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Author: druginteractionchecker_lgaiz4
Probenecid 500 MG Oral Tablet
Generic Name: PROBENECID
Brand Name: Probenecid
- Substance Name(s):
- PROBENECID
WARNINGS
Exacerbation of gout following therapy with probenecid may occur; in such cases colchicine or other appropriate therapy is advisable. Probenecid increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If probenecid is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored. In patients on probenecid the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of probenecid. The biphasic action of salicylates in the renal tubules accounts for the so-called “paradoxical effect” of uricosuric agents. In patients on probenecid who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred. Rarely, severe allergic reactions and anaphylaxis have been reported with the use of probenecid. Most of these have been reported to occur within several hours after readministration following prior usage of the drug. The appearance of hypersensitivity reactions requires cessation of therapy with probenecid. Usage In Pregnancy Probenecid crosses the placental barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against possible hazards.
DRUG INTERACTIONS
Drug Interactions When probenecid is used to elevate plasma concentrations of penicillin or other beta-lactams, or when such drugs are given to patients taking probenecid therapeutically, high plasma concentrations of the other drug may increase the incidence of adverse reactions associated with that drug. In the case of penicillin or other beta-lactams, psychic disturbances have been reported. The use of salicylates antagonizes the uricosuric action of probenecid (see WARNINGS). The uricosuric action of probenecid is also antagonized by pyrazinamide. Probenecid produces an insignificant increase in free sulfonamide plasma concentrations, but a significant increase in total sulfonamide plasma levels. Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when a sulfonamide and probenecid are coadministered for prolonged periods. Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia. It has been reported that patients receiving probenecid require significantly less thiopental for induction of anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving probenecid. The concomitant administration of probenecid increases the mean plasma elimination half-life of a number of drugs which can lead to increased plasma concentrations. These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. Although the clinical significance of this observation has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases in dosage of the drug in question should be made cautiously and in small increments when probenecid is being coadministrated. Although specific instances of toxicity due to this potential interaction have not been observed to date, physicians should be alert to this possibility. Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of probenecid, which probably is not significant under most circumstances. In animals and in humans, probenecid has been reported to increase plasma concentrations of methotrexate (see WARNINGS). Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma.
DESCRIPTION
Probenecid is a uricosuric and renal tubular transport blocking agent. The chemical name for probenecid is 4-[(dipropylamino) sulfonyl] benzoic acid (molecular weight 285.37). It has the following structural formula: C13H19NO4S Probenecid, USP is a white or nearly white, fine, crystalline powder. Probenecid is soluble in dilute alkali, in alcohol, in chloroform, and in acetone; it is practically insoluble in water and in dilute acids. Each tablet for oral administration contains 500 mg of probenecid and the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium carbonate, sodium lauryl sulfate, sodium starch glycolate, cornstarch, titanium dioxide, triacetin, FD&C Yellow #6, D&C Yellow #10, and FD&C Blue #2. Structural Formula
HOW SUPPLIED
Probenecid Tablets, USP are available containing 500 mg of Probenecid, USP. The tablets are capsule shaped, film-coated yellow, debossed with MYLAN 156 on one side, 500 on the other side. They are available as follows: NDC 0378-0156-01 bottles of 100 tablets Store at 20° to 25°C (68° to 77°F). [See USP for Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Mylan Pharmaceuticals Inc. Morgantown, WV 26505 REVISED MARCH 2006 PROB:R4AQ
INDICATIONS AND USAGE
Probenecid tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given.
DOSAGE AND ADMINISTRATION
Gout Therapy with probenecid should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, probenecid may be continued without changing the dosage, and full therapeutic dosage of colchicine, or other appropriate therapy, should be given to control the acute attack. The recommended adult dosage is 250 mg (1/2 probenecid tablet), twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter. Some degree of renal impairment may be present in patients with gout. A daily dosage of 1000 mg may be adequate. However, if necessary, the daily dosage may be increased by 500 mg increments every 4 weeks within tolerance (and usually not above 2000 mg per day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg. As noted, probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less. Gastric intolerance may be indicative of overdosage, and may be corrected by decreasing the dosage. As uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily), or potassium citrate (7.5 g daily) to maintain an alkaline urine (see PRECAUTIONS). Alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear, i.e., during the period when urinary excretion of uric acid is at a high level. Thereafter, alkalization of the urine and the usual restriction of purine-producing foods may be somewhat relaxed. Probenecid should be continued at the dosage that will maintain normal serum urate levels. When acute attacks have been absent for 6 months or more and serum urate levels remain within normal limits, the daily dosage may be decreased by 500 mg every 6 months. The maintenance dosage should not be reduced to the point where serum urate levels tend to rise. Probenecid and Penicillin Therapy (General) Adults The recommended dosage is 2000 mg (4 tablets of probenecid) daily in divided doses. This dosage should be reduced in older patients in whom renal impairment may be present. Children 2–14 years of age: Initial dose: 25 mg/kg body weight (or 0.7 g/square meter body surface). Maintenance Dose: 40 mg/kg body weight (or 1.2 g/square meter body surface) per day, divided into 4 doses. For children weighing more than 50 kg (110 lb) the adult dosage is recommended. Probenecid is contraindicated in children under 2 years of age. The PSP excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about one-fifth the normal rate when dosage of probenecid is adequate. Penicillin Therapy (Gonorrhea)* In uncomplicated gonococcal infections in men and women (urethral, cervical, rectal), 1 g of probenecid should be given orally with 4.8 million units of aqueous procaine penicillin GSee package circulars of manufacturers for detailed information about CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS. (given IM), or 3 g of amoxicillin2 (given orally), or 3.5 g of ampicillin2 (given orally). For further guidance, see CDC recommendations for definition of regimens of choice, alternative regimens, treatment of hypersensitive patients, and other aspects of therapy. *Recommended by the Center for Disease Control, U.S. Department of Health and Human Services, Public Health Service (Morbidity and Mortality Weekly Report Supplement, Volume 34, Number 4S, October 18, 1985).
Ethanol 0.62 ML/ML Topical Solution
Generic Name: ALCOHOL
Brand Name: XtraCare instant Hand Sanitizer Original
- Substance Name(s):
- ALCOHOL
WARNINGS
Warnings: for external use only. Flammable. Keep away from heat and flame. When using this product avoid contact with face, eyes, and broken skin. In case of eye contact, flush with plenty of water and seek medical advice. Stop use and ask a doctor if irritation or redness develops. Keep out of reach of children. if swallowed, get medical help or contact a Poison Control Center.
