Loestrin 24 FE

Generic Name: norethindrone acetate. ethinyl estradiol, ferrous fumarate

Dosage Form: tablets
Loestrin® 24 Fe

(norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets)

Ferrous fumarate tablets are not USP for dissolution and assay.

Rx Only

Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Loestrin 24 FE Description

Loestrin® 24 Fe  provides a dosage regimen consisting of 24 white progestogen-estrogen contraceptive tablets and 4 brown ferrous fumarate (placebo) tablets.

Each white tablet contains 1 mg norethindrone acetate and 20 mcg ethinyl estradiol.

Each white tablet also contains the following inactive ingredients: acacia, lactose, magnesium stearate, starch, confectioner’s sugar, and talc.

Each brown tablet contains ferrous fumarate, microcrystalline cellulose, magnesium stearate, povidone, sodium starch glycolate, and compressible sugar. The ferrous fumarate tablets do not serve any therapeutic purpose.

The structural formulas for the active hormones are:

Ethinyl Estradiol [19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-]

Norethindrone Acetate [19-Norpregn-4-en-20-yn-3-one, 17-(acetyloxy)-, (17α)-]

Loestrin 24 FE - Clinical Pharmacology

Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).

PHARMACOKINETICS

Absorption

Norethindrone acetate appears to be completely and rapidly deacetylated to norethindrone after oral administration, because the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate and ethinyl estradiol are rapidly absorbed from Loestrin 24 FE tablets, with maximum plasma concentrations of norethindrone and ethinyl estradiol occurring 1 to 4 hours postdose. Both are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64% for norethindrone and 43% for ethinyl estradiol.

The plasma norethindrone and ethinyl estradiol pharmacokinetics following single- and multiple-dose administrations of Loestrin 24 FE tablets in 17 healthy female volunteers are provided in Figures 1 and 2, and Table 1.

Following multiple-dose administration of Loestrin 24 FE tablets, mean maximum concentrations of norethindrone and ethinyl estradiol were increased by 95% and 27%, respectively, as compared to single-dose administration. Mean norethindrone and ethinyl estradiol exposures (AUC values) were increased by 164% and 51% respectively, as compared to single-dose administration of Loestrin 24 FE tablets.

Steady-state with respect to norethindrone was reached by Day 17 and steady-state with respect to ethinyl estradiol was reached by Day 13.

Mean SHBG concentrations were increased by 150% from baseline (57.5 nmol/L) to 144 nmol/L at steady-state.

Figure 1. Mean Plasma Norethindrone Concentration-Time Profiles Following Single- and Multiple-Dose Oral Administration of Loestrin 24 FE Tablets to Healthy Female Volunteers under Fasting Condition (n = 17)

Figure 2. Mean Plasma Ethinyl Estradiol Concentration-Time Profiles Following Single- and Multiple-Dose Oral Administration of Loestrin 24 FE Tablets to Healthy Female Volunteers under Fasting Condition (n = 17)

Table 1. Summary of Norethindrone (NE) and Ethinyl Estradiol (EE) Pharmacokinetics Following Single- and Multiple-Dose Oral Administration of Loestrin 24 FE Tablets to Healthy Female Volunteers under Fasting Condition (n = 17)

* The harmonic mean (0.693/mean apparent elimination rate constant) is reported for t½, and the median (range) is reported for tmax. † The SHBG concentration reported here is the pre-dose concentration.
Regimen	Analyte	Arithmetic Mean *(%CV) by Pharmacokinetic Parameter
		Cmax (pg/mL)	tmax (hr)	AUC(0-24) (pg/mL•h)	Cmin (pg/mL)	t½ (hr)	Cavg (pg/mL)
Day 1 (Single Dose)	NE	8420 (31)	1.0 (0.7-4.0)	33390 (40)	--	--	--
	EE	64.5 (27)	1.3 (0.7-4.0)	465.4 (26)	--	--	--
	SHBG	--	--	--	57.5 (37)†	--	--
Day 24 (Multiple Dose)	NE	16400 (26)	1.3 (0.7–4.0)	88160 (30)	880 (51)	8.4	3670 (30)
	EE	81.9 (24)	1.7 (1.0–2.0)	701.3 (28)	11.4 (43)	14.5	29.2 (28)
	SHBG	--	--	--	144 (24)	--	--
Cmax = Maximum plasma concentration; tmax = Time of Cmax ; Cmin = minimum plasma concentration at steady-state ; AUC(0-24) = Area under plasma concentration versus time curve from 0 to 24 hours ; t½ = Apparent first-order terminal elimination half-life ; Cavg = Average plasma concentration = AUC(0–24)/24 %CV = Coefficient of Variation (%); SHBG = Sex Hormone Binding Globulin (nmol/L)

Effect of Food: Loestrin 24 FE tablets may be administered without regard to meals. A single-dose administration of Loestrin 24 FE tablet with food decreased the maximum concentration of norethindrone by 11% and increased the extent of absorption by 27% and decreased the maximum concentration of ethinyl estradiol by 30% but not the extent of absorption.

Distribution

Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg. Plasma protein binding of both steroids is extensive (>95%); norethindrone binds to both albumin and SHBG, whereas ethinyl estradiol binds only to albumin. Although ethinyl estradiol does not bind to SHBG, it induces SHBG synthesis.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.

Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy ethinyl estradiol, formed by the CYP3A4 isoform of cytochrome P450. Part of the first-pass metabolism of ethinyl estradiol is believed to occur in gastrointestinal mucosa. Ethinyl estradiol may undergo enterohepatic circulation.

Excretion

Norethindrone and ethinyl estradiol are excreted in both urine and feces, primarily as metabolites. Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg). Steady-state elimination half-lives of norethindrone and ethinyl estradiol following administration of Loestrin 24 FE tablets are approximately 8 hours and 14 hours, respectively.

Special Populations

Race. The effect of race on the disposition of norethindrone and ethinyl estradiol after Loestrin 24 FE administration has not been evaluated.

Renal Insufficiency. The effect of renal disease on the disposition of norethindrone and ethinyl estradiol after Loestrin 24 FE administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma ethinyl estradiol concentrations were higher and norethindrone concentrations were unchanged compared to concentrations in premenopausal women with normal renal function.

Hepatic Insufficiency. The effect of hepatic disease on the disposition of norethindrone and ethinyl estradiol after Loestrin 24 FE administration has not been evaluated. However, ethinyl estradiol and norethindrone may be poorly metabolized in patients with impaired liver function.

Drug-Drug Interactions

See PRECAUTIONS section—DRUG INTERACTIONS

Indications and Usage for Loestrin 24 FE

Loestrin 24 FE is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.

Oral contraceptives are highly effective. Table 2 lists the typical unplanned pregnancy rates for users of combination 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 2 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.

