11/22/2018 Contraceptive Pills

11/22/2018

Contraceptive Pills:Role of Velivet & Camila on birth control effect.Submitted To:
Dr. Sufia Islam
Professor
Dept. of Pharmacy
East West University
Contributed By:
NAME ID
Khadiza Jahangir Tazally 2016-1-70-006
Mihrab Naba 2016-1-70-059
Shanzida Hossain Anonna 2016-1-70-069
MD. Rakibul Hasan 2016-1-70-078
Khatiza Nawsheen Yousuf 2016-1-70-085

Abstract
Oral contraceptive pill alters menstrual cycle to prevent pregnancy and eliminate ovulation.There are wide range of option of birth control in our country. Two contraceptive pills namely Velivet & Camila are described in this assignment. In case of Velivet, it is combination birth control pill of ethinyl estradiol & desogestrel which inhibit ovulation. When administered orally, it is rapidly absorbed. It prevents pregnancy by suppressing FSH & LH which eventually alter secretion & cellular structure of endometrial linings that ultimately prevents implantation. On the other hand, Camila (mini pill) makes vaginal fluid thicker which prevents sperm from reaching to the egg and ultimately prevents fertilized egg attaching with lining of uterus. However these two pills have side effects. They don’t protect women or her partner against sexually transmitted disease (HIV, gonorrhea, chlamydia), moreover weight gain, vaginal bleeding, headache, missed periods may occur.

Objective
The participants will be able to –
Describe the characteristics of contraceptive pill in a manner that people are understood.

How they work on contraception
Explain how to manage unwanted effects.

Introduction
Contraception is a process which prevents pregnancy. It occurs by keeping the egg and sperm apart or by preventing the production of egg. It also occurs by stopping the fertilized egg get attached to the uterus lining.
There are 15 methods of contraception like – Caps, contraceptive pills, contraceptive injection, contraceptive patch, vaginal ring etc.

We are going to broadly discuss about two contraceptive pills.
They are –
Desogestrel ; ethinyl estradiol:
Its brand name is Velivet.
Company – Teva pharmaceuticals, USA, Inc.

It is combination drug containing estrogen and progestin.

center120650
Figure SEQ Figure * ARABIC 1: Velivet

3314700-3175Norethindrone:
Its brand name is Camila.

Company- Mayne Pharma. Inc
It is a mini pill containing only progestin.

Figure SEQ Figure * ARABIC 2: Camila

Desogestrel ; Ethinyl Estradiol
It is contraceptive pill which is taken orally and it is triphasic. It contains two active component and they are desogestrel and ethinyl estradiol. Three active dosing phases are present in each 28 day treatment cycle pack. They are –
7 beige tablets containing 0.025 mg ethinyl estradiol and 0.1 mg desogestrel.

7 orange tablets containing 0.025 mg ethinyl estradiol and 0.125 mg desogestrel.

Figure 4: Ethinyl Estradiol
3028950435610Figure SEQ Figure * ARABIC 3 Desogestrel
left3784607 pink tablets containing 0.025 mg ethinyl estradiol and 0.15 mg desogestrel.

There are some inactive ingredients which include – Vit E, titanium dioxide, stearic acid, povidone, polyethylene glycol, colloidal silicon dioxide etc. There are iron oxide (red) and iron oxide (yellow) in beige tablets. FD;C Red no. 40 Aluminum Lake FD;C Yellow No. 6 Aluminum Lake are present in pink and orange tablets. There is also 7 white tablets which contain Magnesium stearate, lactose anhydrous, microcrystalline cellulose and pre-gelatinized corn starch.

It should be counseled to the patient that, this product doesn’t provide protection against HIV infection (AIDS) and other sexually transmitted diseases.
Clinical Pharmacology
This contraceptive suppress the gonadotropins. Primary mechanism is to inhibit ovulation, changing the cervical mucus and the endometrium.
Studies in animal, have shown that the biologically active metabolite of desogestrel which is etonogestrel combines high progestational activity with minimal intrinsic androgenicity. The later findings in human is unknown.

