• Known or suspected estrogen-dependent neoplasia Drugs which may decrease the therapeutic effect of Cyproterone acetate+Ethinyl Pregnancy and Breastfeeding • Undiagnosed abnormal vaginal bleeding Combination of Cyproterone acetate and Ethinyl estradiol is contraindicated during estradiol and increase the incidence of breakthrough bleeding • Any ocular lesion arising from ophthalmic vascular disease, such as partial or complete pregnancy and breastfeeding. loss of vision or defect in visual fields Effects on ability to drive and use machines • Concomitant use with other Estrogen+Progestogen combinations or estrogens or Unknown progestogens alone • When pregnancy is suspected or diagnosed Adverse Reactions • Severe diabetes with vascular changes Common adverse reactions includes headaches, nausea, abdominal pain, weight gain, • A history of otosclerosis with deterioration during pregnancy depressed or altered mood and breast pain or tenderness. • Hypersensitivity to this drug or to any ingredient in the formulation or component of the Uncommon adverse reactions include vomiting, diarrhea, fluid retention and migraine. container. Overdose (Cyproterone acetate + Warnings and Precautions There is no antidote and treatment should be symptomatic. Ethinyl estradiol) Discontinue Cyproterone acetate+Ethinyl estradiol tablets at the earliest manifestation of the following: PHARMACOLOGICAL PROPERTIES • Thromboembolic and Cardiovascular Disorders such as thrombophlebitis, pulmonary Pharmacotherapeutic group: Sex hormones and modulators of the genital system, QUALITATIVE AND QUANTITATIVE COMPOSITION embolism, cerebrovascular disorders, myocardial ischemia, mesenteric thrombosis, and anti-androgens and estrogens. ATC code: G03HB01 Each film-coated tablet contains: retinal thrombosis. Cyproterone acetate (Ph.Eur.)………...2 mg • Conditions that predispose to Venous Stasis and to Vascular Thrombosis (eg. Mechanism of action Ethinyl estradiol (USP)……………...0.035 mg immobilization after accidents or confinement to bed during long-term illness). Cyproterone acetate inhibits the synthesis of androgen by the target cell, as it is a • Visual Defects - Partial or Complete competitive antagonist on the androgen receptor, and it has an anti-gonadotropic effect DESCRIPTION • Papilledema, or Ophthalmic Vascular Lesions therefore decreasing androgen blood concentrations. Ethinyl estradiol up-regulates the The chemical name of Cyproterone acetate is 17-acetoxy-6-chloro-1α,2α-methylene-4,6- • Severe Headache of Unknown Etiology, or Worsening of Pre-existing Migraine synthesis of Sex-Hormone-Binding Globulin (SHBG) in plasma which reduces the amount pregnadien-3,20-dione. The molecular formula is C H CIO and the molecular weight is 24 29 4 Headache Modification of Other Drug Action by Estrogen+Progestogen Combinations of free, biologically available androgen in the bloodstream, which amplifies the 416.96. • Onset of Jaundice or Hepatitis anti-gonadotropic effect of cyproterone acetate. The chemical name of Ethinyl estradiol is 19-norpregna-1,3,5(10)-trien-20-yne-3,17-diol, • Itching of the Whole Body The contraceptive effect of Cyproterone acetate and Ethinyl estradiol includes the (17α). The molecular formula is C H O and the molecular weight is 296.41 20 24 2 • Significant Rise in Blood Pressure inhibition of ovulation and changes in the cervical secretion. Cyproterone acetate+Ethinyl • Onset of Severe Depression estradiol is not recommended for contraception alone. SERIOUS WARNINGS AND PRECAUTIONS • Severe Upper Abdominal Pain or Liver Enlargement Pharmacokinetic properties Cyproterone acetate+Ethinyl estradiol, as with all Estrogen+Progestogen combinations, is Carcinogenesis and Mutagenesis contraindicated in women with thrombophlebitis, thromboembolic disorders, or a history of Malignancies may be life-threatening or may have a fatal outcome. Absorption these conditions. Cyproterone acetate+Ethinyl estradiol users appear to have an elevated Breast Cancer Cyproterone acetate risk of venous thromboembolic events compared to users of levonorgestrel-containing Increasing age, a strong family history and long-term users are the most significant risk Following oral administration cyproterone acetate is completely absorbed over a wide combined oral