Locipil

Uses

Desogestrel & Ethinylestradiol is used for prevention of pregnancy or oral contraception.

Locipil is also used to associated treatment for these conditions: ContraceptionMenopausal Osteoporosis, Mild to Moderate Acne, Premenstrual Dysphoric Disorder ( PMDD), Moderate Acne vulgaris, Moderate, severe, Vasomotor Symptoms caused by Menopause, Contraception, Folate supplementation therapy

How Locipil works

Desogestrel enters the cell passively and acts by binding selectively to the progesterone receptor and generating low androgenic activity. Its binding produces an effect like a transcription factor and thus, it produces modifications in the mRNA synthesis.

The active metabolite of desogestrel, etonogestrel, presents a combination of high progestational activity with minimal intrinsic androgenicity.

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

Locipil dosage

Dosing instruction may vary according to the brand.

For 21-day pack: Start dose on 1st day of menstrual cycle. 1 tablet daily for 21 days followed by 7 pill-free days. Start a new pack on the 8th day after the last tablet is taken.

For 28-day pack: Start dose on 1st day of menstrual cycle. 1 tablet daily without interruption.

Dose should be taken at the same time everyday.

Side Effects

Intermenstrual bleeding, post-medication amenorrhoea, changes in cervical secretion, increase in size of uterine fibromyomata, aggravation of endometriosis and certain vaginal infections. Breast tenderness, pain, enlargement or secretion. Nausea, vomiting, cholelithiasis, cholestatic jaundice. Headache, migraine, mood changes, depression. Fluid retention, change in body wt, reduced glucose tolerance.

Toxicity

Administration of large quantities of desogestrel has been shown to produce strong hormonal effects but to lack chronic toxicity. The reported LD50 in rats after oral administration of desogestrel is higher than 2000 mg/kg. Overdose hasn't reported serious effects but only symptoms of nausea and withdrawal of bleeding.

Most reports haven't linked the administration of desogestrel with the increased risk of breast cancer. The increased risk has been reported to be related to the duration of use. However, several reports indicate a desogestrel-driven increased risk in cervical intra-epithelial neoplasia but the results are still not conclusive.

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, glucose intolerance and thromboembolism. May affect serum levels of triglyceride and lipoprotein. Caution when used in patients with familial defects of lipoprotein metabolism. Discontinue treatment if papilledema or retinal vascular lesions are observed on eye examination. Patients with risk factors for coronary artery disease. Patients with depression or history of migraine. Renal impairment. Increased cardiovascular risk in smoking women especially those >35 yr. Treatment should be stopped for 4 wk prior to and for 2 wk after surgery associated with increased risk of thromboembolism or during periods of prolonged immbolisation.

Interaction

Serum levels may be increased when used with paracetamol, ascorbic acid, atorvastatin. Serum levels may be reduced by aprepitant, griseofulvin, modafinil, troglitazone, rifampicin, topiramate, nevirapine, amprenavir, lopinavir, nelfinavir and ritonavir. May affect the efficacy of coumarin derivatives. Concurrent use with aminoglutethimide, carbamazepine, felbamate, phenobarbital, phenytoin or topiramate may lead to decrease in contraceptive effectiveness. May reduce the clearance of alprazolam, chlordiazepoxide and diazepam. May increase the clearance of lorazepam, oxazepam, temazepam, clofibric acid, morphine, salicylic acid. May inhibit the metabolism of theophylline, ciclosporin and prednisolone. May decrease the serum levels of lamotrigine. May increase serum levels of selegiline and TCAs e.g. amitriptyline, imipramine.

Volume of Distribution

The apparent volume of distribution of desogestrel is of 1.5 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

After oral administration, desogestrel is rapidly absorbed and it reaches a peak concentration of 2 ng/ml after 1.5 hours. The bioavailability of desogestrel is reported to be in the range of 60-80% and the reported AUC is of 3000 ng.h/ml. Almost all the administered dose is modified to the active metabolite, etonogestrel.

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 terminal half-life of desogestrel is determined to be of 30 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

The metabolic clearance rate of desogestrel is reported to be of about 2 ml/min/kg.

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

The elimination of desogestrel is found to be mainly renal corresponding to about 6 times the dose eliminated in the bile. The elimination of desogestrel is only done as the metabolites and not as the unchanged drug and about 85% of the administered dose can be excreted as metabolites after 6-8 days.

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

Category X: Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal 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.

Contraindication

History of or current thrombophlebitis or venous thromboembolic disorders; active or recent (within 1 yr) arterial thromboembolic disease e.g. stroke, MI; cerebral vascular disease, coronary artery disease, valvular heart disease with complications. Severe hypertension; DM with vascular involvement; severe headache with focal neurological symptoms. Known or suspected breast carcinoma, endometrial cancer, oestrogen-dependent neoplasms. Undiagnosed abnormal genital bleeding; hepatic dysfunction or tumor. Cholestatic jaundice of pregnancy, jaundice with prior combined hormonal contraceptive use. Major surgery with prolonged immobilisation. Pregnancy.

Acute Overdose

Treatment is symptomatic.

Storage Condition

Store at 25°C.

Innovators Monograph

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