Chariva

Chariva

Manufacturer:

Gedeon Richter

Distributor:

Zuellig Pharma

Marketer:

Abbott
Full Prescribing Info
Contents
Chlormadinone acetate, ethinyl oestradiol.
Description
Each tablet of Chariva contains ethinyl oestradiol 0.03 mg and chlormadinone acetate 2 mg. It also contains the following excipients: Lactose monohydrate, maize starch, povidone K30, magnesium stearate, hypromellose, macrogol 6000, propylene glycol, talc, titanium dioxide (E171), iron oxide (E172).
Action
Pharmacotherapeutic Group: Progestogens and estrogens, fixed combinations. ATC Code: G03AA.
Pharmacology: Pharmacodynamics: The continuous intake of Chariva for 21 days inhibits pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion, and thus ovulation. The endometrium proliferates and undergoes secretory transformation. The consistence of the cervical mucus is changed. This prevents sperm migration through the cervical canal and alters sperm motility.
The lowest daily dose of chlormadinone acetate for complete inhibition of ovulation is 1.7 mg. The full endometrial transformation dose is 25 mg/cycle. Chlormadinone acetate is an antiandrogenic progestogen. Its effect is based on its ability to displace androgens from their receptors.
Clinical Efficacy: In clinical studies in which the administration of Chariva was tested for up to 2 years in 1655 women and >22,000 menstruation cycles, there were 12 pregnancies. In 7 women administration errors, concomitant diseases causing nausea or vomiting, or concomitant administration of medicines known to reduce the contraceptive effect of hormonal contraceptives were present in the period of conception. (See table.)