Source: Trussell J, Stewart F, 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.
* Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year † 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 ‡ Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason § The percentage of women becoming pregnant noted 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% became pregnant in one year. This estimate was lowered slightly (to 85%) to represent the percentage that would become pregnant within one year among women now relying on reversible methods of contraception if they abandon contraception altogether ¶ Foams, creams, gels, vaginal suppositories and vaginal film # Cervical mucous (ovulation) method supplemented by calendar in the preovulatory and basal body temperature in the postovulatory phases Þ With spermicidal cream or jelly ß Without spermicides à 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) è 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
	% of Women Experiencing an Unintended Pregnancy within the First Year of Use		% of Women Continuing Use at One Year*
Method      (1)	Typical Use† (2)	Perfect Use‡ (3)	(4)
Chance§	85	85
Spermicides¶	26	6	40
Periodic abstinence	25		63
Calendar		9
Ovulation Method		3
Sympto-thermal#		2
Post-Ovulation		1
CapÞ
Parous Women	40	26	42
Nulliparous Women	20	9	56
Sponge
Parous Women	40	20	42
Nulliparous Women	20	9	56
DiaphragmÞ	20	6	56
Withdrawal	19	4
Condomß
Female (reality)	21	5	56
Male	14	3	61
Pill	5		71
Progestin only		0.5
Combined		0.1
IUD
Progesterone T	2.0	1.5	81
Copper T 380A	0.8	0.6	78
LNg 20	0.1	0.1	81
Depo-Provera®	0.3	0.3	70
Norplant® and Norplant® 2	0.05	0.05	88
Female Sterilization	0.5	0.5	100
Male Sterilization	0.15	0.10	100
Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces risk of pregnancy by at least 75%à
Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraceptionè

Clinical Studies

In a clinical study, 743 women, 18 to 45 years of age, were treated with Loestrin 24 FE for up to six 28-day cycles providing a total of 3,823 treatment-cycles of exposure. A total of 583 women completed 6 cycles of treatment. There were a total of 5 on-treatment pregnancies in 3,565 treatment cycles during which no backup contraception was used. The Pearl Index for Loestrin 24 FE was 1.82.

Contraindications

Oral contraceptives should not be used in women who currently have the following conditions:

• Thrombophlebitis or thromboembolic disorders


• A past history of deep vein thrombophlebitis or thromboembolic disorders


• Cerebrovascular or coronary artery disease (current or history)


• Valvular heart disease with thrombogenic complications


• Severe hypertension


• Diabetes with vascular involvement


• Headaches with focal neurological symptoms


• Major surgery with prolonged immobilization


• Known or suspected carcinoma of the breast or personal history of breast cancer


• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia


• Undiagnosed abnormal genital bleeding


• Cholestatic jaundice of pregnancy or jaundice with prior pill use


• Hepatic adenomas or carcinomas, or active liver disease


• Known or suspected pregnancy


• Hypersensitivity to any component of this product

Warnings

Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with the extent of smoking (in epidemiologic studies, 15 or more cigarettes per day was associated with a significantly increased risk) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.

The use of oral contraceptives is associated with increased risk of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, 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 certain inherited thrombophilias, 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. 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. 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. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Figure 3) among women who use oral contraceptives.

FIGURE 3. CIRCULATORY DISEASE MORTALITY RATES FOR 100,000 WOMEN-YEARS BY AGE, SMOKING STATUS AND ORAL CONTRACEPTIVE USE

Layde PM, Beral V. Lancet 1981;1:541-546.

Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age, and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS). Such increases in risk factors have been associated with an increased risk of heart disease and the risk increases with the number of risk factors present. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.

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 non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. 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. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped.

A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. 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 to six 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 risk 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, while smoking interacted to increase the risk for hemorrhagic strokes.

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. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers 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. The attributable risk is also greater in older women. Oral contraceptives also increase the risk for stroke in women with other underlying risk factors such as certain inherited or acquired thrombophilias, hyperlipidemias, and obesity. Women with migraine (particularly migraine with aura) who take combination oral contraceptives may be at an increased risk of stroke.

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. A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents. 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 nature and absolute amount of progestogens used in the contraceptive. The 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 persisted for at least 9 years for women 40 to 49 years old who had used oral contraceptives for five or more years but this increased risk was not demonstrated in other age groups. 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. 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 3).

TABLE 3 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

* Deaths are birth related † Deaths are method related
	AGE
Method of control and outcome	15-19	20-24	25-29	30-34	35-39	40-44
No fertility control methods*	7.0	7.4	9.1	14.8	25.7	28.2
Oral contraceptives nonsmoker†	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
Ory HW. Family Planning Perspectives 1983; 15:57-63.

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 risk. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth.

The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970s but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling.

Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risk may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.

Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective and meets the individual patient needs.

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. Although the risk of breast cancer may be slightly increased among current users of oral contraceptives (RR = 1.24), this excess risk decreases over time after oral contraceptive discontinuation and by 10 years after cessation the increased risk disappears. The risk does not increase with duration of use, and no relationships have been found with dose or type of steroid. The patterns of risk are also similar regardless of a woman's reproductive history or her family breast cancer history. The subgroup for whom risk has been found to be significantly elevated is women who first used oral contraceptives before age 20, but because breast cancer is so rare at these young ages, the number of cases attributable to this early oral contraceptive use is extremely small. Breast cancers diagnosed in current or previous oral contraceptive users tend to be less advanced clinically than in never-users. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is a hormone-sensitive tumor.

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. 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 cancer 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 their occurrence 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. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.

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 that may lead to partial or complete loss of vision. 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. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy (see CONTRAINDICATIONS section).

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

Allegra-D 24 Hour Extended-Release Tablets (24 Hour)

Pronunciation: FEX-oh-FEN-a-deen/SOO-doe-e-FED-rin
Generic Name: Fexofenadine/Pseudoephedrine
Brand Name: Allegra-D 24 Hour

Allegra-D 24 Hour Extended-Release Tablets (24 Hour) are used for:

Relieving seasonal allergy symptoms, including sneezing; runny nose; itchy nose, palate, or throat; itchy, watery, or red eyes; and nasal congestion.

Allegra-D 24 Hour Extended-Release Tablets (24 Hour) are an antihistamine and decongestant combination. The antihistamine works by blocking the effects of histamine, which causes allergy symptoms such as sneezing, runny nose, and itchy or watery eyes. The decongestant works by stimulating the body's natural response and reducing the swelling in the blood vessels that supply the mucous membrane, thereby decreasing nasal congestion.

