Medroxyprogesterone

Generic Name: Medroxyprogesterone acetate

Dosage Form: tablet
Medroxyprogesterone Acetate Tablets USP

Iss. 4/2010

11001645

Rx only

(Three Patient Information Leaflet Enclosed-Tear at Perforation)

WARNINGS

CARDIOVASCULAR AND OTHER RISKS

Estrogens with progestins should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders and Dementia.)

The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE 0.625 mg) combined with Medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders and Malignant Neoplasms, Breast Cancer.)

The Women’s Health Initiative Memory Study (WHIMS), a substudy of the WHI study, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE 0.625 mg combined with MPA 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Dementia, and PRECAUTIONS, Geriatric Use.)

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Medroxyprogesterone Description

Medroxyprogesterone Acetate Tablets USP contain Medroxyprogesterone acetate, USP which is a derivative of progesterone. It is a white to off-white, odorless crystalline powder, stable in air, melting between 200 and 210°C. It is freely soluble in chloroform, soluble in acetone and in dioxane, sparingly soluble in alcohol and in methanol, slightly soluble in ether, and insoluble in water.

The chemical name for Medroxyprogesterone acetate is pregn-4-ene-3, 20-dione, 17-(acetyloxy)-6-methyl-, (6α)-. The structural formula is:

Each tablet, for oral administration, contains 2.5 mg, 5 mg or 10 mg of Medroxyprogesterone acetate, USP. In addition, each tablet contains the following inactive ingredients: crospovidone, lactose monohydrate, magnesium stearate, methylcellulose, pregelatinized starch, and sodium lauryl sulfate.

Medroxyprogesterone - Clinical Pharmacology

Medroxyprogesterone acetate (MPA) administered orally or parenterally in the recommended doses to women with adequate endogenous estrogen, transforms proliferative into secretory endometrium. Androgenic and anabolic effects have been noted, but the drug is apparently devoid of significant estrogenic activity. While parenterally administered MPA inhibits gonadotropin production, which in turn prevents follicular maturation and ovulation, available data indicate that this does not occur when the usually recommended oral dosage is given as single daily doses.

Pharmacokinetics

The pharmacokinetics of MPA were determined in 20 postmenopausal women following a single-dose administration of eight Medroxyprogesterone acetate 2.5 mg tablets or a single administra- tion of two Medroxyprogesterone acetate 10 mg tablets under fasting conditions. In another study, the steady-state pharmacokinetics of MPA were determined under fasting conditions in 30 post- menopausal women following daily administration of one Medroxyprogesterone acetate 10 mg tablet for 7 days. In both studies, MPA was quantified in serum using a validated gas chroma- tography-mass spectrometry (GC-MS) method. Estimates of the pharmacokinetic parameters of MPA after single and multiple doses of Medroxyprogesterone acetate tablets were highly variable and are summarized in Table 1.

Table 1. Mean (SD) Pharmacokinetic Parameters for Medroxyprogesterone Acetate (MPA)

* Following Day 7 dose
Tablet Strength	Cmax (ng/mL)	Tmax (h)	Auc0-(∞) (ng·h/mL)	t½ (h)	Vd/f (L)	CL/f (mL/min)
Single Dose
2 x 10 mg	1.01 (0.599)	2.65 (1.41)	6.95 (3.39)	12.1 (3.49)	78024 (47220)	64110 (42662)
8 x 2.5 mg	0.805 (0.413)	2.22 (1.39)	5.62 (2.79)	11.6 (2.81)	62748 (40146)	74123 (35126)
Multiple Dose
10 mg*	0.71 (0.35)	2.83 (1.83)	6.01 (3.16)	16.6 (15)	40564 (38256)	41963 (38402)

A. Absorption

No specific investigation on the absolute bioavailability of MPA in humans has been conducted. MPA is rapidly absorbed from the gastrointestinal tract, and maximum MPA concentrations are obtained between 2 to 4 hours after oral administration.

Administration of Medroxyprogesterone acetate with food increases the bioavailability of MPA. A 10 mg dose of Medroxyprogesterone acetate, taken immediately before or after a meal, in- creased MPA Cmax (50 to 70%) and AUC (18 to 33%). The half-life of MPA was not changed with food.

B. Distribution

MPA is approximately 90% protein bound, primarily to albumin; no MPA binding occurs with sex hormone binding globulin.

C. Metabolism

Following oral dosing, MPA is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine.

D. Excretion

Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.

E. Special Populations

Renal Insufficiency

The pharmacokinetics of MPA in patients with varying degrees of renal insufficiency have not been investigated.

Hepatic Insufficiency

MPA is almost exclusively eliminated via hepatic metabolism. In 14 patients with advanced liver disease, MPA disposition was significantly altered (reduced elimination). In patients with fatty liver, the mean percent dose excreted in the 24-hour urine as intact MPA after a 10 mg or 100 mg dose was 7.3% and 6.4%, respectively.

F. Drug Interactions

No formal pharmacokinetic drug interaction studies have been conducted with Medroxyprogesterone acetate.

