Desogestrel/ethinyl estradiol : Mechanism of action, uses, side effects

Desogestrel-Ethinyl Estradiol Oral : Uses, Side Effects, Interactions

What is desogestrel/ethinyl estradiol?

Contents

Desogestrel and ethinyl estradiol is a combination medicine which is used as a birth control pill. This medication contains female hormones which prevent the process of ovulation (the release of an egg from an ovary). This medication works by thinning the cervical mucus and make changes in the lining of the uterus thereby making it harder for sperm to reach the uterus and hence prevent a fertilized egg to attach to the uterus.

There are multiple brands available in the market for this medicine. There is no medication or method which is 100% effective as birth control. Birth control methods such as having surgery to become sterile or not having sex are more effective than birth control pills. Discuss your options for birth control with your doctor.

Before starting this medication you must know that it does not prevent any kind of sexually transmitted disease, nor it prevents HIV infection. Also one should not use this medication as an emergency contraceptive pill after unprotected sexual contact. You should always use this medication with doctor’s prescription. This medication is available in the tablet form.

Desogestrel/ethinyl-estradiol molecular structure, weight, formula and drug class

Desogestrel:

The molecular structure of desogestrel:

Desogestrel / Ethinyl estradiol : Desogen, Reclipsen, Emoquette

Description: Desogestrel is a synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents.

IUPAC name: (1S,2R,10S,11S,14R,15S)-15-ethyl-14-ethynyl-17-methylidenetetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-ol

Molecular weight: 310.473 g/mol

Molecular formula: C22H30O

Drug class: This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.

Ethinyl estradiol

The molecular structure of ethinyl estradiol:

molecular structure of ethinyl estradiol

Description:

Ethinyl estradiol is a semisynthetic alkylated estradiol with a 17-alpha A semisynthetic alkylated estradiol with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally and is often used as the estrogenic component in oral contraceptives.

Ethinyl estradiol is marketed mostly as a combination oral contraceptive under several brand names such as Alesse, Tri-Cyclen, Triphasil, and Yasmin. The FDA label includes a black box warning that states that combination oral contraceptives should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.

IUPAC name: (1S,10R,11S,14R,15S)-14-ethynyl-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-triene-5,14-diol

Molecular weight: 296.4034 g/mol

Chemical formula: C20H24O2

Drug class: This compound belongs to the class of organic compounds known as estrogens and derivatives which are steroids with a structure containing a 3-hydroxylated estrane.

Mechanism of action of desogestrel/ethinyl estradiol:

Desogestrel: There are target cells in the female reproductive tract, the mammary gland, the hypothalamus and the pituitary, the desogestrel binds to the progesterone and estrogen receptors. Once bound to the receptor, progestins like desogestrel will slow the frequency of release of gonadotropin-releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

Ethinyl estradiol: Just like desogestrel, estrogens also diffuse into target cells and bind to the protein receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary.

Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The estrogen receptors binding initiate this cascade. The combination of an estrogen and a progestin reduces the secretion of the gonadotropin-releasing hormone by suppressing the hypothalamic-pituitary system.

Pharmacokinetics of desogestrel /ethinyl estradiol:

The relative bioavailability of desogestrel is 84% approximately as measured by serum levels of etonogestrel after oral administration. The absolute oral bioavailability is about 76%. The protein binding of desogestrel is 98.3%. Desogestrel is completely and rapidly metabolized by hydroxylation in the intestinal mucosa and on the first pass through the liver.

It is primarily metabolized to 3α-hydroxydesogestrel with small amounts of 3β-hydroxydesogestrel being formed. Both of these metabolites are then rapidly oxidized to its active metabolite, etonogestrel (3-ketodesogestrel). The half-life of desogestrel is 28 hours approximately.

Ethinyl estradiol shows rapid and complete absorption after its oral intake. It shows bioavailability of 43%. It shows protein binding of 97%. Ethinyl estradiol undergoes hepatic metabolism. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens. The half-life of ethinyl estradiol is 36 hours approximately.

What are the indications and usage of desogestrel/ethinyl estradiol?

Desogestrel/ethinyl estradiol tablets are the oral contraceptives which are indicated for the prevention of the pregnancy in women who choose to use an oral contraceptive as a method of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and the Norplant System depends upon the reliability with which they are used.

Correct and consistent use of these methods can result in lower failure rates. Typical accidental pregnancy rates are seen with other methods of contraception as compared to the combined oral contraceptives.