Click on icon to see table/diagram/image

Pharmacokinetics: Chlormadinone Acetate (CMA): Absorption: After oral administration, CMA is rapidly and almost completely absorbed. The systemic bioavailability of CMA is high as it is not subject to first-pass metabolism. Peak plasma concentrations (Cmax) are reached after 1-2 hrs.
Distribution: The binding of CMA to human plasma proteins, mainly albumin, is >95%. Chlormadinone acetate has no binding affinity for sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG). Chlormadinone acetate is stored primarily in the fatty tissue.
Metabolism: Various reduction and oxidation processes and conjugation to glucuronides and sulphates result in a variety of metabolites. The principal metabolites in human plasma are 3α- and 3β-hydroxy-CMA with biological half-lives that do not differ essentially from that of non-metabolised CMA. The 3-hydroxy metabolites show similar antiandrogenic activity as CMA itself. In the urine, the metabolites appear mainly as conjugates. After enzymatic cleavage, the main metabolite is 2α-hydroxy-CMA besides the 3-hydroxy-metabolites and dihydroxy metabolites.
Elimination: CMA is eliminated from the plasma with a mean t½ of about 34 hrs (after a single dose) and about 36-39 hrs (after multiple doses). After oral administration, CMA and its metabolites are excreted both renally and in the faeces in about equal amounts.
Ethinylestradiol (EE): Absorption: Ethinylestradiol is rapidly and almost completely absorbed after oral administration and mean Cmax are reached after 1.5 hrs. On account of presystemic conjugation and first-pass metabolism in the liver, the absolute bioavailability is only about 40% and is subject to considerable interindividual variation (20-65%).
Distribution: The EE plasma concentrations reported in the literature vary considerably. Approximately 98% of the EE is bound to plasma proteins, almost exclusively to albumin.
Metabolism: Like natural estrogens, EE is biotransformed via (cytochrome P-450 mediated) hydroxylation at the aromatic ring. The main metabolite is 2-hydroxy-EE, which is metabolised to other metabolites and conjugates. Ethinylestradiol undergoes presystemic conjugation both in the mucosa of the small intestine and the liver. In the urine mainly glucuronides, and in the bile and plasma mainly sulphates are found.
Elimination: The mean plasma t½ of EE is approximately 12-14 hrs. Ethinylestradiol is excreted via the kidneys and faeces in the ratio of 2:3. The EE sulphate excreted in the bile after hydrolysis by intestinal bacteria is subject to enterohepatic circulation.
Indications/Uses
Chariva is a hormonal contraceptive.
Chariva should be used as an alternative treatment of moderate papulopustular acne in women for whom hormonal contraception with ethinylestradiol/chlormadinone acetate is indicated; for acne treatment in unresponsive women to standard treatment or for acne treatment in women who have signs/symptoms of endocrine disorder (endocrine acne).
Dosage/Direction for Use
Recommended Dose: 1 tablet must be taken everyday at the same time (preferably in the evening) on 21 consecutive days, followed by a 7-day break in which no tablets are taken; menstruation-like withdrawal bleeding should occur 2-4 days after administration of the last tablet. After the 7-day medication-free interval, medication should be continued with the next pack of Chariva, regardless of whether bleeding has ceased or not.
Administration: Before starting treatment with Chariva, a thorough general and gynaecological examination should be carried out and pregnancy ruled out. Unless otherwise prescribed by the physician, the following dosage of Chariva applies. The patient must follow the instructions, otherwise Chariva will not be fully effective.
Start taking Chariva on the 1st day of menstruation, even if the patient had previously been taking a different contraceptive ("pill").
Press out the 1st table at the position on the pack which is marked with the corresponding weekday (eg "Sun" for Sunday) and swallow without chewing. Then, continue taking 1 tablet everyday following the direction of the arrows, if possible at the same time of day, preferably in the evening of the arrows. It is essential to take Chariva regularly in order to ensure its contraceptive reliability. The interval between taking 2 tablets should be 24 hrs as regularly as possible. The days printed on the pack allow the patient to check every day whether the tablet has already been taken for that particular day. After taking the last tablet, there is a 7-day medication-free interval during which bleeding occurs within 2-4 days after taking the last tablet. After the 7-day medication-free interval, the patient should continue taking Chariva with the next pack, regardless of whether the bleeding has already stopped or is still present.
During the use of Chariva, the patient should have a gynaecological check-up about every 6 months.
Contraception starts with the 1st day of intake and also continues during the 7-day medication-free intervals.
If the patient starts taking Chariva very soon after childbirth or miscarriage, the patient must consult the physician whether additional protective measures are necessary during the 1st cycle.
As the acne treatment is only an additional beneficial effect of the hormonal contraception, the dosage regimen and the duration for use, and the posology for the acne treatment is the same as for the hormonal contraception.