Clinical Studies

Effects on the Endometrium

In a 3-year, double-blind, placebo-controlled study of 356 nonhysterectomized, postmenopausal women between 45 and 64 years of age randomized to receive placebo (n=119), 0.625 mg conjugated estrogen only (n=119), or 0.625 mg conjugated estrogen plus cyclic Medroxyprogesterone acetate (n=118), results showed a reduced risk of endometrial hyperplasia in the treatment group receiving 10 mg Medroxyprogesterone acetate plus 0.625 mg conjugated estrogens compared to the group receiving 0.625 mg conjugated estrogens only. See Table 2.

Table 2. Number (%) of Endometrial Biopsy Changes Since Baseline After 3 Years of Treatment*

* Includes most extreme abnormal result
* CEE = conjugated equine estrogens 0.625 mg/day † Medroxyprogesterone acetate = Medroxyprogesterone acetate tablets 10 mg/day for 12 days
Histological Results	Placebo (n=119)	CEE*  (n=119)	Medroxyprogesterone Acetate†  + CEE (n=118)
Normal/No hyperplasia (%)	116 (97)	45 (38)	112 (95)
Simple (cystic) hyperplasia (%)	1 (1)	33 (28)	4 (3)
Complex (adenomatous) hyperplasia (%)	1 (1)	27 (22)	2 (2)
Atypia (%)	0	14 (12)	0
Adenocarcinoma (%)	1 (1)	0	0

In a second 1-year study, 832 postmenopausal women between 45 and 65 years of age were treated with daily 0.625 mg conjugated estrogen (days 1 to 28), plus either 5 mg cyclic Medroxyprogesterone acetate or 10 mg cyclic Medroxyprogesterone acetate (days 1 5to 28), or daily 0.625 mg conjugated estrogen only. The treatment groups receiving 5 or 10 mg cyclic Medroxyprogesterone acetate (days 15 to 28) plus daily conjugated estrogens showed a significantly lower rate of hyperplasia as compared to the conjugated estrogens only group. See Table 3.

Table 3. Number (%) of Women with Endometrial Hyperplasia at 1 Year

* CEE = conjugated equine estrogen 0.625 mg every day of a 28-day cycle. † Cyclic Medroxyprogesterone acetate on days 15 to 28.
	CEE*	MPA†  + CEE*
	(n=283)	MPA 5 mg (n=277)	MPA 10 mg (n=272)
Cystic hyperplasia (%)	55 (19)	3 (1)	0
Adenomatous hyperplasia without atypia	2 (1)	0	0

Women’s Health Initiative Studies

The Women’s Health Initiative (WHI) enrolled approximately 27,000 predominantly healthy postmenopausal women in two substudies to assess the risks and benefits of either the use of daily oral conjugated estrogens (CE 0.625 mg) alone or in combination with Medroxyprogesterone acetate (MPA 2.5 mg) compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardial infarction (MI), silent MI and CHD death), with invasive breast cancer as the primary adverse outcome studied. A “global index” included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer (only in the CE/MPA substudy), colorectal cancer, hip fracture, or death due to other cause. The study did not evaluate the effects of CE or CE/MPA on menopausal symptoms.

The estrogen plus progestin substudy was stopped early. According to the predefined stopping rule, after an average follow-up of 5.2 years of treatment, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the “global index.” The absolute excess risk of events included in the “global index” was 19 per 10,000 women-years (relative risk [RR] 1.15, 95 percent, nominal confidence interval [nCI], 1.03 to 1.28).

For those outcomes included in the WHI “global index,” that reached statistical significance after 5.6 years of follow-up, the absolute excess risks per 10,000 women-years in the group treated with CE/MPA were 6 more CHD events, 7 more strokes, 10 more PEs, and 8 more invasive breast cancers, while the absolute risk reduction per 10,000 women-years were 7 fewer colorectal cancers and 5 fewer hip fractures. (See BOXED WARNINGS, WARNINGS and PRECAUTIONS.)

Results of the CE/MPA substudy which included 16,608 women (average age of 63 years, range 50 to 79; 83.9 percent White, 6.8 percent Black, 5.4 percent Hispanic, 3.9 percent Other) are presented in Table 4. These results reflect centrally adjudicated data after an average follow-up of 5.6 years.

Table 4: RELATIVE AND ABSOLUTE RISK SEEN IN THE ESTROGEN PLUS PROGESTIN SUBSTUDY OF WHI AT AN AVERAGE OF 5.6 YEARS*

* Results are based on centrally adjudicated data. Mortality data was not part of the adjudicated data; however, data at 5.2 years of follow-up showed no difference between the groups in terms of all-cause mortality (RR 0.98, 95 percent nCI, 0.82 to 1.18). † Includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer ‡ Nominal confidence intervals unadjusted for multiple looks and multiple comparisons
Event†	Relative Risk CE/MPA vs placebo (95% nCI‡)		Placebo n = 8102	CE/MPA n = 8506
			Absolute Risk per 10,000 Women-Years
CHD events Non-fatal MI CHD death	1.24 (1.00-1.54) 1.28 (1.00-1.63) 1.10 (0.70-1.75)		33 25 8	39 31 8
All strokes	1.31 (1.02-1.68)		24	31
Ischemic stroke	1.44 (1.09-1.90)		18	26
Deep vein thrombosis	1.95 (1.43-2.67)		13	26
Pulmonary embolism	2.13 (1.45-3.11)		8	18
Invasive breast cancer†	1.24 (1.01-1.54)		33	41
Invasive colorectal cancer	0.56 (0.38-0.81)		16	9
Endometrial cancer	0.81 (0.48-1.36)		7	6
Cervical Cancer	1.44 (0.47-4.42)		1	2
Hip fracture	0.67 (0.47-0.96)		16	11
Vertebral fractures	0.65 (0.46-0.92)		17	11
Lower arm/wrist fractures	0.71 (0.59-0.85)		62	44
Total fractures	0.76 (0.69-0.83)		199	152

Women's Health Initiative Memory Study

The estrogen plus progestin Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47 percent were aged 65 to 69 years, 35 percent were 70 to 74 years, and 18 percent were 75 years of age and older) to evaluate the effects of daily conjugated estrogens (CE 0.625 mg) plus Medroxyprogesterone acetate (MPA 2.5 mg) on the incidence of probable dementia (primary outcome) compared with placebo.

