Jimrost may be available in the countries listed below.
Manidipine dihydrochloride (a derivative of Manidipine) is reported as an ingredient of Jimrost in the following countries:
International Drug Name Search
Geodon is an atypical antipsychotic. It may increase the risk of death when used to treat mental problems caused by dementia in elderly patients. Most of the deaths were linked to heart problems or infection. Geodon is not approved to treat mental problems caused by dementia. Discuss any questions or concerns with your doctor.
Treating acute agitation in patients with schizophrenia who require an injectable medicine. It may also be used for other conditions as determined by your doctor.
Geodon is an antipsychotic. It may work by altering the balance of certain chemicals that occur naturally in the brain, which are responsible for thinking and behavior.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Geodon. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Geodon. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Geodon may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Geodon as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Geodon.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Anxiety; constipation; diarrhea; dizziness; drowsiness; dry mouth; feeling unusually tired or sleepy; headache; increased cough or runny nose; loss of appetite; nausea; pain at the injection site; restlessness; upset stomach; vomiting; weakness; weight gain.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; change in amount of urine produced; confusion; decreased sexual ability; difficulty speaking or swallowing; enlarged breasts; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; inability to move; missed menstrual period; muscle rigidity; muscle spasms or twitching; nipple discharge; pounding in the chest; prolonged or painful erection; seizures; shortness of breath; suicidal thoughts or attempts; sweating; symptoms of high blood sugar (increased thirst, increased urination, confusion, flushing, rapid breathing, or fruity breath odor); tremor; uncontrolled movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual mood or mental changes; vision changes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Geodon side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; irregular heartbeat; seizure; slurring of speech; uncontrolled movement of the head and neck.
Geodon is usually handled and stored by a health care provider. If you are using Geodon at home, store Geodon as directed by your pharmacist or health care provider. Keep Geodon, as well as needles and syringes, out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Geodon. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Treating diabetes mellitus.
Novolin N Vials are an intermediate-acting form of the hormone insulin. It works by helping your body to use sugar properly. This lowers the amount of glucose in the blood, which helps to treat diabetes.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Novolin N Vials. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Novolin N Vials. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Novolin N Vials may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Novolin N Vials as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Novolin N Vials.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Redness, swelling, itching, or mild pain at the injection site.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain); changes in vision; chills; confusion; dizziness; drowsiness; fainting; fast or irregular heartbeat; headache; loss of consciousness; mood changes; seizures; slurred speech; swelling; tremor; trouble breathing; trouble concentrating; unusual hunger; unusual sweating; weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Novolin N side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center or emergency room immediately. Symptoms may include chills; dizziness; drowsiness; fainting; fast or irregular heartbeat; headache; loss of consciousness; nervousness; seizures; shakiness; sweating; tremor; vision changes; weakness.
Store new (unopened) vials in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. Certain brands of the medicine may be stored at room temperature, below 77 degrees F (25 degrees C) for up to 6 weeks (42 days), if refrigeration is not possible. Check with your pharmacist to see if your brand can be stored at room temperature. Keep Novolin N Vials in the carton to protect from light.
Store used (open) vials as directed in the extra patient leaflet or by your health care provider. Check with your pharmacist to see how long unrefrigerated or opened vials may be used. Store away from heat and light. If Novolin N Vials has been frozen or overheated, throw it away.
Do not leave Novolin N Vials in a car on a warm or sunny day. Do not use Novolin N Vials after the expiration date stamped on the label. Keep Novolin N Vials, as well as syringes and needles, out of the reach of children and away from pets. If Novolin N Vials has been mixed with other medicines, you may need to store it differently. Ask your doctor, pharmacist, or other health care provider how to store Novolin N Vials.
This information is a summary only. It does not contain all information about Novolin N Vials. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Necon® 1/50 Tablets provide a continuous oral contraceptive regimen consisting of 21 white tablets containing norethindrone 1 mg and mestranol 0.05 mg and 7 orange tablets containing inert ingredients.
Norethindrone is a potent progestational agent with the chemical name 17-Hydroxy-19-Nor-17α-pregn-4-en-20-yn-3-one. Mestranol is an estrogen with the chemical name 3-Methoxy-19-nor-17α-pregna-1,3,5(10)-trien-20-yn-17-ol. Their structural formulae follow:
The white Necon® 1/50 tablets contain the following inactive ingredients: lactose, magnesium stearate, povidone, and starch.
The inactive orange tablets contain the following ingredients: FD&C Yellow No. 6, lactose, microcrystalline cellulose, and magnesium stearate.
Combination oral contraceptives act by suppression of gonadotrophins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which may reduce the likelihood of implantation).
Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.
Oral contraceptive products such as Necon® 1/50, which contain 50 mcg of estrogen, should not be used unless medically indicated.
