What Cleo-35 Treats: Main Uses and Benefits

Cleo-35 (cyproterone acetate/ethinylestradiol) is generally applied across domains where additional symptomatic support is needed for conditions in women that are linked to systemic imbalance. It is commonly used to help manage specific symptom clusters that may become more disruptive during flare-ups.

The therapeutic domains of use encompass the management of symptoms associated with severe and persistent acne, excessive skin oiliness (seborrhea), and mild unwanted hair growth (hirsutism).

This supportive therapy is applied in clinical settings that involve recurrent or episodic manifestations. It is often used to help manage symptoms that become more disruptive during flare-ups.

“This medication is applied in addressing cases that require additional symptomatic support for persistent skin manifestations.”

The benefit contributes to easing the overall symptom burden, particularly for symptoms related to systemic imbalance, assisting patients with maintaining comfort and stability during symptomatic periods.

Quick Fact: Support for Managing Persistent Skin Symptoms

This medication is generally considered relevant for women whose conditions present with significant symptomatic burden related to persistent skin issues, helping to manage these symptoms when they interfere with daily comfort.

Regulatory References

1. Therapeutic Goods Administration (TGA) product overview

Eligibility Map: Who Can and Cannot Use Cleo-35

The official regulatory documentation for Cleo-35 (cyproterone acetate/ethinylestradiol) specifies a highly restricted patient population and lists extensive absolute contraindications.

Populations for whom use is allowed (as stated in label):

Populations for whom use is contraindicated:

Use is not established for pre-pubertal or post-menopausal patients. The medicine is explicitly prohibited from being used solely for the purpose of contraception.

Interaction-Related Restrictions

The official interaction profile identifies medicinal products that are formally restricted for co-administration. Use with other estrogen/progestogen combinations is contraindicated to avoid exposing the user to an excessive hormone dose. Co-administration is also prohibited with specific Hepatitis C antiviral drug regimens (including ombitasvir, paritaprevir, ritonavir, with or without dasabuvir) due to the documented risk of significant liver enzyme elevations.

Metabolic and Exposure Interactions

Most documented drug-drug interactions are based on pharmacokinetic mechanisms. Medicines that function as hepatic enzyme inducers (such as certain anticonvulsants like Phenytoin or Carbamazepine, the antibiotic Rifampicin, or the herbal remedy St John's wort) increase the clearance of the hormones, potentially reducing the medicine's therapeutic efficacy. Conversely, strong CYP3A4 enzyme inhibitors (including some Azole antifungals and Macrolide antibiotics) are documented to decrease hormone clearance, resulting in an increase in plasma concentrations of the active components.

Pharmacodynamic Effects and Special Cautions

The product may alter the effect of co-administered drugs like anticoagulants (such as Warfarin) and is officially documented to diminish the plasma concentration of Lamotrigine. Regulatory documents specify that following short-term treatment with enzyme-inducing drugs, a 28-day contraceptive separation period is required. The risk of serious vascular adverse effects related to cigarette smoking is officially noted to be more marked in women over 35 years of age.

Cleo-35 is a combined hormonal preparation containing cyproterone acetate and ethinylestradiol. Cyproterone acetate functions primarily as a progestin agonist at the progesterone receptor and an androgen receptor antagonist in target tissues, including the skin and hair follicles. Ethinylestradiol acts as an estrogen receptor agonist. The ethinylestradiol component modulates hepatic protein synthesis, increasing the circulating levels of sex hormone-binding globulin (SHBG). This systemic increase in SHBG results in enhanced binding and sequestration of free androgens in the circulation. Concurrently, the progestational activity of cyproterone acetate exerts a potent negative feedback on the hypothalamic-pituitary-ovarian (HPO) axis. This central inhibition suppresses the release of gonadotropins, specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH), preventing the surge necessary for ovulation. The combined hormonal actions result in systemic androgen level reduction via increased SHBG and a prevention of follicular development and ovulation due to HPO axis suppression.

Official Administration Guidelines for Cleo-35

Cleo-35 (cyproterone acetate and ethinyl estradiol) is an oral medication that must be taken in a fixed 28-day cyclic pattern. It is crucial to adhere strictly to the dosing schedule and procedural instructions.

Administration Scope

Procedural Instructions

• Starting a Course: For the first course of therapy, you must begin taking the first tablet on Day 1 of your menstrual cycle (the first day of menstrual flow). Tablets should be taken in the order directed on the blister pack.
• Subsequent Courses: After the 7-day tablet-free interval, start a new pack on the 8th day—the same day of the week as the first course—regardless of whether withdrawal bleeding is still occurring.
• Duration: Therapy is typically continued for 3 to 4 cycles after symptoms have completely resolved, as determined by the treating physician.

Missed Dose Rules

• If you miss a dose by less than 12 hours: Take the missed tablet immediately, then take the next tablet at your regularly scheduled time.
• If you miss a dose by more than 12 hours: Discard the missed tablet and continue taking the remaining tablets at the usual time to prevent premature withdrawal bleeding. You must use a supplementary non-hormonal method of contraception (e.g., condoms) until the pack is empty.

Research Evidence / Overview of Studies for Cleo-35

This section provides an overview of the research that has explored the use of Cleo-35 (Co-cyprindiol), focusing only on the type of evidence available, the way studies were conducted, and areas where research remains limited, as reported in official scientific and regulatory sources.

1. Evidence for the Study of Androgen-Sensitive Acne and Seborrhea

Research examined the clinical context of Cleo-35 in studies involving subjects with moderate to severe acne and associated excessive skin oiliness (seborrhea). Research examining these skin outcomes related to systemic or functional imbalance has included Randomized Controlled Trials (RCTs), where this medicine was compared against other combined oral preparations, as well as broader systematic reviews that consolidate findings.

