Humulina NPH may be available in the countries listed below.
Insulin, Isophane human (a derivative of Insulin, Isophane) is reported as an ingredient of Humulina NPH in the following countries:
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Epi GRY may be available in the countries listed below.
Epirubicin hydrochloride (a derivative of Epirubicin) is reported as an ingredient of Epi GRY in the following countries:
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Panthenyl may be available in the countries listed below.
Dexpanthenol is reported as an ingredient of Panthenyl in the following countries:
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Reliv may be available in the countries listed below.
Paracetamol is reported as an ingredient of Reliv in the following countries:
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Bécotide may be available in the countries listed below.
Beclometasone 17α,21-dipropionate (a derivative of Beclometasone) is reported as an ingredient of Bécotide in the following countries:
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Amitrox may be available in the countries listed below.
Aciclovir is reported as an ingredient of Amitrox in the following countries:
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Lunapon may be available in the countries listed below.
Fluorouracil is reported as an ingredient of Lunapon in the following countries:
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ProHance Bracco may be available in the countries listed below.
Gadoteridol is reported as an ingredient of ProHance Bracco in the following countries:
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Oxycodone hydrochloride is 4,5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride, a white, odorless, crystalline powder which is derived from the opium alkaloid, thebaine, and may be represented by the structural formula:
Each Oxycodone Hydrochloride Immediate-Release Oral Capsule contains:
Oxycodone Hydrochloride USP .................5 mg
In addition, each capsule contains the following inactive ingredients: black iron oxide, gelatin, lactose, red iron oxide, silicon dioxide, stearic acid, titanium dioxide, yellow iron oxide.
The analgesic ingredient, oxycodone, is a semisynthetic narcotic with multiple actions qualitatively similar to those of morphine; the most prominent of these involve the central nervous system and organs composed of smooth muscle. The principal actions of therapeutic value of oxycodone are analgesia and sedation.
Oxycodone is a pure agonist opioid whose principal therapeutic action is analgesia. Other therapeutic effects of oxycodone include anxiolysis, euphoria and feelings of relaxation. Like all pure opioid agonists, there is no ceiling effect to analgesia, such as is seen with partial agonists or non-opioid analgesics.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and play a role in the analgesic effects of this drug.
Oxycodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves both a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.
Oxycodone depresses the cough reflex by direct effect on the cough center in the medulla. Antitussive effects may occur with doses lower than those usually required for analgesia.
Oxycodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic. Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Oxycodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid-induced effects may include a reduction in gastric, biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
Oxycodone may produce release of histamine with or without associated peripheral vasodilation. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Studies in normal volunteers and patients reveal predictable relationships between oxycodone dosage and plasma oxycodone concentrations, as well as between concentration and certain expected opioid effects. In normal volunteers these include pupillary constriction, sedation and overall “drug effect” and in patients, analgesia and feelings of “relaxation.” In non-tolerant patients, analgesia is not usually seen at a plasma oxycodone concentration of less than 5 to 10 ng/mL.
As with all opioids, the minimum effective plasma concentration for analgesia will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. As a result, patients need to be treated with individualized titration of dosage to the desired effect. The minimum effective analgesic concentration of oxycodone for any individual patient may increase with repeated dosing due to an increase in pain and/or the development of tolerance.
Oxycodone hydrochloride capsules are associated with typical opioid-related adverse experiences similar to those seen with all opioids. There is a general relationship between increasing oxycodone plasma concentration and increasing frequency of dose-related opioid adverse experiences such as nausea, vomiting, CNS effects and respiratory depression. In opioid-tolerant patients, the situation is altered by the development of tolerance to opioid-related side effects, and the relationship is poorly understood.
As with all opioids, the dose must be individualized (see DOSAGE AND ADMINISTRATION), because the effective analgesic dose for some patients will be too high to be tolerated by other patients.
For the relief of moderate to moderately severe pain.
Oxycodone hydrochloride capsules are contraindicated in patients with known hypersensitivity to oxycodone, or in any situation where opioids are contraindicated. This includes patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment), and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone hydrochloride capsules are contraindicated in any patient who has or is suspected of having paralytic ileus.