contraceptives. The risk of venous thromboembolic events with factors for the development of breast cancer. Other established risk factors include dose range. Peak serum concentrations of 15 ng/mL are reached at about 1.6 hours after Cyproterone acetate+Ethinyl estradiol appears to be similar to desogestrel and obesity, nulliparity, and late age for first full-term pregnancy. single ingestion. The absolute bioavailability of cyproterone acetate is unknown. drospirenone-containing combined oral contraceptives. During treatment with Hepatic Cancer Ethinyl estradiol Cyproterone acetate+Ethinyl estradiol, Estrogen+Progestogen combinations should not Recognized 1st line tests for genotoxicity gave negative results, with cyproterone acetate. Orally administered Ethinyl estradiol is rapidly and almost completely absorbed. Peak be used. Cyproterone acetate+Ethinyl estradiol should not be prescribed for the purpose Cardiovascular serum concentrations of about 71 pg/mL are reached within 1-2 hours. Absolute of contraception alone. Estrogens or progestogens should not be taken during treatment Predisposing Factors for Coronary Artery Diseases with Cyproterone acetate+Ethinyl estradiol. The need to continue treatment with bioavailability, as a result of presystemic conjugation and first pass metabolism, is Cigarette smoking increases the risk of serious cardiovascular side effects and mortality. approximately 60%. Cyproterone acetate+Ethinyl estradiol should be evaluated periodically by the treating Hypertension Distribution physician. Cyproterone acetate+Ethinyl estradiol should be discontinued 3 to 4 cycles Close supervision is required in patients with essential hypertension. Cyproterone acetate after signs have completely resolved. Cigarette smoking increases the risk of serious Endocrine and Metabolism adverse effects on the heart and blood vessels from the use of Cyproterone Diabetes Cyproterone acetate is almost exclusively bound to serum albumin. Only 3.5 - 4.0 % of the acetate+Ethinyl estradiol. This risk increases with age and heavy smoking (15 or more Diabetic patients, or those with a family history of diabetes, should be observed closely. total serum drug concentrations are present as free steroid. The apparent volume of cigarettes per day) and is more marked in women over 35 years of age. Women who use Lipid Effects distribution of cyproterone acetate is about 986 ± 437 L. this medication should not smoke. Estrogen+Progestogen combinations may cause an increase in plasma lipoproteins. Ethinyl estradiol Metabolic and Endocrine Diseases Ethinyl estradiol is highly but non-specifically bound to serum albumin (approximately CLINICAL INFORMATION In such disease, careful clinical evaluation and a regular follow-up is recommended. 98.5%) and induces an increase in the serum concentrations of SHBG. The apparent Indications Genitourinary volume of distribution is approximately 5 L/kg. Divestra (Cyproterone acetate+Ethinyl estradiol) Tablets are indicated as follows: Fibroids • Signs of androgenization, in women such as severe acne (involving inflammation or Metabolism Carefully observation is required for enlargement, pain, or tenderness. Cyproterone acetate nodularity or risk of scarring) where prolonged oral antibiotics or local treatment alone has Vaginal Bleeding Cyproterone acetate is subject to extensive metabolism. The main metabolite in plasma is not been successful, or idiopathic hirsutism of mild to moderate degree. Persistent irregular vaginal bleeding requires special diagnostic judgement to exclude the • It will also provide effective oral contraception in this patient group. possibility of pregnancy or neoplasm. known as 15-hydroxy-CPA. The clearance rate from serum is about 3.6 mL/min/kg. Hematologic Ethinyl estradiol If the hirsutism has only recently appeared or has lately intensified to a considerable An increased risk (rare) of arterial and venous thrombotic and thromboembolic diseases. Ethinyl estradiol is subject to presystemic conjugation in both small bowel mucosa and the extent the cause (androgen-producing tumor or an adrenal-enzyme defect) must be liver. Ethinyl estradiol is primarily metabolised by aromatic hydroxylation but a wide variety clarified by differential diagnosis. Interactions of hydroxylated