Consumer medicine information

Cyclogest

Progesterone

BRAND INFORMATION

Brand name

Cyclogest

Active ingredient

Progesterone

Schedule

SUMMARY CMI

CYCLOGEST^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Cyclogest?

Cyclogest contains the active ingredient progesterone. Cyclogest is for women who need extra progesterone while undergoing treatment in an Assisted Reproductive Technology (ART) programme.

For more information, see Section 1 Why am I using Cyclogest? in the full CMI.

2. What should I know before I use Cyclogest?

Do not use if you have ever had an allergic reaction to Cyclogest or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2 What should I know before I use Cyclogest? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Cyclogest and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI

4. How do I use Cyclogest?

A 400 mg pessary is administered vaginally twice a day.

More instructions can be found in Section 4 How do I use Cyclogest? in the full CMI

5. What should I know while using Cyclogest?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using Cyclogest Tell your doctor if you have any undiagnosed vaginal bleeding or have had a missed abortion or ectopic pregnancy Tell your doctor if you have or have had any blood clots Tell your doctor if you have or have had severe liver problems Tell your doctor if you have or have had any tumour that is hormone sensitive Tell your doctor if you have porphyria disorders
Things you should not do	Do not stop using this medicine suddenly Do not use this medicine if you are breastfeeding
Driving or using machines	Do not drive or use machines if you feel dizzy after using Cyclogest.
Drinking alcohol	Tell your doctor if you drink alcohol
Looking after your medicine	Store Cyclogest in a cool, dry place where the temperature is below 25°C.

For more information, see Section 5 What should I know while using Cyclogest? in the full CMI.

6. Are there any side effects?

The most common side effects are fatigue and drowsiness, hot flushes, swelling or pain in your abdomen, constipation and breast pain. Serious side effects include allergic reactions.

For more information, including what to do if you have any side effects, see Section 6 Are there any side effects? in the full CMI.

FULL CMI

CYCLOGEST^®

Active ingredient(s): progesterone

Consumer Medicine Information (CMI)

This leaflet provides important information about using Cyclogest. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Cyclogest.

Where to find information in this leaflet:

1. Why am I using Cyclogest?
2. What should I know before I use Cyclogest?
3. What if I am taking other medicines?
4. How do I use Cyclogest?
5. What should I know while using Cyclogest?
6. Are there any side effects?
7. Product details

1. Why am I using Cyclogest?

Cyclogest contains the active ingredient progesterone. Progesterone is a natural, female sex hormone, produced in the body. Progesterone is for women who need extra progesterone while undergoing treatment in an Assisted Reproductive Technology (ART) programme.

Progesterone acts on the lining of the womb and it helps you to become and to stay pregnant when you are treated for infertility.

2. What should I know before I use Cyclogest?

Warnings

Do not use Cyclogest if you:

are allergic to progesterone or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
have unusual vaginal bleeding that has not been evaluated by your doctor.
have a known or suspected tumour that is hormone sensitive.
have porphyria disorders (a group of inherited or acquired disorders of certain enzymes).
have or have had blood clots in the legs, lungs, eyes or elsewhere in your body.
currently have or have had severe liver problems.
have had a miscarriage and your physician suspects some tissue is still in the uterus or have had a pregnancy outside of the womb.

Check with your doctor if you:

have any other medical conditions
take any medicines for any other condition
have or have had:
- Depression
- Liver problems
- Epilepsy
- Migraine
- Asthma
- Cardiac or renal dysfunction
- Diabetes.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6 Are there any side effects?

Pregnancy and breastfeeding

Cyclogest can be used during the first trimester of pregnancy for women who need extra progesterone while undergoing treatment in an Assisted Reproductive Technology (ART) programme.

The risks of congenital (conditions present at birth) anomalies, including genital abnormalities in male or female infants, from exposure to exogenous progesterone during pregnancy have not been fully established.

Do not use Cyclogest if you are breastfeeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Cyclogest and affect how it works.

The list of medicines may decrease the effectiveness of Cyclogest:

Carbamazine (used to prevent fits, treat certain types of pain or mood disorders)
Rifampicin (to treat infections)
Phenytoin (to prevent fits or treat certain types of pain)

Ketoconazole may increase the effectiveness of Cyclogest.

Use of other vaginal products should be avoided during use of Cyclogest.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Cyclogest.

4. How do I use Cyclogest?

How much to use

Each dose is one pessary.