INDICATIONS AND USAGE
USE: hand sanitizer to help reduce bacteria on the skin that may cause disease.
INACTIVE INGREDIENTS
Inactive ingredients: water, carbomer, triethanolamine, glycerin, propylene glycol, fragrance, tocopheryl acetate (Vitamin E).
PURPOSE
Purpose Antimicrobial
KEEP OUT OF REACH OF CHILDREN
Keep out of reach of children. if swallowed, get medical help or contact a Poison Control Center.
DOSAGE AND ADMINISTRATION
Directions wet hands thoroughly with product and rub into skin until dry. children under 6 years of age should be supervised by an adult when using.
STOP USE
Stop use and ask a doctor if irritation or redness develops.
ACTIVE INGREDIENTS
Active ingredient: Ethyl Alcohol 62.0%
norethindrone 0.5 MG / ethinyl estradiol 0.035 MG Oral Tablet
Generic Name: NORETHINDRONE AND ETHINYL ESTRADIOL
Brand Name: Ortho-Novum 777
WARNINGS
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives, including ORTHO-NOVUM® and MODICON®, should not be used by women who are over 35 years of age and smoke. The use of oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes. 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 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, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population (adapted from refs. 2 and 3 with the author’s permission). For further information, the reader is referred to a text on epidemiological methods. 1. Thromboembolic Disorders and Other Vascular Problems a. Myocardial Infarction 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. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six.4–10 The risk is very low under the age of 30. 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.11 Mortality rates associated with circulatory disease have been shown to increase substantially in smokers, especially in those 35 years of age and older, and in nonsmokers over the age of 40 among women who use oral contraceptives. (See Figure 1). Figure 1. Circulatory Disease Mortality Rates per 100,000 Women-Years by Age, Smoking Status and Oral Contraceptive Use (Adapted from P.M. Layde and V. Beral, ref. #12.) Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity.13 In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism.14–18 Oral contraceptives have been shown to increase blood pressure among users (see Section 9 in ). 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. Table II b. Thromboembolism 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 nonusers 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.2,3,19–24 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.25 The risk of thromboembolic disease associated with oral contraceptives is not related to length of use and disappears after pill use is stopped.2 A two- to four-fold increase in relative risk of post-operative thromboembolic complications has been reported with the use of oral contraceptives.9 The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions.26 If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four weeks after delivery in women who elect not to breastfeed. c. Cerebrovascular diseases Oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, 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 nonusers, for both types of strokes, and smoking interacted to increase the risk of stroke.27–29 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.30 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.30 The attributable risk is also greater in older women.3 d. Dose-related risk of vascular disease from oral contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease.31–33 A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents.14–16 A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease. 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 activity of the progestogen used in the contraceptives. The activity and amount of both hormones should be considered in the choice of an oral contraceptive. 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 which is judged appropriate for the individual patient. e. Persistence of risk of vascular disease There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. 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 five or more years, but this increased risk was not demonstrated in other age groups.8 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.34 However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens. 2. Estimates of Mortality From Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 2). 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 an increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970’s.35 Current clinical recommendation involves the use of lower estrogen dose formulations and a careful consideration of risk factors. In 1989, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the use of oral contraceptives in women 40 years of age and over. 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 also 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. The Committee recommended that the benefits of low-dose 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 an oral contraceptive which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and individual patient needs. Table 2: ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Method of control and outcome 15–19 20–24 25–29 30–34 35–39 40–44 Adapted from H.W. Ory, ref. #35. No fertility-control methodsDeaths are birth-related 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smokerDeaths are method-related 0.3 0.5 0.9 1.9 13.8 31.6 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 3. Carcinoma of the Reproductive Organs and Breasts Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives. The risk of having breast cancer diagnosed may be slightly increased among current and recent users of COCs. However, this excess risk appears to decrease over time after COC discontinuation and by 10 years after cessation the increased risk disappears. Some studies report an increased risk with duration of use while other studies do not and no consistent relationships have been found with dose or type of steroid. Some studies have found a small increase in risk for women who first use COCs before age 20. Most studies show a similar pattern of risk with COC use regardless of a woman’s reproductive history or her family breast cancer history. Breast cancers diagnosed in current or previous OC users tend to be less clinically advanced than in nonusers. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormonally-sensitive tumor. 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.45–48 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 and cervical cancers, a cause-and-effect relationship has not been established. 4. Hepatic Neoplasia 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/100,000 for users, a risk that increases after four or more years of use especially with oral contraceptives of higher dose.49 Rupture of benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.50,51 Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. 5. Ocular Lesions 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. 6. Oral Contraceptive Use Before or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy.56,57 The majority of recent studies also do not indicate a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned,55,56,58,59 when taken inadvertently during early pregnancy. 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 two consecutive periods, pregnancy should be ruled out. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed. 7. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens.60,61 More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal.62–64 The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. 8. Carbohydrate and Lipid Metabolic Effects Oral contraceptives have been shown to cause a decrease in glucose tolerance in a significant percentage of users.17 This effect has been shown to be directly related to estrogen dose.65 Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents.17,66 However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose.67 Because of these demonstrated effects, prediabetic and diabetic women in particular should be carefully monitored while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see 1a and 1d), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. 9. Elevated Blood Pressure Women with significant hypertension should not be started on hormonal contraception.92 An increase in blood pressure has been reported in women taking oral contraceptives68 and this increase is more likely in older oral contraceptive users69 and with extended duration of use.61 Data from the Royal College of General Practitioners12 and subsequent randomized trials have shown that the incidence of hypertension increases with increasing progestational activity. Women with a history of hypertension or hypertension-related diseases, or renal disease70 should be encouraged to use another method of contraception. If these women elect to use oral contraceptives, they should be monitored closely and if a clinically significant persistent elevation of blood pressure (BP) occurs (≥ 160 mm Hg systolic or ≥ 100 mm Hg diastolic) and cannot be adequately controlled, oral contraceptives should be discontinued. In general, women who develop hypertension during hormonal contraceptive therapy should be switched to a non-hormonal contraceptive. If other contraceptive methods are not suitable, hormonal contraceptive therapy may continue combined with antihypertensive therapy. Regular monitoring of BP throughout hormonal contraceptive therapy is recommended.96 For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension between former and never users.68–71 10. Headache 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. 11. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal 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 preexistent. 12. Ectopic Pregnancy Ectopic as well as intrauterine pregnancy may occur in contraceptive failures.
DRUG INTERACTIONS
8. Drug Interactions Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the plasma concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20–25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]). Colesevelam Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Effects of Combined Hormonal Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs.