FDA approved indications for desogestrel/ethinyl estradiol combination are:

  • Dysmenorrhea
  • Dysfunctional Uterine Bleeding
  • Hirsutism
  • Hypermenorrhea
  • Postmenopausal Osteoporosis (PMO)
  • Premenstrual Dysphoric Disorder
  • Severe Acne Vulgaris
  • Moderate Acne vulgaris
  • Moderate vasomotor symptoms
  • Severe vasomotor symptoms

What are the side effects of desogestrel/ethinyl and estradiol?

If you have a sign of allergic reactions such as hives, difficulty in breathing, swelling of your face, lips, tongue, or throat, get medical help immediately. You should call your doctor and stop using birth control pills if you have:

Signs of a stroke–sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance

  • Signs of a blood clot in the lung-chest pain, sudden cough, wheezing, rapid breathing, coughing up blood
  • Signs of a blood clot in your leg–pain, swelling, warmth, or redness in one or both legs
  • Heart attack symptoms–chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating
  • Liver problems–severe stomach pain, fever, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
  • A change in the pattern or severity of migraine headaches
  • Swelling in your hands, ankles, or feet
  • A breast lump
  • Symptoms of depression–sleep problems, weakness, tired feeling, mood changes

Common side effects may include:

  • Light vaginal bleeding or spotting
  • Nausea (especially when you first start taking this medicine), vomiting, bloating
  • Changes in weight or appetite
  • Breast tenderness or swelling
  • Freckles or darkening of facial skin, increased hair growth, loss of scalp hair
  • A headache
  • Vaginal itching or discharge

Can desogestrel/ethinyl estradiol combination be used as an emergency contraception?

No, this medication cannot be used as an emergency contraception such as after unprotected sexual intercourse.

Can desogestrel/ethinyl estradiol help in reducing acne?

During puberty, there is a sudden increase in the male sex hormone i.e. androgen, even in girls, which is responsible for the development of acne. And the women and girls who use contraceptive pills as birth control, they are more prone to get inflammatory and noninflammatory acne.

The pills that help against acne have progestin and estrogen hormone in them; however, most of the contraceptive pills are not approved for the treatment of acne. There are also non-hormonal therapies which can help against acne, some of which have fewer side effects.

A study was done by Cochrane Collaboration (an international research network) on checking the efficacy of the contraceptive pills in the treatment of the acne. And as per the study, all the oral contraceptive pills used in the studies reduced both inflammatory and noninflammatory acne.

The pills that reduced the acne had estradiol in them which was combined with one of the following: levonorgestrel, norethindrone, norgestimate, drospirenone, cyproterone acetate, chlormadinone acetate, dienogest or desogestrel.

Can desogestrel/ethinyl estradiol administration lead to weight gain?

Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.

Can desogestrel/ethinyl estradiol be used for PCOS (polycystic ovarian syndrome)?

There are studies given that proves the efficacy of desogestrel/ethinyl estradiol combination in the treatment of PCOS. However, you should always consult your doctor before taking this medication for PCOS or any other condition. A study was done on few menstruating women.

There are significantly increased the level of testosterone and androgen in those women, moreover, the body weight, hair diameter, and blood pressure were also increased. They have a lower capacity for SHBG (sex hormone binding globulin).

After getting treated with desogestrel/ethinyl estradiol for 8 months, significant changes such as depressed level of total testosterone increased SHBG capacity (up to 5 fold), reduced body weight (in obese women), reduced hair growth was noticed. Moreover, acne which was present before disappeared after the treatment. However, there were no significant changes noted in androstenedione.

Can desogestrel/ethinyl estradiol be responsible for hair loss?

Mostly oral contraceptives are considered as a safe and effective form of birth control, as per ALHA (The American Hair Loss Association). However, a woman should be aware of the effects of oral contraceptives on the normal hair growth, especially those who have a family history of hair loss.

A woman should only use low-androgen index birth control pills, such as norgestimate, norethindrone, desogestrel, or ethynodiol diacetate as these drugs have least androgenic activity. ALHA recommends the use of another method of contraception if there is a strong predisposition for genetic hair loss in your family. One should always consult your doctor before taking such medications.

How should I start the desogestrel/ethinyl estradiol pill?

You should always understand how and when to take oral contraceptives in order to make them safe and reliable as possible. You should also be aware of the expected effects and results of such medications. Usually, these medications always come with patient instructions leaflets.