When to use Cyclogest

Cyclogest should be used twice a day. Start using the medicine on the day of egg retrieval. If pregnancy is confirmed, continue using Cyclogest for 38 days from the start of therapy or as recommended by your doctor. If pregnancy has not occured, the administration of Cyclogest should be discontinued.

How to use Cyclogest

Cyclogest is inserted into your vagina
Always wash your hands throrougly before inserting
To insert the pessary into the vagina, place the pessary between the lips of the vagina and push the pessary upwards and backwards. You may find it easier to do this if you are lying down or squatting.
Throw away any used material and wash your hands thoroughly.

If you forget to use Cyclogest

If you forget to insert a pessary at the usual time, do so as soon as you remember.

If it is almost time for your next dose, skip the dose you missed and use your next dose when you are meant to.

Do not use a double dose to make up for the dose you missed.

If you use too much Cyclogest

If you (or someone else) has accidentally swallowed any of the pessaries or you use too many, you may need urgent medical attention.

You should immediately:
phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Cyclogest?

Things you should do

Call your doctor straight away if you:

experience any of the side effects listed below and they worry you.

Remind any doctor, dentist or pharmacist you visit that you are using Cyclogest.

Things you should not do

Do not stop using Cyclogest suddenly

Ask your doctor or pharmacist for advice if you intend to stop or have stopped using Cyclogest. Stopping the medicine suddenly may cause increased anxiety, moodiness and increased chance of seizures.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Cyclogest affects you.

Cyclogest may cause dizziness in some people. If you feel dizzy you should not drive or use machines until you feel better.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

Store Cyclogest below 25°C

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date located on the carton. The expiry date refers to the last day of that month.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

General

Fatigue
Drowsiness
Dizziness
Hot flushes
Night sweats
Feeling cold or body temperature change and general discomfort
Increase in weight
Change in mood
Change in sense of taste

Gastrointestinal

Abdominal swelling
Abdominal pain
Constipation
Diarrhoea
Vomiting
Flatulence

Pain

Breast pain
Headache
Rash or itchy skin
Itching at the application site

Renal

Frequent urination, involuntary urination

Vaginal

After using Cyclogest you may notice some leakage after the pessary has dissolved. Do not worry, this is quite normal when using medicines that are inserted into the vagina

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

General

Dizziness, faintness or changes in vision or speech, weakness or numbness of an arm or leg indicating possible clots in the brain or eye
Sudden shortness of breath
Worsening of depression

Pain

Pain in the joints, pelvis
Swelling in face, mouth, hands, feet, legs or other parts of your body (including breathlessness, chest pain, and anaphylaxis (a serious allergic reaction)
Severe headache
Pains in the calves or chest

Gastrointestinal

Vomiting

Reproductive

Enlarged ovaries

Bleeding-related

Uterine bleeding
Coughing blood indicating possible clots in the legs, heart, or lungs

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Cyclogest contains

Active ingredient (main ingredient)	Progesterone
Other ingredients (inactive ingredients)	Hard fat

Do not take this medicine if you are allergic to any of these ingredients.

What Cyclogest looks like

Cyclogest is an off-white, torpedo-shaped pessary containing 400 mg of the active ingredient progesterone.

It is supplied in strip packs of 15 pessaries.

The Australian registration number is AUST R 348691

Who distributes Cyclogest

Cyclogest is supplied in Australia by:

Gedeon Richter Australia Pty Ltd
Suite 902/15 Blue Street
North Sydney NSW 2060
AUSTRALIA

Phone: 1300 GEDEON (1300 433 366)

Cyclogest is supplied in New Zealand by:

Pharmacy Retailing (NZ) t/a Healthcare Logistics
58 Richard Pearse Drive
Airport Oaks Mangere, Auckland
NEW ZEALAND

Phone: 0800 GEDEON (0800 433 366)

This leaflet was prepared in July 2023.

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Cyclogest

Active ingredient

Progesterone

Schedule

1 Name of Medicine

Progesterone.

2 Qualitative and Quantitative Composition

Each Cyclogest pessary contains 400 mg progesterone.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Pessary.
Off-white, approximately 10 mm x 30 mm, torpedo shaped pessary.

4 Clinical Particulars

4.1 Therapeutic Indications

Cyclogest is indicated for luteal phase support as part of an Assisted Reproductive Technology (ART) treatment for women.

4.2 Dose and Method of Administration

Dosage.

One 400 mg pessary administered vaginally twice a day (BID) starting at oocyte retrieval. If pregnancy has been confirmed, the administration of progesterone should be continued for 38 days from the start of therapy or up until 12 weeks of pregnancy according to need at the judgement of the treating physician.

