Novelon

Uses

Ethinylestradiol & Drospirenone is used for oral contraception, prevention of pregnancy

Novelon is also used to associated treatment for these conditions: Abnormal Uterine Bleeding, Acne Vulgaris, Endometriosis, Hypermenorrhea, Idiopathic Hirsutism, Menstrual Distress (Dysmenorrhea), Menstrual Irregularities, Osteoporotic Fractures, Pregnant State, Premenstrual Dysphoric Disorder, Vasomotor Symptoms Associated With Menopause, Vulvovaginal Atrophy, Hypoestrogenism, Folate supplementation therapy, Hormone Replacement Therapy, Oral ContraceptivesMenopausal Osteoporosis, Mild to Moderate Acne, Premenstrual Dysphoric Disorder ( PMDD), Moderate Acne vulgaris, Moderate, severe, Vasomotor Symptoms caused by Menopause, Contraception, Folate supplementation therapy

How Novelon works

Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation.

Drospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion. Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism. Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears.

Ethinylestradiol is a synthetic estrogenic compound. Use of estrogens have a number of effects on the body including reduced bone density. Combined oral contraceptives suppress ovulation by suppressing gonadotrophic hormone, thickening cervical mucus to prevent the travel of sperm, and preventing changes in the endometrium required for implantation of a fertilized egg. Ethinylestradiol decreases luteinizing hormone, decreasing vascularity in the endometrium. It also increases sex hormone binding globulin.

Dosage

Novelon dosage

How to Take Ethinylestradiol & Drospirenone

To achieve maximum contraceptive effectiveness, Ethinylestradiol & Drospirenone must be taken in the order directed on the package and at intervals not exceeding 24 hours. Women should be instructed to take the tablets at about the same time every day, preferably after the evening meal or at bedtime. One tablet is to be taken daily for 28 consecutive days. Each subsequent pack is started on the day after the current pack is completed.

• If you have decided to take Ethinylestradiol & Drospirenone for contraception, wait for your next menstruation begins.
• From the first day of your menstruation, start taking the first light yellow tablet from the left corner of the top row (with arrow mark) of your Ethinylestradiol & Drospirenone tablet pack.
• Continue taking one light yellow tablet each day along the arrow mark.
• After taking 21 light yellow tablets for 21 days, then continue taking one white placebo tablet every day from the last row in the pack for next 7 days.
• It is most likely that your menstruation will start while taking the white tablets. Do not discontinue taking the white tablets. Taking of the white tablets for 7 days will help you keep your tablet taking routine. If your menstruation does not start during this time, check with your doctor to make sure you are not pregnant.
• After completing the seven white tablets, start taking light yellow tablets from another Ethinylestradiol & Drospirenone pack and continue taking the tablet as long as you don't want to be pregnant.

Management of Missed Tablets

If you forgot to take a tablet one day, take the missed tablet as soon as you remember. This may mean taking two tablets the very next day. Additionally you should use some other method of contraception while you are taking the tablets & until your next menstruation.

If you forget to take the tablets for two continuous days, then it is likely that you will no longer be protected against pregnancy. You should therefore discontinue taking the tablet and adopt some other temporary methods (condom/foam tablet) till your next menstruation. Discard the unfinished pack of tablets and start taking tablets from the very first white tablet of the top row from a fresh pack from the first day of next menstruation.

How to Delay a Period

To delay a period you should continue with another new pack of Ethinylestradiol & Drospirenone just after finishing the light yellow active tablet of the present pack (that is no need to take white placebo tablet of present pack). The extension can be carried on for as long as wished until the end of the second pack. When you wish your period to begin, just stop tablet taking. While using the second pack woman may have some breakthrough bleeding or spotting. Start with your next pack after the usual 7 day white inactive tablet interval.

Advice in Case of Vomiting

If vomiting occurs within 4 hours after white active tablet taking, absorption may not be complete. In such an event, the advice concerning Management of Missed Tablets is applicable. The woman must take the extra active tablet(s) needed from a back up pack after vomiting.

Side Effects

Different types of tablet suit different types of woman. At the initial stage some women may experience side-effects like dizziness, headache, nausea or inter-menstrual bleeding. If taken regularly, such types of side-effects normally go away after 2-3 months. If she continues to have the side effects beyond 2-3 months, she could consult with a doctor.

After starting one brand of oral contraceptive tablets, if you feel any inconvenience such as migraine, changes in eyesight or speech, unusual pain or swelling in your legs, sharp chest pains or shortness of breath, yellow skin or a rise in blood pressure take advice from your doctor or contact the nearest family planning center.

Toxicity

The oral LD50 of drospirenone in rats is >2000 mg/kg.

Overdose information An overdose of drospirenone, like other oral contraceptives, may lead to cause nausea or withdrawal bleeding. For drospirenone in particular, as an analog of spironolactone, may affect the levels of serum sodium and potassium. Their concentrations should be monitored in cases of overdose in addition to monitoring from metabolic acidosis and hyperkalemia, which may also result.

Female patients experiencing and overdose may present with withdrawal bleeding, nausea, vomiting, breast tenderness, abdominal pain, drowsiness, and fatigue. Overdose should be treated with symptomatic and supportive care including monitoring for potassium concentrations, sodium concentrations, and signs of metabolic acidosis.