Oral contraceptives are highly effective. Table l lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception.1 The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
| % of Women Experiencing an Unintended | % of Women | ||
| Pregnancy within the First Year of Use | Continuing Use | ||
| at One Year3 | |||
| Method | Typical use1 | Perfect use2 | |
| (1) | (2) | (3) | (4) |
| Source: Trussell J. Contraceptive Efficacy Table from Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, in Contraceptive Technology: Seventeenth Revised Edition. New York, NY: Irvington Publishers, 1998. | |||
| 1 Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. | |||
| 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. | |||
| 3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. | |||
| 4 The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. | |||
| 5 Foams, creams, gels, vaginal suppositories, and vaginal film. | |||
| 6 Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. | |||
| 7 With spermicidal cream or jelly. | |||
| 8 Without spermicides. | |||
| 9 The treatment schedule is one dose within 72 hours after unprotected intercourse and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral (1 dose is 2 white pills), Aleese (1 dose is 5 pink pills), Nordette or Levlen (1 dose is 2 light-orange pills), Lo/Ovral (1 dose is 4 white pills), Triphasil or Tri-Levlen (1 dose is 4 yellow pills). | |||
| 10 However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches six months of age. | |||
| Chance4 | 85 | 85 | |
| Spermicides5 | 26 | 6 | 40 |
| Periodic abstinence | 25 | 63 | |
| Calendar | 9 | ||
| Ovulation method | 3 | ||
| Sympto-thermal6 | 2 | ||
| Post-ovulation | 1 | ||
| Withdrawal | 19 | 4 | |
| Cap7 | |||
| Parous women | 40 | 26 | 42 |
| Nulliparous women | 20 | 9 | 56 |
| Sponge | |||
| Parous women | 40 | 20 | 42 |
| Nulliparous women | 20 | 9 | 56 |
| Diaphragm7 | 20 | 6 | 56 |
| Condom8 | |||
| Female (Reality) | 21 | 5 | 56 |
| Male | 14 | 3 | 61 |
| Pill | 5 | 71 | |
| Progestin only | 0.5 | ||
| Combined | 0.1 | ||
| IUD | |||
| Progesterone T | 2.0 | 1.5 | 81 |
| Copper T 380A | 0.8 | 0.6 | 78 |
| LNg 20 | 0.1 | 0.1 | 81 |
| Depo-Provera | 0.3 | 0.3 | 70 |
| Norplant and Norplant-2 | 0.05 | 0.05 | 88 |
| Female sterilization | 0.5 | 0.5 | 100 |
| Male sterilization | 0.15 | 0.10 | 100 |
| Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.9 | |||
| Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception.10 | |||
Oral contraceptives should not be used in women who have the following conditions:
Thrombophlebitis or thromboembolic disorders
A past history of deep vein thrombophlebitis or thromboembolic disorders
Cerebral vascular or coronary artery disease
Known or suspected carcinoma of the breast
Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
Undiagnosed abnormal genital bleeding
Cholestatic jaundice of pregnancy or jaundice with prior pill use
Hepatic adenomas, carcinomas or benign liver tumors
Known or suspected pregnancy
| Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives are strongly advised not to smoke. |
Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks.
The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of both estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined.
Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease. Relative risk, the ratio of the incidence of a disease among oral contraceptive users to that among non-users, cannot be assessed directly from case control studies, but the odds ratio obtained is a measure of relative risk. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide not only a measure of relative risk but a measure of attributable risk, which is the difference in the incidence of disease between the oral contraceptive users and non-users. The attributable risk does provide information about the actual occurrence of a disease in the population (adapted from ref. 12 and 13 with the author’s permission). For further information, the reader is referred to a text on epidemiological methods.
An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity and diabetes.2–5, 13 The relative risk of heart attack for current oral contraceptive users has been estimated to be 2 to 6.2, 14–19 The risk is very low under the age of 30. However, there is the possibility of a risk of cardiovascular disease even in very young women who take oral contraceptives.
Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older, with smoking accounting for the majority of excess cases.20
Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and non-smokers over the age of 40 among women who use oral contraceptives (see Table II).16
| Adapted from P.M. Layde and V. Beral, Table V16 |
Oral contraceptives may compound the effects of well-known risk factors such as hypertension, diabetes, hyperlipidemias, hypercholesterolemia, age and obesity.3, 13, 21 In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism.21–25 Oral contraceptives have been shown to increase blood pressure among users (see WARNINGS, section 9). Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.