Do NOT use Allegra-D 24 Hour Extended-Release Tablets (24 Hour) if:

• you are allergic to any ingredient in Allegra-D 24 Hour Extended-Release Tablets (24 Hour)


• you have severe heart blood vessel disease or severe high blood pressure


• you have narrow-angle glaucoma or are unable to urinate (eg, urinary retention)


• you have had side effects from previous decongestant use (eg, trouble sleeping, involuntary trembling, irregular heart rhythm)


• you are taking droxidopa, furazolidone, a monoamine oxidase inhibitor (MAOI) (eg, phenelzine), or if you have taken an MAOI within the last 14 days

Contact your doctor or health care provider right away if any of these apply to you.

Before using Allegra-D 24 Hour Extended-Release Tablets (24 Hour):

Some medical conditions may interact with Allegra-D 24 Hour Extended-Release Tablets (24 Hour). Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have diabetes, an overactive thyroid, a kidney problem, an enlarged prostate, a seizure disorder (eg, epilepsy), high blood pressure, a heart problem, or glaucoma or increased pressure in the eye


• if you take medicine for high blood pressure

Some MEDICINES MAY INTERACT with Allegra-D 24 Hour Extended-Release Tablets (24 Hour). Tell your health care provider if you are taking any other medicines, especially any of the following:

• Digoxin or droxidopa because the risk of irregular heartbeat may be increased


• Erythromycin, furazolidone, ketoconazole, MAOIs (eg, phenelzine), methyldopa, or urinary alkalinizers (eg, potassium citrate) because they may increase the risk of Allegra-D 24 Hour Extended-Release Tablets (24 Hour)'s side effects


• Bromocriptine because the risk of its side effects may be increased by Allegra-D 24 Hour Extended-Release Tablets (24 Hour)


• Guanadrel, guanethidine, mecamylamine, reserpine, or other medicine for high blood pressure because their effectiveness may be decreased by Allegra-D 24 Hour Extended-Release Tablets (24 Hour)

This may not be a complete list of all interactions that may occur. Ask your health care provider if Allegra-D 24 Hour Extended-Release Tablets (24 Hour) may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Allegra-D 24 Hour Extended-Release Tablets (24 Hour):

Use Allegra-D 24 Hour Extended-Release Tablets (24 Hour) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Allegra-D 24 Hour Extended-Release Tablets (24 Hour) by mouth on an empty stomach at least 1 hour before or 2 hours after eating.


• Swallow Allegra-D 24 Hour Extended-Release Tablets (24 Hour) whole. Do not break, crush, or chew before swallowing.


• Take Allegra-D 24 Hour Extended-Release Tablets (24 Hour) with a full glass of water (8 oz/240 mL).


• Do not drink fruit juice at the same time that you take Allegra-D 24 Hour Extended-Release Tablets (24 Hour). Certain fruit juices (eg, grapefruit, apple, orange) may decrease Allegra-D 24 Hour Extended-Release Tablets (24 Hour)'s effectiveness.


• If you take antacids that contain aluminum or magnesium, do not take them at the same time as Allegra-D 24 Hour Extended-Release Tablets (24 Hour). Ask your doctor or pharmacist how to take them with Allegra-D 24 Hour Extended-Release Tablets (24 Hour).


• Do not take more of Allegra-D 24 Hour Extended-Release Tablets (24 Hour) than recommended by your doctor.


• If you miss a dose of Allegra-D 24 Hour Extended-Release Tablets (24 Hour), take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Allegra-D 24 Hour Extended-Release Tablets (24 Hour).

Important safety information:

• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) may cause dizziness. It does not usually cause drowsiness when used under normal circumstances at the recommended doses. However, these effects may be worse if you take it with alcohol or certain medicines. Use Allegra-D 24 Hour Extended-Release Tablets (24 Hour) with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.


• You may occasionally notice the tablet shell in your stool. This is normal and not a cause for concern.


• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) may interfere with skin allergy tests. If you are scheduled for a skin test, talk to your doctor. You may need to stop taking Allegra-D 24 Hour Extended-Release Tablets (24 Hour) for a few days before the tests.


• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) has an antihistamine and decongestant in it. Before you start any new medicine, check the label to see if it has an antihistamine or decongestant in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Diabetes patients - Allegra-D 24 Hour Extended-Release Tablets (24 Hour) may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Use Allegra-D 24 Hour Extended-Release Tablets (24 Hour) with caution in the ELDERLY; they may be more sensitive to its effects.


• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) should not be used in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Allegra-D 24 Hour Extended-Release Tablets (24 Hour) while you are pregnant. It is not known if Allegra-D 24 Hour Extended-Release Tablets (24 Hour) are found in breast milk. If you are or will be breast-feeding while you use Allegra-D 24 Hour Extended-Release Tablets (24 Hour), check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Allegra-D 24 Hour Extended-Release Tablets (24 Hour):

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dizziness; dry mouth; headache; nausea; nervousness; trouble sleeping.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody diarrhea; chest pain; difficult urination; fast or irregular heartbeat; fever; hallucinations; mental or mood changes; seizures; involuntary shaking or tremor; stomach pain.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Allegra-D 24 Hour (24 Hour) side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include chest pain; difficulty breathing; drowsiness; fast or irregular heartbeat; loss of consciousness; seizures; severe or persistent dizziness or headache; unusual nervousness or excitement.

Proper storage of Allegra-D 24 Hour Extended-Release Tablets (24 Hour):

Store Allegra-D 24 Hour Extended-Release Tablets (24 Hour) at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Allegra-D 24 Hour Extended-Release Tablets (24 Hour) out of the reach of children and away from pets.

General information:

• If you have any questions about Allegra-D 24 Hour Extended-Release Tablets (24 Hour), please talk with your doctor, pharmacist, or other health care provider.


• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Allegra-D 24 Hour Extended-Release Tablets (24 Hour). If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Allegra-D 24 Hour Extended-Release Tablets (24 Hour) resources

• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) Side Effects (in more detail)
• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) Use in Pregnancy & Breastfeeding
• Drug Images
• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) Drug Interactions
• Allegra-D 24 Hour Extended-Release Tablets (24 Hour) Support Group
• 7 Reviews for Allegra-D 24 Hour (24 Hour) - Add your own review/rating

Compare Allegra-D 24 Hour Extended-Release Tablets (24 Hour) with other medications

• Hay Fever

Diovan 40mg film-coated Tablets

1. Name Of The Medicinal Product

Diovan^®

Valsartan

* Intensive monitoring is requested only when used for the recently licensed indications of heart failure and hypertension in children and adolescents 6 to 18 years of age.

2. Qualitative And Quantitative Composition

One film-coated tablet contains 40 mg of valsartan.

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Yellow, ovaloid, film-coated tablet with bevelled edges, slightly convex, scored on one side, with debossing “D” on one side of the score and “O” on the other side of the score and “NVR” on the reverse side of the tablet.

The tablet can be divided into equal halves.

