Co-cyprindiol (cyproterone and ethinylestradiol) oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulation containing cyproterone and ethinylestradiol
Drugs List
Therapeutic Indications
Uses
Acne vulgaris - moderate to severe (in women)
Contraception - oral (in women with androgen dependent skin condition)
Moderately severe hirsutism in women
Treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhoea) and/or hirsutism, in women of reproductive age.
For the treatment of acne, cyproterone acetate and ethinylestradiol should only be used after topical therapy or systemic antibiotic treatments have failed.
Contraception in women with androgen dependent skin condition.
Dosage
Adults
If no withdrawal bleed occurs during the tablet-free interval, exclude pregnancy before the next pack is started.
First treatment course
Commencing on the first day of the menstrual cycle, one tablet daily without interruption for 21 days, followed by a tablet free break of 7 days. Subsequent packs are started after the 7 tablet free days.
Women with amenorrhoea should start treatment immediately. In this case, the first day of tablet taking is considered as the first day of the menstrual cycle.
Changing from 21 day combined oral contraceptives
The first tablet of the first pack should be taken on the first day immediately after the end of the previous contraceptive course. Additional contraceptive precautions are not required.
Changing from a combined every day oral contraceptive
All active tablets from the 'every day pill' pack should be finished. The first new tablet should be taken the next day, the inactive tablets from the 'every day pill' pack should be discarded. Additional contraception is then not required.
Changing from a progestogen-only pill (POP)
The first tablet should be taken on the first day of menstruation, even if a POP has already been taken on that day. Additional contraceptive precautions are then not required. The remaining progestogen-only pills should then be discarded.
Post-partum and post-abortum administration
Non breastfeeding mothers can start taking tablets 21 days after delivery (provided there are no complications). Additional contraception is required for the first 7 days.
Since post-partum ovulation may precede the first bleeding, another method of contraception should be used in the interval between childbirth and the first course of tablets.
If first trimester abortion, tablets may be started immediately in which case no additional contraceptive precautions are required.
If intercourse has already occurred, oral contraceptive use should be delayed until the day of the first menstrual period.
When additional contraceptive precautions are required patients should be advised either not to have sex or to use a cap plus spermicide, or for her partner to use a condom. Rhythm methods are not advisable as the pill disrupts the usual cyclical changes associated with the natural menstrual cycle.
Special circumstances requiring additional contraception
Missed pills
It is important to bear in mind that the critical time for loss of protection is when a pill is omitted at the beginning or end of a cycle (and therefore the pill-free interval is lengthened). A pill is late if it has not been taken at the usual time. A pill is missed if it more than 12 hours since the time it should have been taken. Advise patients that missing pills or starting the pack late may make your pill less effective.
One pill missed anywhere in the pack or started the new pack one day late
The missed pill should be taken as soon as possible if it means taking two pills in one day. The rest of the pack should be taken as usual, additional barrier contraception is required for the next 7 days and the 7 day pill-free break should be taken as normal.
Two or more pills missed or starting the pack two or more days late (more than 48 hours late)
The last missed pill should be taken as soon as possible even if its means taking two pills in one day and any earlier missed pills should be left. The rest of the pack should be taken as usual and an extra method of contraception is required for the next 7 days. Emergency contraception may be needed (see below). The next pack of pills may need to be started without a break (see below).
Emergency Contraception
If unprotected sex has occurred in the previous 7 days and two or more pills have been missed (i.e. more than 48 hours late) in the first week of a pack, emergency contraception may be needed.
Starting the next pack after missing two or more pills (more than 48 hours late)
If seven or more pills are left in the pack after the last missed pill should be taken, the pack should be finished and the usual 7 day break taken.
If less than seven pills are left in the pack after the missed pill the pack should be finished and the next pack started the next day (this means missing out the break).
Diarrhoea and vomiting
Vomiting between 2 to 4 hours after taking a dose or severe diarrhoea can interfere with absorption and limit effectiveness. Additional precautions should therefore be used during and for 7 days after recovery. If the vomiting and diarrhoea occurs during the last 7 tablets, the next pill-free interval should be omitted. A withdrawal bleed should not be expected until the end of the second pack. If the patient does not have a withdrawal bleed during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before starting the next pack. Other methods of contraception should be considered if the gastro-intestinal disorder is likely to be prolonged.