An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease.12, 13, 26–31 Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization.32
The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped.12
A 2- to 6-fold increase in relative risk of post-operative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions.83 If feasible, oral contraceptives should be discontinued at least 4 weeks prior to and for 2 weeks after elective surgery and during and following prolonged immobilization. Since the immediate postpartum period also is associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than 4 to 6 weeks after delivery in women who elect not to breast feed.33
An increase in both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes) has been shown in users of oral contraceptives. In general, the risk is greatest among older (>35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and non-users for both types of strokes while smoking interacted to increase the risk for hemorrhagic strokes.34
In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension.35 The relative risk of hemorrhagic stroke is reported to be 1.2 for non-smokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users, and 25.7 for users with severe hypertension.35 The attributable risk also is greater in women in their mid-thirties or older and among smokers.13
A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease.36–38 A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents.22–24 A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease.39 Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptives. The amount of both hormones should be considered in the choice of an oral contraceptive.37
Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on preparations containing the lowest estrogen content that produces satisfactory results for the individual.
Products containing 50 mcg estrogen should be used only when medically indicated.
There are three studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives.17, 34, 40 In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40–49 years who had used oral contraceptives for 5 or more years, but this increased risk was not demonstrated in other age groups.17 In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small.40 There is a significantly increased relative risk of subarachnoid hemorrhage after termination of use of oral contraceptives.34 However, these studies were performed with oral contraceptive formulations containing 50 mcg or higher of estrogen.
One study gathered data from a variety of sources which have estimated the mortality rates associated with different methods of contraception at different ages (see Table III).41 These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970s – but not reported in the U.S. until 1983.16, 41 However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling.
Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed,78, 79 the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.
Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.80
| Method of control | 15–19 | 20–24 | 25–29 | 30–34 | 35–39 | 40–44 |
| and outcome | ||||||
| Estimates adapted from H.W. Ory, Table 341 | ||||||
| No fertility control | 7.0 | 7.4 | 9.1 | 14.8 | 25.7 | 28.2 |
| methods* | ||||||
| Oral contraceptives | 0.3 | 0.5 | 0.9 | 1.9 | 13.8 | 31.6 |
| non-smoker** | ||||||
| Oral contraceptives smoker** | 2.2 | 3.4 | 6.6 | 13.5 | 51.1 | 117.2 |
| IUD** | 0.8 | 0.8 | 1.0 | 1.0 | 1.4 | 1.4 |
| Condom* | 1.1 | 1.6 | 0.7 | 0.2 | 0.3 | 0.4 |
| Diaphragm/Spermicide* | 1.9 | 1.2 | 1.2 | 1.3 | 2.2 | 2.8 |
| Periodic abstinence* | 2.5 | 1.6 | 1.6 | 1.7 | 2.9 | 3.6 |
| * Deaths are birth-related | ||||||
| ** Deaths are method-related | ||||||
Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. The overwhelming evidence in the literature suggests that use of oral contraceptives is not associated with an increase in the risk of developing breast cancer, regardless of the age and parity of first use or with most of the marketed brands and doses.42-44 The Cancer and Steroid Hormone (CASH) study also showed no latent effect on the risk of breast cancer for at least a decade following long-term use.43 A few studies have shown a slightly increased relative risk of developing breast cancer,44–47 although the methodology of these studies, which included differences in examination of users and non-users and differences in age at start of use, has been questioned.47–49 Some studies have reported an increased relative risk of developing breast cancer, particularly at a younger age. This increased relative risk appears to be related to duration of use.81, 82
Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women.50–53 However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
In spite of many studies of the relationship between oral contraceptive use and breast or cervical cancers, a cause and effect relationship has not been established.
Benign hepatic adenomas are associated with oral contraceptive use although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases per 100,000 for users, a risk that increases after 4 or more years of use.54 Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.55–56
Studies in the United States and Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users.57–59 However, these cancers are rare in the U.S.
There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately.
Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy.60–62 Studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy.60, 61, 63, 64
The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion.
It is recommended that for any patient who has missed 2 consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed.
Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens.65–66 More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal.67 The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens.68
Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users.25 Oral contraceptives containing greater than 75 mcg of estrogen cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance.70 Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents.25, 71 However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose.69 Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives.
Some women may develop persistent hypertriglyceridemia while on the pill.72 As discussed earlier (see WARNINGS, sections 1a. and 1d.), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users.23
An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use.73, 84 Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens.
Women with a history of hypertension or hypertension-related diseases or renal disease should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives and there is no difference in the occurrence of hypertension among ever- and never-users.73–75
The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause.
Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first 3 months of use. Non-hormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out.
Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was pre-existent.
Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.
Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult.
If jaundice develops in any woman receiving oral contraceptives the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function.
Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.
Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.
Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.
Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin and tetracyclines.76
Certain endocrine and liver function tests and blood components may be affected by oral contraceptives:
a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
b. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radio immunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 concentration is unaltered.
c. Other binding proteins may be elevated in serum.
d. Sex steroid binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
e. Triglycerides may be increased.
f. Glucose tolerance may be decreased.
g. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.