OVERDOSAGE
Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.
DESCRIPTION
COMBINED ORAL CONTRACEPTIVES Each of the following products is a combined oral contraceptive containing the progestational compound norethindrone and the estrogenic compound ethinyl estradiol. ORTHO-NOVUM® 7/7/7 Tablets Each white tablet contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include lactose, magnesium stearate and pregelatinized corn starch. Each light peach tablet contains 0.75 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C Yellow No. 6, lactose, magnesium stearate and pregelatinized corn starch. Each peach tablet contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C Yellow No. 6, lactose, magnesium stearate and pregelatinized corn starch. Each green tablet contains only inert ingredients, as follows: D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, lactose, magnesium stearate, microcrystalline cellulose and pregelatinized corn starch. ORTHO-NOVUM® 1/35 Tablets Each peach tablet contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C Yellow No. 6, lactose, magnesium stearate and pregelatinized corn starch. Each green tablet contains only inert ingredients, as listed under green tablets in ORTHO-NOVUM® 7/7/7. MODICON® Tablets Each white tablet contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include lactose, magnesium stearate and pregelatinized corn starch. Each green tablet contains only inert ingredients, as listed under green tablets in ORTHO-NOVUM® 7/7/7. The chemical name for norethindrone is 17-Hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one, and for ethinyl estradiol is 19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. Their structural formulas are as follows: Chemical Structure
HOW SUPPLIED
Repackaged by A-S Medication Solutions – Libertyville, IL See REPACKAGING INFORMATION for available configurations. ORTHO-NOVUM® 7/7/7 Tablets are available in a blister card with a DIALPAK® Tablet Dispenser (unfilled) (NDC 50458-178-00). The blister card contains 28 tablets, as follows: 7 white, round, flat-faced, beveled edged tablets imprinted with “Ortho 535” on both sides (0.5 mg norethindrone and 0.035 mg ethinyl estradiol), 7 light peach, round, flat-faced, beveled edged tablets imprinted with “Ortho 75” on both sides (0.75 mg norethindrone and 0.035 mg ethinyl estradiol), 7 peach, round, flat-faced, beveled edged tablets imprinted with “Ortho 135” on both sides (1 mg norethindrone and 0.035 mg ethinyl estradiol) and 7 green, round, flat-faced, beveled edged tablets imprinted “Ortho” on both sides containing inert ingredients. ORTHO-NOVUM® 7/7/7 Tablets are packaged in a carton containing 6 blister cards and 6 unfilled DIALPAK® Tablet Dispensers (NDC 50458-178-15). ORTHO-NOVUM® 7/7/7 is available for clinic usage in a VERIDATE® Tablet Dispenser (unfilled) and VERIDATE® refills (NDC 50458-178-20). ORTHO-NOVUM® 1/35 Tablets are available in a blister card with a DIALPAK® Tablet Dispenser (unfilled) (NDC 50458-176-00). The blister card contains 28 tablets, as follows: 21 peach, round, flat-faced, beveled edged tablets imprinted “Ortho 135” on both sides (1 mg norethindrone and 0.035 mg ethinyl estradiol) and 7 green, round, flat-faced, beveled edged tablets imprinted “Ortho” on both sides containing inert ingredients. ORTHO-NOVUM® 1/35 Tablets are packaged in a carton containing 6 blister cards and 6 unfilled DIALPAK® Tablet Dispensers (NDC 50458-176-15). MODICON® Tablets are available in a blister card with a DIALPAK® Tablet Dispenser (unfilled) (NDC 50458-171-00). The blister card contains 28 tablets, as follows: 21 white, round, flat-faced, beveled edged tablets imprinted “Ortho 535” on both sides (0.5 mg norethindrone and 0.035 mg ethinyl estradiol) and 7 green, round, flat-faced, beveled edged tablets imprinted “Ortho” on both sides containing inert ingredients. MODICON® Tablets are packaged in a carton containing 6 blister cards and 6 unfilled DIALPAK® Tablet Dispensers (NDC 50458-171-15). Store at 25°C (77°F), excursions permitted to 15°–30°C (59°–86°F).
GERIATRIC USE
14. Geriatric Use This product has not been studied in women over 65 years of age and is not indicated in this population.
INDICATIONS AND USAGE
ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON® Tablets are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combined oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and the NORPLANT® System depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. Table 1: Percentage of Women Experiencing an Unintended Pregnancy During the First Year of Typical Use and the First Year of Perfect Use of Contraception and the Percentage Continuing Use at the End of the First Year. United States. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One YearAmong couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. Method (1) Typical Use 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) Perfect UseAmong 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) (4) Adapted from Hatcher et al, 1998, Ref. # 1. Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.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), Alesse® (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). Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception.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. Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York, NY: Irvington Publishers, 1998. ChanceThe 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. 85 85 SpermicidesFoams, creams, gels, vaginal suppositories, and vaginal film. 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-ThermalCervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. 2 Post-Ovulation 1 CapWith spermicidal cream or jelly. Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm 20 6 56 Withdrawal 19 4 CondomWithout spermicides. 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 T380A 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 ORTHO-NOVUM ® 7/7/7, ORTHO-NOVUM® 1/35 and MODICON® have not been studied for and are not indicated for use in emergency contraception.
PEDIATRIC USE
13. Pediatric Use Safety and efficacy of ORTHO-NOVUM® Tablets and MODICON® Tablets 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 this product before menarche is not indicated.
PREGNANCY
11. Pregnancy Pregnancy Category X See CONTRAINDICATIONS and WARNINGS.
NUSRING MOTHERS
12. Nursing Mothers 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, combined 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 combined oral contraceptives but to use other forms of contraception until she has completely weaned her child.
BOXED WARNING
WARNINGS: CARDIOVASCULAR RISK ASSOCIATED WITH SMOKING Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives, including ORTHO-NOVUM® and MODICON®, should not be used by women who are over 35 years of age and smoke.
INFORMATION FOR PATIENTS
INFORMATION FOR THE PATIENT See Patient Labeling printed below.
