Regulon Special Precautions

Warnings: If any of the conditions or risk factors mentioned as follows is present, the suitability of Regulon should be discussed with the woman.
In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised to contact a doctor to determine whether the use of Regulon should be discontinued.
Circulatory disorders: Risk of venous thromboembolism (VTE): The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with the lowest risk of VTE. Other products such as Regulon may have up to twice this level of risk. The decision to use any product other than one with the lowest VTE risk should be taken only after a discussion with the woman to ensure understanding of the risk of VTE with Regulon, how current risk factors influence this risk, and that VTE risk is highest in the first ever year of use. There is also some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more.
In women who do not use a CHC and are not pregnant about 2 out of 10,000 will develop a VTE over the period of one year. However, in any individual woman the risk may be far higher, depending on the underlying risk factors (see as follows).
It is estimated¹ that out of 10,000 women who use a CHC containing desogestrel between 9 and 12 women will develop a VTE in one year; this compares with about 6² in women who use a levonorgestrel-containing CHC.
In both cases, the number of VTEs per year is fewer than the number expected during pregnancy or in the postpartum period.
VTE may be fatal in 1-2% of cases.
¹ These incidences were estimated from the totality of the epidemiological study data, using relative risks for the different products compared with levonorgestrel-containing CHCs.
² Mid-point of range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel versus non-use of approximately 2.3 to 3.6. (See figure.)

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Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries.
Risk factors for VTE: The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see Table 1).
Regulon is contraindicated if a woman has multiple risk factors that puts the woman at high risk of venous thrombosis (see Contraindications). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case the total risk of VTE should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see Contraindications). (See Table 1.)

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There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis.
The increased risk of thromboembolism in pregnancy, and particularly the 6-week period of the puerperium, must be considered (for information see Use in Pregnancy & Lactation).
Symptoms of VTE (deep vein thrombosis and pulmonary embolism): In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that the patient is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include: unilateral swelling of the leg and/or foot or along a vein in the leg; pain or tenderness in the leg which may be felt only when standing or walking, increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include: sudden onset of unexplained shortness of breath or rapid breathing; sudden coughing which may be associated with haemoptysis; sharp chest pain; severe light headedness or dizziness; rapid or irregular heartbeat.
Some of these symptoms (e.g. "shortness of breath", "coughing") are non-specific and might be misinterpreted as more common or less severe events (e.g. respiratory tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision. Sometimes loss of vision can occur almost immediately.
Risk of arterial thromboembolism (ATE): Epidemiological studies have associated the use of CHCs with an increased risk for arterial thromboembolism (myocardial infarction) or for cerebrovascular accident (e.g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal.
Risk factors for ATE: The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women with risk factors (see Table 2). Regulon is contraindicated if a woman has one serious or multiple risk factors for ATE that puts the patient at high risk of arterial thrombosis (see Contraindications). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case the total risk should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed (see Contraindications). (See Table 2.)