  • Always read and follow the instructions carefully. In case you have any doubts, ask your doctor or pharmacist about it.
  • It is available in a blister pack, each blister contains tablets of different colors that need to be taken on per the directions and order are given in the pack.
  • For the first 7 days of your first cycle of pills, use any other form of contraception such as condom, spermicide, or a diaphragm because when you begin using this medicine, your body requires at least 7 days to adjust prior to the prevention of pregnancy.
  • Make a regular schedule for this medicine, and try to take the medicine at the same time each day.
  • Avoid any delay in taking your pill by more than 24 hours. You could get pregnant if you miss a dose.
  • You must ask for the different ways to remember to take your medicine on time or you can also opt for any other method of contraception.
  • In the beginning, you may feel sick or nauseated by this medicine (mainly in first few months). Call your doctor, if your nausea does not go away.
  • Follow the instructions in the patient leaflet or call your doctor if you vomit or have diarrhea within 3 to 4 hours of taking this medicine.

What is the right dose of desogestrel/ethinyl estradiol?

The dose of this medicine will be different for different patients. You should follow the directions of the label or your doctor’s order. Do not change the dosage of your medication, unless your doctor told you to do so.

You should start this medication on the first day of your menstrual period (say Day 1 start) or you can also start it after your menstrual period starts (if you start it on Sunday then say it Sunday start). It is very important to follow the schedule if you begin it on a certain day.

You should never change the schedule of this medication on your own. If the schedule that you use is not convenient, check with your doctor about changing it. For a Sunday start, you need to use another form of birth control (eg, condom, diaphragm, spermicide) for the first 7 days.

As the first regimen begins, on a certain day of the week, you should begin your next and all subsequent 28-day regimens of therapy on the same day of the week as the first regimen began and follow the same schedule.

  • For oral dosage form (tablets):
    • For contraception (to prevent pregnancy):
      • Adults and teenagers—One light orange tablet is taken at the same time each day for 21 consecutive days followed by one green (inert) tablet daily for 7 days per menstrual cycle.
    • Children—Use and dose must be determined by your doctor.

What should I do if I miss a dose of desogestrel/ethinyl estradiol?

This medicine has specific patient instructions on what to do if you miss a dose. Read and follow these instructions carefully and call your doctor if you have any questions.

Whenever you miss a dose, use another form of birth control for 7 days in order to prevent pregnancy. Keep an eye on the regularity of your periods, because if you miss your periods for two months in a row, this could mean that you are pregnant. In case of any doubt, keep your doctor updated for any changes in your menstrual cycle. You may not have a period for that month if you miss more than one dose or change your schedule.

You could have light bleeding or spotting if you do not take a pill on time. The more pills you miss, the more likely you are to have to bleed.

What are the risk factors associated with the use of desogestrel/ethinyl estradiol?

The use of oral contraceptives is associated with various risk factors. Some of which are very severe and can even cause death. Some risk factors are:

Risk of developing blood clots: Use of oral contraceptive can be associated with blood clots and blockage of blood vessels; moreover, it can cause death or serious disability. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs.

Oral contraceptive mainly those which contain desogestrel contain more risk of causing these side effects as compared to other low dose pills. Sometimes it can cause blindness, double vision or impaired vision when there is a clot developed in the blood vessels of the eye.

You may be at more risk of developing clots if you have recently delivered a baby or you may even need to stay in bed for a prolonged period of time after surgery.  The risk of venous thromboembolic disease associated with oral contraceptives does not increase with length of use and disappears after pill use is stopped.

Heart attacks: The tendency to develop strokes (stoppage or rupture of blood vessels in the brain), angina pectoris and heart attacks is increased with the use of oral contraceptives. A serious disability or even death can be caused by these conditions. Smoking also acts as additional factors in these conditions.

Gallbladder disease: As compare to the nonusers of oral contraceptives, people who use oral contraceptives are at more of developing gallbladder disease. However, high doses of estrogens can increase the risk of these diseases.

Liver tumors: Oral contraceptives can cause benign but dangerous liver tumors in rare cases. Fatal internal bleeding can be caused by these benign liver tumors.

Cancer of reproductive organs and breast: There are various studies that give conflicts reports on the relationship between breast cancer and oral contraceptive use. After using hormonal contraceptives at a younger age, your chances of getting diagnosed with breast cancers are slightly increased.  After you stop using hormonal contraceptives, the chances of having breast cancer diagnosed begin to go back down.

You should have regular breast examinations by a healthcare professional and examine your own breasts monthly. Tell your healthcare professional if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormone-sensitive tumor.

Can desogestrel/ethinyl estradiol be taken with carbamazepine?

