Herz

Drospirenone, ethinylestradiol.

24 Active Tablets: Each active tablet contains Drospirenone 3 mg, Ethinylestradiol 0.02 mg.
4 Placebo Tablets: Each placebo tablet does not contain any active ingredients.

Pharmacology: Pharmacodynamics: HERZ is combination oral contraceptives that inhibit ovulation by suppressing the gonadotropins, FSH and LH. Additionally, alteration in the cervical mucus (which inhibits sperm penetration) and the endometrium (which reduces the likelihood of implantation), may contribute to contraceptive effectiveness.
Drospirenone has beneficial properties in addition to contraception. Drospirenone has antimineralocorticoid activity that can prevent weight gain and other symptoms caused by fluid retention. It counteracts the estrogen-related sodium retention, providing for a very good tolerance and has positive effects on the premenstrual syndrome (PMS). Originator product was studied in PMDD. PMDD is a severe form of PMS. In two placebo controlled phase 3 studies including over 500 subjects, originator product showed clinical superiority in relief of symptoms of PMDD. In combination with ethinylestradiol, drospirenone displays a favorable lipid profile with an increase in HDL. Drospirenone exerts antiandrogenic activity leading to a positive effect on the skin and to a reduction in acne lesions and sebum production. In addition, drospirenone does not counteract the ethinylestradiol - related SHBG increase which is useful for binding and inactivating the endogenous androgens.
In two multicenter, double blind, randomized, placebo controlled studies on the efficacy and safety of originator product as an acne therapy in women with moderate acne vulgaris, it produced clinically and statistically significant anti-acne effects on all the primary efficacy variables (inflammatory lesion, non-inflammatory lesion, total lesion counts, and the number and percentage of subjects with a 'clear' or 'almost clear' rating on the Investigator's Stated Global Assessment (ISGA) scale) and on the majority of secondary efficacy variables. Drospirenone is devoid of any androgenic, estrogenic, glucocorticoid, and antiglucocorticoid activity. This, in combination with the antimineralocorticoid and antiandrogenic properties, gives drospirenone a biochemical and pharmacological profile closely resembling the natural hormone progesterone. Apart from this, there is evidence of a reduced risk of endometrial cancer and ovarian cancer. Furthermore, the higher dosed COCs (0.05 mg ethinylestradiol) have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Whether this also applies to lower-dosed CPCs remains to be confirmed.
More about the Pill: The combined pill may also have non-contraceptive health benefits.
The period may be lighter and shorter. As a result, the risk of anemia may be lower. The period pains may become less severe or may completely disappear.
In addition, some serious disorders have been reported as occurring less frequently in users of Pills containing 50 microgram ethinylestradiol ('high-dose Pills'). These are benign breast disease, ovarian cysts, pelvic infections (pelvic inflammatory disease or PID), ectopic pregnancy (pregnancy in which the embryo implants outside of the womb) and cancer of the endometrium (lining of the womb) and ovaries. This may also be the case for low-dose Pills but so far this has only been confirmed for endometrial and ovarian cancer.
One of the hormones in HERZ, drospirenone, has special properties leading to beneficial effects in addition to contraception. Drospirenone can prevent weight-gain, and other symptoms such as bloating or swelling, related to fluid retention and caused by hormones both in oral contraceptives and occurring at certain times in the menstrual cycle.
Drospirenone also has antiandrogenic activity which can help to reduce acne (pimples) and greasiness of the skin and hair. These special properties make drospirenone similar to the natural progesterone hormone produced by the body.
In a large study of originator product, the specific pill intake scheme with 24 tablets containing hormones as compared to 21 in conventional combined oral contraceptives showed a very high contraceptive efficacy.
Pharmacokinetics: Absorption: Orally administered drospirenone is rapidly and almost completely absorbed.
Peak serum concentrations of drospirenone are reached 1 to 3 hours after administration. Ethinylestradiol is rapidly absorbed with peak concentrations attained within 2 hours.
Distribution: Drospirenone is about 97% protein bound, presumably to albumin. Ethinylestradiol is about 98% protein bound, mainly to albumin. But it is non-specifically binding Drospirenone and ethinylestradiol do not appear to bind to sex hormone binding globulin (SHBG).
Metabolism: Drospirenone is metabolized to 2 major inactive metabolites, which formed without involvement of the P450 system.
Ethinylestradiol appears to undergo extensive first-pass metabolism. Ethinylestradiol is mainly metabolized via aromatic hydroxylation by hepatic microsomal isoenzyme cytochrome P-450 (CYP) 3A4. The major hydroxylated metabolite of ethinylestradiol is 2-hydroxyethinylestradiol, which is thought to contribute to some of the adverse cardiovascular effects of the drug. The hydroxylated metabolite is further metabolized by methylation and glucuronidation prior to urinary and fecal excretion. Ethinylestradiol and its metabolites undergo glucuronide and sulfate conjugation. Ethinylestradiol undergoes extensive enterohepatic circulation as glucuronide and sulfate conjugation.
Excretion: The elimination half-life has been reported to be 30 hours for drospirenone. Drospirenone is excreted only in trace amounts in unchanged form. The metabolites of drospirenone are excreted with the feces and urine. The elimination half-life has been reported to be 6-45 hours for ethinylestradiol. Ethinylestradiol is not excreted in unchanged form to any significant extent. The metabolites of ethinylestradiol are excreted at a urinary to biliary ratio of 4:6.