Mechanism of action
It is a combination therapy of two hormones Progestin and Estrogen. It works mainly by preventing the release of an ovum during menstrual cycle. It also makes vaginal fluid thicker to help prevent sperm from reaching an ovum and changes the lining of the uterus to prevent attachment of a fertilized ovum. If a fertilized ovum does not attach to the uterus, it will wash out from the body.
Pharmacokinetics
Generally by pharmacokinetics we understand about ADME that means absorption, distribution, metabolism and excretion.
Absorption:
Desogestrel is the active component which is rapidly and completely absorbed and converted to etonogestrel. Oral administration is followed by the relative bioavailability of desogestrel based on the highest and lowest strength of tablet. 0.150 mg desogestrel/ 0.025 mg ethinyl estradiol and 0.100mg desogestrel/ 0.025mg ethinyl estradiol, compared to solution, as measured by serum levels of etonogestrel is approximately 100%. On the other side ethinyl estradiol is also completely and rapidly absorbed. The highest and lowest tablet strength are when 0.150 mg desogestrel/ 0.025 mg ethinyl estradiol and 0.100 mg desogestrel/ 0.025 mg ethinyl estradiol, compared to solution , the bioavailability was 92% and 98%.

Distribution:
Active metabolite of desogestrel, which is etonogestrel, was found that it is 98% protein bound, primarily to sex hormone binding globulin (SHBG). Ethinyl estradiol is bound to plasma protein primarily. It doesn’t bind to SHBG but it promotes synthesis of SHBG. In combination with estradiol, desogestrel doesn’t inhibit the estrogen induced increase in SHBG, resulting in lower serum levels of free testosterone.

Metabolism:
Desogestrel: It is completely and rapidly metabolized by hydroxylation on first pass through the liver to etonogestrel and in the intestinal mucosa. In vitro, an important data was suggested that role for the cytochromeP450, Cyp2C9 in the bio activation of desogestrel is important. Etonogestrel is further metabolized into 6-beta-hydroxy etonogestrel, 6-beta-13 ethyl dihydroxylated metabolites as major metabolites is catalyzed by CYP3A4. There are some other metabolites and they undergo glucuronide and sulphate conjugation.

Ethinyl estradiol: A significant degree of presystemic conjugation was subjected by ethinyl estradiol. By escaping the gut wall conjugation, it undergoes phase-1 metabolism and hepatic conjugation. 2-OH-ethinyl estradiol and 2-methoxy ethinyl estradiol are major phase-1 metabolites.

Excretion:
These APIs are primarily eliminated in feces, bile and urine. In day no. 21, the elimination half-lives of ethinyl estradiol and etonogestrel are 28.2 (10.5) hours and 37.1(14.8) hours.

Drug Interaction with velivet
Drug interaction may change the way a drug works and increases the risk of side effects. Some products that interact with velivet are aromatase inhibitors, ospemifere and tranexamic acid. Other drugs like griseofulvin, modafinil, rifamycins may cause decrease in amount of birth control hormones in the body. This effect can result in pregnancy.

Contraindications of velivet
In AIDS or HIV infection this oral contraceptive drug will not prevent the transmission of HIV or other diseases to the partner.

If pregnancy occur there is increased risk of variety of fetal abnormalities, including modified development of sexual organs, cardiovascular anomalies and limb defects. It also change folate metabolism so if a woman discontinues to take it, she has to wait for three months to obtain folate concentration to normal level.

In patient with cholestasis, gallbladder disease, hepatic disease, hepatocellular cancer, jaundice should not take this oral contraceptive. This can cause acute or chronic disturbance in liver function.

Small amount of this drug has been appeared to be excreted into breast milking. This dug can cause maternal postpartum clot risks following obstetric delivery.

Others such as thromboembolic disorders, cerebral vascular or coronary disease, diabetes.

Side effects of velivet
Nausea
Vomiting
Headache
Bloating
Breast tenderness
Weight gain
Vaginal bleeding
Missed or irregular period
Adverse effect of velivet
Breakthrough bleeding
Amenorrhea
Transient delay of ovulation
Edema
Chloasma
Liver disease
Hypertension
Thromboembolic diseases
Norethindrone
The active ingredient of Camila is norethindrone and each pink tablet contains 0.35 mg norethindrone. There are some inactive ingredients in it which are magnesium stearate, corn starch, povidone, sodium starch glycolate, lactose monohydrate, FD&C red no. 40 aluminum lake.
10096506350
Figure 5: Norethindrone

Therapeutic class- Oral contraceptive.