Concurrent administration of desogestrel/ethinyl estradiol and carbamazepine can cause major interaction. The effects and blood levels of ethinyl estradiol can be reduced by the carbamazepine.

The risk of breakthrough bleeding and unintended pregnancy can be increased when you are using low dose contraceptives. You should opt for another option of birth control during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) anticonvulsant therapy (carbamazepine) or discuss it with your doctor.

If the symptoms are not getting controlled with the medications that you are taking for menopause, or in case you experience abnormal bleeding while on medicines, talk to your healthcare provider.

You should know about the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy of this medication with an anticonvulsant such as carbamazepine, your doctor may also inform you about the same.  For women with the etonogestrel subdermal implant, the addition of a barrier method is recommended during concomitant use and for 28 days after discontinuation of hepatic enzyme-inducing drugs.

Can desogestrel/ethinyl estradiol be taken with tizanidine?

You should talk to your doctor before taking desogestrel/ethinyl estradiol together. The effects of concentrations and effects of tizanidine can be increased by oral contraceptives. The mechanism behind this is known as the inhibition of metabolism of tizanidine.

The concurrent administration of both these medications can cause severe symptoms, such as drowsiness, confusion, slow heart rate, shallow breathing, feeling light-headed, fainting, or coma. Moreover, the excretion of metabolites of the tizanidine is much higher in the patients using oral contraceptives.

Tizanidine to metabolite ratios in plasma and urine were 2 to 10 times higher in the contraceptive users than in control subjects, and the excretion of unchanged tizanidine into urine was on average 3.8 times greater in the contraceptive group.

In order to take both medications together, you may need a dose adjustment. In case you are using other medications such as vitamins, herbs, prescription drugs and nonprescription drugs, let your doctor know about it.

Can desogestrel/ethinyl estradiol be taken with St.John’s wort?

The efficacy of contraceptive hormones can be reduced when administered with St. John’s wort. The mechanism behind is believed to be the reduced absorption as well as accelerated clearance of hormones due to induction of intestinal P-glycoprotein drug efflux transporter and intestinal/hepatic CYP450 3A4 metabolism by the constituents of St. John’s wort.

In patients, receiving long term oral contraceptives with addition of St. John’s wort reported to see the menstrual breakthrough and unintended pregnancies.

In order to manage the administration, patients should always confirm to the healthcare provider for the herbal or alternative medicine. Women using hormonal contraceptives should also be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with St. John’s wort.

A woman should consider another method of contraception after long term or short term administration of St. John wort therapy. If a combination oral contraceptive pill is used, a regimen containing at least 50 mcg of ethinyl estradiol per day or equivalent should be selected.

Can desogestrel/ethinyl estradiol be taken with griseofulvin?

Concurrent administration of both griseofulvin and ethinyl estradiol can create a major interaction therefore one should talk to their doctor before administration these medication altogether.

The effects of the ethinyl estradiol and its blood levels can be reduced by concurrent administration of griseofulvin. You may have an increased risk of breakthrough bleeding and unintended pregnancy, if you are using low-dose oral contraceptives.

While you are on the treatment with griseofulvin, it is important that you should not become pregnant because griseofulvin can cause major birth defects. Also you should opt for other methods of contraception.

Also, griseofulvin known to interact with the desogestrel, because just like ethinyl estradiol, the effects and blood levels of the desogestrel can also be decreased by the concurrent administration of the griseofulvin.

Your doctor may also be able to prescribe alternatives that do not interact. Notify your doctor if medication (such as hormonal replacement that you are taking for menopause) is no longer controlling your symptoms or you experience abnormal bleeding. In case you need to use both medications safely, you may need a dose adjustment.

Can desogestrel/ethinyl estradiol be taken with ampicillin?

The concomitant administration of the antimicrobial agents can impair the effectiveness of estrogen containing oral contraceptives. However, the risk appears to be small as per uncontrolled or poorly control studies. An additional contraceptive is recommended in case patient is advised ampicillin therapy.

The mechanism behind this is believed to be that the antimicrobials interferes with the enterohepatic recirculation of estrogens by decreasing bacterial hydrolytic enzymes in the gastrointestinal tract that are responsible for regenerating parent estrogen molecules following first-pass metabolism.

Other possible reason could be that a very less number of the women are susceptible to the contraceptive failure and therefore more responsive to the effects of the antimicrobials.

Women using oral contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant antimicrobial therapy. For the initial weeks of the long term administration of the antimicrobial therapy, the risk can be greatest therefore it is advisable to use other contraceptive method at that time.

