daily; initiate 96 hours after first injection and continue until and including the day of hCG administration.1 2 5 (See Duration under Pharmacokinetics.)

0.25 mg once daily in combination with COS therapy; initiate on day 5 (morning or evening) or on the morning of day 6 of COS therapy.1 3 4 Continue until an adequate follicular response to stimulation therapy is achieved; a median duration of 5 days was required in clinical trials.1 3 4 (See General under Dosage and Administration.)

Contraindications

• Known hypersensitivity to cetrorelix acetate, mannitol, or any ingredient in the formulation.1

• Known hypersensitivity to extrinsic peptide hormones, GnRH, or any other GnRH analog.1

• Severe renal impairment.a b

• Known or suspected pregnancy or lactation.1 b (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Warnings

May cause fetal harm; embryolethality reported in animals.a Congenital anomalies reported in women who received cetrorelix during pregnancy.1

Exclude pregnancy prior to initiation of therapy.1

Sensitivity Reactions

Severe anaphylaxis associated with cough, rash, and hypotension during therapy exceeding recommended dosages (10 mg daily for 7 months for an indication other than infertility) reported.1 Monitor patients carefully after initial injection.1 5 Take special care in women with signs and symptoms of active allergic conditions or history of allergies.a Use not recommended in women with severe allergic conditions.a

General Precautions

Elevations in liver function test results including ALT, AST, γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP), and alkaline phosphatase reported.1

Specific Populations

Category X.1 May result in fetal loss secondary to antigonadotropic properties.1 (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Not known whether cetrorelix is distributed into milk.1 Use not recommended.1

Not intended for use in pediatric patients.5

Not intended for use in patients ≥65 years of age.1

Common Adverse Effects

Ovarian hyperstimulation syndrome,1 2 3 4 nausea,1 headache.1

• Competitively blocks GnRH receptors on the anterior pituitary and induces a rapid, reversible suppression of LH and FSH secretion.1 2 3 4 5

• Prevents the LH surges associated with COS therapy with gonadotropins.1 3 4 By delaying premature ovulation, oocytic meiosis, and luteinization, sufficient follicular growth is more likely to occur with such stimulation therapy.1 3 4

• Improves implantation and pregnancy rates associated with ART programs.1 4 5

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Geriatric

Cetrorelix is not intended for use in patients over the age of 65 years.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Kidney disease—May increase your chance of side effects from cetrorelix.

Take this medicine only as directed by your doctor. If you are to begin on Day 5, count the first day of your menstrual period as Day 1. Beginning on Day 5, take the correct dose every day for as many days as your doctor ordered. To help you to remember to take your dose of medicine, take it at the same time every day.

• Read the paper with information for the patient carefully.
• Understand and use the proper method of safely preparing the medicine.
• Wash your hands with soap and water and use a clean work area to prepare your injection.
• Make sure you clearly understand and carefully follow your doctor's instructions on how to give yourself an injection, including using the proper needle and syringe. Remember to change the site of injection to different areas to prevent skin problems from developing.
• Throw away needles, syringes, bottles, and unused medicine after the injection in a safe manner.

Tell your doctor when you use the last dose of cetrorelix . Cetrorelix often requires that another hormone called human chorionic gonadotropin (hCG) be given as a single dose the day after the last dose of cetrorelix is given. Your doctor will give you this medicine or arrange for you to get this medicine at the right time.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For treatment of female infertility:
    • Adults—3 milligrams (mg) injected under the skin one time on Day 7 of your menstrual cycle, or 0.25 mg injected under the skin starting on Day 5 or 6 of your menstrual cycle and continuing until HCG administration occurs.

Missed Dose

Call your doctor or pharmacist for instructions.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Store the 0.25 mg vials in the refrigerator. Store the 3 mg vials at room temperature.

It is very important that your doctor check you using ultrasound examination at regular visits to make sure that you are ready for injection with another drug (HCG) to induce ovulation.

Call your doctor immediately if you have taken more of the medication than your doctor ordered..

• It is used to help women get pregnant.
• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Cough.
• Very bad dizziness or passing out.
• Ovarian hyperstimulation syndrome (OHSS) is a very bad side effect that may happen in some women who use this medicine. Call your doctor right away if you have very bad stomach pain or bloating; very upset stomach, throwing up, or loose stools (diarrhea); a big weight gain; shortness of breath; or change in how much urine is passed.

Cetrotide® 0.25 mg

Active ingredient: cetrorelix acetate

Summary

Cetrotide® blocks the effects of a natural hormone, called gonadotropin-releasing hormone (GnRH). GnRH controls the secretion of another hormone, called luteinizing hormone (LH), which induces ovulation during the menstrual cycle. During hormone treatment for ovarian stimulation, premature ovulation may lead to eggs that are not suitable for fertilization. Cetrotide® blocks such undesirable premature ovulation.

Uses

Cetrotide® is used to prevent premature ovulation during controlled ovarian stimulation.

General Cautions

Do not use Cetrotide® if you

• have kidney disease
• are allergic to cetrorelix acetate, mannitol or exogenous peptide hormones (medicines similar to Cetrotide®) or
• are pregnant, or think that you might be pregnant, or if you are breast-feeding.

Consult your doctor before taking Cetrotide® if you have had severe allergic reactions.

Proper Use

Ovarian stimulation therapy is started on cycle Day 2 or 3. Cetrotide® 0.25 mg is injected under the skin once daily , as directed by your physician. When an ultrasound examination shows that you are ready, another drug (hCG) is injected to induce ovulation.

How should you use Cetrotide®?

You may self-inject Cetrotide® after special instruction from your doctor.

To fully benefit from Cetrotide®, please read carefully and follow the instructions given below, unless your doctor advises you otherwise.

Cetrotide® is for injection under the skin of the lower abdominal area, preferably around, but staying at least one inch away from the belly button. Choose a different injection site each day to minimize local irritation.

Dissolve Cetrotide® powder only with the water contained in the pre-filled syringe. Do not use a Cetrotide® solution if it contains particles or if it is not clear.

Before you inject Cetrotide® yourself, please read the following instructions carefully:

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

SPECIAL ADVICE

What do you do if you have used too much Cetrotide®?

Contact your doctor in case of overdosage immediately to check whether an adjustment of the further ovarian stimulation procedure is required.

Possible Side Effects

Mild and short lasting reactions may occur at the injection site like reddening, itching, and swelling. Nausea and headache have also been reported.

Call your doctor if you have any side effect not mentioned in this leaflet or if you are unsure about the effect of this medicine.

Storage

How is Cetrotide® to be stored?

Store Cetrotide® in a cool dry place protected from excess moisture and heat.

Store Cetrotide® 0.25 mg in the refrigerator at 2-8°C (36-46°F). Keep the packaged tray in the outer carton in order to protect it from light.

How long may Cetrotide® be stored?

Do not use the Cetrotide® powder or the pre-filled syringe after the expiration date, which is printed on the labels and on the carton, and dispose of the vial and the syringe properly.

How long can you keep Cetrotide® after preparation of the solution?

The solution should be used immediately after preparation.

Store the medicine out of the reach of children.

If you suspect that you may have taken more than the prescribed dose of this medicine, contact your doctor immediately. This medicine was prescribed for your particular condition. Do not use it for another condition or give the drug to others.

This leaflet provides a summary of the information about Cetrotide®. Medicines are sometimes prescribed for uses other than those listed in the Leaflet. If you have any questions or concerns, or want more information about Cetrotide®, contact your doctor or pharmacist.

This Leaflet has been approved by the U.S. Food and Drug Administration.

June 2017