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Symptoms of ATE: In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that the patient is taking a CHC.
Symptoms of a cerebrovascular accident can include: sudden numbness or weakness of the face, arm or leg, especially on one side of the body; sudden trouble walking, dizziness, loss of balance or coordination; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden, severe or prolonged headache with no known cause; loss of consciousness or fainting with or without seizure.
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of myocardial infarction (MI) can include: pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the breastbone; discomfort radiating to the back, jaw, throat, arm, stomach; feeling of being full, having indigestion or choking; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats.
Tumours: Epidemiological studies indicate that the long-term use of oral contraceptives displays an additional risk factor for the development of cervical cancer in women infected with human papillomavirus (HPV). However, there is still uncertainty about the extent to which this finding is influenced by confounding effects (e.g. differences in number of sexual partners or in use of barrier contraceptives).
A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using CHCs. This increased risk gradually declines for 10 years after cessation of COCs. Since breast cancer is a rare condition in women below 40 years of age, the increase in the number of diagnosed cases of breast cancer in present and former users of COCs is low compared to the risk of breast cancer in their entire lifetime. These studies do not put forward evidence of a causal relationship. The observed pattern of an increased risk may be due to an earlier diagnosing of breast cancer in users of COCs, the biological effects of COCs or a combination of both. The diagnosed cases of breast cancer in users of COCs have a tendency to be less clinically advanced compared to the diagnosed cases of breast cancer in never-users.
In rare cases, benign liver tumours, and even more rarely, malignant liver tumours have been reported in users of CHCs. In isolated cases, these tumours have led to life-threatening intra-abdominal haemorrhages. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage occur in women taking CHCs.
Other conditions: Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use (see Adverse Reactions). Depression can be serious and is a well-known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.
Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using CHCs.
Although small increases in blood pressure have been reported in many women taking CHCs, clinically relevant increases are rare. A systematic relationship between COC use and clinical hypertension has not been established. However, if a sustained clinically significant hypertension develops during the use of a CHC then it is prudent for the physician to withdraw the CHC and treat the hypertension. Where considered appropriate, CHC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both pregnancy and CHC use, but the evidence of a relationship with use of COC is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis-related hearing loss.
Exogenous estrogens may induce or exacerbate symptoms of hereditary and acquired angioedema.
Acute or chronic disturbances of liver function may necessitate the discontinuation of COCs until liver function parameters have been normalised. Recurrent cholestatic jaundice which occurred for the first time during pregnancy or during previous use of sexual hormones, requires discontinuation of COCs.
Although CHCs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in well controlled diabetics using CHCs. However, diabetic women should be carefully observed while taking CHCs.
Crohn's disease and ulcerative colitis have been reported during CHC use.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking CHCs.
When counselling the choice of contraceptive method(s), all the previously mentioned information should be taken into account.
Medical examination/consultation: Prior to the initiation or reinstitution of Regulon a complete medical history (including family history) should be taken and pregnancy must be ruled out. Blood pressure should be measured and a physical examination should be performed, guided by the contraindications (see Contraindications) and warnings (see previously mentioned). It is important to draw a woman's attention to the information on venous and arterial thrombosis, including the risk of Regulon compared with other CHCs, the symptoms of VTE and ATE, the known risk factors and what to do in the event of a suspected thrombosis.
The woman should also be instructed to carefully read the package leaflet and to adhere to the advice given. The frequency and nature of examinations should be based on established practice guidelines and be adapted to the individual woman.
Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
Reduced efficacy: The efficacy of CHCs may be reduced in the event of e.g., missed tablets (see Dosage & Administration), gastrointestinal disturbances (see Dosage & Administration) or concomitant medication that decrease the plasma concentration of ethinylestradiol and/or etonogestrel, the active metabolite of desogestrel (see Interactions).
Herbal preparations containing St. John's wort (Hypericum perforatum) should not be used while taking Regulon due to the risk of decreased plasma concentrations and reduced clinical effects of Regulon (see Interactions).
Reduced cycle control: With all CHCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about three cycles.
If bleeding irregularities persist or occur after previously regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may not occur during the tablet-free interval. If the CHC has been taken according to the directions described in Dosage & Administration, it is unlikely that the woman is pregnant. However, if the CHC has not been taken according to these directions prior to the first missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out before CHC use is continued.
ALT elevations: During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs). Additionally, also in patients treated with glecaprevir/pibrentasvir, ALT elevations were observed in women using ethinylestradiol-containing medications such as CHCs. Patients who are taking ethinylestradiol-containing medicinal products must switch to an alternative method of contraception (e.g. progestin-only contraception or non-hormonal methods) prior to initiating ombitasvir/paritaprevir/ritonavir and dasabuvir therapy (see Contraindications and Interactions).
Excipient: This medical product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Regulon has no influence or negligible influence on the ability to drive and use machines.