and methylated metabolites are formed, and these are present as free Drugs which may decrease the therapeutic effect of Cyproterone acetate+Ethinyl metabolites and as conjugates with glucuronides and sulfate. The metabolic clearance Dosage and Administration estradiol and increase the incidence of breakthrough bleeding rate is about 5 mL/min/kg. First treatment course One tablet is to be taken daily for 21 consecutive days beginning on day 1 of the menstrual Elimination Class of Drug Proposed Mechanism Cyproterone acetate cycle. (For the first cycle only the first day of menstrual flow is considered Day 1.) The Compound tablets are then discontinued for 7 days (1 week). Cyproterone acetate serum levels decrease in two phases which are characterised by Antacids Decreased intestinal Subsequent courses half-lives of about 0.8 h and about 2.3 to 3.3 days. Cyproterone acetate is partly excreted absorption of progestogen*. The patient begins her next and all subsequent 21-day course of tablets with (following the in unchanged form. Its metabolites are excreted at a urinary to biliary ratio of about 1:2. same 21 days on, 7 days off) on the same day of the week that the woman began her first Antibiotics Ampicillin, Enterohepatic circulation The half-life of metabolite excretion is about 1.9 days. course. The course begins with taking tablets for 7 days after discontinuation, regardless Cotrimoxazole, disturbance, intestinal hurry. Ethinyl estradiol of whether or not withdrawal bleeding is still in progress. Penicillin (V) Ethinyl estradiol serum levels decrease in two phases, the terminal disposition phase is Length of Use Rifampin Increased metabolism of characterised by half-life of approximately 24 hours. Unchanged drug is not excreted, Length of use depends on the severity of the symptoms of androgenization and their progestins. Suspected Ethinyl estradiol metabolites are excreted at a urinary to biliary ratio of 4:6. The half-life of acceleration of estrogen response to treatment. In general, treatment should be continued for several months, metabolite excretion is about 1 day. since improvement may not be observed for at least three months. The need to continue metabolism. treatment with Divestra (Cyproterone acetate+Ethinyl estradiol) should be evaluated Chloramphenicol, Induction of hepatic PHARMACEUTICAL INFORMATION periodically by the treating physician. Divestra (Cyproterone acetate+Ethinyl estradiol) Metronidazole, microsomal enzymes. Also Shelf life should be discontinued 3 to 4 cycles after signs have completely resolved. Neomycin, disturbance of enterohepatic 2 years Dosage Adjustment Nitrofurantoin, circulation. Children and adolescents Sulfonamides, Divestra (Cyproterone acetate+Ethinyl estradiol) is only indicated after menarche. Tetracyclines Special precautions for storage Use in the Elderly • 0 Troleandomycin May retard metabolism of Store below 30 C. Divestra (Cyproterone acetate+Ethinyl estradiol) is not indicated after menopause. • Cyproterone Protect from light and moisture. Patients with hepatic impairment • Keep out of the reach of children. Divestra (Cyproterone acetate+Ethinyl estradiol) is contraindicated in women with severe acetate+Ethinyl estradiol , increasing the risk of hepatic diseases as long as liver function values have not returned to normal. To be sold on the prescription of a registered Patients with renal impairment cholestatic jaundice. medical practitioner only. Divestra (Cyproterone acetate+Ethinyl estradiol) has not been evaluated in renally Anticonvulsants Carbamazepine, Induction of hepatic impaired patients. Ethosuximide, microsomal enzymes. Rapid Administration Requirement Lamotrigine, metabolism of estrogen and Nature and contents of container Treatment should be continued for several months. Should there be a recurrence, weeks Phenobarbital, increased binding of Divestra (Cyproterone acetate+Ethinyl estradiol) 2 mg + 0.035 mg tablets are available in or months after discontinuation of tablet-taking, treatment with Divestra Tablets may be Phenytoin, Primidone progestogen and ethinyl a blister pack of 21’s (1 x 21’s). resumed. In case of a restart of Divestra (Cyproterone acetate+Ethinyl estradiol) Tablets estradiol to SHBG. (following a 4-week or greater tablet interval), the