HERZ is contraceptive pill and is used to prevent pregnancy. The patient may also experience the following additional benefits: Improvement in symptoms such as bloating, swelling or weight-gain, due to fluid retention.
HERZ is used for the treatment of moderate acne in women who decide to use oral contraception.
HERZ is used for the treatment of symptoms of premenstrual dysphoric disorder in women who decide to use oral contraception.
HERZ is used for the treatment of dysmenorrhea in women who elect to use oral contraception.

How to take HERZ: HERZ containing 24 active tablets are administered once daily for 24 consecutive days, followed by placebo tablets for 4 days.
Withdrawal bleeding usually occurs within 2 or 3 days after last hormonally active tablet has been taken. Repeat dosage cycles begin on the same day of week as the initial cycle. Do not leave a gap between packs. Repeat cycles should generally begin regardless of whether menstruation has stopped.
When taken correctly, combined oral contraceptives, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.
When can the patient start with the first pack: If the patient has not used a contraceptive with hormones during the previous month.
Start taking HERZ on the first day of the cycle (that is, the first day of the period). Then follow the days in order. HERZ will work immediately, it is not necessary to use an additional contraceptive method. The patient may also start on days 2-5 of the cycle, but in that case make sure to also use an additional contraceptive method (barrier method) for the first 7 days of taking the tablets in the first cycle.
Switch from a different contraceptive: Another combined hormonal contraceptive pill: Start on the day after taking the last tablet from the present Pill pack (this means no tablet-free break). If the present Pill pack also contains hormone-free tablets the patient can start HERZ on the day after taking the last tablet containing hormones (if not sure which it is, ask the doctor or pharmacist). The patient can also start later, but never later than the day following the tablet-free break of the present Pill (or the day after the last hormone-free tablet of the present Pill).
Combined contraceptive vaginal ring or patch: Start using HERZ preferably on the day of removal but at the latest when the next application would have been due. If the patient follows these instructions, it is not necessary to use an additional contraceptive method.
Progestogen-only pill, injection, implant or a progestogen-releasing 'IUS', intrauterine system: The patient may switch from the progestogen-only pill any day (from an implant or the IUS on the day of its removal, from an injectable when the next injection would be due) but in all of these cases the patient must use extra protective measures (for example, a condom) during the first 7 days of HERZ use.
After a miscarriage: Follow the advice of the doctor.
After having a baby: If the patient has just had a baby, the doctor may tell to wait until after the first normal period before starting taking HERZ. Sometimes it is possible to start sooner. The doctor will advise the patient.
If, after having a baby, the patient has had sex before starting HERZ, be sure that she is not pregnant or wait until the next menstrual period.
If the patient wants to start HERZ after having a baby and is breast-feeding, discuss this first with the doctor.
Ask the doctor what to do if the patient is not sure when to start.
Missed doses: Depending on the day of the cycle on which one tablet has been missed, the patient may need to take additional contraceptive precautions, for example a barrier method such as a condom. Take the tablets according to the following principles. In case of doubt, contact the doctor.
If the patient forgot to take any of the 4 placebo tablets (the last 4 tablets in the blister), she is still protected against pregnancy because they do not contain any hormones. However, to make sure that the patient does not change the pill taking rhythm, which is important for the contraceptive reliability of the Pill, she should proceed with the next tablet at the normal time and discard the forgotten tablet(s) to avoid any confusion. If the patient forgot the last placebo tablet of the current pack it is important that she still takes the first tablet from the next pack at the correct time.
If the patient forgot to take the active tablets (those containing hormones) (tablets 1-24 of the blister): If the patient is less than 24 hours late when taking a tablet, the protection against pregnancy is not reduced. Take the tablet as soon as remembered and then continue taking the tablets again at the usual time.
If the patient is more than 24 hours late in taking any of light pink tablets the protection against pregnancy may be reduced. The more light pink tablets the patient has forgotten, the greater the risk that the protection from pregnancy is reduced. There is a particularly high risk of becoming pregnant if the patient misses tablets at the beginning of the pack or at the end (the last of the 24 light pink tablets).
More than one tablet forgotten in a pack: Contact the doctor.