Method of administration.

For vaginal insertion.

Patient instructions.

The pessary should be removed from its wrapper and inserted deep into the vagina, by pushing the pessary upwards and backwards while either in a squatting position or lying down. If a recommended twice daily dose is being administered, then a preferable time of dosing is in the morning and at night before retiring.

Missed dose.

A missed dose should be administered as soon as remembered, unless the missed dose is noticed at the day of the next dose. In the latter case, the missed dose should be omitted and the regular dosing regimen continued.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.
Undiagnosed vaginal bleeding.
Known or suspected progesterone sensitive malignant tumours.
Porphyria.
Known missed abortion or ectopic pregnancy.
Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
Severe hepatic dysfunction or disease.

4.4 Special Warnings and Precautions for Use

Cyclogest is not indicated in threatened miscarriage. Treatment should be discontinued in the event of a missed miscarriage.
Progesterone should be discontinued if any of the following conditions are suspected:
myocardial infarction;
cerebrovascular disorders;
arterial or venous thromboembolism (venous thromboembolism or pulmonary embolism);
thrombophlebitis;
retinal thrombosis.
Although risk of thromboembolism has been associated with oestrogens a definite causative effect has not been established for progestins. Therefore, in women with generally recognised risk factors for thromboembolic events, such as personal or family history, treatment with progesterone may further increase the risk. In these women, the benefits of progesterone administration need to be weighed against the risks. It should be noted however, that pregnancy itself carries an increased risk of thromboembolic events.
Patients with a history of depression need to be closely observed. Consider discontinuation if symptoms worsen.
Because progesterone may cause some degree of fluid retention, conditions that might be influenced by this factor (e.g. epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.
A decrease in glucose tolerance has been observed in a small number of patients on oestrogen/progestin combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progestin therapy.
Progesterone is metabolised in the liver and should be used with caution in patients with hepatic dysfunction.
Abrupt discontinuation of progesterone dosing may cause increased anxiety, moodiness and increased sensibility to seizures.

Use in special populations.

There is no experience with use of progesterone in patients with impaired liver or renal function.

Use in the elderly.

No clinical data have been collected in patients over age 65.

Paediatric use.

There is no relevant use of progesterone in the paediatric population.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drugs known to induce the hepatic cytochrome-P450-3A4 system (e.g. rifampicin, carbamazepine or phenytoin) may increase the elimination rate and thereby decrease the bioavailability of progesterone.
Ketoconazole and other inhibitors of CY3A4 may increase the bioavailability of progesterone.
The effect of concomitant vaginal products on the exposure of progesterone from Cyclogest 400 mg pessary has not been assessed and is therefore not recommended.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.1 Therapeutic Indications. Exogenously administered progesterone has been shown to inhibit ovulation in a number of species and it is expected that high doses given for an extended duration could impair fertility until the cessation of treatment.
(Category A)
Cyclogest 400 mg pessary is only indicated during the first trimester of pregnancy for use as part of an assisted reproduction (ART) treatment (see Section 4.1 Therapeutic Indications for full details). Progesterone crosses the placenta. There is limited and inconclusive data on the risk of congenital anomalies, including genital abnormalities in male or female infants, following intrauterine exposure during pregnancy. The rates of congenital anomalies, spontaneous abortion and ectopic pregnancies observed during the clinical trial were comparable with the event rate described in the general population although the total exposure is too low to allow conclusions to be drawn.
Detectable amounts of progesterone have been identified in the milk of mothers. Therefore Cyclogest 400 mg pessary should not be used during lactation.

4.7 Effects on Ability to Drive and Use Machines

Progesterone may cause dizziness. Therefore, caution is advised in drivers and users of machines.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions in patients undergoing luteal support as a part of ART treatment is presented in Table 1 displaying the adverse reactions by system organ classes (SOC) and frequencies:
As with other vaginal preparations, some leakage of the pessary base may occur.

Clinical trials.

Adverse effects reported from a Phase III clinical trial (Cyclogest Study: ACT-CYC-300-2013-01) comparing Cyclogest with Crinone 8% gel (90 mg) (see Section 5.1 Pharmacodynamic Properties, Clinical trials) the frequencies of patients reporting AEs were comparable for both treatments (Cyclogest: 43.6% and Crinone: 44.6%) are tabulated in Table 2.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is a wide margin of safety with progesterone pessaries, but overdosing may produce euphoria or dysmenorrhoea.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate oestrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain the pregnancy.

Clinical trials.