After an average follow-up of 4 years, 40 women in the estrogen plus progestin group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the hormone therapy group was 2.05 (95 percent CI, 1.21 to 3.48) compared to placebo.

Indications and Usage for Medroxyprogesterone

Medroxyprogesterone Acetate Tablets USP are a progestin indicated for the treatment of secondary amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as fibroids or uterine cancer. Medroxyprogesterone Acetate Tablets USP are also indicated to reduce the incidence of endometrial hyperplasia in nonhysterectomized postmenopausal women receiving daily oral conjugated estrogens 0.625 mg tablets.

Contraindications

Medroxyprogesterone Acetate Tablets USP should not be used in women with any of the following conditions:

1. Undiagnosed abnormal genital bleeding.


2. Known, suspected, or history of cancer of the breast.


3. Known or suspected estrogen- or progesterone-dependent neoplasia.


4. Active deep vein thrombosis, pulmonary embolism or a history of these conditions.


5. Active or recent (within the past year) arterial thromboembolic disease (for example, stroke and myocardial infarction).


6. Known liver dysfunction or disease.


7. Missed abortion.


8. As a diagnostic test for pregnancy.


9. Known hypersensitivity to the ingredients in Medroxyprogesterone acetate tablets.


10. Known or suspected pregnancy.

Warnings

See BOXED WARNINGS.

1. Cardiovascular Disorders.

An increased risk of stroke, deep vein thrombosis (DVT), pulmonary embolism, and myocardial infarction has been reported with estrogen plus progestin therapy. Should any of these events occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.

Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (for example, personal history or family history of venous thromboembolism [VTE]), obesity, and systemic lupus erythematosus should be managed appropriately.

a. Stroke

In the estrogen plus progestin substudy of the Women’s Health Initiative (WHI) a statistically significant increased risk of stroke was reported in women receiving daily conjugated estrogens (CE 0.625 mg) plus Medroxyprogesterone acetate (MPA 2.5 mg) compared to women receiving placebo (31 versus 24 per 10,000 women-years). The increase in risk was demonstrated after the first year and persisted. (See CLINICAL STUDIES.)

b. Coronary heart disease

In the estrogen plus progestin substudy of WHI, no statistically significant increase of CHD events (defined as non-fatal myocardial infarction [MI], silent MI or CHD death was reported in women receiving CE/MPA compared to women receiving placebo (39 versus 33 per 10,000 women-years). An increase in relative risk was demonstrated in year one, and a trend toward decreasing relative risk was reported in years 2 through 5. (See CLINICAL STUDIES.)

In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estro- gen/Progestin Replacement Study [HERS]), treatment with daily CE 0.625 mg/ MPA 2.5 mg per day demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE/MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE/MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred and twenty one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE/MPA group and the placebo group in HERS, HERS II, and overall.

c. Venous thromboembolism (VTE)

In the estrogen plus progestin substudy of WHI, a statistically significant two-fold greater rate of VTE, (DVT and pulmonary embolism [PE]), was reported in women receiving daily CE/MPA compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was observed during the first year and persisted. (See CLINICAL STUDIES.)

2. Malignant Neoplasms

a. Breast cancer

The use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer in some studies. Observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen alone therapy, after several years of use. The risk increased with duration of use and appeared to return to baseline in about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen alone therapy. However, these studies have not found significant variation in the risk of breast cancer among different estrogens or among different estrogen plus progestin combinations, doses, or routes of administration.

The most important randomized clinical trial providing information about this issue is the Women’s Health Initiative (WHI) substudy of daily conjugated estrogens (CE 0.625 mg) plus Medroxyprogesterone acetate (MPA 2.5 mg) (See CLINICAL STUDIES.)

In the estrogen plus progestin substudy of WHI, after a mean follow-up of 5.6 years, the WHI substudy reported an increased risk of breast cancer in women who took daily CE/MPA. In this substudy, prior use of estrogen alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24 (95 percent nominal confidence interval [nCI], 1.01 to 1.54), and the absolute risk was 41 versus 33 cases per 10,000 women-years, for estrogen plus progestin compared with placebo, respectively. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years, for estrogen plus progestin compared with placebo. In the same substudy, invasive breast cancers were larger and diagnosed at a more advanced stage in the CE/MPA group compared with the placebo group. Metastatic disease was rare with no apparent difference between the two groups. Other prognostic factors such as histologic subtype, grade, and hormone receptor status did not differ between the groups.

The use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a health care provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.

b. Endometrial cancer

An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12 times greater than in nonusers, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with the use of estrogens for less than 1 year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more. This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.