Do not take more than 2 tablets on a given day, to make up for missed pills: If the patient has forgotten tablets in a pack, and does not have the expected bleeding that should start at the end of the blister (while taking the last 4 placebo tablets), she may be pregnant. Contact the doctor before starting the next pack.
1 tablet missed during day 1-7: If the patient has forgotten to start a new pack, or has missed tablet(s) during the first 7 days of the pack, there is a risk that she is already pregnant (if she had sex in the 7 days before forgetting the tablet). In that case, contact the doctor before starting the next pack.
If the patient had no sex in the 7 days before the oversight, take the missed pink tablet as soon as remembered (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Use extra contraceptive precautions (barrier method) for the next 7 days.
1 tablet missed during day 8-14: Take the missed pink tablet as soon as remembered (even if this means taking two tablets at the same time) and take the next tablets at the usual time. The reliability of the Pill is maintained. The patient need not use extra contraceptive precautions.
1 tablet missed during day 15-24: The patient may choose either of the following options, without the need for extra contraceptive precautions: 1. Take the missed pink tablet as soon as remembered (even if this means taking two tablets at the same time) and take the next tablets at the usual time (unless there are no pink tablets left in the current pack). Discard the current pack as soon as the pink tablets are finished (do not take the remaining 4 placebo tablets) and start the next pack so that no gap is left between packs. The patient may not have a withdrawal bleed until she has finished the pink tablets of the second pack but may have spotting or breakthrough bleeding while taking the tablets; or
2. Stop taking tablets from the current pack, have a tablet-free break of 4 days or less (also count the day the patient missed the tablet) and continue with the next pack.
If the patient vomits or has severe diarrhea: If the patient vomits or has severe diarrhea after taking any of the pink tablets, the active ingredients in that tablet may not have been completely absorbed. If the patient vomits within 3 to 4 hours after taking the tablet, this is like missing a tablet. Therefore, follow the advice under Missed doses as previously mentioned. If the patient has severe diarrhea, please contact the doctor. Vomiting or diarrhea while taking the 4 placebo tablets at the end of the blister does not have an influence on the contraceptive reliability.
If the patient stops taking HERZ: The patient can stop taking HERZ at any time. If she does not want to become pregnant, ask the doctor for advice about other reliable methods of birth control. If the patient wants to become pregnant, stop taking HERZ and wait for a menstrual period before starting to try to become pregnant. The patient will be able to calculate the expected delivery date more easily.
If the patient wants to delay a period: The patient can delay the period if she starts with the next pack of HERZ immediately after having finished the pink tablets of the current blister (do not take the 4 placebo tablets at the end of the blister). The patient can continue with the second pack for as long as she wishes, e.g. until the pack is empty, to get a period approx. 3 weeks later than usual. If the patient wishes the period to begin earlier than that, just stop taking pink tablets from the second pack, discard the pack and have a pill-free interval of a maximum of 4 days and then start a new pack. In this case, approx. 2-3 days after the patient takes the last light pink tablet from the second pack she should get the period. While using the second pack the patient may have some breakthrough bleeding or spotting on tablet-taking days.
If the patient wants to change the starting day of the period: If the patient takes the tablets as directed, she will have the period on about the same day every 4 weeks. If the patient wants to change this, do not use up the placebo tablets at the end of the blister, before starting the next pack. For example, if the period usually starts on a Friday and in future the patient wants it to start on Tuesday (3 days earlier) she should now start the next pack 3 days sooner than she usually does, discard the last 3 placebo tablets at the end of the previous pack and then continue with the next pack without having a break between the packs. The less placebo tablets taken, the higher is the probability that the patient will not have a bleeding. The patient may have some breakthrough bleeding or spotting during the use of the next pack.
If the patient has any further questions on the use of this product, ask the doctor or pharmacist.
Additional information on special populations: Use in children: Not to be used prior to menarche.
Use in older women: Not to be used after the menopause.
Women with hepatic dysfunction: Contraindicated in patients with hepatic dysfunction.
Women with renal dysfunction: Do not take HERZ if the patient is suffering from poorly functioning kidneys or acute kidney failure.