Duration of Treatment: If the patient wishes to have hormonal contraception, Chariva must be taken for years if the patient pays attention to the contraindications and the other information in the patient leaflet.
After the patient stop taking Chariva, the reproductive glands rapidly resume their full function in most cases and the ability to conceive is restored. The 1st cycle is usually prolonged by about 1 week. If, however, a normal cycle does not develop within the first 2-3 months, the patient should consult a physician.
Overdosage
Intake errors, vomiting or intestinal diseases accompanied by diarrhoea, long-term use of certain medicines at the same time (see Interactions) and very rare individual metabolic disorders may affect contraceptive effectiveness. Mild laxatives do not reduce reliability.
Acute poisoning due to taking a large number of tablets at once is unlikely, except in extreme cases, and is not life-threatening. Possible symptoms are mainly stomach or bowel complaints, disorders of liver function and the water and electrolyte balance, and withdrawal bleeding in women. Preventive measures or countermeasures are only necessary in rare cases following an overdose.
If the patient forget to take a tablet at the usual time, the missed dose must be taken within the next 12 hrs at the latest. If the usual intake interval is exceeded by >12 hrs, effective contraception is no longer guaranteed during this cycle. In such cases, the patient should continue taking pills from the current calendar pack as scheduled, but leaving out the tablet that have forgotten in order to prevent premature bleeding. Mechanical protective measures should also be taken.
The hormones contained in Chariva are usually rapidly absorbed by the body. Only if vomiting or diarrhoea occurs shortly after taking Chariva (up to 4 hrs afterwards), the patient should immediately take the next tablet in order to ensure continued contraceptive protection. The patient's cycle will then be shortened by 1 day.
If the patient vomits several times or complaints persist for >12 hrs, continue taking the tablets for the cycle, but also use of additional mechanical methods of contraception (eg, condoms).
Contraindications
Hypersensitivity to ethinylestradiol or chlormadinone acetate or to any of the excipients of Chariva. Patients suffering from or have history of blood clots in the veins or arteries (eg, deep vein thrombosis, pulmonary embolism, heart attack, stroke).
If the 1st stages of signs of a blood clot is noticed, inflammation of the veins or embolism eg, fleeting stabbing pain, chest pain or feeling of tightness in the chest; forced to rest for a long period of time (eg, on strict bed rest or due to a plaster cast) or is planning to have an operation (stop taking Chariva at least 4 weeks before the scheduled date of the operation); diabetes and uncontrolled blood sugar fluctuations or have changes in the blood vessels; uncontrolled hypertension or blood pressure rises considerably (values constantly >140/90 mmHg); disturbance of blood clotting (eg, C-protein deficiency); suffering from inflammation of the liver (eg, due to a virus) or from jaundice and liver values have not yet returned to normal; itching all over the body or suffering from a bile flow disorder, particularly if this occurred in connection with a previous pregnancy or oestrogen treatment; increased bilirubin (a degradation production of blood pigment) in blood, eg, due to an inborn excretion disorder (Dubin-Johnson or Rotor syndrome); exisiting or history of liver tumour; severe stomachache, a liver enlargement or signs of abdominal bleeding; first occurrence or recurrence of porphyria (a disorder of blood pigment metabolism); suspected hormone-dependent malignant tumour eg, breast or uterine cancer; suffering from severe disorders of fat metabolism, inflammation of the pancreas associated with severely increased blood fats (triglycerides), migraine for the first time; severe, frequent or long-lasting headache, migraine accompanied by disorders of sensation, perception and/or movement (migraine accompagnee); sudden perception disorders (sight or hearing); movement disorders (in particular signs of paralysis); worsening of epileptic fits; suffering from severe depression, a certain type of deafness (otosclerosis) that worsen during previous pregnancies; no period for some unknown reason; abnormal overgrowth of the inner layer of the womb (endometrial hyperplasia); vaginal bleeding for some unknown reason.
If the one of these conditions occurs during administration of Chariva, discontinue use immediately.
Chariva should not be taken or discontinue abruptly, if patient has a serious or several risks of blood clotting disorders.
Listed as follows are the cases in which Chariva should be taken under certain conditions and with caution: Heart and kidney diseases, migraine, epilepsy, history of asthma because these may be affected by fluid accumulation; history of inflammation of the veins (phlebitis); marked tendency towards varicose veins (varicosis); multiple sclerosis; St. Vitus' dance (chorea minor); muscle cramps (tetany); tendency of diabetes mellitus; history of liver disease; fat metabolism disorders; considerable overweight; elevated blood pressure; benign overgrowth of the mucous membranes of the womb (endometriosis); benign tumors of the womb (myomatous uterus); breast diseases (mastopathy); otosceloris (a certain form of middle-ear deafness).