Clinical surveillance of all women using estrogen plus progestin therapy is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

c. Ovarian cancer

The estrogen plus progestin substudy of WHI reported that daily CE/MPA increased the risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE/MPA versus placebo was 1.58 (95 percent nCI, 0.77 to 3.24) but was not statistically significant. The absolute risk for CE/MPA was 4.2 versus 2.7 cases per 10,000 women-years.

3. Dementia

In the estrogen plus progestin Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, a population of 4,532 postmenopausal women aged 65 to 79 years was randomized to daily conjugated estrogens (CE 0.625 mg) plus Medroxyprogesterone acetate (MPA 2.5 mg) or placebo.

After an average follow-up of 4 years, 40 women in the CE/MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE/MPA versus placebo was 2.05 (95 percent CI, 1.21 to 3.48). The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years. It is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS and PRECAUTIONS, Geriatric Use.)

4. Visual Abnormalities

Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be permanently discontinued.

Precautions

A. General

1. Addition of a progestin when a woman has not had a hysterectomy Studies of the addition
   
   of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (lowering HDL, raising LDL) and impairment of glucose tolerance.


2. Undiagnosed abnormal vaginal bleeding
   
   In cases of undiagnosed abnormal vaginal bleeding, adequate diagnostic measures are indicated.


3. Elevated blood pressure
   
   Blood pressure should be monitored at regular intervals with estrogen plus progestin therapy.


4. Hypertriglyceridemia
   
   In patients with pre-existing hypertriglyceridemia, estrogen plus progestin therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications.


5. Impaired liver function and past history of cholestatic jaundice
   
   Estrogens plus progestins may be poorly metabolized in patients with impaired liver function. For patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued.


6. Fluid Retention
   
   Progestins may cause some degree of fluid retention. Patients who have conditions which might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogen plus progestin are prescribed.


7. Hypocalcemia
   
   Estrogen plus progestin therapy should be used with caution in individuals with severe hypocalcemia.


8. Exacerbation of other conditions
   
   Estrogen plus progestin therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

B. Patient Information

Physicians are advised to discuss the Patient Information leaflet with patients for whom they prescribe Medroxyprogesterone acetate.

There may be an increased risk of minor birth defects in children whose mothers are exposed to progestins during the first trimester of pregnancy. The possible risk to the male baby is hypospadias, a condition in which the opening of the penis is on the underside rather than the tip of the penis. This condition occurs naturally in approximately 5 to 8 per 1,000 male births. The risk may be increased with exposure to Medroxyprogesterone acetate. Enlargement of the clitoris and fusion of the labia may occur in female babies. However, a clear association between hypospadias, clitoral enlargement and labial fusion with use of Medroxyprogesterone acetate has not been established.

Inform the patient of the importance of reporting exposure to Medroxyprogesterone acetate in early pregnancy.

 C. Drug/Laboratory Test Interactions

The following laboratory results may be altered by the use of estrogen plus progestin therapy:

1. Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.


2. Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay, T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.


3. Other binding proteins may be elevated in serum (i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) leading to increased circulating corticosteroid and sex steroids, respectively. Free or biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).


4. Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels.


5. Impaired glucose metabolism.

D. Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term intramuscular administration of Medroxyprogesterone acetate has been shown to produce mammary tumors in beagle dogs. There was no evidence of a carcinogenic effect associated with the oral administration of Medroxyprogesterone acetate to rats and mice. Medroxyprogesterone acetate was not mutagenic in a battery of in vitro or in vivo genetic toxicity assays.

Medroxyprogesterone acetate at high doses is an antifertility drug and high doses would be expected to impair fertility until the cessation of treatment.

Long-term continuous administration of estrogen plus progestin therapy, has shown an increased risk of breast cancer and ovarian cancer. (See WARNINGS and PRECAUTIONS.)

E. Pregnancy

Teratogenic Effects

Pregnancy Category X

Medroxyprogesterone acetate should not be used during pregnancy. (See CONTRAINDICATIONS.)

There may be increased risks for hypospadias, clitoral enlargement and labial fusion in children whose mothers are exposed to Medroxyprogesterone acetate during the first trimester of pregnancy. However, a clear association between these conditions with use of Medroxyprogesterone acetate has not been established.

F. Nursing Mothers

Medroxyprogesterone acetate should not be used during lactation. Detectable amounts of progestin have been identified in the milk of nursing mothers receiving progestins.

G. Pediatric Use

Medroxyprogesterone acetate is not intended for pediatric use and no clinical data has been collected in children.

H. Geriatric Use

Of the total number of subjects in the estrogen plus progestin substudy of the Women’s Health Initiative (WHI), 44 percent (n = 7,320) were 65 years and older, while 6.6 percent (n = 1,095) were 75 years and older. In women 75 and older compared to women less than 75 years of age, there was a higher relative risk of non-fatal stroke and invasive breast cancer in the estrogen plus progestin group versus placebo. In women greater than 75 years of age, the increased risk of non-fatal stroke and invasive breast cancer observed in the estrogen plus progestin group compared to placebo was 75 versus 24 per 10,000 women-years and 52 versus 12 per 10,000 women-years, respectively.