Respiratory depression is the chief hazard from all opioid agonist preparations. Respiratory depression occurs most frequently in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration.
Oxycodone should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.
Oxycodone hydrochloride capsules, like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Oxycodone hydrochloride capsules may produce orthostatic hypotension in ambulatory patients. Oxycodone hydrochloride capsules, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.
Oxycodone can produce drug dependence of the morphine type, and therefore, has the potential for being abused. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of this drug, and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic containing medications. Like other narcotic containing medications, this drug is subject to the Federal Controlled Substances Act.
Oxycodone may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient using this drug should be cautioned accordingly.
Patients receiving other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with oxycodone hydrochloride may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Safe use in pregnancy has not been established relative to possible adverse effects on fetal development. Therefore, this drug should not be used in pregnant women unless, in the judgment of the physician, the potential benefits outweigh the possible hazards.
This drug should not be administered to children.
Opioid analgesics given on a fixed-dosage schedule have a narrow therapeutic index in certain patient populations, especially when combined with other drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension.
Use of oxycodone hydrochloride capsules is associated with increased potential risks and should be used only with caution in the following conditions: acute alcoholism; adrenocortical insufficiency (e.g., Addison’s disease); CNS depression or coma; delirium tremens; debilitated patients; kyphoscoliosis associated with respiratory depression; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; severe impairment of hepatic, pulmonary or renal function; and toxic psychosis.
The administration of oxycodone, like all opioid analgesics, may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxycodone may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.
Agonist/antagonist and partial agonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as oxycodone. In this situation, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal symptoms in these patients.
Oxycodone may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone may cause increases in the serum amylase level.
The respiratory depressant effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions which may obscure the clinical course of patients with head injuries.
The administration of this drug or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
If clinically advisable, patients receiving oxycodone hydrochloride capsules or their caregivers should be given the following information by the physician, nurse, pharmacist or caregiver:
Due to the broad range of plasma concentrations seen in clinical populations, the varying degrees of pain, and the development of tolerance, plasma oxycodone measurements are usually not helpful in clinical management. Plasma concentrations of the active drug substance may be of value in selected, unusual or complex cases.
Oxycodone hydrochloride capsules are opioids with no approved use in the management of addictive disorders. Their proper usage in individuals with drug or alcohol dependence, either active or in remission, is for the management of pain requiring opioid analgesia.
The CNS depressant effects of oxycodone hydrochloride may be additive with that of other CNS depressants (see WARNINGS).
Opioid analgesics, including oxycodone hydrochloride capsules, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Oxycodone is metabolized in part to oxymorphone via CYP2D6. While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs and antidepressants), such blockade has not yet been shown to be of clinical significance with this agent. Clinicians should be aware of this possible interaction, however.
Oxycodone was not mutagenic in the following assays: Ames Salmonella and E. Coli test with and without metabolic activation at doses of up to 5000 mcg, chromosomal aberration test in human lymphocytes in the absence of metabolic activation at doses of up to 1500 mcg/mL and with activation 48 hours after exposure at doses of up to 5000 mcg/mL, and in the in vivo bone marrow micronucleus test in mice (at plasma levels of up to 48 mcg/mL). Mutagenic results occurred in the presence of metabolic activation in the human chromosomal aberration test (at greater than or equal to 1250 mcg/mL) at 24 but not 48 hours of exposure and in the mouse lymphoma assay at doses of 50 mcg/mL or greater with metabolic activation and at 400 mcg/mL or greater without metabolic activation. The data from these tests indicate that the genotoxic risk to humans may be considered low.
Studies of oxycodone in animals to evaluate its carcinogenic potential have not been conducted owing to the length of clinical experience with the drug substance.
Oxycodone hydrochloride capsules are not recommended for use in women during and immediately prior to labor and delivery because oral opioids may cause respiratory depression in the newborn.
Low concentrations of oxycodone have been detected in breast milk. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of an opioid analgesic is stopped. Ordinarily, nursing should not be undertaken while a patient is receiving oxycodone hydrochloride capsules since oxycodone may be excreted in the milk.
Safety and effectiveness in pediatric patients have not been established.
This drug should be given with caution to certain patients such as the elderly or debilitated, and those with severe impairment of hepatic or renal function, hypothyroidism, Addison’s disease and prostatic hypertrophy or urethral stricture.