Special Precautions
Serious effects on patient's health may occur due to thromboembolic events (see Adverse Reactions). Therefore predisposing factors (eg, varicose veins, previous inflammation of the veins, thrombosis, heart disease, considerable overweight, blood clotting disorders) and thromboembolism of the veins occurring in close relatives at an early age should be determined and taken into account when deciding whether to use Chariva.
Smokers taking hormone preparations for contraception are at an increased risk of suffering from, in some cases, serious consequences of changes in the vessels (eg, heart attack, stroke). The risk increases with age and rising cigarette consumption.
In particular, women >30 years should therefore refrain from smoking when taking hormone preparations for contraception. If smoking cannot be stopped, other methods of contraception should be used. Surveillance studies have shown that the incidence of thromboembolic diseases may decrease when taking preparation with a low oestrogen dosage (≤50 mg), which led to the development of contraceptives containing smaller amounts of hormones. It is still not certain that women taking such low-dosed preparations will in fact suffer less frequently from thrombotic or thromboembolic blockage of the vessels.
Therefore even when taking low-dose hormonal contraceptives, patients should be examined for factors promoting the formation of blood clots (see previous texts) and the risks should be weighed against the potential benefits of this method of contraception.
The occurrence of thromboembolic diseases in relatives at an early age may be evidence of disorder of the blood clotting system. Such diseases include deep vein thrombosis, pulmonary embolism, stroke, sudden disorders of sensation and perception (eyesight, hearing), speech and motion disorders, in particular paralysis, heart attack and angina pectoris. If the patient has a family history of such diseases, blood clotting must be examined carefully before prescribing Chariva (eg, ATIII, protein C and S).
Women >40 yrs require special supervision because the tendency towards thrombosis increases with age.
With combined oral contraceptives (COC) the risk of a blood clot blocking the veins (thromboembolism) is higher than if they are not taken. The additional risk is highest during the 1st year of 1st taking a COC. This increased risk on the use of a COC is lower than the risk of thrombosis during pregnancy, which is estimated to be 60 cases/100,000 pregnancies. In 1-2% of the cases eg, blockage of the vessels, is fatal.
Symptoms of thrombosis or pulmonary embolism eg, pain and swelling in the arms and/or legs, or shortness of breath and stabbing pain in the chest should be addressed by the patient to the physician immediately. It is not known what effect of Chariva has on the risk of blockage of the veins in comparison with other COCs.
Chariva should be used for treatment of moderate papulopustular acne in women for whom hormonal contraception with ethinylestradiol/chlormadinone acetate is indicated. It should therefore not be used for treatment of moderate papulopustular acne in pregnant woman or women planning to get pregnant.
Use in pregnancy: Chariva is not indicated during pregnancy. If the patient becomes pregnant while taking Chariva, stop taking it immediately. Previous use of Chariva, however, does not justify an abortion. Chlormadinone acetate has exhibited embryolethal effects in rabbits, rats and mice. Moreover, teratogenicity was observed at embryotoxic doses in rabbits and already at lowest dose tested (1 mg/kg/day). The significance of these findings for human administration is unclear.
Use in lactation: If Chariva is taken, milk production may be reduced and its quality is affected. Very small amounts of the active substances pass into the milk. Oral contraceptives eg, Chariva should only be taken after breastfeeding had stopped. In general, however, contraception is only indicated if women breastfeed for a long time, because women will not usually have a cycle during a short period of breastfeeding. If possible, nonhormonal methods of contraception should be used until the baby has been fully weaned.
Use In Pregnancy & Lactation
Use in pregnancy: Chariva is not indicated during pregnancy. If the patient becomes pregnant while taking Chariva, stop taking it immediately. Previous use of Chariva, however, does not justify an abortion. Chlormadinone acetate has exhibited embryolethal effects in rabbits, rats and mice. Moreover, teratogenicity was observed at embryotoxic doses in rabbits and already at lowest dose tested (1 mg/kg/day). The significance of these findings for human administration is unclear.
Use in lactation: If Chariva is taken, milk production may be reduced and its quality is affected. Very small amounts of the active substances pass into the milk. Oral contraceptives eg, Chariva should only be taken after breastfeeding had stopped. In general, however, contraception is only indicated if women breastfeed for a long time, because women will not usually have a cycle during a short period of breastfeeding. If possible, nonhormonal methods of contraception should be used until the baby has been fully weaned.
Adverse Reactions