Skipped period or to alter date of period
The patient should begin a new pack the day after finishing the current pack (i.e. skips the tablets-free days). To change the date of a period, shorten the period of non-tablet taking days. Slight spotting or breakthrough bleeding may be seen during the second pack.
Contraindications
Family history of idiopathic venous thromboembolism
Predisposition to arterial disease
Predisposition to thromboembolic disease
Prolonged immobilisation
Abnormal liver function test
Atherogenic lipid profile
Breastfeeding - until weaning or 6 months post partum
Cardiovascular disorder
Cerebrovascular disorder
Cholelithiasis
Cholestatic jaundice
Diabetes mellitus with vascular involvement
Focal migraine
Hepatic neoplasm
Hepatitis
History of hormone dependent neoplasm
History of meningioma
History of thromboembolic disorder
Hormone dependent neoplasm
Ischaemic heart disease
Meningioma
Porphyria
Pregnancy
Pulmonary embolism
Recent trophoblastic disorder
Severe dyslipoproteinaemia
Severe hypertension
Severe migraine
Systemic lupus erythematosus
Thrombosis
Transient cerebral ischaemic attack without headache
Undiagnosed gynaecological haemorrhage
Valvular heart disease with pulmonary hypertension
Valvular heart disease with risk of mural thrombi
Precautions and Warnings
Family history of arterial disease
Family history of breast cancer
Females over 35 years
History of chorea during pregnancy
Obesity
Risk factor for oestrogen-dependent neoplasm
Tobacco smoking
Atrial fibrillation
Cardiac valvulopathy
Chloasma
Coagulopathy
Diabetes mellitus
Dyslipoproteinaemia
Endometriosis
Epileptic disorder
Familial hypertriglyceridaemia
Galactosaemia
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History during pregnancy of pemphigoid gestationis
History of chloasma
History of cholelithiasis
History of cholestatic jaundice during pregnancy
History of haemolytic uraemic syndrome
History of migraine
History of pregnancy-related deterioration in otosclerosis
History of pruritus during pregnancy
History of severe depression
History of steroid induced jaundice
Hyperlipidaemia
Hyperprolactinaemia
Hypertension
Inflammatory bowel disease
Lactose intolerance
Non focal aura migraine
Severe depression
Sickle cell disease
Thrombophlebitis
Uterine fibroids
Assess family medical history prior to commencing treatment
Exclude oestrogen dependent neoplasm before treatment
Pre-treatment medical history and clinical examination
Some formulations contain lactose
Some formulations contain sucrose
Resume use only after 2wks full ambulation from surgery/immobilisation
Exclude pregnancy prior to initiation of treatment
If upper abdominal complaints/liver enlargement consider liver tumour
Monitor blood glucose closely in patients with diabetes mellitus
Monitor patients with a history of depression and/or suicide attempts
May affect results of some laboratory tests
Discontinue 4 - 6 weeks before major surgery
Advise patient to seek advice at first indications of pregnancy
Discontinue at first signs of jaundice, hepatitis or whole body itching
Discontinue at first signs of thrombophlebitis or thromboembolism
Discontinue if depression worsens or recurs
Discontinue if epilepsy is exacerbated
Discontinue if headache assoc with weakness/numbness one side/part occurs
Discontinue if headache associated with sudden dysphasia or vertigo occurs
Discontinue if headache associated with sudden motor disturbances occurs
Discontinue if headache associated with sudden onset of diplopia occurs
Discontinue if headache associated with syncope or collapse occurs
Discontinue if headache with sudden partial/complete vision loss occurs
Discontinue if hypertension develops
Discontinue if liver function tests become abnormal
Discontinue if severe pain in the calf of one leg occurs
Discontinue if sudden breathlessness (or cough with blood stained sputum)
Discontinue if sudden occurrence of visual/hearing/perceptual disorders
Discontinue if sudden pain in the chest occurs
Discontinue if sudden, severe pain in stomach occurs
Discontinue if suspicion of thrombosis/infarction
Discontinue-first occurrence/worsening migraine/severe or frequent headache
Advise patient grapefruit products may increase plasma level
Advise patient concurrent St John's wort may reduce contraceptive effect
All contraceptive pills slightly increase the risk of breast cancer
Ensure patient is informed of risks of treatment
Treatment does not protect against risk of sexually transmitted disease
Women with a history of chloasma should avoid exposure to sun/UV light
Pregnancy and Lactation
Pregnancy
Cyproterone acetate and ethinylestradiol is contraindicated in pregnancy.