Studies explored outcomes related to physical discomfort by using objective measurements of skin status and patient-reported outcomes describing perceived discomfort. Findings describe patterns observed in the studies that help contextualize how symptoms evolved in the observed populations, which included women of reproductive age who presented with persistent acne symptoms, including those with hyperandrogenism, such as from Polycystic Ovary Syndrome (PCOS).

2. Evidence for the Study of Hirsutism (Excessive Unwanted Hair Growth)

The evidence base for hirsutism (excessive unwanted hair growth) includes Randomized Controlled Trials (RCTs) and meta-analyses that explored outcomes related to physical discomfort. Research examined conditions characterized by fluctuating or episodic manifestations, focusing on the use of validated scoring systems, such as the Ferriman-Gallwey Score, to quantify changes in unwanted hair growth.

Because the natural hair growth cycle is slow, studies conducted during periods of increased symptom activity used prolonged observation periods, with formal study outcomes often assessed after six to twelve months of continuous administration. Findings describe a slow and gradual pattern of change over this time. Research highlights that changes measured during the study period required a long duration, and comparative evidence is lacking in certain subgroups.

3. Long-Term Studies and Follow-Up Duration

Most of the principal clinical trials were relevant in trials assessing short-term or episodic symptom patterns, providing sufficient data for the typical administration period of six to twelve months. Evidence explores symptom patterns over the intermediate term, but there is limited information for long-term outcomes.

Key Studies & References Systematic Review on Combined oral contraceptives containing cyproterone acetate for acne and hirsutism

Common questions about Cleo-35 (FAQ)

Q: What is Cleo-35 and how does it work?

A: Cleo-35 is a prescription medication containing two active ingredients: cyproterone acetate and ethinylestradiol. It belongs to a class of medicines known as anti-androgens combined with estrogens.

• Cyproterone acetate works by blocking the effects of androgens (male sex hormones) in the body. In women, androgens can contribute to conditions like acne and excessive hair growth.
• Ethinylestradiol is a synthetic estrogen that helps to stabilize the menstrual cycle and improve the effectiveness of the anti-androgen component.

It is primarily used in women for the treatment of moderate to severe acne and excessive hair growth (hirsutism) on the face and body, especially when these conditions are caused by an overproduction or increased sensitivity to androgens, or when they have not responded to other treatments.

Q: How should I take Cleo-35?

A: Cleo-35 is taken orally, usually as one tablet once a day, for 21 consecutive days, followed by a 7-day tablet-free interval. During this 7-day break, a withdrawal bleed (similar to a menstrual period) typically occurs.

• Tablets should be taken at the same time each day with a little water.
• Starting the next pack: After the 7-day interval, a new pack is started, even if the bleeding has not stopped.

Always follow the specific dosing instructions provided by your prescriber and the patient information leaflet.

Q: What should I do if I miss a tablet?

A: What you should do depends on when you remember the missed tablet:

• If you are less than 12 hours late: Take the missed tablet as soon as you remember and then continue taking the rest of the pack at the usual time. Contraceptive protection is maintained.
• If you are more than 12 hours late: Contraceptive protection may be reduced. Take the last missed tablet as soon as you remember, even if it means taking two tablets in one day. Then, continue with the remaining tablets at the usual time. Use an additional non-hormonal barrier method (like condoms) for the next 7 days.

If you miss tablets in the first week of the pack and had sex in the previous 7 days, the risk of pregnancy should be considered, and medical advice should be sought.

Q: Are there any serious side effects associated with Cleo-35?

A: Like all medicines, Cleo-35 can cause side effects, some of which can be serious. Serious but rare side effects include the risk of developing blood clots (thrombosis) in the veins (deep vein thrombosis, pulmonary embolism) or arteries (myocardial infarction, stroke).

• The risk of blood clots is increased when using this medication, especially during the first year and if you have certain risk factors (e.g., being overweight, smoking, having a family history of blood clots).
• Stop taking Cleo-35 immediately and seek emergency medical attention if you notice possible signs of a blood clot, such as:
  • Severe pain or swelling in one leg.
  • Sudden, severe chest pain or shortness of breath.
  • Sudden weakness or numbness in the face, arm, or leg (especially on one side of the body).

Other potential serious effects include liver problems and changes in mood, including depression.

Q: Can Cleo-35 be used solely for contraception?

A: No. While Cleo-35 does have contraceptive properties because it contains ethinylestradiol, it is not approved or intended to be used solely as a contraceptive pill. It is a treatment for androgen-related skin conditions (acne and hirsutism).

Because of the increased risk of blood clots compared to standard oral contraceptives, it should only be prescribed when the primary goal is to treat the skin condition, and when other treatments have failed or are unsuitable. Contraception is considered an additional benefit of the treatment.

How to Store and Dispose of Cleo-35

The storage and disposal instructions for Cleo-35 (cyproterone acetate/ethinylestradiol) are based on regulatory guidance to maintain the medication's stability and ensure environmental safety.

Storage Requirements

Cleo-35 must be stored at room temperature, generally defined as below 25 C or 30 C. The tablets require protection from excessive heat, moisture, and direct sunlight and should be kept in a dry place (not a bathroom). The medicine must be kept out of the sight and reach of children and pets to prevent accidental ingestion. It should not be used past the expiry date printed on the packaging.

Disposal Instructions

To prevent environmental contamination, official instructions mandate that Cleo-35 must not be thrown into household garbage or disposed of in wastewater (flushed down the toilet or sink). Unused or expired medication should be returned to a pharmacist for proper and safe disposal.