Symptoms: Overdosage of estrogen-plus-progestin therapy may cause nausea and vomiting, breast tenderness, abdominal pain, drowsiness/fatigue, and withdrawal bleeding may occur in women.
Even girls who have not yet started to menstruate but have accidentally taken this medicine may experience such bleeding.
If the patient has taken too many HERZ tablets, or discovers that a child has taken some, ask the doctor or pharmacist for advice.

WHAT THE PATIENT NEEDS TO KNOW BEFORE TAKING HERZ: Before the patient can begin taking HERZ, the doctor will ask some questions about her personal health history and that of her close relatives. The doctor will also measure blood pressure and, depending upon her personal situation, may also carry out some other tests.
In this monograph, several situations are described where the patient should stop using HERZ, or where the reliability of HERZ may be decreased. In such situations the patient should either not have sex or should take extra non-hormonal contraceptive precautions, e.g. use a condom or another barrier method. Do not use rhythm or temperature methods. These methods can be unreliable because HERZ alters the monthly changes of body temperature and cervical mucus.
HERZ, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or any other sexually transmitted disease.
Do not use HERZ if the patient has any of the conditions listed as follows. If any of these apply to the patient, tell the doctor before starting to use HERZ. The doctor may advise to use a different type of pill or an entirely different (including non-hormonal) method of birth control.
If the patient has (or has ever had) a blood clot in a blood vessel of the leg (thrombosis), of the lung (pulmonary embolism) or other parts of the body.
If the patient has (or has ever had) a heart attack or stroke (caused by a blood clot or a rupture of a blood vessel in the brain).
If the patient has (or has ever had) a disease that can be an indicator of a future heart attack (for example, angina pectoris which causes severe chest pain which may spread to the left arm) or of a stroke (for example, a minor stroke with no residual effects, a so-called transient ischaemic attack).
If the patient has a high risk of venous or arterial blood clots (see The Pill and blood clots under Precautions and consult the doctor who will decide whether the patient may use the Pill).
If the patient (or has ever had) a certain kind of migraine (with so-called focal neurological symptoms such as visual symptoms, speech disability, or weakness or numbness in any part of the body).
If the patient has diabetes mellitus with damaged blood vessels.
If the patient has (or has ever had) a liver disease (symptoms of which may be yellowing of the skin or itching over the whole body) and the liver is still not working normally.
If the patient is taking any antiviral medicines which contain ombitasvir, paritaprevir, or dasabuvir, and combinations of these. These antiviral medicines are used to treat chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus).
If the patient has (or has ever had) a cancer that may grow under the influence of sex hormones (e.g. of the breast or the genital organs).
If the patient has a severe kidney insufficiency or acute kidney failure.
If the patient has (or has ever had) a benign or malignant tumor of the liver.
If the patient has any unexplained bleeding from the vagina.
If the patient is pregnant or thinks she might be pregnant.
If the patient is allergic (hypersensitive) to ethinylestradiol, drospirenone or any of the other ingredients in HERZ. This may cause, for example, itching, rash or swelling.
If any of these conditions appear for the first time while using the Pill, stop taking it at once and consult the doctor. In the meantime, use non-hormonal contraceptive measures.