Can desogestrel/ethinyl estradiol be given to the patients with abnormal vaginal bleeding?

In patients with undiagnosed, abnormal vaginal bleeding, the use of oral contraceptives such as estrogens is highly contraindicated. Significant and dose-related carcinoma may be associated with prolonged (more than one year) and unopposed use of estrogens. The addition of progestin can reduce the risk, however, may not be able to abolish the risk completely.

In patients with abnormal vaginal bleeding, appropriate tests should be done, before initiating estrogen therapy in order to rule out the endometrial malignancy. The same applies if recurrent or persistent bleeding develops during estrogen therapy.

Can desogestrel/ethinyl estradiol be given to patients with hypertension?

In patients with hypertension, the risk of myocardial infarction, strokes (mainly those associated with oral contraceptives use and estrogen use) can be increased. Moreover, hypertension can worsen and use of oral contraceptives can also elevate the blood pressure.

In patients receiving high doses or treated with oral contraceptive (which have high progestational activity), the blood pressure can be increased significantly. The effect also increases with duration of therapy and patient age. One should practice precaution when using therapy with estrogens in patients with preexisting hypertension.

The changes in cardiovascular status should be monitored and antihypertensive regimen should be adjusted accordingly or one can also opt for withdrawing the estrogen therapy, if necessary in such patients.  Alternative methods of contraception should be considered, in patients who need contraception and also are hypertensive, over the age of 35, and in those who smoke.

Can desogestrel/ethinyl estradiol be given to the patients with liver disease?

In patients with impaired hepatic function or liver disease, the use of progestogens is contraindicated because they can cause major interactions when used concomitantly. There is no sufficient data that supports the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, the liver is known to extensively metabolize most hormones including progestational.

In women with the significant liver disease, medroxyprogesterone should not be used and if jaundice or disturbances of liver functions occurs, it should be discontinued immediately.

Can desogestrel/ethinyl estradiol be given to the patients with depression?

The incidence of depression can be increased by administration of oral contraceptives. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression.

Close monitoring is necessary for patients with a history of depression and receiving estrogens or progesterone therapy. The re-administration of estrogens in patients with a history of depression should be completely avoided as per manufacturer of the medroxyprogesterone. Moreover, if depression recurs in such patients, the hormones therapy should be discontinued.

Can desogestrel/ethinyl estradiol be given to the patients with glucose intolerance?

Impaired glucose tolerance can occur in some patients who administer oral contraceptives and the impaired glucose tolerance is found related to the estrogen dose.

However, the insulin secretion can be increased by the progestogens, and also insulin resistance can be increased to varying degrees, depending upon the agent. One should monitor the patient closely when they are on estrogen or progesterone therapy, the dose should be adjusted in their antidiabetic regimen.

Can desogestrel/ethinyl estradiol be given to the patients with fluid retention?

When given in high doses or for a prolonged period of time, estrogens and progestogens may cause fluid retention. In patients who have preexisting problems with excess fluid, or have a problem of fluid retention, the estrogens therapy should be used with caution.

Moreover, during therapy with estrogen or progesterone, patients (with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction) should be monitored for exacerbation of condition.

What are some things I need to know or do while I take Ethinyl Estradiol and Desogestrel?

  • Tell all of your healthcare providers that if you are taking ethinyl estradiol/desogestrel. This includes your doctors, nurses, pharmacists, and dentists. This medicine may need to be stopped before certain types of surgery as your doctor has told you. If ethinyl estradiol and desogestrel is stopped, your healthcare provider will tell you when to start taking ethinyl estradiol and desogestrel again after your surgery or procedure.
  • This medicine may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
  • Talk with your doctor if you will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise your chance of blood clots.
  • If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
  • Check your blood sugar as you have been told by your doctor.
  • High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Be sure to have regular breast exams and gynecology check-ups. Your doctor will tell you how often to have these. You will also need to do breast self-exams as your doctor has told you. Talk with your doctor.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take ethinyl estradiol/desogestrel.
  • Certain drugs, herbal products, or health problems could cause ethinyl estradiol and desogestrel to not work as well. Be sure your doctor knows about all of your drugs and health problems.
  • This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
  • Do not use in children who have not had their first menstrual period.
  • If you have any signs of pregnancy or if you have a positive pregnancy test, call your doctor right away.

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About Miljan Krcobic 363 Articles
Miljan Krčobić. has bachelor degree in Pharmacy.