See WARNINGS section.
Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS sections.
Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child.
Safety and efficacy have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of the product before menarche is not indicated.
INFORMATION FOR THE PATIENT
See PATIENT LABELING printed below.
An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):
Thrombophlebitis
Arterial thromboembolism
Pulmonary embolism
Myocardial infarction
Cerebral hemorrhage
Cerebral thrombosis
Hypertension
Gallbladder disease
Hepatic adenomas, carcinomas or benign liver tumors
There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed:
Mesenteric thrombosis
Retinal thrombosis
The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related:
Nausea
Vomiting
Gastrointestinal symptoms (such as abdominal cramps and bloating)
Breakthrough bleeding
Spotting
Change in menstrual flow
Amenorrhea
Temporary infertility after discontinuation of treatment
Edema
Melasma which may persist
Breast changes: tenderness, enlargement, secretion
Change in weight (increase or decrease)
Change in cervical erosion and secretion
Diminution in lactation when given immediately postpartum
Cholestatic jaundice
Migraine
Rash (allergic)
Mental depression
Reduced tolerance to carbohydrates
Vaginal candidiasis
Change in corneal curvature (steepening)
Intolerance to contact lenses
The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted:
Pre-menstrual syndrome
Cataracts
Changes in appetite
Cystitis-like syndrome
Headache
Nervousness
Dizziness
Hirsutism
Loss of scalp hair
Erythema multiforme
Erythema nodosum
Hemorrhagic eruption
Vaginitis
Porphyria
Impaired renal function
Hemolytic uremic syndrome
Budd-Chiari syndrome
Acne
Changes in libido
Colitis
Serious ill effects have not been reported foll
Generic Name: aliskiren and valsartan (a LIS ke rin and val SAR tan)
Brand Names: Valturna
Aliskiren is an anti-hypertensive (blood pressure lowering) medication. It works by decreasing substances in the body that narrow blood vessels and raise blood pressure.
Valsartan is in a group of drugs called angiotensin II receptor antagonists. Valsartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.
The combination of aliskiren and valsartan is used to treat high blood pressure (hypertension).
Aliskiren and valsartan may also be used for purposes not listed in this medication guide.
Before you take aliskiren and valsartan, tell your doctor if you have kidney or liver disease, high levels of potassium in your blood (hyperkalemia), heart disease or recent heart attack, congestive heart failure, or if you are on a low-salt diet.
If you take aliskiren and valsartan with meals, avoid high-fat foods. They can make it harder for your body to absorb aliskiren and valsartan.
Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking aliskiren and valsartan. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.
To make sure you can safely take aliskiren and valsartan, tell your doctor if you have any of these other conditions:
kidney disease (or if you are on dialysis);
liver disease;
high levels of potassium in your blood (hyperkalemia);
congestive heart failure;
heart disease or recent heart attack; or
if you are on a low-salt diet.
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Your doctor may occasionally change your dose to make sure you get the best results.
You may take aliskiren and valsartan with or without food, but take it the same way every time.
If you take aliskiren and valsartan with meals, avoid high-fat foods. They can make it harder for your body to absorb aliskiren and valsartan.
Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking aliskiren and valsartan. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.
See also: Valturna dosage (in more detail)
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
Overdose symptoms may include fast or slow heart rate, feeling light-headed, or fainting.
Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.
feeling like you might pass out; or
slow heart rate, weak pulse, muscle weakness, tingly feeling.
Less serious side effects may be more likely to occur, such as:
tired feeling;
stuffy nose, sore throat, cough;
stomach pain or upset, diarrhea, heartburn;
numbness or tingly feeling; or
muscle cramps.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Tell your doctor about all other medications you use, especially other blood pressure medications, or:
atorvastatin (Lipitor);
a diuretic (water pill) such as furosemide (Lasix);
an antibiotic such as ketoconazole (Nizoral) or rifampin (Rifater, Rifadin, Rifamate);
a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others;
a potassium supplement such as K-Dur, Klor-Con; or
salt substitutes that contain potassium.
This list is not complete and other drugs may interact with aliskiren and valsartan. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
See also: Valturna side effects (in more detail)
Trinovum Oral Contraceptive Tablets
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Tablets
Oral contraception and the recognised indications for such oestrogen/progestogen combinations. .
For oral administration.
4.2.1 Adults
How to take Trinovum:
One tablet is taken daily at the same time (preferably in the evening) without interruption for 21 days, followed by a break of 7 tablet-free days. (A white tablet is taken every day for 7 days, then a light peach coloured tablet is taken every day for 7 days, then a peach coloured tablet every day for 7 days, then 7 tablet-free days. Each subsequent pack is started after the 7 tablet-free days have elapsed. Additional contraceptive precautions are not then required. During the tablet-free period, bleeding can be expected, usually beginning 2 to 4 days after the last tablet.