4. Clinical Particulars

4.1 Therapeutic Indications

Hypertension

Treatment of hypertension in children and adolescents 6 to 18 years of age.

Recent myocardial infarction

Treatment of clinically stable adult patients with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction after a recent (12 hours

Heart failure

Treatment of symptomatic heart failure in adult patients when Angiotensin Converting Enzyme (ACE) inhibitors cannot be used, or as add-on therapy to ACE inhibitors when beta blockers cannot be used (see sections 4.4 and 5.1).

4.2 Posology And Method Of Administration

Posology

Recent myocardial infarction

In clinically stable patients, therapy may be initiated as early as 12 hours after a myocardial infarction. After an initial dose of 20 mg twice daily, valsartan should be titrated to 40 mg, 80 mg, and 160 mg twice daily over the next few weeks. The starting dose is provided by the 40 mg divisible tablet. The target maximum dose is 160 mg twice daily. In general, it is recommended that patients achieve a dose level of 80 mg twice daily by two weeks after treatment initiation and that the target maximum dose, 160 mg twice daily, be achieved by three months, based on the patient's tolerability. If symptomatic hypotension or renal dysfunction occur, consideration should be given to a dose reduction.

Valsartan may be used in patients treated with other post-myocardial infarction therapies, e.g. thrombolytics, acetylsalicylic acid, beta blockers, statins, and diuretics. The combination with ACE inhibitors is not recommended (see sections 4.4 and 5.1).

Evaluation of post-myocardial infarction patients should always include assessment of renal function.

Heart failure

The recommended starting dose of Diovan is 40 mg twice daily. Uptitration to 80 mg and 160 mg twice daily should be done at intervals of at least two weeks to the highest dose, as tolerated by the patient. Consideration should be given to reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses.

Valsartan may be administered with other heart failure therapies. However, the triple combination of an ACE inhibitor, a beta blocker and valsartan is not recommended (see sections 4.4 and 5.1).

Evaluation of patients with heart failure should always include assessment of renal function.

Additional information on special populations

Elderly

No dose adjustment is required in elderly patients.

Renal impairment

No dose adjustment is required for patients with a creatinine clearance> 10ml/min. (see sections 4.4 and 5.2).

Hepatic impairment

Diovan is contraindicated in patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis (see sections 4.3, 4.4 and 5.2). In patients with mild to moderate hepatic impairment without cholestasis, the dose of valsartan should not exceed 80 mg.

Paediatric population

Paediatric hypertension

Children and adolescents 6 to 18 years of age

The initial dose is 40 mg once daily for children weighing below 35 kg and 80 mg once daily for those weighing 35 kg or more. The dose should be adjusted based on blood pressure response. For maximum doses studied in clinical trials please refer to the table below.

Doses higher than those listed have not been studied and are therefore not recommended.

Weight	Maximum dose studied in clinical trials
	80 mg
	160 mg
	320 mg

Children less than 6 years of age

Available data are described in sections 4.8, 5.1 and 5.2. However safety and efficacy of Diovan in children aged 1 to 6 years have not been established.

Use in paediatric patients aged 6 to 18 years with renal impairment

Use in paediatric patients with a creatinine clearance <30 ml/min and paediatric patients undergoing dialysis has not been studied, therefore valsartan is not recommended in these patients. No dose adjustment is required for paediatric patients with a creatinine clearance >30 ml/min. Renal function and serum potassium should be closely monitored (see sections 4.4 and 5.2).

Use in paediatric patients aged 6 to 18 years with hepatic impairment

As in adults, Diovan is contraindicated in paediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis (see sections 4.3, 4.4 and 5.2). There is limited clinical experience with Diovan in paediatric patients with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in these patients.

Paediatric heart failure and recent myocardial infarction

Diovan is not recommended for the treatment of heart failure or recent myocardial infarction in children and adolescents below the age of 18 years due to the lack of data on safety and efficacy.

Method of administration

Diovan may be taken independently of a meal and should be administered with water.

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients.

- Severe hepatic impairment, biliary cirrhosis and cholestasis.

- Second and third trimester of pregnancy (see sections 4.4 and 4.6)

4.4 Special Warnings And Precautions For Use

Hyperkalaemia

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin, etc.) is not recommended. Monitoring of potassium should be undertaken as appropriate.

Impaired renal function

There is currently no experience on the safe use in patients with a creatinine clearance <10 ml/min and patients undergoing dialysis, therefore valsartan should be used with caution in these patients. No dose adjustment is required for adult patients with a creatinine clearance>10 ml/min (see sections 4.2 and 5.2).

Hepatic impairment:

In patients with mild to moderate hepatic impairment without cholestasis, Diovan should be used with caution (see sections 4.2 and 5.2).

Sodium- and/or volume-depleted patients

In severely sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with Diovan. Sodium and/or volume depletion should be corrected before starting treatment with Diovan, for example by reducing the diuretic dose.

Renal artery stenosis

In patients with bilateral renal artery stenosis or stenosis to a solitary kidney, the safe use of Diovan has not been established.

Short-term administration of Diovan to twelve patients with renovascular hypertension secondary to unilateral renal artery stenosis did not induce any significant changes in renal haemodynamics, serum creatinine, or blood urea nitrogen (BUN). However, other agents that affect the renin-angiotensin system may increase blood urea and serum creatinine in patients with unilateral renal artery stenosis, therefore monitoring of renal function is recommended when patients are treated with valsartan.

Kidney transplantation

There is currently no experience on the safe use of Diovan in patients who have recently undergone kidney transplantation.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism should not be treated with Diovan as their renin-angiotensin system is not activated.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).

Pregnancy

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Recent-myocardial infarction

The combination of captopril and valsartan has shown no additional clinical benefit, instead the risk for adverse events increased compared to treatment with the respective therapies (see sections 4.2 and 5.1). Therefore, the combination of valsartan with an ACE inhibitor is not recommended.

Caution should be observed when initiating therapy in post-myocardial infarction patients. Evaluation of post-myocardial infarction patients should always include assessment of renal function (see section 4.2).

Use of Diovan in post-myocardial infarction patients commonly results in some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension is not usually necessary provided dosing instructions are followed (see section 4.2).

Heart Failure

In patients with heart failure, the triple combination of an ACE inhibitor, a beta blocker and Diovan has not shown any clinical benefit (see section 5.1). This combination apparently increases the risk for adverse events and is therefore not recommended.

Caution should be observed when initiating therapy in patients with heart failure. Evaluation of patients with heart failure should always include assessment of renal function (see section 4.2).

Use of Diovan in patients with heart failure commonly results in some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension is not usually necessary provided dosing instructions are followed (see section 4.2).