increased risk of venous Antifungals Griseofulvin Stimulation of hepatic MANUFACTURED BY: thromboembolism (VTE) should be considered. metabolism of Cyproterone OBS Pakistan (Pvt.) Ltd. acetate+Ethinyl estradiol C-14, Manghopir Road, S.I.T.E., Karachi-75700, Pakistan. Contraindications may occur. • History of or actual thrombophlebitis or thromboembolic disorders MANUFACTURED FOR: • History of or actual cerebrovascular disorders * Dose two hours apart • History of or actual myocardial infarction or coronary arterial disease Substance decreasing the clearance of Cyproterone acetate+Ethinyl estradiol • Active liver disease Strong and moderate CYP3A4 inhibitors such as azole antifungals, verapamil, • Previous or existing liver tumors (benign or malignant) macrolides, diltiazem and grapefruit juice can increase plasma concenrations of the Aspin Pharma (Pvt.) Ltd. • History of cholestatic jaundice estrogen or the progestin or both. • Plot No. 10 & 25, Sector No. 20, Use with the Hepatitis C virus combination drug regimen ombitasvir, paritaprevir, Etoricoxib and Vitamin C are known to increase plasma concentrations. ritonavir, with or without dasabuvir Korangi Industrial Area, Karachi - 74900, • Known or suspected carcinoma of the breast Pakistan. www.aspin.com.pk • Known or suspected estrogen-dependent neoplasia Drugs which may decrease the therapeutic effect of Cyproterone acetate+Ethinyl Pregnancy and Breastfeeding • Undiagnosed abnormal vaginal bleeding Combination of Cyproterone acetate and Ethinyl estradiol is contraindicated during estradiol and increase the incidence of breakthrough bleeding • Any ocular lesion arising from ophthalmic vascular disease, such as partial or complete pregnancy and breastfeeding. loss of vision or defect in visual fields Class of Drug Proposed Mechanism Effects on ability to drive and use machines • Concomitant use with other Estrogen+Progestogen combinations or estrogens or Compound Unknown progestogens alone Cholesterol Clofibrate Reduces elevated serum • Adverse Reactions When pregnancy is suspected or diagnosed triglycerides and cholesterol; • Lowering Agents Common adverse reactions includes headaches, nausea, abdominal pain, weight gain, Severe diabetes with vascular changes this reduces Cyproterone • A history of otosclerosis with deterioration during pregnancy depressed or altered mood and breast pain or tenderness. acetate+Ethinyloestradiol • Hypersensitivity to this drug or to any ingredient in the formulation or component of the Uncommon adverse reactions include vomiting, diarrhea, fluid retention and migraine. efficacy. container. Ritonavir Induction of hepatic HIV Protease Overdose Inhibitors microsomal enzymes. Warnings and Precautions There is no antidote and treatment should be symptomatic. Discontinue Cyproterone acetate+Ethinyl estradiol tablets at the earliest manifestation of Non-nucleoside Nevirapine Induction of hepatic Reverse microsomal enzymes. the following: PHARMACOLOGICAL PROPERTIES • Transcriptase Thromboembolic and Cardiovascular Disorders such as thrombophlebitis, pulmonary Pharmacotherapeutic group: Sex hormones and modulators of the genital system, QUALITATIVE AND QUANTITATIVE COMPOSITION embolism, cerebrovascular disorders, myocardial ischemia, mesenteric thrombosis, and Inhibitors anti-androgens and estrogens. ATC code: G03HB01 Each film-coated tablet contains: retinal thrombosis. Sedatives and Barbiturates Induction of hepatic Cyproterone acetate (Ph.Eur.)………...2 mg • Conditions that predispose to Venous Stasis and to Vascular Thrombosis (eg. Hypnotics Benzodiazepines microsomal enzymes. Mechanism of action Ethinyl estradiol (USP)……………...0.035 mg immobilization after accidents or confinement to bed during long-term illness). Chloral hydrate Cyproterone acetate inhibits the synthesis of androgen by the target cell, as it is a • Visual Defects - Partial or Complete Glutethimide competitive antagonist on the androgen receptor, and it has an anti-gonadotropic effect DESCRIPTION • Papilledema, or Ophthalmic Vascular Lesions Meprobamate therefore decreasing androgen blood concentrations. Ethinyl estradiol up-regulates the The chemical name of Cyproterone acetate is 17-acetoxy-6-chloro-1α,2α-methylene-4,6- • Severe Headache of Unknown Etiology, or Worsening