Starting treatment:
It is preferable that tablet intake from the first pack is started up to and including day 5 of menstruation in which case no extra contraceptive precautions are necessary.
Trinovum can be started at any other time, if pregnancy can reasonably be excluded. In this case additional contraceptive precautions must be taken for the first 7 days of tablet taking.
Switching from another contraceptive
Hormonal methods: Trinovum can be started immediately if the patient has been using the current hormonal method consistently and correctly, or if pregnancy can reasonably be excluded. There is no need to wait for the next menstruation. Additional contraceptive precautions are not required.
Non-hormonal methods: If Trinovum is started after the first 5 days of menstruation, additional contraceptive precautions are required for the next 7 days.
Post-partum administration
Following a vaginal delivery, oral contraceptive administration to non-breast-feeding mothers can be started 21 days post-partum provided the patient is fully ambulant and there are no puerperal complications. No additional contraceptive precautions are required. If post-partum administration begins more than 21 days after delivery, additional contraceptive precautions are required for the first 7 days of pill-taking.
If intercourse has taken place post-partum, oral contraceptive use should be delayed until the first day of the first menstrual period.
For information on breast-feeding mothers, see sections 4.3, 4.4 and 4.6.
Use after Abortion or Miscarriage
After an abortion or miscarriage that occurs prior to 24 weeks gestation, oral contraceptives can be started immediately. An additional method of contraception is not needed.
After an induced or spontaneous abortion that occurs at or after 24 weeks gestation, hormonal contraceptives may be started either on Day 21 post-abortion or on the first day of the first spontaneous menstruation, whichever comes first. No additional contraceptive precautions are required.
To skip a period
To skip a period, a new pack of Trinovum should be started on the day after finishing the current pack (the patient skips the tablet-free days). Tablet-taking should be continued in the usual way.
During the use of the second pack she may experience slight spotting or break-through bleeding but contraceptive protection will not be diminished provided there are no tablet omissions.
The next pack of Trinovum is started after the usual 7 tablet-free days, regardless of whether the period has completely finished or not.
Reduced reliability
When Trinovum is taken according to the directions for use, the occurrence of pregnancy is highly unlikely. However, the reliability of oral contraceptives may be reduced under the following circumstances:
(i) Missed tablets
If the patient forgets to take one tablet or if a new strip is started one day late, she should take it as soon as she remembers and take the next tablet at the normal time. This may mean that two tablets are taken in one day. No additional contraceptive precautions are required.
If more than one tablet is missed or if a new strip is started more than one day late, she should take the last missed tablet as soon as she remembers but leave the other missed tablets in the strip. She should continue to take the rest of the strip as usual but must use extra precautions (e.g. condom, diaphragm, plus spermicide) for the next 7 days.
If the tablets are missed:
• In week 1 If unprotected sex has taken place, the use of emergency contraception should be considered. The usual 7-day break can be left before starting the next strip.
• In week 2 The usual 7-day break can be left before starting the next strip.
• In week 3 When the strip is finished the next strip should be started the next day without a break. If withdrawal bleeding does not occur at the end of the second strip, a pregnancy test should be performed.
(ii) Vomiting or diarrhoea
If a patient vomits within two hours of taking a tablet she should take another tablet from a spare strip.
If severe vomiting or diarrhoea continues for more than 1 day, she should follow the procedure for missed tablets (and continue taking the tablets if she can).
4.2.2 Elderly
Use of this product is not indicated in post-menopausal women.
4.2.3 Children
Use of this product before menarche is not indicated.
− Breast-feeding mothers less than 6 weeks post-partum
− Venous thrombo-embolism (VTE) requiring concurrent anticoagulant therapy, personal history of confirmed VTE or known thrombogenic mutations.
− Major surgery with prolonged immobilisation.
− Moderate to severe hypertension (systolic
− Complicated valvular and congenital heart disease (e.g. with pulmonary hypertension, artrial fibrillation, history of subacute bacterial endocarditis)
− Migraine with focal aura.
− Diabetes with nephropathy/retinopathy/neuropathy or other vascular involvement or > 20 years' duration.
− Smoking 15 or more cigarettes per day in patients aged 35 years or more.
− Acute or chronic liver disease, including hepatitis (viral or non-viral) or severe cirrhosis, or a history of these conditions until at least 3 months after abnormal liver function tests have returned to normal; hepatic adenomas or carcinomas.
− Known or suspected carcinoma of the breast.
− Raynaud's disease, with Systemic Lupus Erythematosus (SLE) if lupus anticoagulant is present.