In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotaemia and in rare cases with acute renal failure and/or death. As valsartan is an angiotensin II antagonist, it cannot be excluded that the use of Diovan may be associated with impairment of the renal function.

Paediatric population

Impaired renal function

Use in paediatric patients with a creatinine clearance <30 ml/min and paediatric patients undergoing dialysis has not been studied, therefore valsartan is not recommended in these patients. No dose adjustment is required for paediatric patients with a creatinine clearance >30 ml/min (see sections 4.2 and 5.2). Renal function and serum potassium should be closely monitored during treatment with valsartan. This applies particularly when valsartan is given in the presence of other conditions (fever, dehydration) likely to impair renal function.

Impaired hepatic function

As in adults, Diovan is contraindicated in paediatric patients with severe hepatic impairment, biliary cirrhosis and in patients with cholestasis (see sections 4.3 and 5.2). There is limited clinical experience with Diovan in paediatric patients with mild to moderate hepatic impairment. The dose of valsartan should not exceed 80 mg in these patients.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant use not recommended

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concurrent use of ACE inhibitors. Due to the lack of experience with concomitant use of valsartan and lithium, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels

If a medicinal product that affects potassium levels is considered necessary in combination with valsartan, monitoring of potassium plasma levels is advised.

Caution required with concomitant use

Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid>3 g/day), and non-selective NSAIDs

When angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.

Others

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan or any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipine, glibenclamide.

Paediatric population

In hypertension in children and adolescents, where underlying renal abnormalities are common, caution is recommended with the concomitant use of valsartan and other substances that inhibit the renin angiotensin aldosterone system which may increase serum potassium. Renal function and serum potassium should be closely monitored.

4.6 Pregnancy And Lactation

Pregnancy

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contra-indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however, a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with AIIRAs, similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.

AIIRAs therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia); see also section 5.3 “Preclinical safety data”.

Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see also sections 4.3 and 4.4).

Lactation

Because no information is available regarding the use of valsartan during breastfeeding, Diovan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Fertility

Valsartan had no adverse effects on the reproductive performance of male or female rats at oral doses up to 200 mg/kg/day. This dose is 6 times the maximum recommended human dose on a mg/m² basis (calculations assume an oral dose of 320 mg/day and a 60-kg patient).

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.

4.8 Undesirable Effects

In controlled clinical studies in adult patients with hypertension, the overall incidence of adverse reactions (ADRs) was comparable with placebo and is consistent with the pharmacology of valsartan. The incidence of ADRs did not appear to be related to dose or treatment duration and also showed no association with gender, age or race.

The ADRs reported from clinical studies, post-marketing experience and laboratory findings are listed below according to system organ class.

Adverse reactions are ranked by frequency, the most frequent first, using the following convention: very common (

For all the ADRs reported from post-marketing experience and laboratory findings, it is not possible to apply any ADR frequency and therefore they are mentioned with a "not known" frequency.

• Hypertension

Blood and lymphatic system disorders
Not known	Decrease in haemoglobin, Decrease in haematocrit, Neutropenia, Thrombocytopenia
Immune system disorders
Not known	Hypersensitivity including serum sickness
Metabolism and nutrition disorders
Not known	Increase of serum potassium
Ear and labyrinth system disorders
Uncommon	Vertigo
Vascular disorders
Not known	Vasculitis
Respiratory, thoracic and mediastinal disorders
Uncommon	Cough
Gastrointestinal disorders
Uncommon	Abdominal pain
Hepato-biliary Disorders
Not known	Elevation of liver function values including increase of serum bilirubin.
Skin and subcutaneous tissue disorders
Not known	Angioedema, Rash, Pruritus
Musculoskeletal and connective tissue disorders
Not known	Myalgia
Renal and urinary disorders
Not known	Renal failure and impairment, Elevation of serum creatinine
General disorders and administration site conditions
Uncommon:	Fatigue

Paediatric population

Hypertension

The antihypertensive effect of valsartan has been evaluated in two randomised, double-blind clinical studies in 561 paediatric patients from 6 to 18 years of age. With the exception of isolated gastrointestinal disorders (like abdominal pain, nausea, vomiting) and dizziness, no relevant differences in terms of type, frequency and severity of adverse reactions were identified between the safety profile for paediatric patients aged 6 to 18 years and that previously reported for adult patients.

Neurocognitive and developmental assessment of paediatric patients aged 6 to 16 years of age revealed no overall clinically relevant adverse impact after treatment with Diovan for up to one year.

In a double-blind randomized study in 90 children aged 1 to 6 years, which was followed by a one-year open-label extension, two deaths and isolated cases of marked liver transaminases elevations were observed. These cases occurred in a population who had significant comorbidities. A causal relationship to Diovan has not been established. In a second study in which 75 children aged 1 to 6 years were randomised, no significant liver transaminase elevations or death occurred with valsartan treatment.

Hyperkalaemia was more frequently observed in children and adolescents aged 6 to 18 years with underlying chronic kidney disease.

The safety profile seen in controlled-clinical studies in patients with post-myocardial infarction and/or heart failure varies from the overall safety profile seen in hypertensive patients. This may relate to the patients underlying disease. ADRs that occurred in post-myocardial infarction and/or heart failure patients are listed below:

• Post-myocardial infarction and/or heart failure (studied in adult patients only)

Blood and lymphatic system disorders
Not known	Thrombocytopenia
Immune system disorders
Not known	Hypersensitivity including serum sickness
Metabolism and nutrition disorders
Uncommon	Hyperkalaemia
Not known	Increase of serum potassium
Nervous system disorders
Common	Dizziness, Postural dizziness
Uncommon	Syncope, Headache
Ear and labyrinth system disorders
Uncommon	Vertigo
Cardiac disorders
Uncommon	Cardiac failure
Vascular disorders
Common	Hypotension, Orthostatic hypotension
Not known	Vasculitis
Respiratory, thoracic and mediastinal disorders
Uncommon	Cough
Gastrointestinal disorders
Uncommon	Nausea, Diarrhoea
Hepatobiliary Disorders
Not known	Elevation of liver function values
Skin and subcutaneous tissue disorders
Uncommon	Angioedema
Not known	Rash, Pruritus
Musculoskeletal and connective tissue disorders
Not known	Myalgia
Renal and urinary disorders
Common	Renal failure and impairment
Uncommon	Acute renal failure, Elevation of serum creatinine
Not known	Increase in Blood Urea Nitrogen
General disorders and administration site conditions
Uncommon	Asthenia, Fatigue

4.9 Overdose

Symptoms

Overdose with Diovan may result in marked hypotension, which could lead to depressed levels of consciousness, circulatory collapse and/or shock.

Treatment

The therapeutic measures depend on the time of ingestion and the type and severity of the symptoms; stabilisation of the circulatory condition is of prime importance.