DOSAGE AND ADMINISTRATION
To achieve maximum contraceptive effectiveness, ORTHO-NOVUM® Tablets and MODICON® Tablets must be taken exactly as directed and at intervals not exceeding 24 hours. ORTHO-NOVUM® Tablets and MODICON® Tablets are available with the DIALPAK® Tablet Dispenser which is preset for a Sunday Start. Day 1 Start is also available. Sunday Start When taking ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON®, the first “active” tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first “active” tablet should be taken that day. Take one active tablet daily for 21 days followed by one green “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception such as a condom or spermicide should be used until after the first 7 consecutive days of administration. If the patient misses one (1) “active” tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) “active” tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) “active” tablets in the third week or misses three (3) or more “active” tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling (“How to Take the Pill” section). Day 1 Start The dosage of ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON®, for the initial cycle of therapy, is one “active” tablet administered daily from the 1st through the 21st day of the menstrual cycle, counting the first day of menstrual flow as “Day 1” followed by one green “reminder” tablet daily for 7 days. Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day. If the patient misses one (1) “active” tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) “active” tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) “active” tablets in the third week or misses three (3) or more “active” tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling (“How to Take the Pill” section). The use of ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON® for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) The possibility of ovulation and conception prior to initiation of medication should be considered. (See Discussion of Dose-Related Risk of Vascular Disease from Oral Contraceptives.)
ethyl alcohol 62 % Topical Solution
Generic Name: ALCOHOL
Brand Name: XtraCare instant Hand Sanitizer Original
- Substance Name(s):
- ALCOHOL
WARNINGS
Warnings: for external use only. Flammable. Keep away from heat and flame. When using this product avoid contact with face, eyes, and broken skin. In case of eye contact, flush with plenty of water and seek medical advice. Stop use and ask a doctor if irritation or redness develops. Keep out of reach of children. if swallowed, get medical help or contact a Poison Control Center.
INDICATIONS AND USAGE
USE: hand sanitizer to help reduce bacteria on the skin that may cause disease.
INACTIVE INGREDIENTS
Inactive ingredients: water, carbomer, triethanolamine, glycerin, propylene glycol, fragrance, tocopheryl acetate (Vitamin E).
PURPOSE
Purpose Antimicrobial
KEEP OUT OF REACH OF CHILDREN
Keep out of reach of children. if swallowed, get medical help or contact a Poison Control Center.
DOSAGE AND ADMINISTRATION
Directions wet hands thoroughly with product and rub into skin until dry. children under 6 years of age should be supervised by an adult when using.
STOP USE
Stop use and ask a doctor if irritation or redness develops.
ACTIVE INGREDIENTS
Active ingredient: Ethyl Alcohol 62.0%
norgestimate 0.25 MG / ethinyl estradiol 0.035 MG Oral Tablet
Generic Name: NORGESTIMATE AND ETHINYL ESTRADIOL
Brand Name: Previfem
DRUG INTERACTIONS
7 Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. No drug-drug interaction studies were conducted with norgestimate and ethinyl estradiol tablets. Drugs or herbal products that induce certain enzymes including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. (7.1) 7.1 Effects of Other Drugs on Combined Oral Contraceptives Substances decreasing the plasma concentrations of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Colesevelam: Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE. The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]). 7.2 Effects of Combined Oral Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs. 7.3 Interference with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.
OVERDOSAGE
10 There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.
DESCRIPTION
11 Each of the following products is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-, oxime,(17α)-(+)-) and ethinyl estradiol is designated as (19-nor-17α-pregna,1,3,5(10)-trien-20-yne-3,17-diol). Previfem® Each active blue tablet contains 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C Blue No. 1 HT Aluminum Lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, and pregelatinized starch. Each light-green placebo tablet contains only inert ingredients, as follows: FD&C Blue No. 2, hypromellose, iron oxide yellow, lactose monohydrate, magnesium stearate, polyethylene glycol, and pregelatinized starch. Tri-Previfem® Each active white tablet contains 0.18 mg of norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, and pregelatinized starch. Each active light-blue tablet contains 0.215 mg of norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C Blue No. 1 Aluminum Lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, and pregelatinized starch. Each active blue tablet contains 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C Blue No. 1 Aluminum Lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, and pregelatinized starch. Each light-green placebo tablet contains only inert ingredients, as follows: FD&C Blue No. 2, hypromellose, iron oxide yellow, lactose monohydrate, magnesium stearate, polyethylene glycol, and pregelatinized starch. Chemical structure of Norgestimate and Ethinyl Estradiol
CLINICAL STUDIES
14 14.1 Contraception In three US clinical trials with norgestimate and ethinyl estradiol tablets 0.25 mg/0.035 mg, 1,651 women aged 18 to 38 years were studied for up to 24 cycles, proving a total of 24,272 cycles of exposure. The racial demographic was about 73-86% Caucasian, 8-13% African-American, 6-14% Hispanic with the remainder Asian or Other (≤1%). There were no exclusions on the basis of weight; the weight range for women treated was 82-303 lbs, with a mean weight of about 135 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years. In four clinical trials with norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, 4,756 women aged 15 to 41 years were studied for 24 cycles, providing a total of 45,244 cycles of exposure. The racial demographic was about 87-90% Caucasian, 6-10% African-American, with the remainder Asian (≤1%) or Other (2-5%). There were no exclusions on the basis of weight; the weight range for women treated was 80-310 lbs, with a mean weight of about 132 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years. 14.2 Acne Norgestimate and Ethinyl Estradiol Tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg was evaluated for the treatment of acne vulgaris in two randomized, double-blind, placebo-controlled, multicenter, six- (28 day) cycle studies. Two hundred twenty- one patients received norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg and 234 patients received placebo. Mean age at enrollment for both groups was 28 years. At the end of 6 months, the mean total lesion count changed from 55 to 31 (42% reduction) in patients treated with norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg and from 54 to 38 (27% reduction) in patients similarly treated with placebo. Table 4 summarizes the changes in lesion count for each type of lesion. Based on the investigator’s global assessment conducted at the final visit, patients treated with norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg showed a statistically significant improvement in total lesions compared to those treated with placebo. Table 4: Acne Vulgaris Indication. Combined Results: Two Multicenter, Placebo-Controlled Trials. Observed Means at Six Months (LOCF)1 and at Baseline. Intent-to-Treat Population. norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg (N=221) Placebo (N=234) Difference in Counts between norgestimate and ethinyl estradiol tablets, 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg and Placebo at 6 Months # of Lesions Counts % Reduction Counts % Reduction INFLAMMATORY LESIONS Baseline Mean 19 19 Sixth Month Mean 10 48% 13 30% 3 (95% CI: -1.2, 5.1) NON-INFLAMMATORY LESIONS Baseline Mean 36 35 Sixth Month Mean 22 34% 25 21% 3 (95% CI: -0.2, 7.8) TOTAL LESIONS Baseline Mean 55 54 Sixth Month Mean 31 42% 38 27% 7 (95% CI: 2.0, 11.9) 1LOCF: Last Observation Carried Forward
HOW SUPPLIED
16 /STORAGE AND HANDLING 16.1 How Supplied Previfem® Previfem® (norgestimate and ethinyl estradiol tablets USP) is packaged in cartons of 6 blister pack tablet dispensers containing 28 tablets as follows: 21 blue tablets containing 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol which are round, unscored, film-coated tablets debossed with “93” and “748” on each side and 7 light-green, round, film-coated tablets debossed with “93” and “743” containing inert ingredients. Blister pack tablet dispenser NDC 0603-7642-01. Boxes of 6 blister pack tablet dispensers NDC 0603-7642-17. Tri-Previfem® Tri-Previfem® (norgestimate and ethinyl estradiol tablets USP) is packaged in cartons of 6 blister pack tablet dispensers, each blister pack tablet dispenser contains 28 tablets as follows: Each white tablet contains 0.18 mg of norgestimate and 0.035 mg of ethinyl estradiol. Each light-blue tablet contains 0.215 mg of norgestimate and 0.035 mg of ethinyl estradiol. Each blue tablet contains 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol. Each light-green tablet contains inert ingredients. The white tablets are round, unscored film-coated, imprinted with “93” on one side and “746” on the other side; the light-blue tablets are round, unscored film-coated, imprinted with “93” on one side and “747” on the other side; the blue tablets are round, unscored film-coated, imprinted with “93” on one side and “748” on the other side; the light-green tablets are round, film-coated, imprinted with “93” on one side and “743” on the other side. Blister pack tablet dispenser NDC 0603-7663-01. Boxes of 6 blister pack tablet dispensers NDC 0603-7663-17. Keep out of reach of children. 16.2 Storage Conditions Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light.