In some situations the patient needs to take special care while taking HERZ or any other combined pill, and the doctor may need to examine her regularly. Consult the doctor before starting to use HERZ if any of the following conditions apply or if any of them develop or worsen while taking HERZ: if the patient smokes.
If the patient has diabetes.
If the patient is overweight.
If the patient has high blood pressure.
If the patient has a heart valve disorder or a certain heart rhythm disorder.
If the patient has an inflammation of the veins (superficial phlebitis).
If the patient has varicose veins.
If anyone in the immediate family has ever had a blood clot (thrombosis in the leg, lung 'pulmonary embolism', or elsewhere), a heart attack or a stroke at a young age.
If the patient suffers from migraine.
If the patient has epilepsy.
If the patient has an increased potassium blood level (e.g. due to problems with the kidneys) and also use diuretics that may increase the potassium in the blood (ask the doctor if not sure).
If the patient or someone in the immediate family has ever had high blood levels of cholesterol or triglycerides (fatty substances).
If a close relative has or has ever had breast cancer.
If the patient has a disease of the liver or gall bladder.
If the patient has Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease).
If the patient has systemic lupus erythematosus (or SLE, a disease of the immune system).
If the patient has hemolytic uremic syndrome (or 'HUS', a disorder of blood coagulation causing failure of the kidneys).
If the patient has sickle cell disease.
If the patient has a condition that occurred for the first time or worsened during pregnancy or previous use of sex hormones (e.g. hearing loss, a metabolic disease called porphyria, a skin disease called herpes gestationis, or a neurological disease called Sydenham's chorea).
If the patient has (or has ever had) golden brown pigment patches so-called 'pregnancy patches' especially on the face (chloasma). If this is the case, avoid direct exposure to sunlight or ultraviolet light.
If the patient has hereditary angioedema. Consult the doctor immediately if the patient experiences symptoms of angioedema such as swollen face, tongue or throat, and/or difficulty swallowing, or hives, together with difficulty breathing. Products containing estrogens may induce or worsen symptoms of angioedema.
If any of the previously mentioned conditions appear for the first time, recur or worsen while using the Pill, contact the doctor.
The Pill and blood clots: A thrombosis is the formation of a blood clot which may block a blood vessel.
A thrombosis sometimes occurs in the deep veins of the legs (deep venous thrombosis). Venous thromboembolism (VTE) can develop whether or not the patient is taking the pill. It can also happen if the patient becomes pregnant. If a blood clot breaks away from the vein where it has formed; it may reach and block the arteries of the lungs, causing a so-called 'pulmonary embolism'. Blood clots can also occur very rarely in the blood vessels of the heart (causing a heart attack). Blood clots or a ruptured blood vessel in the brain may cause a stroke.
From the Long-term studies, they have suggested that there may be a link between the use of the pill and an increased risk of venous and arterial blood clots, embolism, heart attack or stroke. The occurrence of these events is rare.
The risk of venous thromboembolism is highest during the first year of use. This increased risk is present after initially starting the combined pill or restarting (following a 4 week or greater pill free interval) the same or a different combined pill. Data from a large study suggest that this increased risk is mainly present during the first 3 months.
Overall the risk for venous thromboembolism in users of low estrogen dose (< 50 µg ethinylestradiol) pills is two to threefold higher than for non-users of combined oral contraceptives who are not pregnant and remains lower than the risk associated with pregnancy and delivery.
Very occasionally venous or arterial thromboembolic events may cause serious permanent disabilities, may be life-threatening, or may even be fatal.
Venous thromboembolism, manifesting as deep venous thrombosis and/or pulmonary embolism, may occur during the use of all combined pills.
Extremely rarely blood clots can occur in other parts of the body including the liver, gut, kidney, brain or eye.
Stop taking the pill and contact a doctor immediately if the patient notices signs of: deep venous thrombosis, such as: swelling of one leg 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 discolored skin on the leg.
Pulmonary embolism, such as: sudden onset of unexplained shortness of breath or rapid breathing; sudden coughing which may bring up blood; sharp chest pain which may increase with deep breathing; sense of anxiety; severe lightheadedness 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 event (e.g. respiratory tract infection).
Arterial thromboembolism (arterial blood vessels blocked by blood clots and such blood clots which have broken away): stroke such as: sudden numbness or weakness of the face, arm or leg, especially on one side of the body; sudden confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no known cause; loss of consciousness or fainting with or without seizure.