of Pre-existing Migraine synthesis of Sex-Hormone-Binding Globulin (SHBG) in plasma which reduces the amount pregnadien-3,20-dione. The molecular formula is C H CIO and the molecular weight is 24 29 4 Headache Modification of Other Drug Action by Estrogen+Progestogen Combinations of free, biologically available androgen in the bloodstream, which amplifies the 416.96. • Onset of Jaundice or Hepatitis anti-gonadotropic effect of cyproterone acetate. The chemical name of Ethinyl estradiol is 19-norpregna-1,3,5(10)-trien-20-yne-3,17-diol, • Itching of the Whole Body Class of Drug Modification of Drug The contraceptive effect of Cyproterone acetate and Ethinyl estradiol includes the (17α). The molecular formula is C H O and the molecular weight is 296.41 20 24 2 • Significant Rise in Blood Pressure Compound Action inhibition of ovulation and changes in the cervical secretion. Cyproterone acetate+Ethinyl • Onset of Severe Depression Alcohol Possible increased levels of estradiol is not recommended for contraception alone. SERIOUS WARNINGS AND PRECAUTIONS • Severe Upper Abdominal Pain or Liver Enlargement ethanol or acetaldehyde Pharmacokinetic properties Cyproterone acetate+Ethinyl estradiol, as with all Estrogen+Progestogen combinations, is Carcinogenesis and Mutagenesis contraindicated in women with thrombophlebitis, thromboembolic disorders, or a history of Malignancies may be life-threatening or may have a fatal outcome. Alpha-II Clonidine Sedation effect increased. Absorption these conditions. Cyproterone acetate+Ethinyl estradiol users appear to have an elevated Breast Cancer adrenoreceptor Cyproterone acetate risk of venous thromboembolic events compared to users of levonorgestrel-containing Increasing age, a strong family history and long-term users are the most significant risk Agents Following oral administration cyproterone acetate is completely absorbed over a wide combined oral contraceptives. The risk of venous thromboembolic events with factors for the development of breast cancer. Other established risk factors include Anticoagulants All Increase clotting factors, dose range. Peak serum concentrations of 15 ng/mL are reached at about 1.6 hours after Cyproterone acetate+Ethinyl estradiol appears to be similar to desogestrel and obesity, nulliparity, and late age for first full-term pregnancy. decrease efficacy. However, single ingestion. The absolute bioavailability of cyproterone acetate is unknown. drospirenone-containing combined oral contraceptives. During treatment with Hepatic Cancer Estrogen+Progestogen Ethinyl estradiol Cyproterone acetate+Ethinyl estradiol, Estrogen+Progestogen combinations should not Recognized 1st line tests for genotoxicity gave negative results, with cyproterone acetate. combinations may potentiate Orally administered Ethinyl estradiol is rapidly and almost completely absorbed. Peak be used. Cyproterone acetate+Ethinyl estradiol should not be prescribed for the purpose Cardiovascular action in some patients. serum concentrations of about 71 pg/mL are reached within 1-2 hours. Absolute of contraception alone. Estrogens or progestogens should not be taken during treatment Predisposing Factors for Coronary Artery Diseases All Fluid retention may increase with Cyproterone acetate+Ethinyl estradiol. The need to continue treatment with Anticonvulsants bioavailability, as a result of presystemic conjugation and first pass metabolism, is Cigarette smoking increases the risk of serious cardiovascular side effects and mortality. risk of seizures. approximately 60%. Cyproterone acetate+Ethinyl estradiol should be evaluated periodically by the treating Hypertension Antidiabetic Oral hypoglycemics Combination may impair Distribution physician. Cyproterone acetate+Ethinyl estradiol should be discontinued 3 to 4 cycles Close supervision is required in patients with essential hypertension. after signs have completely resolved. Cigarette smoking increases the risk of serious drugs and insulin glucose tolerance and Cyproterone acetate Endocrine and Metabolism increase blood glucose. adverse effects on the heart and blood vessels from the use of Cyproterone Diabetes Cyproterone acetate is almost exclusively bound to serum albumin. Only 3.5 - 4.0 % of the acetate+Ethinyl estradiol. This risk increases