Before starting treatment, pregnancy must be excluded.
The preparation should be withdrawn immediately if pregnancy occurs while taking oral contraception.
Animal studies have revealed that feminisation of male foetuses may occur if cyproterone acetate is administered during the phase of embryogenesis at which differentiation of external genitalia occurs.
The effects on human pregnancies are not known, however the possibility of feminisation of male foetuses in pregnancies where the patient has been treated with co-cyprindiol after the 45th day of pregnancy must be considered.
It has been suggested by some investigations that oral contraceptives taken in early pregnancy may slightly increase the risk of foetal malformations, such as cardiovascular defects, eye and ear anomalies and increased frequency of Down's syndrome, although other studies have failed to support these findings. The possibility cannot be excluded, but it is certain that if a risk exists at all, it is very small.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Cyproterone acetate and ethinylestradiol is contraindicated in breastfeeding.
The use of this preparation may lead to reduction in the volume of milk produced and to a change in its composition. Very small amounts of the active substances may be excreted in the milk. Combined oral contraceptives should be avoided until weaning (or at least 6 months post partum). Oral progestogen-only pills are preferred.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
"Spotting" bleeds (early cycles)
Abdominal pain
Absence of withdrawal bleeding
Aggravation of porphyria
Angioedema
Aphasia
Breast enlargement
Breast pain
Breast secretion
Breast tenderness
Breathlessness
Cardiovascular accident
Cerebrovascular accident
Changes in cervical secretion
Changes in libido
Chest pain
Chloasma
Cholelithiasis
Cholestatic jaundice
Chorea
Coagulation disorders
Collapse
Contact lenses may irritate
Cough (with blood stained sputum)
Decreased glucose tolerance
Deep vein thrombosis (DVT)
Depression
Diarrhoea
Diplopia
Endometriosis (aggravation of)
Epileptic seizures
Erythema multiforme
Erythema nodosum
Exacerbation of Crohn's disease
Exacerbation of otosclerosis
Exacerbation of sickle-cell anaemia
Fainting
Fluid retention
Headache
Hepatic impairment
Hepatic tumours
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Increased blood pressure
Increased risk of breast cancer
Increased risk of cervical cancer
Intermenstrual bleeding
Menstrual bleeding decreased
Migraine
Mood changes
Motor disturbances
Nausea
Numbness
Pain in calf
Photosensitivity
Post medication amenorrhoea
Pulmonary embolism
Rash
Renal impairment
Skin reactions
Suppression of lactation post-partum
Systemic lupus erythematosus
Thrombosis
Ulcerative colitis
Urticaria
Vaginal discharge
Vertigo
Visual disturbances
Vomiting
Weakness
Weight changes
Effects on Laboratory Tests
Oral contraceptives may influence the results of certain laboratory tests including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Laboratory staff should therefore be informed about oral contraceptive use when laboratory tests are requested
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2015
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Co-Cyprindiol 2000/35 Coated Tablets. Somex Pharma. Revised March 2014.
Summary of Product Characteristics: Co-Cyprindiol 2000/35 Tablets. Kent Pharma UK Limited. Revised July 2020.
Summary of Product Characteristics: Cyproterone Acetate 2.00 mg Ethinylestradiol 0.035 mg Coated Tablets. Sandoz Limited. Revised April 2014.
Summary of Product Characteristics: Clairette. Stragen UK Limited. Revised January 2014.
Summary of Product Characteristics: Dianette tablets. Bayer plc. Revised August 2020.
Summary of Product Characteristics: Teragezza 2000/35 microgram film-coated tablets. Morningside Healthcare Ltd. Revised March 2015.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 27 July 2017
The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.org
Last revised: 16 April 2010
Last accessed: 20 November 2015
Faculty of Sexual and Reproductive Healthcare Clinical Guidance: Missed Pill Recommendations
Available at: https://www.fsrh.org/pdfs/CEUStatementMissedPills.pdf
Last accessed: 20 November 2015
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