Blood clots blocking other arterial blood vessels, such as: sudden pain, swelling and slight blue discoloration of an extremity; "acute" abdomen.
Heart attack such as: 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; fullness, indigestion or choking feeling; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats.
The doctor will check, e.g. whether the patient has a higher risk of getting a thrombosis due to a combination of risk factors or perhaps one very strong risk factor. In the case of a combination of factors the risk may be higher than simply adding two individual risks. If the risk is too high, the doctor will not prescribe the Pill.
The risk of venous or arterial blood clots (e.g. deep venous thrombosis, pulmonary embolism, heart attack) or stroke increases: with age.
If the patient is overweight.
If anyone in the immediate family has ever had a blood clot (thrombosis in the leg, lung 'pulmonary embolism', or elsewhere), a heart attack or a stroke at a young age, or if the patient or any of the relatives are known or suspected of having a hereditary blood clotting disorder increasing the risk for developing blood clots. In this case the patient should see a specialist before deciding about using any combined oral contraceptive. Certain blood factors that may suggest the patient has tendency for venous or arterial thrombosis include activated protein C (APC) resistance, hyperhomocysteinemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
With prolonged immobilization (for example, when the patient has her leg or legs in plaster or splints), major surgery, any surgery to the legs; or major trauma. In these situations it is better to stop taking the pill (if the surgery is planned the patient should stop at least four weeks beforehand) and not to start again until two weeks after the patient is fully on her feet again.
If the patient smokes (the risk increases the more the patient smokes and the older she gets, especially in women over 35 years of age). When using the pill the patient should stop smoking, especially if she is older than about 35 years of age.
If the patient or someone in the immediate family has or has ever had high blood levels of cholesterol or triglycerides (fatty substances).
If the patient has high blood pressure. If she develops high blood pressure while using the pill, she may be told to stop using it.
If the patient suffers from migraine.
If the patient has a heart valve disorder or a certain heart rhythm disorder.
Directly after giving birth, women are at an increased risk of blood clots so the patient should ask the doctor how soon after delivery she can start taking a combined pill.
The Pill and cancer: Breast cancer has been observed slightly more often in women using combined pills, but it is not known whether this is caused by the treatment itself. For example, it may be that more tumors are detected in women on combined pills because they are examined by their doctor more often. The risk of breast tumors becomes gradually less after stopping the combined hormonal contraceptive. It is important to regularly check the breasts and the patient should contact the doctor if she feels any lump.
In rare cases, benign liver tumors, and in even fewer cases malignant liver tumors have been reported in contraceptive pill users. In isolated cases, these tumors have led to life-threatening internal bleeding. Contact the doctor if the patient has unusually severe abdominal pain.
The most important risk factor for cervical cancer is persistent Human Papilloma Virus (HPV) infection. Some studies suggest that long-term use of the pill increases a woman's risk of developing cervical cancer. However, it is not clear to what extent sexual behavior or other factors such as Human Papilloma Virus increases this risk.
The previously mentioned tumors may be life-threatening or may have a fatal outcome.
Bleeding between periods: With all Pills, for the first few months, the patient can have irregular vaginal bleeding (spotting or breakthrough bleeding) between the periods. The patient may need to use sanitary protection, but continue to take the tablets as normal. Irregular vaginal bleeding usually stops once the body has adjusted to the Pill (usually after about 3 tablet-taking cycles). If it continues, becomes heavy or starts again, tell the doctor.
What to do if no bleeding occurs: If the patient has taken all the tablets correctly, has not had any vomiting or severe diarrhea and she has not taken any other medicines, it is highly unlikely that she is pregnant. Continue to take HERZ as usual.
If the patient has taken the tablets incorrectly, or, if she has taken the tablets correctly but the expected bleeding does not happen twice in a row, she may be pregnant. Contact the doctor immediately. Do not start the next pack until the patient is sure that she is not pregnant. In the meantime, use non-hormonal contraceptive measures.
EFFECT ON ABILITY TO DRIVE AND USE MACHINE: Referring the studies of originator product, no studies on the effects of the ability to drive and use machines have been performed.