A multi-centre, multi-national, open-label, randomised, parallel group, non-inferiority phase III trial in premenopausal women (Cyclogest study: ACT-CYC-300-2013-01 (2014)) was performed to compare Cyclogest 400 mg pessary twice daily (BID) to Crinone 8% gel (90 mg) once daily (QD).
The primary endpoint of the study was the clinical pregnancy rate (foetal heart movement measured by transvaginal ultrasonography (TVUS)) achieved after 38 days of Luteal Phase Support (LPS) in patients undergoing ART.
812 patients were enrolled and 769 patients were randomised to receive either Cyclogest 400 mg pessary BID (n=385) or Crinone 8% vaginal progesterone gel (90 mg) QD (n=384), both for a period of 10 weeks. Subjects ranged in age from 18 to 40 years. The study drug was initiated on the day after oocyte retrieval.
In the Full Analysis Set (FAS), the pregnancy rate on Day 38 was 38.3% for Cyclogest and 39.9% for Crinone (Table 3). The Cyclogest-Crinone pregnancy rate difference was -1.6% with a 97.5% CI lower bound of -8.6%.
In the Per Protocol (PP) set, the pregnancy rate on Day 38 was 38.1% for Cyclogest and 40.4% for Crinone (Table 3). The Cyclogest-Crinone pregnancy rate difference was -2.4% with a 97.5% CI lower bound of -9.5%.
The pre-determined non-inferiority margin was -9% based on a reference pregnancy rate of 30% and a one-sided significance level of 2.5%. For the primary efficacy outcome measure using unadjusted data, the results were consistent with the criteria for non-inferiority for the FAS dataset, but not for the PP dataset. After a post hoc adjustment of the non-inferiority margin to -10% based on an observed reference pregnancy rate of 40%, the results of both sets were consistent with the post hoc non-inferiority criteria.

In fact, both analyses (FAS and PP set) showed similar results in this trial i.e. a difference in the clinical pregnancy rates of about -2% points (Cyclogest minus Crinone) associated with lower limits of the 95% confidence interval around -9%. Thus, non-inferiority of Cyclogest in comparison to Crinone can be concluded.

5.2 Pharmacokinetic Properties

Absorption.

Vaginal administration of Cyclogest 400 mg every 12 h in healthy women has been shown effective in rapidly achieving and maintaining serum progesterone concentrations at physiological levels appropriate to the midluteal phase of the ovarian cycle and early pregnancy. The mean C_max after 10 days of multiple dosing was 18.4 nanogram/mL and C_trough was 10.5 nanogram/mL.

Distribution.

Progesterone is approximately 96% to 99% bound to serum proteins, primarily to serum albumin and corticosteroid binding globulin.

Metabolism.

Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones.
Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization.

Excretion.

Progesterone undergoes renal and biliary elimination.

5.3 Preclinical Safety Data

Genotoxicity.

Progesterone did not induce chromosomal aberrations or sister chromatid exchanges in cultured human cells nor old chromosomal aberration or DNA strand breaks end in rodent cells. Progesterone did not induce dominant lethal mutation in mice or chromosomal aberrations in the bone marrow rats in vivo although in vivo studies for chromosome damage have yield positive results in mice at oral doses of 1000 mg/kg and 2000 mg/kg. Weak clastogenic activity was from progesterone in the rat hepatocyte micronucleus test after treatment with high oral dose (100 mg/kg). Studies on transformation of rodent cells in vitro were inconclusive. Variable results were obtained with progesterone in the mouse lymphoma tk assay. In assays for induction of DNA repair, progesterone produces variable results rats hepatocytes and negative results in human hepatocytes progesterone was not beta genic to bacteria.

Carcinogenicity.

Animal studies showed that progesterone was able to induce and/ or promote the formation of mammary, uterine, ovarian, endometrial, cervical and vagina tumours. When implanted into female mice, progesterone produces mammary carcinomas, ovarian granulosa cell tumours and endometrial stromal sarcomas. In dogs, long-term intramuscular injections produced nodular hyperplasia and benign and malignant memory tumours. Subcutaneous or intramuscular injections of progesterone decreased the latency period and increased the incidence of mammary tumours in rats previously treated with chemical carcinogen. The clinical relevance of these findings remains unclear.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hard fat.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

PVC/PE strip packs.

Pack sizes.

15 pessaries.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital system; Progestogens; Pregnen-(4) derivatives.
ATC code: G03DA04.

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Consumer medicine information

Cyclogest

Progesterone

Keep track of your medicines

BRAND INFORMATION

Cyclogest 400 mg Pessaries