If hypotension occurs, the patient should be placed in a supine position and blood volume correction should be undertaken.

Valsartan is unlikely to be removed by haemodialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic groups: Angiotensin II Antagonists. Plain, ATC code: C09CA03

Valsartan is an orally active, potent, and specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT₁ receptor subtype, which is responsible for the known actions of angiotensin II. The increased plasma levels of Ang II following AT₁ receptor blockade with valsartan may stimulate the unblocked AT₂ receptor, which appears to counterbalance the effect of the AT₁ receptor. Valsartan does not exhibit any partial agonist activity at the AT₁ receptor and has much (about 20,000 fold) greater affinity for the AT₁ receptor than for the AT₂ receptor. Valsartan is not known to bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Valsartan does not inhibit ACE (also known as kininase II) which converts Ang I to Ang II and degrades bradykinin. Since there is no effect on ACE and no potentiation of bradykinin or substance P, angiotensin II antagonists are unlikely to be associated with coughing. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (P < 0.05) less in patients treated with valsartan than in those treated with an ACE inhibitor (2.6 % versus 7.9 % respectively). In a clinical trial of patients with a history of dry cough during ACE inhibitor therapy, 19.5 % of trial subjects receiving valsartan and 19.0 % of those receiving a thiazide diuretic experienced cough compared to 68.5 % of those treated with an ACE inhibitor (P < 0.05).

Recent myocardial infarction

The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) was a randomised, controlled, multinational, double-blind study in 14,703 patients with acute myocardial infarction and signs, symptoms or radiological evidence of congestive heart failure and/or evidence of left ventricular systolic dysfunction (manifested as an ejection fraction

Valsartan was as effective as captopril in reducing all-cause mortality after myocardial infarction. All-cause mortality was similar in the valsartan (19.9 %), captopril (19.5 %), and valsartan + captopril (19.3 %) groups. Combining valsartan with captopril did not add further benefit over captopril alone. There was no difference between valsartan and captopril in all-cause mortality based on age, gender, race, baseline therapies or underlying disease. Valsartan was also effective in prolonging the time to and reducing cardiovascular mortality, hospitalisation for heart failure, recurrent myocardial infarction, resuscitated cardiac arrest, and non-fatal stroke (secondary composite endpoint).

The safety profile of valsartan was consistent with the clinical course of patients treated in the post-myocardial infraction setting. Regarding renal function, doubling of serum creatinine was observed in 4.2% of valsartan-treated patients, 4.8 % of valsartan+captopril-treated patients and 3.4% of captopril-treated patients. Discontinuations due to various types of renal dysfunction occurred in 1.1% of valsartan-treated patients, 1.3% in valsartan+captopril patients, and 0.8% of captopril patients. An assessment of renal function should be included in the evaluation of patients post-myocardial infarction.

There was no difference in all-cause mortality, cardiovascular mortality or morbidity when beta-blockers were administered together with the combination of valsartan + captopril, valsartan alone, or captopril alone. Irrespective of treatment, mortality was lower in the group of patients treated with a beta-blocker, suggesting that the known beta blocker benefit in this population was maintained in this trial.

Heart failure

Val-HeFT was a randomised, controlled, multinational clinical trial of valsartan compared with placebo on morbidity and mortality in 5,010 NYHA class II (62%), III (36%) and IV (2%) heart failure patients receiving usual therapy with LVEF <40% and left ventricular internal diastolic diameter (LVIDD)>2.9 cm/m². Baseline therapy included ACE inhibitors (93%), diuretics (86%), digoxin (67%) and beta blockers (36%). The mean duration of follow-up was nearly two years. The mean daily dose of Diovan in Val-HeFT was 254 mg. The study had two primary endpoints: all cause mortality (time to death) and composite mortality and heart failure morbidity (time to first morbid event) defined as death, sudden death with resuscitation, hospitalisation for heart failure, or administration of intravenous inotropic or vasodilator agents for four hours or more without hospitalisation.

All cause mortality was similar (p=NS) in the valsartan (19.7%) and placebo (19.4%) groups. The primary benefit was a 27.5% (95% CI: 17 to 37%) reduction in risk for time to first heart failure hospitalisation (13.9% vs. 18.5%). Results appearing to favour placebo (composite mortality and morbidity was 21.9% in placebo vs. 25.4% in valsartan group) were observed for those patients receiving the triple combination of an ACE inhibitor, a beta blocker and valsartan.

In a subgroup of patients not receiving an ACE inhibitor (n=366), the morbidity benefits were greatest. In this subgroup all-cause mortality was significantly reduced with valsartan compared to placebo by 33% (95% CI: –6% to 58%) (17.3% valsartan vs. 27.1% placebo) and the composite mortality and morbidity risk was significantly reduced by 44% (24.9% valsartan vs. 42.5% placebo).

In patients receiving an ACE inhibitor without a beta-blocker, all cause mortality was similar (p=NS) in the valsartan (21.8%) and placebo (22.5%) groups. Composite mortality and morbidity risk was significantly reduced by 18.3% (95% CI: 8% to 28%) with valsartan compared with placebo (31.0% vs. 36.3%).

In the overall Val-HeFT population, valsartan treated patients showed significant improvement in NYHA class, and heart failure signs and symptoms, including dyspnoea, fatigue, oedema and rales compared to placebo. Patients treated with valsartan had a better quality of life as demonstrated by change in the Minnesota Living with Heart Failure Quality of Life score from baseline at endpoint than placebo. Ejection fraction in valsartan treated patients was significantly increased and LVIDD significantly reduced from baseline at endpoint compared to placebo.

Paediatric population

Hypertension

The antihypertensive effect of valsartan have been evaluated in four randomized, double-blind clinical studies in 561 paediatric patients from 6 to 18 years of age and 165 paediatric patients 1 to 6 years of age. Renal and urinary disorders, and obesity were the most common underlying medical conditions potentially contributing to hypertension in the children enrolled in these studies.

Clinical experience in children at or above 6 years of age

In a clinical study involving 261 hypertensive paediatric patients 6 to 16 years of age, patients who weighed <35 kg received 10, 40 or 80 mg of valsartan tablets daily (low, medium and high doses), and patients who weighed

In another clinical study involving 300 hypertensive paediatric patients 6 to 18 years of age, eligible patients were randomized to receive valsartan or enalapril tablets for 12 weeks. Children weighing between

Clinical experience in children less than 6 years of age

Two clinical studies were conducted in patients aged 1 to 6 years with 90 and 75 patients, respectively. No children below the age of 1 year were enrolled in these studies. In the first study, the efficacy of valsartan was confirmed compared to placebo but a dose-response could not be demonstrated. In the second study, higher doses of valsartan were associated with greater BP reductions, but the dose response trend did not achieve statistical significance and the treatment difference compared to placebo was not significant. Because of these inconsistencies, valsartan is not recommended in this age group (see section 4.8).