with age and heavy smoking (15 or more Antihypertensive Guanethidine and Estrogen component causes total serum drug concentrations are present as free steroid. The apparent volume of Diabetic patients, or those with a family history of diabetes, should be observed closely. methyldopa sodium retention, progestin cigarettes per day) and is more marked in women over 35 years of age. Women who use agents distribution of cyproterone acetate is about 986 ± 437 L. Lipid Effects has no effect. this medication should not smoke. Ethinyl estradiol Estrogen+Progestogen combinations may cause an increase in plasma lipoproteins. Beta blockers Increased drug effect Metabolic and Endocrine Diseases (decreased metabolism). Ethinyl estradiol is highly but non-specifically bound to serum albumin (approximately CLINICAL INFORMATION In such disease, careful clinical evaluation and a regular follow-up is recommended. Antipyretics Acetaminophen Increased metabolism and 98.5%) and induces an increase in the serum concentrations of SHBG. The apparent Indications Genitourinary renal clearance. volume of distribution is approximately 5 L/kg. Divestra (Cyproterone acetate+Ethinyl estradiol) Tablets are indicated as follows: Fibroids • Signs of androgenization, in women such as severe acne (involving inflammation or Antipyrine Impaired metabolism. Metabolism Carefully observation is required for enlargement, pain, or tenderness. Cyproterone acetate nodularity or risk of scarring) where prolonged oral antibiotics or local treatment alone has Vaginal Bleeding ASA Effects of ASA may be Cyproterone acetate is subject to extensive metabolism. The main metabolite in plasma is not been successful, or idiopathic hirsutism of mild to moderate degree. Persistent irregular vaginal bleeding requires special diagnostic judgement to exclude the decreased by the short-term • It will also provide effective oral contraception in this patient group. possibility of pregnancy or neoplasm. use.. known as 15-hydroxy-CPA. The clearance rate from serum is about 3.6 mL/min/kg. Hematologic Aminocaproic Theoretically, a Ethinyl estradiol If the hirsutism has only recently appeared or has lately intensified to a considerable An increased risk (rare) of arterial and venous thrombotic and thromboembolic diseases. acid hypercoagulable state may Ethinyl estradiol is subject to presystemic conjugation in both small bowel mucosa and the extent the cause (androgen-producing tumor or an adrenal-enzyme defect) must be occur. liver. Ethinyl estradiol is primarily metabolised by aromatic hydroxylation but a wide variety clarified by differential diagnosis. Interactions Betamimetic Isoproterenol Estrogen causes decreased of hydroxylated and methylated metabolites are formed, and these are present as free Drugs which may decrease the therapeutic effect of Cyproterone acetate+Ethinyl agents response to these drugs. metabolites and as conjugates with glucuronides and sulfate. The metabolic clearance Dosage and Administration estradiol and increase the incidence of breakthrough bleeding Caffeine The actions of caffeine may rate is about 5 mL/min/kg. First treatment course be enhanced. Elimination One tablet is to be taken daily for 21 consecutive days beginning on day 1 of the menstrual Cholesterol Clofibrate Their action may be cycle. (For the first cycle only the first day of menstrual flow is considered Day 1.) The Cyproterone acetate lowering agents antagonized, may also Cyproterone acetate serum levels decrease in two phases which are characterised by tablets are then discontinued for 7 days (1 week). increase metabolism of half-lives of about 0.8 h and about 2.3 to 3.3 days. Cyproterone acetate is partly excreted Subsequent courses clofibrate. in unchanged form. Its metabolites are excreted at a urinary to biliary ratio of about 1:2. The patient begins her next and all subsequent 21-day course of tablets with (following the Corticosteroids Prednisone Markedly increased serum same 21 days on, 7 days off) on the same day of the week that the woman began her first levels. The half-life of metabolite excretion is about 1.9 days. course. The course begins with taking tablets for 7 days after discontinuation, regardless Cyclosporine May lead to an increase in Ethinyl estradiol of whether