In the estrogen plus progestin Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, a population of 4,532 postmenopausal women, aged 65 to 70 years, was randomized to receive daily CE 0.625 mg/MPA 2.5 mg or placebo. In the estrogen plus progestin group, after an average follow-up of 4 years, the relative risk (CE/MPA versus placebo) of probable dementia was 2.05 (95 percent CI, 1.21 to 3.48). The absolute risk of developing probable dementia with CE/MPA was 45 versus 22 cases per 10,000 women-years compared with placebo.

Eighty-two percent of the cases of probable dementia occurred in women that were older than 70 in the CE/MPA group. The most common classification of probable dementia in the estrogen plus progestin and placebo groups was Alzheimer’s disease.

When data from the estrogen alone and estrogen plus progestin WHIMS substudies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19 to 2.60). Since both substudies were conducted in women aged 65 to 79 years, it is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS and WARNINGS, Dementia.)

ADVERSE REACTIONS

See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions have been reported in women taking progestins, including Medroxyprogesterone acetate tablets, without concomitant estrogens treatment:

1. Genitourinary System

Abnormal uterine bleeding (irregular, increase, decrease), change in menstrual flow, breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and cervical secretions.

2. Breasts

Breast tenderness, mastodynia or galactorrhea has been reported.

3. Cardiovascular

Thromboembolic disorders including thrombophlebitis and pulmonary embolism have been reported.

4. Gastrointestinal

Nausea, cholestatic jaundice.

5. Skin

Sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash have occurred. Acne, alopecia and hirsutism have been reported.

6. Eyes

Neuro-ocular lesions, for example, retinal thrombosis, and optic neuritis.

7. Central Nervous System

Mental depression, insomnia, somnolence, dizziness, headache, nervousness.

8. Miscellaneous

Hypersensitivity reactions (for example, anaphylaxis and anaphylactoid reactions, angioedema), rash (allergic) with and without pruritus, change in weight (increase or decrease), pyrexia, edema/fluid retention, fatigue, decreased glucose tolerance.

The following additional adverse reactions have been reported with estrogen and/or progestin therapy.

1. Genitourinary System

Abnormal uterine bleeding/spotting, or flow; breakthrough bleeding; spotting; dysmenorrheal/pelvic pain; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.

Viibryd

Pronunciation: vil-AZ-oh-done
Generic Name: Vilazodone
Brand Name: Viibryd

Antidepressants may increase the risk of suicidal thoughts or actions in children, teenagers, and young adults. However, depression and certain other mental problems may also increase the risk of suicide. Talk with the patient's doctor to be sure that the benefits of using Viibryd outweigh the risks.

Families and caregivers must closely watch patients who take Viibryd. It is important to keep in close contact with the patient's doctor. Tell the doctor right away if the patient has symptoms like worsened depression, suicidal thoughts, or changes in behavior. Discuss any questions with the patient's doctor.

Viibryd is used for:

Treating depression. It may also be used for other conditions as determined by your doctor.

Viibryd is an antidepressant. It is thought to work by increasing the activity of one of the brain chemicals (serotonin), which helps elevate mood.

Do NOT use Viibryd if:

• you are allergic to any ingredient in Viibryd or to nefazodone


• you are taking rasagiline or tryptophan


• you are taking or have taken linezolid, methylene blue, a monoamine oxidase inhibitor (MAOI) (eg, phenelzine), or St. John's wort within the last 14 days

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

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

Before using Viibryd:

Some medical conditions may interact with Viibryd. 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 low blood volume, low blood pressure, or low blood sodium levels; you are dehydrated; or you are on a low-salt (sodium) diet


• if you or a family member has a history of bipolar disorder (manic-depression) or other mental or mood problems (eg, depression), suicidal thoughts or attempts, alcohol or substance abuse, or if you drink alcohol


• if you have a history of liver problems, kidney problems, bleeding problems, or seizures

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

• Anticoagulants (eg, warfarin), nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen, intranasal ketorolac), or salicylates (eg, aspirin) because the risk of bleeding may be increased


• Antipsychotics (eg, olanzapine, haloperidol), buspirone, fenfluramine or its derivatives (eg, dexfenfluramine), linezolid, MAOIs, (eg, phenelzine), methylene blue, metoclopramide, narcotic (opioid) pain medicines (eg, morphine), phenothiazines (eg, thioridazine), rasagiline, selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), selegiline, serotonin-norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, venlafaxine), sibutramine, St. John's wort, tramadol, "triptans" (eg, sumatriptan), or tryptophan because severe side effects, such as a reaction that may include fever, rigid muscles, blood pressure changes, mental changes, confusion, irritability, agitation, delirium, or coma, may occur


• Diuretics (eg, furosemide, hydrochlorothiazide) because the risk of low blood sodium levels may be increased


• Azole antifungals (eg, itraconazole, ketoconazole), HIV protease inhibitors (eg, indinavir, ritonavir), macrolide antibiotics (eg, clarithromycin, erythromycin), nefazodone, or telithromycin because the risk of Viibryd's side effects may be increased


• Cyproheptadine because it may decrease Viibryd's effectiveness


• Lithium because the risk of its side effects may be increased by Viibryd

This may not be a complete list of all interactions that may occur. Ask your health care provider if Viibryd 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 Viibryd:

Use Viibryd as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Viibryd comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Viibryd refilled.


• Take Viibryd by mouth with food.