Precaution

May increase risk of breast cancer, thromboembolism and glucose intolerance. May lead to hyperkalaemia in patients with adrenal insufficiency. May affect serum triglycerides and lipoprotein levels. May cause retinal vascular thrombosis; discontinue treatment if papilloedema or retinal vascular lesions occur. Caution when used in patients with depression, history of migraines or risk factors for coronary arterial diseases. Patients with diseases which may be worsened by fluid retention. May have dose-related risk of gall bladder disease. Increased risk of CV side effects when used in smokers, especially if they are >35 yr of age. Recommended to stop treatment 4 wk before and for 2 wk after elective surgery associated with high risk of thromboembolism or periods of immobilisation. Lactation.

Interaction

Interactions between ethinylestradiol and other drugs may lead to decreased or increased ethinylestradiol concentrations, respectively.Decreased ethinylestradiol serum concentrations may cause an increased incidence of breakthrough bleeding and menstrual irregularities and may possibly reduce efficacy of the oral contraceptive. Example of substances that may decrease serum ethinylestradiol concentrations include rifampicin, phenytoin, primidone, rifabutin, dexamethasone, griseofulvin, topiramate, some protease inhibitors, modafinil, ritonavir and barbiturates. Certain antibiotics including ampicillin, other penicillins and tetracyclines may reduce the efficacy of oral contraceptives. During concomitant use of Ethinylestradiol & Drospirenone & other drugs that may lead to decreased ethinylestradiol serum concentrations, it is recommended that a non-hormonal back-up method of contraception to be used in addition to the regular intake of Ethinylestradiol & Drospirenone.

Volume of Distribution

The volume of distribution of drospirenone is estimated to be 4 L/kg, according to the FDA label for Yaz. Prescribing information from a combination of estradiol and drospirenone estimates the volume of distribution to range from 3.7- 4.2 L/kg.

A 30µg oral dose has an apparent volume of distribution of 625.3±228.7L and a 1.2mg topical dose has an apparent volume of distribution of 11745.3±15934.8L.

Elimination Route

The absolute bioavailability of drospirenone is approximately 76% due to first-pass effects. The maximum plasma concentration of drospirenone occurs within 1 to 2 hours after oral administration and is estimated to range between 60 and 87 ng/mL. A European prescribing monograph for the combination product of estradiol and drospirenone indicates that drospirenone is both completely and rapidly absorbed. It reports a Cmax of 21.9 ng/ml, achieved approximately 1-hour post-administration. The absolute bioavailability is reported to range between 76 to 85%.

A 30µg oral dose of ethinylestradiol reaches a C_max of 74.1±35.6pg/mL, with a T_max of 1.5±0.5h, and an AUC of 487.4±166.6pg*h/mL. A 1.2mg dose delivered via a patch reaches a C_max of 28.8±10.3pg/mL, with a T_max of 86±31h, and an AUC of3895±1423pg*h/mL.

Half Life

The serum half-life of drospirenone is estimated to be 30 hours. The half-life of drospirenone metabolite excretion in the urine and feces is approximately 40 hours.

A 30µg oral dose has a half life of 8.4±4.8h and a 1.2mg topical dose has a half life of 27.7±34.2h.

Clearance

Drospirenone is rapidly cleared, typically within 2-3 days of administration of the last active tablet. The rate of clearance of drospirenone calculated in the serum ranges from 1.2-1.5 ml/min/kg, however, this value can vary by up to 25% according to the patient.

Ethinylestradiol has an intravenous clearance of 16.47L/h, and an estimated renal clearance of approximately 2.1L/h. A 30µg oral dose has a clearance of 58.0±19.8L/h and a 1.2mg topical dose has a clearance of 303.5±100.5L/h.

Elimination Route

Various metabolites of drospirenone are measured in the urine and feces. Drospirenone elimination from the body is almost after 10 days post-administration when negligible amounts of drospirenone are found unchanged in both the urine and feces. Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine. In the feces, approximately 17% to 20% of identifiable metabolites are found to be excreted as glucuronides and sulfates.

Ethinylestradiol is 59.2% eliminated in the urine and bile, while 2-3% is eliminated in the feces. Over 90% of ethinylestradiol is eliminated as the unchanged parent drug.

Pregnancy & Breastfeeding use

Pregnancy: Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Lactation: Oestrogen-containing oral contraceptives given in the postpartum period may interfere with lactation. There may be a decrease in the quantity and a change in the composition of the breast milk. Furthermore, small amounts of contraceptive steroids and/or metabolites have been identified in the milk of mothers receiving them. A few adverse effects have been reported, including jaundice and breast enlargement. The use of oestrogen-containing oral contraceptives should be deferred until the infant has been completely weaned.

Contraindication

Contraindicated in-

• If you are pregnant
• If you are over 45 years of age
• If you are a heavy smoker (more than 20 cigarette/day)
• If you have got heart disease, clotting of blood in the vein
• If you suffer from liver disease or jaundice
• If you are suffer from high blood pressure, migraine, feel something hard in your breast, diabetes with vascular involvement, experience excessive bleeding for which no reason has yet been ascertained
• Hypersensitivity to any of the components of Drospirenone + Ethinylestradiol

Special Warning

Paediatric Use: Ethinylestradiol & Drospirenone is only indicated after menarche. There is no data suggesting the need for a dosage adjustment.

Use in the Elderly: Ethinylestradiol & Drospirenone is not indicated after menopause.

Acute Overdose

Symptoms of oral contraceptive overdosage in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue; withdrawal bleeding may occur in females. There is no specific antidote and further treatment of overdose, if necessary, is directed to the symptoms.

Storage Condition

Store in a cool and dry place. Keep away from light & out of reach of children.

Innovators Monograph

You find simplified version here Novelon