The most frequently observed reactions include light-headedness, dizziness, sedation, nausea and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Many of these adverse events will cease or decrease in intensity as oxycodone therapy is continued and some degree of tolerance is developed.
Other adverse reactions include euphoria, dysphoria, constipation, skin rash and pruritus.
Oxycodone products are common targets for both drug abusers and drug addicts.
Drug addiction (drug dependence, psychological dependence) is characterized by a preoccupation with the procurement, hoarding, and abuse of drugs for non-medicinal purposes. Drug dependence is treatable, utilizing a multi-disciplinary approach, but relapse is common. “Drug seeking” behavior is very common to addicts. Tolerance and physical dependence in pain patients are not signs of psychological dependence. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Most chronic pain patients limit their intake of opioids to achieve a balance between the benefits of the drug and dose-limiting side effects. Physicians should be aware that psychological dependence may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true psychological dependence and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances.
Serious overdose of oxycodone hydrochloride is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.
Primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including oxycodone. Therefore, an appropriate dose of naloxone (usual initial adult dose: 0.4 mg) should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxycodone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.
Gastric emptying may be useful in removing unabsorbed drug.
Dosage should be adjusted to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effects of opioids. This drug is given orally. The usual adult dosage is 5 mg every 6 hours as needed for pain.
Oxycodone Hydrochloride Immediate-Release Oral Capsules, 5 mg are available as opaque brown cap, imprinted “0554”, and opaque light brown body imprinted
Dispense in a tight, light-resistant container with a child-resistant closure.
Protect from moisture. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
COVIDIEN™
Mallinckrodt
Mallinckrodt Inc.,
Hazelwood, MO 63042 USA.
Rev 020409
NDC 0406-0554-01
100 CAPSULES
OXYCODONE HYDROCHLORIDE
IMMEDIATE-RELEASE CAPSULES
CII
5 mg
Each capsule contains:
Oxycodone Hydrochloride USP . . . . . . . 5 mg
Rx only
Mallinckrodt
| OXYCODONE HYDROCHLORIDE IMMEDIATE-RELEASE oxycodone hydrochloride capsule | ||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| unapproved other | 06/18/2009 | ||
| Labeler - Mallinckrodt Inc. (047021092) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Mallinckrodt Inc. | 957414238 | analysis, manufacture | |
Ovranette may be available in the countries listed below.
UK matches:
Ethinylestradiol is reported as an ingredient of Ovranette in the following countries:
Levonorgestrel is reported as an ingredient of Ovranette in the following countries:
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Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that "natural" estrogens are more or less hazardous than "synthetic" estrogens at equi-estrogenic doses.
There is no indication for estrogen therapy during pregnancy or during the immediate postpartum period. Estrogens are ineffective for the prevention or treatment of threatened, or habitual abortion. Estrogens are not indicated for the prevention of postpartum breast engorgement.
Estrogen therapy during pregnancy is associated with an increased risk of congenital defects in the reproductive organs of the fetus, and possibly other birth defects. Studies of women who received diethylstilbestrol (DES) during pregnancy have shown that female offspring have an increased risk of vaginal adenosis, squamous cell dysplasia of the uterine cervix, and clear cell vaginal cancer later in life; male offspring have an increased risk of urogenital abnormalities and possibly testicular cancer later in life. The 1985 DES Task Force concluded that use of DES during pregnancy is associated with a subsequent increased risk of breast cancer in the mothers, although a causal relationship remains unproven and the observed level of excess risk is similar to that for a number of other breast cancer risk factors.
OGEN (estropipate vaginal cream, USP), (formerly piperazine estrone sulfate), is a natural estrogenic substance prepared from purified crystalline estrone, solubilized as the sulfate and stabilized with piperazine. It is appreciably soluble in water and has almost no odor or taste. The amount of piperazine in OGEN is not sufficient to exert a pharmacological action. Its addition ensures solubility, stability, and uniform potency of the estrone sulfate. Chemically estropipate, molecular weight: 436.56, is represented by estra-1,3,5(10)-trien-17-one,3-(sulfooxy)-, compound with piperazine (1:1). The structural formula may be represented as follows:
Each gram of OGEN Vaginal Cream contains 1.5 mg estropipate in a base composed of the following ingredients: glycerin, mineral oil, glyceryl monostearate, polyethylene glycol ether complex of higher fatty alcohols, cetyl alcohol, anhydrous lanolin, sodium biphosphate, cis-N-(3-chloroallyl) hexaminium chloride, propylparaben, methylparaben, piperazine hexahydrate, citric acid and water.