The European Medicines Agency has waived the obligation to submit the results of studies with Diovan in all subsets of the paediatric population in heart failure and heart failure after recent myocardial infarction. See section 4.2 for information on paediatric use.

5.2 Pharmacokinetic Properties

Absorption:

Following oral administration of valsartan alone, peak plasma concentrations of valsartan are reached in 2–4 hours with tablets and 1–2 hours with solution formulation. Mean absolute bioavailability is 23% and 39% with tablets and solution formulation, respectively. Food decreases exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (C_max) by about 50%, although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in the therapeutic effect, and valsartan can therefore be given either with or without food.

Distribution:

The steady-state volume of distribution of valsartan after intravenous administration is about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is highly bound to serum proteins (94–97%), mainly serum albumin.

Biotransformation:

Valsartan is not biotransformed to a high extent as only about 20% of dose is recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations (less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive.

Excretion:

Valsartan shows multiexponential decay kinetics (t_½α <1 h and t_½ß about 9 h). Valsartan is primarily eliminated by biliary excretion in faeces (about 83% of dose) and renally in urine (about 13% of dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of valsartan is 6 hours.

In heart failure patients:

The average time to peak concentration and elimination half-life of valsartan in heart failure patients are similar to that observed in healthy volunteers. AUC and C_max values of valsartan are almost proportional with increasing dose over the clinical dosing range (40 to 160 mg twice a day). The average accumulation factor is about 1.7. The apparent clearance of valsartan following oral administration is approximately 4.5 l/h. Age does not affect the apparent clearance in heart failure patients.

Special populations

Elderly

A somewhat higher systemic exposure to valsartan was observed in some elderly subjects than in young subjects; however, this has not been shown to have any clinical significance.

Impaired renal function

As expected for a compound where renal clearance accounts for only 30% of total plasma clearance, no correlation was seen between renal function and systemic exposure to valsartan. Dose adjustment is therefore not required in patients with renal impairment (creatinine clearance>10 ml/min). There is currently no experience on the safe use in patients with a creatinine clearance <10 ml/min and patients undergoing dialysis, therefore valsartan should be used with caution in these patients (see sections 4.2 and 4.4). Valsartan is highly bound to plasma protein and is unlikely to be removed by dialysis.

Hepatic impairment

Approximately 70% of the dose absorbed is eliminated in the bile, essentially in the unchanged form. Valsartan does not undergo any noteworthy biotransformation. A doubling of exposure (AUC) was observed in patients with mild to moderate hepatic impairment compared to healthy subjects. However, no correlation was observed between plasma valsartan concentration versus degree of hepatic dysfunction. Diovan has not been studied in patients with severe hepatic dysfunction (see sections 4.2, 4.3 and 4.4).

Paediatric population

In a

Urex

Generic Name: methenamine (meh THEH na meen)

Brand Names: Hiprex, Mandelamine, Urex

What is Urex (methenamine)?

Methenamine is a urinary antiinfective medicine. Methenamine fights bacteria in the urine and bladder.

Methenamine may be used to treat and prevent urinary tract infections.

Methenamine may also be used for purposes other than those listed here.

What is the most important information I should know about Urex (methenamine)?

Take all of the methenamine that has been prescribed for you even if you begin to feel better. Symptoms may start to improve before the infection is completely treated. Take each dose with a full glass of water. Plenty of fluid should be consumed while taking methenamine.

Your healthcare provider may recommend drinking additional water and/or certain fruit juices (e.g., cranberry, plum, prune) and increased protein in the diet while taking methenamine to ensure adequate hydration and acidity of the urine. It may also be recommended to avoid citrus fruits and juices (e.g., orange, grapefruit, lemon), milk and dairy products, and antacids during treatment with methenamine. These products may decrease the effectiveness of methenamine. Follow your healthcare provider's instructions.

What should I discuss with my healthcare provider before taking Urex (methenamine)?

Before taking methenamine, talk to your doctor if you

• have liver problems;


• have kidney problems;


• 
  

  have other medical conditions; or

  
  


• 
  

  take other medications.

  
  

You may not be able to take methenamine, or you may require a dosage adjustment or special monitoring during treatment.

Methenamine is in the FDA pregnancy category C. This means that it is not known whether it will be harmful to an unborn baby. Do not take methenamine without first talking to your doctor if you are pregnant or could become pregnant during treatment. Methenamine passes into breast milk and may affect a nursing baby. Do not take methenamine without first talking to your doctor if you are breast-feeding a baby.

How should I take Urex (methenamine)?

Take methenamine exactly as directed by your doctor. If you do not understand these instructions, ask your doctor, nurse, or pharmacist to explain them to you.

Take each dose with a full glass of water. Plenty of fluid should be consumed while taking methenamine. Methenamine should be taken with food to reduce stomach upset. Do not crush or chew the enteric-coated tablets. Swallow them whole. They are specially formulated to be less irritating to the stomach. Talk to your doctor if swallowing the tablets is difficult. Shake the liquid form of methenamine well before measuring a dose. To ensure that you get the correct dose, measure the suspension with a dose-measuring spoon, dropper, or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

It is important to take methenamine at regularly scheduled intervals to get the most benefit.

Take all of the methenamine that has been prescribed for you even if you begin to feel better. Symptoms may start to improve before the infection is completely treated.

Your healthcare provider may recommend drinking additional water and/or certain fruit juices (e.g., cranberry, plum, prune) and increased protein in the diet while taking methenamine to ensure adequate hydration and acidity of the urine. It may also be recommended to avoid citrus fruits and juices (e.g., orange, grapefruit, lemon), milk and dairy products, and antacids during treatment with methenamine. These products may decrease the effectiveness of methenamine. Follow your healthcare provider's instructions.

Store methenamine at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the dose you missed and take only the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.

What happens if I overdose?

Seek emergency medical attention if an overdose is suspected.

Symptoms of a methenamine overdose are not known.

What should I avoid while taking Urex (methenamine)?

Your healthcare provider may recommend drinking additional water and/or certain fruit juices (e.g., cranberry, plum, prune) and increased protein in the diet while taking methenamine to ensure adequate hydration and acidity of the urine. It may also be recommended to avoid citrus fruits and juices (e.g., orange, grapefruit, lemon), milk and dairy products, and antacids during treatment with methenamine. These products may decrease the effectiveness of methenamine. Follow your healthcare provider's instructions.

Urex (methenamine) side effects

If you experience any of the following serious side effects, stop taking methenamine and seek emergency medical attention or contact your doctor immediately:

• 
  

  an allergic reaction (shortness of breath; closing of the throat; swelling of the lips, face, or tongue; or hives;

  
  


• 
  

  lower back or side pain;

  
  


• 
  

  blood in urine; or

  
  


• 
  

  increasingly painful or difficult urination.