GERIATRIC USE
8.5 Geriatric Use Norgestimate and Ethinyl Estradiol Tablets have not been studied in postmenopausal women and are not indicated in this population.
DOSAGE FORMS AND STRENGTHS
3 Previfem®: Previfem® (norgestimate and ethinyl estradiol tablets USP) is packaged in cartons of 6 blister pack tablet dispensers containing 28 tablets as follows: 21 blue tablets containing 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol which are round, unscored, film-coated tablets debossed with “93” and “748” on each side. 7 light-green, round, film-coated tablets debossed with “93” and “743” containing inert ingredients. Tri-Previfem®: Tri-Previfem® (norgestimate and ethinyl estradiol tablets USP) is packaged in cartons of 6 blister pack tablet dispensers, each blister pack tablet dispenser contains 28 tablets as follows: Each white tablet contains 0.18 mg norgestimate and 0.035 mg of ethinyl estradiol. Each light-blue tablet contains 0.215 mg of norgestimate and 0.035 mg ethinyl estradiol. Each blue tablet contains 0.25 mg of, norgestimate and 0.035 mg of ethinyl estradiol. Each light-green tablet contains inert ingredients. The white tablets are round, unscored film-coated, imprinted with “93” on one side and “746” on the other side; the light-blue tablets are round, unscored film-coated, imprinted with “93” on one side and “747” on the other side; the blue tablets are round, unscored film-coated, imprinted with “93” on one side and “748” on the other side; the light-green tablets are round, film-coated, imprinted with “93” on one side and “743” on the other side. Previfem® (norgestimate/ethinyl estradiol tablets USP) consists of 28 round, unscored, film-coated tablets in the following order (3): • 21 blue tablets each containing 0.25 mg norgestimate and 0.035 mg ethinyl estradiol • 7 light-green tablets (inert) Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) consists of 28 round, unscored, film-coated tablets in the following order (3): • 7 white tablets each containing 0.18 mg norgestimate and 0.035 mg ethinyl estradiol • 7 light blue tablets each containing 0.215 mg norgestimate and 0.035 mg ethinyl estradiol • 7 blue tablets each containing 0.25 mg norgestimate and 0.035 mg ethinyl estradiol • 7 light-green tablets (inert)
MECHANISM OF ACTION
12.1 Mechanism of Action Oral Contraception COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation. Acne Acne is a skin condition with a multifactorial etiology, including androgen stimulation of sebum production. While the combination of ethinyl estradiol and norgestimate increases sex hormone-binding globulin (SHBG) and decreases free testosterone, the relationship between these changes and a decrease in the severity of facial acne in otherwise healthy women with this skin condition has not been established.
INDICATIONS AND USAGE
1 Previfem® (norgestimate/ethinyl estradiol tablets USP) and Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) are estrogen/progestin COCs, indicated for use by women to prevent pregnancy. (1.1) Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) is also indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control. (1.2) 1.1 Oral Contraceptive Previfem® (norgestimate/ethinyl estradiol tablets USP) and Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) are indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies (14)]. 1.2 Acne Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) is indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Previfem® (norgestimate/ethinyl estradiol tablets USP) should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [see Clinical Studies (14)].
PEDIATRIC USE
8.4 Pediatric Use Safety and efficacy of norgestimate and ethinyl estradiol tablets have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated. There was no significant difference between norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg and placebo in mean change in total lumbar spine (L1-L4) and total hip bone mineral density between baseline and Cycle 13 in 123 adolescent females with anorexia nervosa in a double-blind, placebo-controlled, multicenter, one-year treatment duration clinical trial for the Intent To Treat (ITT) population.
PREGNANCY
8.1 Pregnancy There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy. Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.