Estrogen drug products act by regulating the transcription of a limited number of genes. Estrogens diffuse through cell membranes, distribute themselves throughout the cell, and bind to and activate the nuclear estrogen receptor, a DNA-binding protein which is found in estrogen-responsive tissues. The activated estrogen receptor binds to specific DNA sequences, or hormone-response elements, which enhance the transcription of adjacent genes and in turn lead to the observed effects. Estrogen receptors have been identified in tissues of the reproductive tract, breast, pituitary, hypothalamus, liver, and bone of women.
Estrogens are important in the development and maintenance of the female reproductive system and secondary sex characteristics. By a direct action, they cause growth and development of the uterus, fallopian tubes, and vagina. With other hormones, such as pituitary hormones and progesterone, they cause enlargement of the breasts through promotion of ductal growth, stromal development, and the accretion of fat. Estrogens are intricately involved with other hormones, especially progesterone, in the processes of the ovulatory menstrual cycle and pregnancy, and affect the release of pituitary gonadotropins. They also contribute to the shaping of the skeleton, maintenance of tone and elasticity of urogenital structures, changes in the epiphyses of the long bones that allow for the pubertal growth spurt and its termination, and pigmentation of the nipples and genitals.
Estrogens occur naturally in several forms. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 micrograms of estradiol daily, depending on the phase of the menstrual cycle. This is converted primarily to estrone, which circulates in roughly equal proportion to estradiol, and to small amounts of estriol. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone – especially in its sulfate ester form – is the most abundant circulating estrogen in postmenopausal women. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than estrone or estriol at the receptor.
Estrogens used in therapy are well absorbed through the skin, mucous membranes, and gastrointestinal tract. When applied for a local action, absorption is usually sufficient to cause systemic effects. When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks.
Administered estrogens and their esters are handled within the body essentially the same as the endogenous hormones. Metabolic conversion of estrogens occurs primarily in the liver (first pass effect), but also at local target tissue sites. Complex metabolic processes result in a dynamic equilibrium of circulating conjugated and unconjugated estrogenic forms which are continually interconverted, especially between estrone and estradiol and between esterified and unesterified forms. Although naturally-occurring estrogens circulate in the blood largely bound to sex hormone-binding globulin and albumin, only unbound estrogens enter target tissue cells. A significant proportion of the circulating estrogen exists as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogenic species. A certain proportion of the estrogen is excreted into the bile and then reabsorbed from the intestine. During this enterohepatic recirculation, estrogens are desulfated and resulfated and undergo degradation through conversion to less active estrogens (estriol and other estrogens), oxidation to nonestrogenic substances (catecholestrogens, which interact with catecholamine metabolism, especially in the central nervous system), and conjugation with glucuronic acids (which are then rapidly excreted in the urine).
When given orally, naturally-occurring estrogens and their esters are extensively metabolized (first pass effect) and circulate primarily as estrone sulfate, with smaller amounts of other conjugated and unconjugated estrogenic species. This results in limited oral potency. By contrast, synthetic estrogens, such as ethinyl estradiol and the nonsteroidal estrogens, are degraded very slowly in the liver and other tissues, which results in their high intrinsic potency. Estrogen drug products administered by non-oral routes are not subject to first-pass metabolism, but also undergo significant hepatic uptake, metabolism, and enterohepatic recycling.
OGEN Vaginal Cream is indicated for the treatment of vulval and vaginal atrophy.
Estrogens should not be used in individuals with any of the following conditions:
OGEN Vaginal Cream (estropipate) is contraindicated in patients hypersensitive to its ingredients.