• When starting Viibryd, your doctor may slowly increase your dose to avoid side effects. Discuss any questions or concerns with your doctor.


• It may take 1 to 4 weeks for Viibryd to work. Do not stop taking Viibryd without checking with your doctor.


• Do not suddenly stop taking Viibryd. You may have an increased risk of side effects. If you need to stop Viibryd, your doctor will gradually lower your dose.


• If you miss a dose of Viibryd, 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 Viibryd.

Important safety information:

• Viibryd may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Viibryd with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol while you are using Viibryd.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Viibryd; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Be sure to keep all doctor appointments while you are taking Viibryd.


• Children, teenagers, and young adults who take Viibryd may be at increased risk of suicidal thoughts or actions. Watch all patients who take Viibryd closely. Contact the doctor at once if new, worsened, or sudden symptoms, such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or any unusual change in mood or behavior, occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.


• Neuroleptic malignant syndrome (NMS) is a possibly fatal syndrome that can be caused by Viibryd. Symptoms may include fever; stiff muscles; confusion; abnormal thinking; fast or irregular heartbeat; and sweating. Contact your doctor at once if you have any of these symptoms.


• Serotonin syndrome is a possibly fatal syndrome that can be caused by Viibryd. Your risk may be greater if you take Viibryd with certain other medicines (eg, "triptans," MAOIs). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.


• Tell your doctor or dentist that you take Viibryd before you receive any medical or dental care, emergency care, or surgery.


• Use Viibryd with caution in the ELDERLY; they may be more sensitive to its effects, especially low blood sodium levels.


• Viibryd should not be used in CHILDREN or TEENAGERS; safety and effectiveness in children and teenagers have not been confirmed. Children and teenagers may also be more sensitive to its effects, especially the increased risk of suicidal thoughts or actions.


• PREGNANCY and BREAST-FEEDING: Viibryd may cause harm to the fetus if taken during the third trimester of pregnancy. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Viibryd while you are pregnant. Viibryd is found in breast milk. If you are or will be breast-feeding while you take Viibryd, check with your doctor. Discuss any possible risks to your baby.

Do not suddenly stop taking Viibryd. If you do, you may have WITHDRAWAL symptoms. These may include feeling unwell or unhappy, anxious or irritable, dizzy, confused, or sluggish. You may also have nausea, unusual skin sensations, mood swings, headache, trouble sleeping, or sweating. If you need to stop Viibryd, your doctor will lower your dose over time.

Possible side effects of Viibryd:

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:

Decreased sexual desire or ability; diarrhea; dizziness; drowsiness; dry mouth; nausea; vomiting.

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); behavior changes; black, tarry, or bloody stools; bloody or dark urine; blurred vision; decreased coordination; fainting; hallucinations; irregular heartbeat; new or worsening agitation, anxiety, depression, panic attacks, aggressiveness, impulsiveness, irritability, hostility, exaggerated feeling of well-being, restlessness, trouble sleeping, or inability to sit still; seizures; severe or persistent dizziness; suicidal thoughts or actions; symptoms of low blood sodium levels (eg, confusion, severe or persistent headache, trouble concentrating, memory problems, weakness, unsteadiness, sluggishness); tremor; unusual bruising or bleeding; vomit that looks like coffee grounds.

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: Viibryd 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 agitation; confusion; disorientation; excessive sweating; fast or irregular heartbeat; fever; hallucinations; loss of consciousness or coma; nausea, vomiting, or diarrhea; restlessness; tiredness or weakness; tremor.

Proper storage of Viibryd:

Store Viibryd at 77 degrees F (25 degrees C) in a tight, light-resistant container. Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Viibryd out of the reach of children and away from pets.

General information:

• If you have any questions about Viibryd, please talk with your doctor, pharmacist, or other health care provider.


• Viibryd is 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 summary only. It does not contain all information about Viibryd. 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 Viibryd resources

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

• Viibryd Prescribing Information (FDA)


• Viibryd Advanced Consumer (Micromedex) - Includes Dosage Information


• Viibryd Consumer Overview

Compare Viibryd with other medications

• Depression

Excedrin Tension Headache Caplet

Generic Name: acetaminophen and caffeine (a SEET a MIN oh fen and KAF een)

Brand Names: Excedrin Quick Tab Peppermint, Excedrin Quick Tab Spearmint, Excedrin Tension Headache, Excedrin Tension Headache Caplet, Excedrin Tension Headache Express Gels, Excedrin Tension Headache Geltab, Valorin Extra

What is Excedrin Tension Headache Caplet (acetaminophen and caffeine)?

Acetaminophen is a pain reliever and a fever reducer.

Caffeine is used in this product to increase the pain relieving effects of acetaminophen.

The combination of acetaminophen and caffeine is used to treat pain from conditions such as headache, muscle aches, menstrual cramps, arthritis, backache, toothaches, colds and fevers.

Acetaminophen and caffeine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Excedrin Tension Headache Caplet (acetaminophen and caffeine)?

Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

What should I discuss with my healthcare provider before taking Excedrin Tension Headache Caplet (acetaminophen and caffeine)?

Do not take this medication if you are allergic to acetaminophen (Tylenol) or caffeine. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have kidney or liver disease, or a history of alcoholism.