− Hypersensitivity to norethisterone or ethinylestradiol or to any of the excipients.
Should any of these conditions occur for the first time during use of Trinovum, the tablets should be discontinued immediately.
Assessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications (Section 4.3) and warnings for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.
Exclude likelihood of pregnancy before starting treatment.
Undiagnosed vaginal bleeding should be investigated further.
Oral contraceptives DO NOT protect against HIV infections (AIDS) or any other sexually transmitted disease.
Conditions requiring supervision:
The theoretical or proven risks usually outweigh the advantages of using Combined Oral Contraceptives (COCs) in the conditions listed below. Consequently the decision to prescribe the COC must be made with specialist clinical judgement and in consultation with the individual patient. If any of these conditions appears for the first time, or is aggravated, whilst the patient is taking Trinovum, consideration should be given to discontinuing its use.
− Non-breast-feeding mothers less than 21 days post-partum.
− Breast-feeding mothers 6 weeks to 6 months post-partum.
− Increased risk of venous thrombo-embolic disorders (See “Circulatory disorders” below).
− Presence of multiple risk factors for arterial disease (See “Circulatory disorders” below).
− Adequately controlled hypertension (persistently elevated baseline systolic values 140-159 mm Hg or diastolic values 90-94 mm Hg)
− Obesity (BMI 2)
− Past history (
− History of cholestasis (related to COCs), current or medically treated gall bladder disease, porphyria.
− History of breast cancer, 5 years disease-free.
− Diabetes mellitus with mild nephropathy, neuropathy or retinopathy.
Circulatory disorders
Venous Thrombo-Embolism (VTE)
An increased risk of venous thrombo-embolic disease (VTE) associated with the use of oral contraceptives is well established but is smaller than that associated with pregnancy, which has been estimated at 60 cases per 100,000 pregnancies. Some epidemiological studies have reported a greater risk of VTE for women using combined oral contraceptives containing desogestrel or gestodene (the so-called 'third generation' pills) than for women using pills containing levonorgestrel or norethisterone (the so-called 'second generation' pills).
The spontaneous incidence of VTE in healthy non-pregnant women (not taking any oral contraceptive) is about 5 cases per 100,000 per year. The incidence in users of second generation pills is about 15 per 100,000 women per year of use. The incidence in users of third generation pills is about 25 cases per 100,000 women per year of use; this excess incidence has not been satisfactorily explained by bias or confounding. The level of all of these risks of VTE increases with age and is likely to be further increased in women with other known risk factors for VTE such as obesity. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive.
The risk of venous thrombo-embolism increases with
− Increasing age
− Family history (VTE in first degree relative less than 45 years of age)
− Obesity (BMI 2)
− Prolonged immobilisation, major surgery, any surgery to the legs, major trauma. Hormonal contraception should be discontinued 4-6 weeks before elective surgery and not recommenced until two weeks after complete remobilisation. In case of emergency surgery, thrombotic prophylaxis is usually indicated e.g. with subcutaneous heparin.
There is no consensus about the role of varicose veins in VTE.
Symptoms of venous thrombotic or thrombo-embolic events can include:
• unusual unilateral leg pain and/or redness and swelling, typically of the calf
• sudden breathlessness or onset of coughing
• sudden partial or complete loss of vision.
Arterial thrombo-embolism
Epidemiological studies have also associated the use of COCs with an increased risk for arterial thrombo-embolism (e.g. myocardial infarction, transient ischaemic attack or stroke). This increased risk is likely to be extremely small in women who do not smoke and who do not have other risk factors of arterial thrombo-embolic complications (see below).
The risk of arterial thrombo-embolic complications increases with:
− Increasing age
− Smoking. The risk increases with age and with heavy smoking and is more marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.
− Obesity (BMI 2)
− Hyperlipidaemia
− Hypertension or a history of hypertension
− Valvular heart disease
− Atrial fibrillation
− Family history of arterial thrombo-embolic complications
− Diabetes mellitus
− Sickle cell haemoglobinopathy.
Symptoms of an arterial or cerebrovascular event can include:
• sudden severe pain in the chest, whether or not it radiates to the left arm
• any unusual, severe, prolonged headache, especially if it occurs for the first time or gets progressively worse
• diplopia or sudden partial or complete loss of vision
• slurred speech or aphasia
• weakness or very marked numbness suddenly affecting one side or one part of the body
• collapse with or without focal seizure, motor disturbances, vertigo.
Hepatic adenomas
Malignant hepatic tumours have been reported on rare occasions in long-term users of oral contraceptives. Benign hepatic tumours have also been associated with oral contraceptive usage. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occur. In isolated cases, life-threatening intra-abdominal haemorrhage may occur.