The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use – with increased risks of 15 to 24-fold for five to ten years or more. In three studies, persistence of risk was demonstrated for 8 to over 15 years after cessation of estrogen treatment. In one study a significant decrease in the incidence of endometrial cancer occurred six months after estrogen withdrawal. Concurrent progestin therapy may offset this risk but the overall health impact in postmenopausal women is not known (see PRECAUTIONS).
While the majority of studies have not shown an increased risk of breast cancer in women who have ever used estrogen replacement therapy, some have reported a moderately increased risk (relative risks of 1.3–2.0) in those taking higher doses or those taking lower doses for prolonged periods of time, especially in excess of 10 years. Other studies have not shown this relationship.
Estrogen therapy during pregnancy is associated with an increased risk of fetal congenital reproductive tract disorders, and possibly other birth defects. Studies of women who received DES during pregnancy have shown that female offspring have an increased risk of vaginal adenosis, squamous cell dysplasia of the uterine cervix, and clear cell vaginal cancer later in life; male offspring have an increased risk of urogenital abnormalities and possibly testicular cancer later in life. Although some of these changes are benign, others are precursors of malignancy.
Two studies have reported a 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in women receiving postmenopausal estrogens.
Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis. These risks cannot necessarily be extrapolated from men to women. However, to avoid the theoretical cardiovascular risk to women caused by high estrogen doses, the dose for estrogen replacement therapy should not exceed the lowest effective dose.
Occasional blood pressure increases during estrogen replacement therapy have been attributed to idiosyncratic reactions to estrogens. More often, blood pressure has remained the same or has dropped. One study showed that postmenopausal estrogen users have higher blood pressure than nonusers. Two other studies showed slightly lower blood pressure among estrogen users compared to nonusers. Postmenopausal estrogen use does not increase the risk of stroke. Nonetheless, blood pressure should be monitored at regular intervals with estrogen use.
Administration of estrogens may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If this occurs, the drug should be stopped and appropriate measures taken to reduce the serum calcium level.
Studies of the addition of a progestin for seven or more days of a cycle of estrogen administration have reported a lowered incidence of endometrial hyperplasia which would otherwise be induced by estrogen treatment. Morphological and biochemical studies of endometrium suggest that 10 to 14 days of progestin are needed to provide maximal maturation of the endometrium and to eliminate any hyperplastic changes. There are possible additional risks which may be associated with the inclusion of progestins in estrogen replacement regimens. These include: (1) adverse effects on lipoprotein metabolism (lowering HDL and raising LDL) which may diminish the possible cardioprotective effect of estrogen therapy (see PRECAUTIONS, D.4., below); (2) impairment of glucose tolerance; and (3) possible enhancement of mitotic activity in breast epithelial tissue (although few epidemiological data are available to address this point). The choice of progestin, its dose, and its regimen may be important in minimizing these adverse effects, but these issues remain to be clarified.
A complete medical and family history should be taken prior to the initiation of any estrogen therapy. The pretreatment and periodic physical examinations should include special reference to blood pressure, breasts, abdomen, and pelvic organs, and should include a Papanicolaou smear. As a general rule, estrogen should not be prescribed for longer than one year without reexamining the patient.
Some studies have shown that women taking estrogen replacement therapy have hypercoagulability, primarily related to decreased antithrombin activity. This effect appears dose- and duration-dependent and is less pronounced than that associated with oral contraceptive use. Also, postmenopausal women tend to have increased coagulation parameters at baseline compared to premenopausal women. There is some suggestion that low dose postmenopausal mestranol may increase the risk of thromboembolism, although the majority of studies (of primarily conjugated estrogens users) report no such increase. There is insufficient information on hypercoagulability in women who have had previous thromboembolic disease.
Estrogen therapy may be associated with massive elevations of plasma triglycerides leading to pancreatitis and other complications in patients with familial defects of lipoprotein metabolism.
Because estrogens may cause some degree of fluid retention, conditions which might be exacerbated by this factor, such as asthma, epilepsy, migraine, and cardiac or renal dysfunction, require careful observation.
Certain patients may develop undesirable manifestations of estrogenic stimulation, such as abnormal uterine bleeding and mastodynia.
Estrogen may be poorly metabolized in patients with impaired liver function and should be administered with caution.
See text of Patient Package Insert that appears after HOW SUPPLIED section.