It is not known whether this medicine will harm an unborn baby. Do not take acetaminophen and caffeine without medical advice if you are pregnant. Acetaminophen and caffeine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Excedrin Tension Headache Caplet (acetaminophen and caffeine)?

Use this medication exactly as directed on the label, or as prescribed by your doctor.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

One acetaminophen and caffeine pill contains 500 mg of acetaminophen. Know the amount of acetaminophen in the specific product you are taking.

The orally disintegrating tablet (Excedrin QuickTabs) should be placed directly on the tongue. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. Swallow several times as the tablet dissolves. If desired, you may drink liquid to help swallow the dissolved tablet.

Call your doctor if your symptoms do not improve, especially if you still have a fever after 3 days of using this medication, or pain after 10 days of use. Stop taking acetaminophen and caffeine and call your doctor at any time if your symptoms get worse.

Acetaminophen may cause false urine glucose test results. Talk to your doctor if you have diabetes and you notice changes in glucose test results while taking acetaminophen and caffeine.

Store at room temperature away from heat and moisture.

What happens if I miss a dose?

Since acetaminophen and caffeine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include loss of appetite, confusion, nausea, vomiting, diarrhea, sweating, fast or uneven heart rate, seizure (convulsions), pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

What should I avoid while taking Excedrin Tension Headache Caplet (acetaminophen and caffeine)?

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Avoid coffee, tea, cola, energy drinks or other sources of caffeine while taking this medication. They can add to the side effects of the caffeine in the medication.

Excedrin Tension Headache Caplet (acetaminophen and caffeine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using acetaminophen and caffeine and call your doctor at once if you have a serious side effect such as:

• 
  

  low fever with nausea, stomach pain, and loss of appetite;

  
  


• 
  

  dark urine, clay-colored stools; or

  
  


• 
  

  jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

• 
  

  sleep problems (insomnia); or

  
  


• 
  

  feeling nervous, irritable, or jittery.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Excedrin Tension Headache Caplet (acetaminophen and caffeine)?

There may be other drugs that can interact with acetaminophen and caffeine. Tell your doctor about all medications you use. This includes prescription, over the counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Excedrin Tension Headache Caplet resources

• Excedrin Tension Headache Caplet Side Effects (in more detail)
• Excedrin Tension Headache Caplet Use in Pregnancy & Breastfeeding
• Excedrin Tension Headache Caplet Drug Interactions
• Excedrin Tension Headache Caplet Support Group
• 2 Reviews for Excedrin Tension Headache Caplet - Add your own review/rating

Compare Excedrin Tension Headache Caplet with other medications

• Cold Symptoms
• Headache
• Osteoarthritis
• Pain
• Period Pain
• Sinusitis

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen and caffeine.

See also: Excedrin Tension Headache Caplet side effects (in more detail)

hydrochlorothiazide and captopril

Generic Name: hydrochlorothiazide and captopril (hye droe klor oh THY a zide and KAP toe pril)

Brand Names: Capozide 25/15, Capozide 25/25, Capozide 50/15, Capozide 50/25

What is hydrochlorothiazide and captopril?

Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Captopril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme. Captopril lowers blood pressure and also relieves symptoms of fluid retention.

The combination of hydrochlorothiazide and captopril is used to treat hypertension (high blood pressure).

Hydrochlorothiazide and captopril may also be used for purposes not listed in this medication guide.

What is the most important information I should know about hydrochlorothiazide and captopril?

You should not use this medication if you are allergic to hydrochlorothiazide or captopril, or if you have a history of asthma or allergies, or you are unable to urinate.

You should not use this medication if you are allergic to any other ACE inhibitor, such as benazepril (Lotensin), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

Before taking hydrochlorothiazide and captopril, tell your doctor if you have kidney disease (or are on dialysis), liver disease, glaucoma, congestive heart failure, gout, lupus, diabetes, or an allergy to sulfa drugs or penicillin.

Do not use hydrochlorothiazide and captopril if you are pregnant. It could harm the unborn baby.

Do not use potassium supplements or salt substitutes while you are taking hydrochlorothiazide and captopril, unless your doctor has told you to.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking hydrochlorothiazide and captopril. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

What should I discuss with my healthcare provider before taking hydrochlorothiazide and captopril?

Do not use this medication if you are allergic to hydrochlorothiazide or captopril, or if you have:

• 
  

  a history of asthma or allergies; or

  
  


• 
  

  if you are unable to urinate.

  
  

You should not use this medication if you are allergic to any other ACE inhibitor, such as benazepril (Lotensin), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

To make sure you can safely take hydrochlorothiazide and captopril, tell your doctor if you have any of these other conditions:

• kidney disease (or if you are on dialysis);


• liver disease;


• 
  

  glaucoma;

  
  


• 
  

  congestive heart failure;

  
  


• 
  

  gout;

  
  


• 
  

  lupus;

  
  


• 
  

  diabetes; or

  
  


• 
  

  an allergy to sulfa drugs or penicillin

  
  

FDA pregnancy category D. Do not use hydrochlorothiazide and captopril if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant. Use effective birth control while taking hydrochlorothiazide and captopril. Hydrochlorothiazide can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take hydrochlorothiazide and captopril?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Take each dose with a full glass of water.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking hydrochlorothiazide and captopril. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Your blood pressure will need to be checked often. Your blood and urine may also be tested if you have been vomiting or are dehydrated. Visit your doctor regularly.