NUSRING MOTHERS
8.3 Nursing Mothers Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
BOXED WARNING
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see Contraindications (4)]. WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. Previfem® or Tri-Previfem® (norgestimate/ethinyl estradiol tablets) are contraindicated in women over 35 years old who smoke. (4) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. (4)
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS • Thromboembolic Disorders and Other Vascular Problems: Stop Previfem® or Tri-Previfem® if a thrombotic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. (5.1) • Liver disease: Discontinue Previfem® or Tri-Previfem® if jaundice occurs. (5.2) • High blood pressure: If used in women with well-controlled hypertension monitor blood pressure and stop Previfem® or Tri-Previfem® if blood pressure rises significantly. (5.3) • Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking Previfem® or Tri-Previfem®. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. (5.5) • Headache: Evaluate significant change in headaches and discontinue Previfem® or Tri-Previfem® if indicated. (5.6) • Bleeding Irregularities and Amenorrhea: Evaluate irregular bleeding or amenorrhea. (5.7) 5.1 Thromboembolic Disorders and Other Vascular Problems Stop Previfem® or Tri-Previfem® if an arterial thrombotic event or venous thromboembolic (VTE) event occurs. Stop Previfem® or Tri-Previfem® if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately [see Adverse Reactions (6.2)]. If feasible, stop Previfem® or Tri-Previfem® at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization. Start Previfem® or Tri-Previfem® no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week. The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued. Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). This risk increases with age, particularly in women over 35 years of age who smoke. Use COCs with caution in women with cardiovascular disease risk factors. 5.2 Liver Disease Impaired Liver Function Do not use Previfem® or Tri-Previfem® in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of liver [see Contraindications (4) ]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue Previfem® or Tri-Previfem® if jaundice develops. Liver Tumors Previfem® and Tri-Previfem® are contraindicated in women with benign and malignant liver tumors [see Contraindications (4)]. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) COC users. However, the risk of liver cancers in COC users is less than one case per million users. 5.3 High Blood Pressure Previfem® and Tri-Previfem® are contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see Contraindications (4)]. For women with well-controlled hypertension, monitor blood pressure and stop Previfem® and Tri-Previfem® if blood pressure rises significantly. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing concentrations of progestin. 5.4 Gallbladder Disease Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis. 5.5 Carbohydrate and Lipid Metabolic Effects Carefully monitor prediabetic and diabetic women who take Previfem® or Tri-Previfem®. COCs may decrease glucose tolerance. Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs. Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs. 5.6 Headache If a woman taking Previfem® or Tri-Previfem® develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Previfem® or Tri-Previfem® if indicated. Consider discontinuation of Previfem® or Tri-Previfem® in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event). 5.7 Bleeding Irregularities and Amenorrhea Unscheduled Bleeding and Spotting Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product. In clinical trials of norgestimate and ethinyl estradiol tablets 0.25 mg/0.035 mg and norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, the frequency and duration of breakthrough bleeding and/or spotting was assessed in 1,647 patients (21,275 evaluable cycles) and 4,826 patients (35,546 evaluable cycles), respectively. A total of 100 (7.5%) women discontinued norgestimate and ethinyl estradiol tablets 0.25 mg/0.035 mg and 231 (4.8%) women discontinued norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 14-34% of women using norgestimate and ethinyl estradiol tablets 0.25 mg/0.035 mg experienced unscheduled bleeding per cycle in the first year; for norgestimate and ethinyl estradiol tablets 0.18 mg/0.035 mg, 0.215 mg/0.035 mg, 0.25 mg/0.035 mg, the respective numbers were 13-38%. The percent of women who experienced breakthrough/unscheduled bleeding tended to decrease over time. Amenorrhea and Oligomenorrhea Women who use Previfem® or Tri-Previfem® may experience amenorrhea. Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was pre-existent. If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. 5.8 COC Use Before or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue Previfem® or Tri-Previfem® use if pregnancy is confirmed. Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations (8.1)]. 5.9 Depression Carefully observe women with a history of depression and discontinue Previfem® or Tri-Previfem® if depression recurs to a serious degree. 5.10 Carcinoma of Breast and Cervix Previfem® and Tri-Previfem® are contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)]. There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings. Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. 5.11 Effect on Binding Globulins The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased. 5.12 Monitoring A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare. 5.13 Hereditary Angioedema In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema. 5.14 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 while taking Tri-Previfem® or Previfem®.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information and Instructions for Use). Counsel patients about the following information: Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see Boxed Warning]. Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see Warnings and Precautions (5.1)]. Previfem® and Tri-Previfem® do not protect against HIV infection (AIDS) and other sexually transmitted infections. Previfem® and Tri-Previfem® are not to be used during pregnancy; if pregnancy occurs during use of Previfem® or Tri-Previfem® instruct the patient to stop further use [see Warnings and Precautions (5.8)]. Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see Dosage and Administration (2.2)]. Use a back-up or alternative method of contraception when enzyme inducers are used with Previfem® or Tri-Previfem® [see Drug Interactions (7.1)]. COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see Use in Specific Populations (8.3)]. Women who start COCs postpartum, and who have not yet had a period, should use an additional method of contraception until they have taken an active tablet for 7 consecutive days [see Dosage and Administration (2.2)]. Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see Warnings and Precautions (5.7)].
DOSAGE AND ADMINISTRATION
2 • Take one tablet daily by mouth at the same time every day. (2.2) • Take tablets in the order directed on the blister pack. (2.2) • Do not skip or delay tablet intake. (2.2) 2.1 How to Start Previfem® (norgestimate/ethinyl estradiol tablets) or Tri-Previfem® (norgestimate/ethinyl estradiol tablets) Previfem® (norgestimate/ethinyl estradiol tablets USP) and Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) are dispensed in a blister pack tablet dispenser [see How Supplied/Storage and Handling (16)]. Previfem® (norgestimate/ethinyl estradiol tablets USP) and Tri-Previfem® (norgestimate/ethinyl estradiol tablets USP) may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration. 2.2 How to Take Previfem® or Tri-Previfem® Table 1: Instructions for Administration of Previfem® or Tri-Previfem® Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: Previfem® active tablets are blue (Day 1 to Day 21). Tri-Previfem® active tablets are white (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21). Previfem® and Tri-Previfem® both have light-green inactive tablets (Day 22 to Day 28). Day 1 Start: Take first active tablet without regard to meals on the first day of menses. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one light-green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet) Sunday Start: Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Previfem® or Tri-Previfem®. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one light-green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to Previfem® or Tri-Previfem® from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to Previfem® or Tri-Previfem® Start Previfem® or Tri-Previfem® : Transdermal patch On the day when next application would have been scheduled Vaginal ring On the day when next insertion would have been scheduled Injection On the day when next injection would have been scheduled Intrauterine contraceptive On the day of removal If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. Implant On the day of removal Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting Previfem® and Tri-Previfem® after Abortion or Miscarriage First-trimester After a first-trimester abortion or miscarriage, Previfem® or Tri-Previfem® may be started immediately. An additional method of contraception is not needed if Previfem® or Tri-Previfem® is started immediately. If Previfem® or Tri-Previfem® is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of Previfem® or Tri-Previfem®. Second-trimester Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Previfem® or Tri-Previfem®, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Previfem® or Tri-Previfem® [see Contraindications (4) , Warnings and Precautions (5.1) , and FDA-Approved Patient Labeling]. Starting Previfem® or Tri-Previfem® after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Previfem® or Tri-Previfem® following the instructions in Table 1 for women not currently using hormonal contraception. Previfem® or Tri-Previfem® are not recommended for use in lactating women [see Use in Specific Populations (8.3)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Previfem® or Tri-Previfem® [see Contraindications (4) , Warnings and Precautions (5.1) , Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling]. Previfem ® and Tri-Previfem ® come in a blister pack pill dispenser. Read the instructions below for using the blister pack pill dispenser. The blister package consists of three parts, the calendar label, the sleeve and the blister pack containing 28 individually sealed pills. Note that the pills are arranged in four numbered rows of 7 pills, with the pre-printed days of the week printed above them. Refer to the sample of the blister pack below: Previfem® consists of 21 blue “active” birth control pills and 7 light green “reminder” pills. Tri-Previfem® consists of 7 white “active” pills, 7 light-blue “active” pills, 7 blue “active” pills and 7 light green “reminder” pills. There are two ways to start taking birth-control pills, Sunday Start or Day 1 Start. How to use Blister Cards for the 28 tablets 1. If Sunday Start, the patient discards the stickers and takes the first active pill on the first Sunday after their menstrual period begins. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Previfem® or Tri-Previfem®. 2. If Day 1 Start, the patient picks the Days of the Week Sticker that starts the first day of their period. When the patient has picked the right sticker, they need to throw away the others and place the sticker on the blister card over the preprinted days of the week and make sure it lines up with the pills. 3. The patient removes the first pill by pushing down on the pill and waits 24 hours to take their next pill. The patient continues to take one pill each day until all the pills have been taken. 4. The pill should be taken at the same time each day. 5. After taking the last pill, the patient starts a new blister pack the very next day, no matter when their next period starts. 6. The patient should take the pills in each new package as before and start with the pill on the first row and take one pill each day, left to right, until the last pill has been taken. Blister card guide 2.3 Missed Tablets Table 2: Instructions for Missed Previfem® or Tri-Previfem® Tablets If one active tablet is missed in Weeks 1, 2, or 3 Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. If two active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out the rest of the pack and start a new pack that same day. Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. 2.4 Advice in Case of Gastrointestinal Disturbances In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling]. 2.5 Tri-Previfem® Use for Acne The timing of initiation of dosing with Tri-Previfem® for acne should follow the guidelines for use of Tri-Previfem® as an oral contraceptive. Consult the section (2.1) for instructions.
Advil 100 MG Chewable Tablet
WARNINGS
Allergy alert: Ibuprofen may cause a severe allergic reaction, especially in people allergic to aspirin. Symptoms may include: hives facial swelling asthma (wheezing) shock skin reddening rash blisters If an allergic reaction occurs, stop use and seek medical help right away. Stomach bleeding warning: This product contains an NSAID, which may cause severe stomach bleeding. The chance is higher if the child has had stomach ulcers or bleeding problems takes a blood thinning (anticoagulant) or steroid drug takes other drugs containing prescription or nonprescription NSAIDs [aspirin, ibuprofen, naproxen, or others] takes more or for a longer time than directed Heart attack and stroke warning NSAIDs, except aspirin, increase the risk of heart attack, heart failure, and stroke. These can be fatal. The risk is higher if you use more than directed or for longer than directed. Sore throat warning: Severe or persistent sore throat or sore throat accompanied by high fever, headache, nausea, and vomiting may be serious. Consult doctor promptly. Do not use more than 2 days or administer to children under 3 years of age unless directed by doctor. Do not use if the child has ever had an allergic reaction to any other pain reliever/fever reducer right before or after heart surgery Ask a doctor before use if stomach bleeding warning applies to the child child has problems or serious side effects from taking pain relievers or fever reducers child has a history of stomach problems, such as heartburn child has high blood pressure, heart disease, liver cirrhosis, kidney disease, asthma, or had a stroke child has not been drinking fluids child has lost a lot of fluid due to vomiting or diarrhea child is taking a diuretic Ask a doctor or pharmacist before use if the child is under a doctor’s care for any serious condition taking any other drug When using this product take with food or milk if stomach upset occurs Stop use and ask a doctor if child experiences any of the following signs of stomach bleeding: feels faint vomits blood has bloody or black stools has stomach pain that does not get better child has symptoms of heart problems or stroke: chest pain trouble breathing weakness in one part or side of body slurred speech leg swelling child does not get any relief within first day (24 hours) of treatment fever or pain gets worse or lasts more than 3 days redness or swelling is present in the painful area any new symptoms appear Keep out of reach of children In case of overdose, get medical help or contact a Poison Control Center right away.
INDICATIONS AND USAGE
USES temporarily: reduces fever relieves minor aches and pains due to the common cold, flu, sore throat, headaches and toothaches
INACTIVE INGREDIENTS
aspartame, cellacefate, colloidal silicon dioxide, D&C red no. 30 aluminum lake, FD&C blue no. 2 aluminum lake, gelatin, magnesium stearate, mannitol, microcrystalline cellulose, natural and artificial flavors, sodium starch glycolate
PURPOSE
Fever reducer/Pain reliever
KEEP OUT OF REACH OF CHILDREN
Keep out of reach of children In case of overdose, get medical help or contact a Poison Control Center right away.
ASK DOCTOR
Ask a doctor before use if stomach bleeding warning applies to the child child has problems or serious side effects from taking pain relievers or fever reducers child has a history of stomach problems, such as heartburn child has high blood pressure, heart disease, liver cirrhosis, kidney disease, asthma, or had a stroke child has not been drinking fluids child has lost a lot of fluid due to vomiting or diarrhea child is taking a diuretic
DOSAGE AND ADMINISTRATION
DIRECTIONS this product does not contain directions or complete warnings for adult use do not give more than directed find right dose on chart below. If possible, use weight to dose; otherwise use age. repeat dose every 6-8 hours, if needed do not use more than 4 times a day Dosing Chart Weight (lb) Age (yr) Dose (tablets) under 48 lb under 6 yr ask a doctor 48-59 lb 6-8 yr 2 tablets 60-71 lb 9-10 yr 2 1/2 tablets 72-95 lb 11yr 3 tablets
DO NOT USE
Do not use if the child has ever had an allergic reaction to any other pain reliever/fever reducer right before or after heart surgery
STOP USE
Stop use and ask a doctor if child experiences any of the following signs of stomach bleeding: feels faint vomits blood has bloody or black stools has stomach pain that does not get better child has symptoms of heart problems or stroke: chest pain trouble breathing weakness in one part or side of body slurred speech leg swelling child does not get any relief within first day (24 hours) of treatment fever or pain gets worse or lasts more than 3 days redness or swelling is present in the painful area any new symptoms appear
ACTIVE INGREDIENTS
ACTIVE INGREDIENT (IN EACH TABLET) Ibuprofen 100 mg (NSAID)* *nonsteroidal anti-inflammatory drug
ASK DOCTOR OR PHARMACIST
Ask a doctor or pharmacist before use if the child is under a doctor’s care for any serious condition taking any other drug
Simethicone 180 MG Oral Capsule
Generic Name: SIMETHICONE
Brand Name: Ultra Strength Gas Relief
- Substance Name(s):
- DIMETHICONE
WARNINGS
Warnings Stop use and ask a doctor if condition persists Keep out of reach of children.