The frequencies with which adverse reactions have been reported are defined as follows: Very Common (Affecting >1 in 10 Users): Nausea, vaginal discharge, menstrual pain, amenorrhea, breakthrough bleeding, spotting, headache, pain in the breasts.
Common (Affecting <1 in 10, but >1 in 100 Users): Ovarian cyst, benign tumours (fibroadenomas), feeling of tension in the breasts, depression, irritability, nervousness, dizziness, migraine (and/or aggravation of these), visual disorders, vomiting, acne, pain in the belly, tiredness, feeling of heaviness in the legs, water retention; increased weight, blood pressure.
Uncommon (Affecting <1 in 100, but >1 in 1,000 Users): Stomachache, stomach and bowel problems, drug hypersensitivity including allergic skin reaction, rumbling in the bowels, diarrhoea, pigmentation problems, brown blotches on the face (chloasma) that become worse on long periods of sunbathing, hair loss, dry skin, back pain, muscle problems, secretion from the breasts, benign changes in the connective tissues of the breasts, fungal infection of the vagina, decrease in libido, tendency to sweat, changes in blood fats including increased triglycerides.
Rare (Affecting <1 in 1,000, but >1 in 10,000 Users): Conjunctivitis, discomfort when wearing contact lenses, deafness, tinnitus, high and low blood pressure, blood circulation collapse, varicose veins, venous thrombosis, hives, nettlerash, eczema, dermatitis (inflamed skin), itching, fleeting acne, worsening of psoriasis, excessive hair on the body or on the face, breast enlargement, inflammation of the vagina, longer and/or more intense menstruation, premenstrual syndrome (physical and emotional problems before the start of menstruation), increased appetite.
Very Rare (Affecting <1 in 10,000 Users) including isolated cases erythema nodosum.
Combined Oral Contraceptives Have Also Been Linked With An Increase of Risks for Serious Diseases and Side-Effects: Risk of blockage of the veins and arteries; diseases of the bile tract and tumours (eg, liver tumours, which in isolated cases cause life-threatening bleeding into the abdominal cavity, cancer of the neck of the womb or breasts); aggravation of chronic inflammation of the bowels (Crohn's disease, ulcerative colitis).
Cycle-Specific Adverse Reactions: Spotting: Spotting may occur particularly during the 1st few intake cycles of Chariva; in such cases, the patient should generally continue taking Chariva. If heavy spotting that is similar to normal menstrual bleeding happened, the patient should seek medical help because such bleeding may have organic causes.
The same applies to spotting occurring at irregular intervals in several successive cycles, or for the 1st time after taking Chariva for a long time. Such spotting may also occur as a result of interactions with other medicines taken at the same time (see Interactions).
Absence of Withdrawal Bleeding: If in very rare cases there is no withdrawal bleeding during the medication free day, the patient may continue taking Chariva if pregnancy is ruled out within the first 10 days of the new medication cycle. If withdrawal bleeding does not occur in 2 successive cycles, the patient should seek medical help whether to continue taking Chariva or not.
Effect on the Development of Breast Cancer: Sex hormones have an effect on breast tissue. Altering the hormone balance (eg, by taking hormonal contraceptives) may make the breast tissue more sensitive to other factors that encourage cancer, which in itself may encourage cancer. Analyses of the results of epidemiological studies on the possibility of a connection between taking hormonal contraceptives and cancer of the breast indicate that the occurrence of cancer of the breast in women up to middle age is more frequently associated with the long term use of oral contraceptives started at an early age. However, this is only of several possible risk factors. Breast secretion and enlargement have been observed in isolated cases.
Effect on Laboratory Tests: Normal laboratory values may be affected by hormonal contraceptive (eg, blood sedimentation rate may rise without illness). Increased levels of serum copper and iron or alkaline leukocyte phosphatase, have been reported, in addition to change in other values.
Drug Interactions
The contraceptive effectiveness of Chariva may be affected if substances that speed up the biological breakdown of steroid hormones eg, barbiturates, rifampicin, griseofulvin, phenylbutazone, antiepileptics (eg, barbexaclone, carbamazepine, phenytoin, primidone) and preparations containing St. John's wort and oral contraceptives at the same time spotting has been reported.
Reduced active substance levels have also been observed due to changes in the bowel flora when antibiotics eg, ampicillin or tetracyclines were taken at the same time, and also after taking activated charcoal. Also, increased rates of spotting and in isolated cases, pregnancy have been recorded. Requirements of insulin or antidiabetic medicines taken by mouth may be altered due to effects on glucose tolerance. The excretion of theophylline or caffeine is reduced during the use of oral contraceptives with the result that the effect of theophylline or caffeine may be increased and prolonged.
Storage
Do not store above 30°C.
MIMS Class
ATC Classification
G03AA - Progestogens and estrogens, fixed combinations ; Used as systemic contraceptives.
Presentation/Packing
Tab (pale pink, round, biconvex) 21's.
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