Estrogen administration should generally be guided by clinical response at the smallest dose, rather than laboratory monitoring, for relief of symptoms for those indications in which symptoms are observable.
Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. See CONTRAINDICATIONS and WARNINGS sections.
Estrogens should not be used during pregnancy. See CONTRAINDICATIONS and boxed WARNING.
As a general principle, the administration of any drug to nursing mothers should be done only when clearly necessary since many drugs are excreted in human milk. In addition, estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk.
Hypersensitivity reactions, systemic effects such as breast tenderness, and rarely, withdrawal bleeding, have occurred with the use of topical estrogens. Local irritation (especially when prior inflammation is present) has occurred at initiation of therapy.
The following additional adverse reactions have been reported with estrogen therapy (see WARNINGS regarding induction of neoplasia, adverse effects on the fetus, increased incidence of gallbladder disease, cardiovascular disease, elevated blood pressure, and hypercalcemia).
Serious ill effects have not been reported following acute ingestion of large doses of estrogen-containing oral contraceptives by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.
Attempts to discontinue or taper medication should be made at 3-month to 6-month intervals.
Intravaginally, 2 to 4 grams of OGEN Vaginal Cream daily, depending upon the severity of the condition.
The following instructions for use are intended for the patient and are printed on the carton label for OGEN Vaginal Cream (estropipate):
Between uses, pull plunger out of barrel and wash applicator in warm, soapy water. DO NOT PUT APPLICATOR IN HOT OR BOILING WATER.
OGEN (estropipate vaginal cream, USP), 1.5 mg estropipate per gram, is available in packages containing a 1½ oz (42.5 g) tube with one plastic applicator calibrated at 1, 2, 3, and 4 g levels, (NDC 0009-3776-01).
Store below 86° F (30° C).
Rx only
INTRODUCTION
This leaflet describes when and how to use estrogens, and the risks and benefits of estrogen treatment.
Estrogens have important benefits but also some risks. You must decide, with your doctor, whether the risks to you of estrogen use are acceptable because of their benefits. If you use estrogens, check with your doctor to be sure you are using the lowest possible dose that works, and that you don't use them longer than necessary. How long you need to use estrogens will depend on the reason for use.
ESTROGENS INCREASE THE RISK OF CANCER OF THE UTERUS IN WOMEN WHO HAVE HAD THEIR MENOPAUSE ("CHANGE OF LIFE").
If you use any estrogen-containing drug, it is important to visit your doctor regularly and report any unusual vaginal bleeding right away. Vaginal bleeding after menopause may be a warning sign of uterine cancer. Your doctor should evaluate any unusual vaginal bleeding to find out the cause.
ESTROGENS SHOULD NOT BE USED DURING PREGNANCY.
Estrogens do not prevent miscarriage (spontaneous abortion) and are not needed in the days following childbirth. If you take estrogens during pregnancy, your unborn child has a greater than usual chance of having birth defects. The risk of developing these defects is small, but clearly larger than the risk in children whose mothers did not take estrogens during pregnancy. These birth defects may affect the baby's urinary system and sex organs. Daughters born to mothers who took DES (an estrogen drug) have a higher than usual chance of developing cancer of the vagina or cervix when they become teenagers or young adults. Sons may have a higher than usual chance of developing cancer of the testicles when they become teenagers or young adults.
(Not every estrogen drug is approved for every use listed in this section. If you want to know which of these possible uses are approved for the medicine prescribed for you, ask your doctor or pharmacist to show you the professional labeling. You can also look up the specific estrogen product in a book called the "Physicians' Desk Reference," which is available in many book stores and public libraries. Generic drugs carry virtually the same labeling information as their brand name versions.)
+ To reduce moderate or severe menopausal symptoms. Estrogens are hormones made by the ovaries of normal women. Between ages 45 and 55, the ovaries normally stop making estrogens. This leads to a drop in body estrogen levels which causes the "change of life" or menopause (the end of monthly menstrual periods). If both ovaries are removed during an operation before natural menopause takes place, the sudden drop in estrogen levels causes "surgical menopause."