  
  

Other, less serious side effects may be more likely to occur. Continue to take methenamine and talk to your doctor if you experience

• 
  

  nausea or upset stomach;

  
  


• 
  

  decreased appetite; or

  
  


• 
  

  skin rash.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Urex (methenamine)?

Do not take methenamine without first talking to your doctor if you are taking:

• 
  

  a carbonic anhydrase inhibitor such as acetazolamide (Diamox), dichlorphenamide (Daranide), or methazolamide (Glauctabs, MZM, Neptazane);

  
  


• 
  

  a sulfa product such as sulfadiazine, sulfamethoxazole (Bactrim, Septra, others), sulfasalazine (Azulfidine), and others;

  
  


• 
  

  a diuretic (water pill); or

  
  


• 
  

  a product that contains aluminum, calcium, magnesium, sodium bicarbonate, potassium or sodium citrate, or citric acid (such as antacids, vitamin or mineral pills, urinary alkalinizers, and other medications).

  
  

You may not be able to take methenamine, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with methenamine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

More Urex resources

• Urex Side Effects (in more detail)
• Urex Use in Pregnancy & Breastfeeding
• Drug Images
• Urex Drug Interactions
• Urex Support Group
• 0 Reviews for Urex - Add your own review/rating

• Urex MedFacts Consumer Leaflet (Wolters Kluwer)


• Urex Advanced Consumer (Micromedex) - Includes Dosage Information


• Methenamine Prescribing Information (FDA)


• Methenamine Monograph (AHFS DI)


• Hiprex Prescribing Information (FDA)

Compare Urex with other medications

• Bladder Infection
• Prevention of Bladder infection

Where can I get more information?

• Your pharmacist has additional information about methenamine written for health professionals that you may read.

See also: Urex side effects (in more detail)

Aluminum/Magnesium Chewable Tablets

Pronunciation: a-LOO-min-uhm/mag-NEE-zee-uhm
Generic Name: Aluminum/Magnesium
Brand Name: Alamag

Aluminum/Magnesium Chewable Tablets are used for:

Treating acid indigestion, heartburn, and sour stomach. It may also be used for other conditions as determined by your doctor.

Aluminum/Magnesium Chewable Tablets are an antacid. It works by neutralizing acid in the stomach.

Do NOT use Aluminum/Magnesium Chewable Tablets if:

• you are allergic to any ingredient in Aluminum/Magnesium Chewable Tablets


• you are also taking citrate salts (found in some calcium supplements, antacids, and laxatives)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Aluminum/Magnesium Chewable Tablets:

Some medical conditions may interact with Aluminum/Magnesium Chewable Tablets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have Alzheimer disease, appendicitis, diarrhea, a stomach blockage, kidney problems, or an ileostomy


• if you have recently had stomach bleeding

Some MEDICINES MAY INTERACT with Aluminum/Magnesium Chewable Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Cation exchange resins (eg, sodium polystyrene sulfonate) and citrate salts (found in some calcium supplements, antacids, and laxatives) because they may increase the actions and the risk of Aluminum/Magnesium Chewable Tablets's side effects


• Anticoagulants (eg, warfarin), quinidine, or sulfonylureas (eg, glyburide) because their actions and side effects may be increased by Aluminum/Magnesium Chewable Tablets


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), beta-blockers (eg, propranolol), bisphosphonates (eg, risedronate), cephalosporins (eg, cephalexin), corticosteroids (eg, hydrocortisone), cyclosporine, delavirdine, digoxin, imidazoles (eg, ketoconazole), mycophenolate, penicillamine, quinolones (eg, ciprofloxacin), tetracyclines (eg, doxycycline), or thyroid hormones (eg, levothyroxine) because their effectiveness may be decreased by Aluminum/Magnesium Chewable Tablets, especially when taken at the same time as Aluminum/Magnesium Chewable Tablets

This may not be a complete list of all interactions that may occur. Ask your health care provider if Aluminum/Magnesium Chewable Tablets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Aluminum/Magnesium Chewable Tablets:

Use Aluminum/Magnesium Chewable Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Aluminum/Magnesium Chewable Tablets by mouth with or without food.


• Chew thoroughly before swallowing.


• Do not use Aluminum/Magnesium Chewable Tablets within 2 hours before or after taking a beta-blocker (eg, propranolol), bisphosphonate (eg, risedronate), cephalosporin (eg, cephalexin), corticosteroid (eg, hydrocortisone), delavirdine, digoxin, imidazole (eg, ketoconazole), penicillamine, or sulfonylurea (eg, glyburide) because their effectiveness may be decreased by Aluminum/Magnesium Chewable Tablets.


• If you miss a dose of Aluminum/Magnesium Chewable Tablets and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Aluminum/Magnesium Chewable Tablets.

Important safety information:

• Do NOT take more than the recommended dose or take the maximum dose for longer than 2 weeks without checking with your doctor.


• If your symptoms do not get better within 2 weeks or if they get worse, or if you experience black, tarry stools or vomit that looks like coffee grounds, check with your doctor.


• Aluminum/Magnesium Chewable Tablets has aluminum and magnesium in it. Before you begin taking any new prescription or over-the-counter medicine, read the ingredients to see has aluminum or magnesium in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Aluminum/Magnesium Chewable Tablets while you are pregnant. If you are or will be breast-feeding while you use Aluminum/Magnesium Chewable Tablets, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Aluminum/Magnesium Chewable Tablets:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); loss of appetite; muscle weakness; nausea; slow reflexes; vomiting.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center (http://www.aapcc.org ), or emergency room immediately.

Proper storage of Aluminum/Magnesium Chewable Tablets:

Store Aluminum/Magnesium Chewable Tablets between 59 and 86 degrees F (15 and 30 degrees C). Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Aluminum/Magnesium Chewable Tablets out of the reach of children and away from pets.

General information:

• If you have any questions about Aluminum/Magnesium Chewable Tablets, please talk with your doctor, pharmacist, or other health care provider.


• Aluminum/Magnesium Chewable Tablets are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Aluminum/Magnesium Chewable Tablets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Aluminum/Magnesium resources

• Aluminum/Magnesium Use in Pregnancy & Breastfeeding
• Aluminum/Magnesium Drug Interactions
• Aluminum/Magnesium Support Group
• 0 Reviews for Aluminum/Magnesium - Add your own review/rating

Compare Aluminum/Magnesium with other medications

• Duodenal Ulcer
• Erosive Esophagitis
• GERD
• Indigestion
• Stress Ulcer Prophylaxis
• Zollinger-Ellison Syndrome