Pregnancy: Do not take HERZ if the patient is pregnant, or, if she thinks she may be pregnant. If the patient becomes pregnant while taking HERZ, stop taking it immediately and contact the doctor. If the patient wants to become pregnant, she can stop taking HERZ at any time.
Lactation: HERZ is generally not recommended for use during breastfeeding. If the patient wants to take the Pill while she is breast-feeding she should contact the doctor.

Like all medicines, HERZ can cause side effects, although not everybody gets them. If any of the side effects gets serious, or if the patient notices any side effects not listed in this monograph, please tell the doctor or pharmacist.
Serious side effects: See also The Pill and blood clots and The Pill and cancer under Precautions for side effects, including serious reactions, associated with the use of the Pill and Contraindications. Please read these sections carefully and consult the doctor at once where appropriate.
The following side effects were reported in the studies of originator product that use for oral contraceptive, for the treatment of moderate acne in women who decided to use oral contraception and for the treatment of symptoms of Premenstrual Dysphoric Disorder (PMDD) in women who decided to use oral contraception.
Common side effects (may affect up to 1 in 10): emotional lability (mood swings), depression/depressive mood; migraine; nausea^a; breast pain^a, unscheduled uterine bleeding (bleeding between periods)^a, genital tract bleeding (vaginal bleeding) not further specified.
Uncommon side effects (may affect up to 1 in 100 people): decrease and loss of libido (reduced or loss of sex drive)^b.
Rare side effects (may affect up to 1 in 1,000 people): venous and arterial thromboembolic events*.
* Estimated frequency, from epidemiological studies of originator product that encompassing a group of combined oral contraceptives. Frequency was borderline to Very Rare.
The term venous and arterial thromboembolic events covers the following: any blockage or clot in a deep peripheral vein, clots which travel through the venous blood system (e.g. to the lung known as pulmonary embolism or as pulmonary infarction), heart attack caused by blood clots, stroke caused by blockage of the blood supply to or in the brain.
^a Incidence in trials evaluating PMDD was Very Common > 10/100.
^b Incidence in trials evaluating PMDD was Common ≥1/100.
Side effects that have been reported with the use of the Pill, without knowing their precise frequency: erythema multiforme (a skin condition characterized by itchy red blotches or swollen patches of skin).
Description of selected adverse reactions: Adverse reactions with very low frequency or with delayed onset of symptoms which are considered to be related to the group of combined oral contraceptives are listed as follows: Tumors: The frequency of diagnosis of breast cancer is very slightly increased among users of oral contraceptives. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer. It is not known whether there is a direct link to users of combined oral contraceptives.
Liver tumors (benign and malignant).
Other conditions: erythema nodosum (a skin condition characterized by tender red nodules).
Women with hypertriglyceridemia (increased blood fats resulting in an increased risk of pancreatitis when using combined oral contraceptives).
High blood pressure.
Occurrence or worsening of conditions for which a link to combined oral contraceptives is not definite: jaundice and/or itching related to cholestasis (blocked bile flow); gallstone formation; a metabolic condition called porphyria; systemic lupus erythematosus (a chronic autoimmune disease); hemolytic uremic syndrome (a blood clotting disease); a neurological condition called Sydenham's chorea; herpes gestationis (a type of skin condition that occurs during pregnancy); otosclerosis-related hearing loss.
In women with hereditary angioedema (characterized by sudden swelling of e.g. the eyes, mouth, throat etc.) external estrogens may induce or worsen symptoms of angioedema.
Disturbed liver function.
Changes in glucose tolerance or effect on peripheral insulin resistance.
Crohn's disease, ulcerative colitis.
Chloasma.
Hypersensitivity (including symptoms such as rash, urticaria).
Interactions: Unexpected bleeding and/or contraceptive failure may result from interactions of other drugs with oral contraceptives (e.g. the herbal remedy St. John's wort, or drugs for epilepsy, tuberculosis, HIV infections and other infections).