When the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating ("hot flashes" or "hot flushes"). Using estrogen drugs can help the body adjust to lower estrogen levels and reduce these symptoms. Most women have only mild menopausal symptoms or none at all and do not need to use estrogen drugs for these symptoms. Others may need to take estrogens for a few months while their bodies adjust to lower estrogen levels. The majority of women do not need estrogen replacement for longer than six months for these symptoms.
+ To treat vulval and vaginal atrophy (itching, burning, dryness in or around the vagina, difficulty or burning on urination) associated with menopause.
+ To treat certain conditions in which a young woman's ovaries do not produce enough estrogen naturally.
+ To treat certain types of abnormal vaginal bleeding due to hormonal imbalance when your doctor has found no serious cause of the bleeding.
+ To treat certain cancers in special situations, in men and women.
+ To prevent thinning of bones. Osteoporosis is a thinning of the bones that makes them weaker and allows them to break more easily. The bones of the spine, wrists and hips break most often in osteoporosis. Both men and women start to lose bone mass after about age 40, but women lose bone mass faster after the menopause. Using estrogens after the menopause slows down bone thinning and may prevent bones from breaking. Lifelong adequate calcium intake, either in the diet (such as dairy products) or by calcium supplements (to reach a total daily intake of 1000 milligrams per day before menopause or 1500 milligrams per day after menopause), may help to prevent osteoporosis. Regular weight-bearing exercise (like walking and running for an hour, two or three times a week) may also help to prevent osteoporosis. Before you change your calcium intake or exercise habits, it is important to discuss these lifestyle changes with your doctor to find out if they are safe for you.
Since estrogen use has some risks, only women who are likely to develop osteoporosis should use estrogens for prevention. Women who are likely to develop osteoporosis often have the following characteristics: white or Asian race, slim, cigarette smokers, and a family history of osteoporosis in a mother, sister, or aunt. Women who have relatively early menopause, often because their ovaries were removed during an operation ("surgical menopause"), are more likely to develop osteoporosis than women whose menopause happens at the average age.
WHO SHOULD NOT USE ESTROGENS
Estrogens should not be used:
+ During pregnancy (see boxed WARNING). If you think you may be pregnant, do not use any form of estrogen-containing drug. Using estrogens while you are pregnant may cause your unborn child to have birth defects. Estrogens do not prevent miscarriage.
+ If you have unusual vaginal bleeding which has not been evaluated by your doctor (see boxed WARNING). Unusual vaginal bleeding can be a warning sign of cancer of the uterus, especially if it happens after menopause. Your doctor must find out the cause of the bleeding so that he or she can recommend the proper treatment. Taking estrogens without visiting your doctor can cause you serious harm if your vaginal bleeding is caused by cancer of the uterus.
+ If you have had cancer. Since estrogens increase the risk of certain types of cancer, you should not use estrogens if you have ever had cancer of the breast or uterus, unless your doctor recommends that the drug may help in the cancer treatment. (For certain patients with breast or prostate cancer, estrogens may help.)
+ If you have any circulation problems. Estrogen drugs should not be used except in unusually special situations in which your doctor judges that you need estrogen therapy so much that the risks are acceptable. Men and women with abnormal blood clotting conditions should avoid estrogen use (see DANGERS OF ESTROGENS, below).
+ When they do not work. During menopause, some women develop nervous symptoms or depression. Estrogens do not relieve these symptoms. You may have heard that taking estrogens for years after menopause will keep your skin soft and supple and keep you feeling young. There is no evidence for these claims and such long-term estrogen use may have serious risks.
+ After childbirth or when breastfeeding a baby. Estrogens should not be used to try to stop the breasts from filling with milk after a baby is born. Such treatment may increase the risk of developing blood clots (see DANGERS OF ESTROGENS, below).
If you are breastfeeding, you should avoid using any drugs because many drugs pass through to the baby in the milk. While nursing a baby, you should take drugs only on the advice of your health care provider.
+ Cancer of the uterus. Your risk of developing cancer of the uterus gets higher the longer you use estrogens and the larger doses you use. One study showed that after women stop taking estrogens, this higher cancer risk quickly returns to the usual level of risk (as if you had never used estrogen therapy). Three other studies showed that the cancer risk stayed high for 8 to more than 15 years after stopping estrogen treatment. Because of this risk, IT IS IMPORTANT TO TAKE THE LOWEST DOSE THAT WORKS AND TO TAKE IT ONLY AS LONG AS YOU NEED IT.