Breast cancer
A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The additional breast cancers diagnosed in current users of COCs or in women who have used COCs in the last 10 years are more likely to be localised to the breast than those in women who never used COCs.
Breast cancer is rare among women under 40 years of age whether or not they take COCs. Whilst this background risk increases with age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer (see bar chart).
The most important risk factor for breast cancer in COC users is the age women discontinue the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.
The possible increase in risk of breast cancer should be discussed with the user and weighed against the benefits of COCs taking into account the evidence that they offer substantial protection against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).
Cervical cancer
The most important risk factor for cervical cancer is persistent Human Papilloma Virus (HPV) infection. Some epidemiological studies have indicated that long-term use of COCs may further contribute to this increased risk but there continues to be controversy about the extent to which this finding is attributable to confounding effects, e.g. cervical screening and sexual behaviour including use of barrier contraceptives.
There is some theoretical concern that COCs enhance progression of Cervical Intraepithelial Neoplasia (CIN) to invasive disease. For women with diagnosed cervical cancer, COCs may be used whilst awaiting treatment.
Other tumours
Numerous epidemiological studies have been reported on the risk of ovarian and endometrial cancer in women using COCs. The evidence is clear that COCs offer substantial protection against both ovarian and endometrial cancer.
Bleeding irregularities
Breakthrough bleeding, spotting and/or absence of withdrawal flow may be encountered in patients on oral contraceptives, especially during the first three months of use.
If bleeding irregularities persist beyond three cycles or occur after previously regular cycles, non-hormonal causes should be considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy.
Some women may experience post-pill amenorrhoea or oligomenorrhoea, especially when such a condition was pre-existing.
Laboratory tests
In the literature, at least a hundred different laboratory test parameters have been reported to possibly be influenced by oral contraceptive use, predominantly by the oestrogenic component. Among these are: biochemical parameters of the liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins and lipid/lipoprotein fractions and parameters of coagulation and fibrinolysis.
Other conditions
In the following conditions the benefit of oral contraception generally outweighs the theoretical or known risk. However, they may need to be considered before prescribing to individual patients:
• Known hyperlipidaemias. A small proportion of women will have persistent hypertriglyceridemia while on the pill. Changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. However, routine screening of women with hypertriglyceridaemia is not considered appropriate.
• Diabetes without vascular involvement (although all patients with diabetes are at increased risk of arterial disease).
• Decreased glucose tolerance. The oestrogen component of Trinovum may cause a decrease in glucose tolerance, while the progestogens may increase insulin secretion and create insulin resistance. Because of these demonstrated effects, pre-diabetic and diabetic women in particular should be carefully monitored while taking oral contraceptives.
• Asymptomatic gall bladder disease or cholecystectomy
• Benign liver tumours (focal nodular hyperplasia). There is limited, direct evidence that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia.
• Migraine without focal aura. The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause.
If any of the following conditions developed or worsened during a prior pregnancy or during previous COC use, they may occur while taking Trinovum:
• elevated blood pressure
• cholestasis
• herpes gestationis
• otosclerosis
• SLE
• severe headaches.
Chloasma
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking this preparation. Chloasma is often not fully reversible.
Additional contraceptive precautions
When additional contraceptive precautions are required, the patient should be advised either not to have sex, or to use a cap plus spermicide or for her partner to use a condom. Rhythm methods should not be advised as the pill disrupts the usual cyclical changes associated with the natural menstrual cycle, eg changes in temperature and cervical mucus.
Excipients
The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Potential Reduction in Contraceptive Effectiveness Associated With Co-Administration of Other Drugs:
Hepatic enzyme inducers
Drugs or herbal products that induce enzymes, especially CYP3A4, may decrease the plasma concentrations of contraceptive hormones, and may decrease their effectiveness and/or increase breakthrough bleeding.
Examples include:
• barbiturates
• bosentan
• carbamazepine
• felbamate
• griseofulvin
• some HIV protease inhibitors (e.g. ritonavir)
• modafinil
• some non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine)
• oxcarbazepine
• phenytoin
• rifampicin and rifabutin
• St. John’s Wort
• topiramate
Antibacterial drugs that are not enzyme inducers
There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.
Management
For women on long-term treatment with drugs and herbal products that interact with hormonal contraception, another reliable, non-hormonal method of contraception is recommended.
Women on short-term treatment with drugs and herbal products that interact with hormonal contraception and may decrease plasma levels of contraceptive hormones could have their contraceptive effectiveness reduced. They should be advised to use a barrier contraceptive method (e.g. condoms, diaphragm) in addition to Trinovum as follows:
• Women using liver enzyme-inducing drugs should temporarily use a barrier contraceptive method in addition to Trinovum during the time of concomitant medicinal product administration and for 28 days after their discontinuation.