Always tell the doctor which medicines or herbal products the patient is already using. There are some medicines the patient must not take with HERZ. Also tell any other doctor or dentist who prescribes another medicine (or the pharmacist from whom the patient got the medicine) that she is taking HERZ. They can tell the patient if she needs to take additional contraceptive precautions (for example condoms) and if so, for how long, or, whether the use of another medicine she needs must be changed.
Some medicines: can have an influence on the blood levels of HERZ; can make it less effective in preventing pregnancy; can cause unexpected bleeding.
These include: medicines used for the treatment of: Epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate); tuberculosis (e.g. rifampicin); HIV and Hepatitis C Virus infections (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors); fungal infections (griseofulvin, azole antifungals, e.g. itraconazole, voriconazole, fluconazole, ketoconazole); bacterial infections (macrolide antibiotics, e.g. clarithromycin, erythromycin); certain heart diseases, high blood pressure (calcium channel blockers, e.g. verapamil, diltiazem); arthritis, arthrosis (etoricoxib); the herbal remedy St. John's wort; grapefruit juice.
HERZ may influence the effect of other medicines, e.g. cyclosporine, lamotrigine, melatonin, midazolam, theophylline, tizanidine.
In theory the potassium levels may increase if the patient is taking HERZ with other drugs that can also increase potassium levels.
Please tell the doctor or pharmacist if the patient is taking or has recently taken any other medicines, including medicines obtained without a prescription.
Laboratory tests: If the patient needs a blood test or other laboratory tests tell the doctor or the laboratory staff that she is taking the Pill because oral contraceptives can affect the results of some tests.
Taking HERZ with food and drink: The patient may take HERZ with or without food, if necessary with a small amount of water.

Do not store above 30°C.

Oral Contraceptives

G03AA12 - drospirenone and ethinylestradiol ; Belongs to the class of progestogens and estrogens in fixed combinations. Used as systemic contraceptives.

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