or not withdrawal bleeding is still in progress. cyclosporine levels and Ethinyl estradiol serum levels decrease in two phases, the terminal disposition phase is Length of Use hepatotoxicity. characterised by half-life of approximately 24 hours. Unchanged drug is not excreted, Length of use depends on the severity of the symptoms of androgenization and their Direct-acting Ombitasvir, Associated with increases in Ethinyl estradiol metabolites are excreted at a urinary to biliary ratio of 4:6. The half-life of response to treatment. In general, treatment should be continued for several months, metabolite excretion is about 1 day. since improvement may not be observed for at least three months. The need to continue antiviral (DAA) Paritaprevir, Ritonavir, ALT levels 5 to >20 times treatment with Divestra (Cyproterone acetate+Ethinyl estradiol) should be evaluated medicinal with and without the upper limit of normal in periodically by the treating physician. Divestra (Cyproterone acetate+Ethinyl estradiol) products Dasabuvir healthy female subjects and PHARMACEUTICAL INFORMATION should be discontinued 3 to 4 cycles after signs have completely resolved. HCV infected women. Shelf life Dosage Adjustment Meperidine Possible increased 2 years Children and adolescents analgesia and CNS Divestra (Cyproterone acetate+Ethinyl estradiol) is only indicated after menarche. depression due to Special precautions for storage Use in the Elderly decreased metabolism of • Store below 300C. meperidine. Divestra (Cyproterone acetate+Ethinyl estradiol) is not indicated after menopause. • Protect from light and moisture. Phenothiazine All phenothiazines, Estrogen potentiates the Patients with hepatic impairment • Keep out of the reach of children. Divestra (Cyproterone acetate+Ethinyl estradiol) is contraindicated in women with severe tranquilizers reserpine and similar hyperprolactinemia effect of drugs these drugs. hepatic diseases as long as liver function values have not returned to normal. To be sold on the prescription of a registered Patients with renal impairment Sedatives and Chlordiazepoxide Increased effect (increased medical practitioner only. Divestra (Cyproterone acetate+Ethinyl estradiol) has not been evaluated in renally hypnotics Diazepam metabolism). impaired patients. Lorazepam Administration Requirement Oxazepam Nature and contents of container Treatment should be continued for several months. Should there be a recurrence, weeks Theophylline All Decreased oxidation, Divestra (Cyproterone acetate+Ethinyl estradiol) 2 mg + 0.035 mg tablets are available in or months after discontinuation of tablet-taking, treatment with Divestra Tablets may be leading to possible toxicity. a blister pack of 21’s (1 x 21’s). resumed. In case of a restart of Divestra (Cyproterone acetate+Ethinyl estradiol) Tablets Tricyclic Clomipramine Increased side effects: ie. (following a 4-week or greater tablet interval), the increased risk of venous antidepressants (possibly others) depression MANUFACTURED BY: thromboembolism (VTE) should be considered. Vitamin B12 Estrogen+Progestogen OBS Pakistan (Pvt.) Ltd. combinations have been C-14, Manghopir Road, S.I.T.E., Karachi-75700, Pakistan. Contraindications reported to reduce serum • History of or actual thrombophlebitis or thromboembolic disorders levels of Vitamin B12 MANUFACTURED FOR: • History of or actual cerebrovascular disorders * Dose two hours apart • History of or actual myocardial infarction or coronary arterial disease Substance decreasing the clearance of Cyproterone acetate+Ethinyl estradiol • Active liver disease Strong and moderate CYP3A4 inhibitors such as azole antifungals, verapamil, • Previous or existing liver tumors (benign or malignant) macrolides, diltiazem and grapefruit juice can increase plasma concenrations of the REVISION DATE • Aspin Pharma (Pvt.) Ltd. History of cholestatic jaundice estrogen or the progestin or both. February 2020 • Plot No. 10 & 25, Sector No. 20, Use with the Hepatitis C virus combination drug regimen ombitasvir, paritaprevir, Etoricoxib and Vitamin C are known to increase plasma concentrations. ritonavir, with or without dasabuvir Korangi Industrial Area, Karachi - 74900, PIL-DI-0220/1 • Known or suspected carcinoma of the breast Pakistan. www.aspin.com.pk