It should be counseled to the patient that this contraceptive doesn’t protect against transmission of HIV (AIDS) and other sexually transmitted diseases like genital herpes, chlamydia, genital wart, gonorrhea, syphilis, hepatitis B.

Clinical pharmacology
This is the only contraceptive which work by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, slowing the movement of the ovum to the fallopian tube, lowering the mid cycle LH ; FSH peaks and altering the endometrium.
Mechanism of action
This medication is used to prevent pregnancy. It is often referred to as ‘mini pill’ because it doesn’t contain any estrogen. Norethindrone is a hormone that makes the vaginal fluid thicker and doesn’t let the sperm to reach an ovum. It also stops ovulation in about half of a women’s menstrual cycle.

Pharmacokinetics
Absorption:
Rapid absorption with maximum plasma concentration occurs in norethindrone within 1 to 2 hours after Camila administration. Absolute bioavailability of approximately 65% is resulted after subjecting to first pass metabolism. Norethindrone is completely absorbed.
Here, peak plasma concentration = 1 hour.

The mean (SD) Cmax. = 4816.8pg/ml
The mean (SD) Cavg. = 885pg/ml
The mean concentration at 24 hours = 130pg/ml
The rate and extent of norethindrone absorption after Camila administration is effected by food.

Distribution:
Norethindrone bounds to SHBG by 36% and to albumin is 61%. Distribution volume is 4L/kg.

Metabolism:
Extensive biotransformation was undergone by norethindrone and primarily via reduction which is followed by sulphate and glucuronide conjugation. Unchanged excretion occurs with less than 5% of norethindrone. Excretion in urine and feces occurs with greater than 50% and (22-40) % of a dose. Majority of metabolites are sulphate and urinary metabolites.

Excretion:
Approximately 600L/Day is the plasma clearance rate for norethindrone. In both urinary and fecal way it is excreted
Interaction with Camila
Drugs like griseofulvin, rifampin, barbiturates, carbamazepine, felbamate, and phenytoin interact with camila. HIV drugs such as nevirapine, ritonavir also have some interaction which decreases the efficiency of camila.

Contraindication of Camila
Patient suffering from breast cancer, diabetes, porphyria, migraine, lung embolism, stroke, liver problems, kidney disease, and systemiclupus erythematosus should not take camila.
Others such as chronic heart failure, high risk of blood clot, smoking, seizures should be checked before taking camila.

Side effects of Camila
Mild nausea
Vomiting
Stomach cramps
Breast pain
Vaginal itching or discharge
Skin rash
Swelling in feet
Pelvic pain
Adverse effects of Camila
Edema
Anorexia
Deep vein thrombosis
Depression
Dizziness
Headache
Nervousness
Breast tenderness
Weight gain
Cholestatic jaundice
Bibliography:
Empr.com. (2018). VELIVET Dosage & Rx Info | Uses, Side Effects – MPR. online Available at: http://www.empr.com/velivet/drug/2584/?fbclid=IwAR2FBw61jPJzUKP7t7qqYqOlvLkclQ3PGdKpSSKP1LNnK64FF-Q3fE9e6G0 Accessed 19 Nov. 2018.

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Reference.medscape.com. (2018). Camila, Errin (norethindrone) dosing, indications, interactions, adverse effects, and more. online Available at: https://reference.medscape.com/drug/camila-errin-norethindrone-342791?fbclid=IwAR1zNmp3JE94tXHHmSnMhkWI1HFOkuWksPmi2Cu6jL9E4gWKsdqATgtRFTQ#4 Accessed 19 Nov. 2018.

nhs.uk. (2018). What is contraception?. online Available at: https://www.nhs.uk/conditions/contraception/what-is-contraception/ Accessed 19 Nov. 2018.

Dailymed.nlm.nih.gov. (2018). Velivet® (desogestrel and ethinyl estradiol tablets USP – triphasic regimen) Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.. online Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a3ce5125-62ba-4983-93f0-91f254271605 Accessed 19 Nov. 2018.

Reference.medscape.com. (2018). Camila, Errin (norethindrone) dosing, indications, interactions, adverse effects, and more. online Available at: https://reference.medscape.com/drug/camila-errin-norethindrone-342791?fbclid=IwAR1zNmp3JE94tXHHmSnMhkWI1HFOkuWksPmi2Cu6jL9E4gWKsdqATgtRFTQ#4 Accessed 19 Nov. 2018.