Using progestin therapy together with estrogen therapy may reduce the higher risk of uterine cancer related to estrogen use (but see OTHER INFORMATION, below).
If you have had your uterus removed (total hysterectomy), there is no danger of developing cancer of the uterus.
+ Cancer of the breast. Most studies have not shown a higher risk of breast cancer in women who have ever used estrogens. However, some studies have reported that breast cancer developed more often (up to twice the usual rate) in women who used estrogens for long periods of time (especially more than 10 years), or who used higher doses for shorter time periods.
Regular breast examinations by a health professional and monthly self-examination are recommended for all women.
+ Gallbladder disease. Women who use estrogens after menopause are more likely to develop gallbladder disease needing surgery than women who do not use estrogens.
+ Abnormal blood clotting. Taking estrogens may cause changes in your blood clotting system. These changes allow the blood to clot more easily, possibly allowing clots to form in your bloodstream. If blood clots do form in your bloodstream, they can cut off the blood supply to vital organs, causing serious problems. These problems may include a stroke (by cutting off blood to the brain), a heart attack (by cutting off blood to the heart), a pulmonary embolus (by cutting off blood to the lungs), or other problems. Any of these conditions may cause death or serious long-term disability. However, most studies of low dose estrogen usage by women do not show an increased risk of these complications.
SIDE EFFECTS
In addition to the risks listed above, the following side effects have been reported with estrogen use:
REDUCING RISK OF ESTROGEN USE
If you use estrogens, you can reduce your risks by doing these things:
+ See your doctor regularly. While you are using estrogens, it is important to visit your doctor at least once a year for a check-up. If you develop vaginal bleeding while taking estrogens, you may need further evaluation. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram (breast X-ray), you may need to have more frequent breast examinations.
+ Reassess your need for estrogens. You and your doctor should reevaluate whether or not you still need estrogens at least every six months.
+ Be alert for signs of trouble. If any of these warning signals (or any other unusual symptoms) happen while you are using estrogens, call your doctor immediately:
Some doctors may choose to prescribe a progestin, a different hormonal drug, for you to take together with your estrogen treatment. Progestins lower your risk of developing endometrial hyperplasia (a possible pre-cancerous condition of the uterus) while using estrogens. Taking estrogens and progestins together may also protect you from the higher risk of uterine cancer, but this has not been clearly established. Combined use of progestin and estrogen treatment may have additional risks, however. The possible risks include unhealthy effects on blood fats (especially a lowering of HDL cholesterol, the "good" blood fat which protects against heart disease risk), unhealthy effects on blood sugar (which might worsen a diabetic condition), and a possible further increase in the breast cancer risk which may be associated with long-term estrogen use. The type of progestin drug used and its dosage schedule may be important in minimizing these effects.
Your doctor has prescribed this drug for you and you alone. Do not give the drug to anyone else.
If you will be taking calcium supplements as part of the treatment to help prevent osteoporosis, check with your doctor about how much to take.
Keep this and all drugs out of the reach of children. In case of overdose, call your doctor, hospital or poison control center immediately.
This leaflet provides a summary of the most important information about estrogens. If you want more information, ask your doctor or pharmacist to show you the professional labeling. The professional labeling is also published in a book called the "Physicians' Desk Reference," which is available in book stores and public libraries. Generic drugs carry virtually the same labeling information as their brand name versions.
HOW SUPPLIED
OGEN (estropipate vaginal cream, USP), 1.5 mg estropipate per gram, is available in packages containing a 1½ oz (42.5 g) tube with one plastic applicator calibrated at 1, 2, 3, and 4 g levels, (NDC 0009-3776-01).
RECOMMENDED STORAGE: Store below 86° F (30° C).
Rx only
Manufactured by
Abbott Laboratories,
North Chicago, IL 60064, USA
LAB-0092-2.0
July 2006
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In the US, Itch-X (hydrocortisone topical) is a member of the drug class topical anesthetics and is used to treat Anal Itching and Pruritus.
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Pramocaine hydrochloride (a derivative of Pramocaine) is reported as an ingredient of Itch-X in the following countries:
International Drug Name Search