INDICATIONS AND USAGE
Uses relieves bloating, pressure or fullness commonly referred to as gas
INACTIVE INGREDIENTS
Inactive ingredients FD&C yellow#6, gelatin, glycerin, purified water and white edible ink
PURPOSE
Purpose Anti-gas
KEEP OUT OF REACH OF CHILDREN
Keep out of reach of children.
DOSAGE AND ADMINISTRATION
Directions swallow 1 or 2 softgels as needed after a meal do not exceed two softgels per day except under the advice and supervision of a physician
STOP USE
Stop use and ask a doctor if condition persists
ACTIVE INGREDIENTS
Active ingredient (in each softgel) Simethicone 180 mg
Miralax 17 GM per 4 OZ Powder for Oral Solution
WARNINGS
Warnings Allergy alert Do not use if you are allergic to polyethylene glycol Do not use if you have kidney disease, except under the advice and supervision of a doctor Ask a doctor before use if you have •nausea, vomiting or abdominal pain •a sudden change in bowel habits that lasts over 2 weeks •irritable bowel syndrome Ask a doctor or pharmacist before use if you are taking a prescription drug When using this product you may have loose, watery, more frequent stools Stop use and ask a doctor if •you have rectal bleeding or your nausea, bloating, cramping or abdominal pain gets worse. These may be signs of a serious condition. •you get diarrhea •you need to use a laxative for longer than 1 week If pregnant or breast-feeding, ask a health professional before use. Keep out of the reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. This package is intended for institutional use only. Keep this and all drugs out of the reach of children.
INDICATIONS AND USAGE
Use •relieves occasional constipation (irregularity) •generally produces a bowel movement in 1 to 3 days
INACTIVE INGREDIENTS
Inactive ingredients none
PURPOSE
Purpose Osmotic Laxative, powder for Solution Unflavored powder grit free Each Packet contains one dose, net wt 0.5 oz (17g) NeatPAX Relieves occasional constipation / irregularity Softens stool ONCE-DAILY DOSES
KEEP OUT OF REACH OF CHILDREN
Keep out of the reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. This package is intended for institutional use only. Keep this and all drugs out of the reach of children.
ASK DOCTOR
Ask a doctor before use if you have •nausea, vomiting or abdominal pain •a sudden change in bowel habits that lasts over 2 weeks •irritable bowel syndrome
DOSAGE AND ADMINISTRATION
Directions (Packet Only) • do not take more than directed unless advised by your doctor •adults and children 17 years of age and older: •stir and dissolve one packet of powder (17 g) in any 4 to 8 ounces of beverage (cold, hot or room temperature) then drink •use once a day •use no more than 7 days •children 16 years of age or under: ask a doctor
PREGNANCY AND BREAST FEEDING
If pregnant or breast-feeding, ask a health professional before use.
DO NOT USE
Do not use if you have kidney disease, except under the advice and supervision of a doctor
STOP USE
Stop use and ask a doctor if •you have rectal bleeding or your nausea, bloating, cramping or abdominal pain gets worse. These may be signs of a serious condition. •you get diarrhea •you need to use a laxative for longer than 1 week
ACTIVE INGREDIENTS
Active ingredient (in each dose) (Packet Only) Polyethylene Glycol 3350, 17 g
ASK DOCTOR OR PHARMACIST
Ask a doctor or pharmacist before use if you are taking a prescription drug
Metamucil 3.4 GM per 8 OZ Powder for Oral Suspension
Generic Name: PSYLLIUM HUSK
Brand Name: Metamucil Therapy for Regularity
- Substance Name(s):
- PSYLLIUM HUSK
WARNINGS
Warnings Choking Taking this product without adequate fluid may cause it to swell and block your throat or esophagus and may cause choking. Do not take this product if you have difficulty in swallowing. If you experience chest pain, vomiting, or difficulty in swallowing or breathing after taking this product, seek immediate medical attention. Allergy alert This product may cause allergic reaction in people sensitive to inhaled or ingested psyllium. Ask a doctor before use if you have a sudden change in bowel habits persisting for 2 weeks abdominal pain, nausea or vomiting Stop use and ask a doctor if constipation lasts more than 7 days rectal bleeding occurs These may be signs of a serious condition. Keep out of reach of children. In case of overdose, contact a doctor or a Poison Control Center right away.
INDICATIONS AND USAGE
Uses effective in treating occasional constipation and restoring regularity
INACTIVE INGREDIENTS
Inactive ingredients citric acid, FD&C Yellow No. 6, natural and artificial orange flavor, sucrose
PURPOSE
Purpose Fiber therapy for regularity
KEEP OUT OF REACH OF CHILDREN
Keep out of reach of children. In case of overdose, contact a doctor or a Poison Control Center right away.
ASK DOCTOR
Ask a doctor before use if you have a sudden change in bowel habits persisting for 2 weeks abdominal pain, nausea or vomiting
DOSAGE AND ADMINISTRATION
Directions Put one dose into an empty glass. Mix this product (child or adult dose) with at least 8 ounces (a full glass) of water or other fluid. Taking this product without enough liquid may cause choking. See choking warning. Stir briskly and drink promptly. If mixture thickens, add more liquid and stir. Adults 12 yrs. & older 1 rounded TABLESPOON in 8 oz of liquid at the first sign of irregularity. Can be taken up to 3 times daily. Generally produces effect in 12 – 72 hours. 6 – 11 yrs. ½ adult dose in 8 oz of liquid, up to 3 times daily Under 6 yrs. Consult a doctor Bulk-forming fibers like psyllium husk may affect how well other medicines work. If you are taking a prescription medicine by mouth, take this product at least 2 hours before or 2 hours after the prescribed medicine. As your body adjusts to increased fiber intake, you may experience changes in bowel habits or minor bloating. New Users Start with 1 dose per day; gradually increase to 3 doses per day as necessary.
STOP USE
Stop use and ask a doctor if constipation lasts more than 7 days rectal bleeding occurs These may be signs of a serious condition.
ACTIVE INGREDIENTS
Active ingredient (in each TABLESPOON) Psyllium husk approximately 3.4 g