• In the case of modafinil, use of a barrier contraceptive method should continue for 56 days after discontinuation.
If discontinuation of the concomitant medicinal product occurs in week three or runs beyond the end of the tablets in the strip, the next strip should be started the next day without a break.
Changes in Plasma Levels of Co-Administered Drugs that may be of Clinical Significance:
Combination hormonal contraceptives may also affect the pharmacokinetics of some other drugs if used concomitantly.
Drugs whose plasma levels may be increased (due to CYP inhibition)
Examples include:
• ciclosporin
• prednisolone
• theophylline
Drugs whose plasma levels may be decreased (due to induction of glucuronidation)
Examples include:
• lamotrigine
Management
Physicians are advised to consult the labelling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives and the possible need to adjust dosages
4.6.1. Use during pregnancy
Not indicated during pregnancy. Confirm suspected pregnancy before discontinuing treatment.
The majority of recent studies do not indicate a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy.
4.6.2. Use during lactation
Contraceptive steroids and/or their metabolites may be excreted in breast milk.
The use of COCs is contraindicated for breast-feeding mothers less than 6 weeks post-partum (see section 4.3) and should be used with clinical judgement for breast-feeding mothers between 6 weeks and 6 months post-partum (see section 4.4).
Mothers who are breast-feeding should be advised not to use the combined pill since this may reduce the amount of breast milk, but may be advised instead to use a progestogen-only pill (POP).
Not applicable.
Certain Adverse Drug Reactions (ADRs) that have been associated with oral contraceptive use may require immediate medical attention and/or cessation of oral contraceptive use. These ADRs include: myocardial infarction, deep venous thrombosis, pulmonary embolism, cerebrovascular accidents, retinal vein thrombosis, new onset of migraine -type headache, breast cancer, hepatic tumours (benign and malignant), high blood pressure, angioedema and urticaria (possible hypersensitivity).
Alternative non-hormonal methods of contraception should be used, while appropriate diagnostic and therapeutic measures are undertaken.
Headache was the most frequently reported ADR (12%) in clinical trials.
The following are all the ADRs that were reported in clinical trials and from post-marketing experience.
Clinical Trial ADRs: The list of ADRs includes data from evaluation of the clinical safety that was based on two studies: a four cell, double blind, controlled study evaluating a total of 488 women for four cycles and a two cell study evaluating norethisterone for 12 cycles (n=669).
The following terms and frequencies are applied: very common (
Post-marketing reports: The frequency of post-marketing ADRs cannot be estimated from the available data and are therefore reported as 'Frequency not known'.
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*Not seen in clinical trials but frequency based on standard reporting rates for similar combined oral contraceptives (see section 4.4).
There have been no reports of serious ill-health from overdose. Symptoms that may occur are nausea, vomiting and vaginal bleeding. There are no antidotes and further treatment should be symptomatic.
Trinovum oral contraceptive tablets act through the mechanism of gonadotrophin suppression by the oestrogenic and progestational actions of the ethinylosetradial and norethisterone.
The primary mechanism of action is inhibition of ovulation, but alterations to the cervical mucus and to the endometrium may also contribute to the efficacy of the product.
Norethisterone and ethinylestradiol are absorbed from the gastro-intestinal tract and metabolised in the liver. To obtain maximal contraceptive effectiveness the tablet should be taken as directed and at approximately the same time each day. If the patient has vomiting or diarrhoea, absorption of the hormones will be impaired, making it advisable use an additional reliable method of contraception until her next menstrual Period.
Because the active ingredients are metabolised in the liver, reduced contraceptive efficacy has been associated with concomitant use of oral contraceptives and rifampicin.
A similar association has been suggested with oral contraceptives and barbiturates, phenytoin sodium, phenylbutazone griseofulvin and ampicillin..
No relevant information additional to that contained elsewhere in the summary of characteristics
White tablets:
Lactose, Pregelatinised starch, Magnesium stearate, Methanol* Purified water,
Light Peach tablet
Lactose, Pregelatinised starch, FD&C Yellow number6(E110)Magnesium stearate. Methanol* Purified water
Peach Tablets:
Lactose, Pregelatinised starch, FD&C Yellow number6(E110)Magnesium stearate. Methanol* Purified water(* not detected in final product)
None stated
2 years
Do not store above 30°C. Protect from light.
Clear uncoloured PVC/foil Blister strips of 21 tablets. Strips are packaged with a patient information leaflet with or without a plastic or card wallet in a cardboard carton. Park sizes:1x21*,3x21,6x21*,50x21* and 100x21*(* Not marketed)
None stated
Janssen-Cilag Limited
50-100 Holmers Farm Way
High Wycombe
Buckinghamshire
HP12 4EG
UK
PL 00242/0279
01 September 1995
10th November 2011