Hydrochlorothiazide can interfere with the results of a thyroid test. Tell any doctor who treats you that you are using a thiazide diuretic.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture, heat, and light.

See also: Hydrochlorothiazide and captopril dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include nausea, weakness, dizziness, dry mouth, thirst, muscle pain or weakness, or feeling like you might pass out.

What should I avoid while taking hydrochlorothiazide and captopril?

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall. Drinking alcohol can further lower your blood pressure and may increase certain side effects of hydrochlorothiazide and captopril.

Do not use potassium supplements or salt substitutes while you are taking hydrochlorothiazide and captopril, unless your doctor has told you to.

Hydrochlorothiazide and captopril side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  eye pain, vision problems;

  
  


• 
  

  high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling);

  
  


• 
  

  low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling);

  
  


• 
  

  dry mouth, thirst, nausea, vomiting;

  
  


• 
  

  feeling weak, drowsy, restless, or light-headed;

  
  


• 
  

  a red, blistering, peeling skin rash;

  
  


• 
  

  jaundice (yellowing of the skin or eyes);

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  swelling, weight gain, feeling short of breath; or

  
  


• 
  

  fever, chills, body aches, flu symptoms.

  
  

Less serious side effects may include:

• 
  

  cough;

  
  


• 
  

  dizziness, headache, tired feeling;

  
  


• 
  

  blurred vision;

  
  


• 
  

  diarrhea, constipation, upset stomach; or

  
  


• 
  

  mild skin rash, increased sweating.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Hydrochlorothiazide and captopril Dosing Information

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 1 tablet of (captopril-hydrochlorothiazide 25 mg/15 mg) orally once a day, one hour before meals. Determine dosage by individual titration.
Maintenance dose: May use additional captopril or hydrochlorothiazide as individual components or change to an increased strength of the combination tablet. May give the combination tablet in divided doses up to 3 times a day. In general, daily doses of captopril should not exceed 150 mg and of hydrochlorothiazide should not exceed 50 mg.

Usual Adult Dose for Hypertension:

Initial dose: 1 tablet of (captopril-hydrochlorothiazide 25 mg/15 mg) orally once a day, one hour before meals. Determine dosage by individual titration.
Maintenance dose: May use additional captopril or hydrochlorothiazide as individual components or change to an increased strength of the combination tablet. May give the combination tablet in divided doses up to 3 times a day. In general, daily doses of captopril should not exceed 150 mg and of hydrochlorothiazide should not exceed 50 mg.

What other drugs will affect hydrochlorothiazide and captopril?

Cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to the side effects of hydrochlorothiazide and captopril. Tell your doctor if you regularly use any of these medicines, or any other blood pressure medications.

Tell your doctor about all other medicines you use, especially:

• 
  

  gold injections to treat arthritis;

  
  


• 
  

  other diuretics (water pills) or blood pressure medications;

  
  


• 
  

  lithium (Lithobid, Eskalith);

  
  


• 
  

  a blood thinner such as warfarin (Coumadin, Jantoven);

  
  


• 
  

  digoxin (Lanoxin);

  
  


• 
  

  nitroglycerin (Nitrolingual, Nitrostat, Nitro-Dur, and others);

  
  


• 
  

  cholestyramine (Prevalite, Questran) or colestipol (Colestid);

  
  


• 
  

  steroids (prednisone and others);

  
  


• 
  

  NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others; or

  
  


• 
  

  insulin or diabetes medicine taken by mouth.

  
  

This list is not complete and other drugs may interact with hydrochlorothiazide and captopril. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More hydrochlorothiazide and captopril resources

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

Compare hydrochlorothiazide and captopril with other medications

• Heart Failure
• High Blood Pressure

Where can I get more information?

• Your pharmacist can provide more information about hydrochlorothiazide and captopril.

See also: hydrochlorothiazide and captopril side effects (in more detail)

Flumazenil

Pronunciation: FLOO-may-ze-nil
Generic Name: Flumazenil
Brand Name: Romazicon

Flumazenil may cause seizures, especially in patients who have been on benzodiazepines (eg, diazepam) for a long time or if a patient has taken too much of a benzodiazepine (overdose).

Flumazenil is used for:

Reversing drowsiness, sedation, and other effects caused by benzodiazepines.

Flumazenil is a benzodiazepine antagonist. It works by blocking receptors in the brain and central nervous system that benzodiazepines need to reach to be active, which helps reduce drowsiness and sedation.

Do NOT use Flumazenil if:

• you are allergic to any ingredient in Flumazenil or to benzodiazepines (eg, alprazolam)


• you have been given a benzodiazepine for control of a potentially life-threatening condition (eg, increased pressure in the head, seizures)


• you are experiencing side effects due to an overdose of a medicine used to treat depression

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

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

Before using Flumazenil:

Some medical conditions may interact with Flumazenil. 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 (especially benzodiazepines), herbal preparation, or dietary supplement


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


• if you have a history of seizures, panic disorder, liver problems, alcohol or other substance abuse, or you have had a recent head injury

Some MEDICINES MAY INTERACT with Flumazenil. However, no specific interactions with Flumazenil are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Flumazenil 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 Flumazenil:

Use Flumazenil as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Flumazenil is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Flumazenil at home, carefully follow the injection procedures taught to you by your health care provider.


• If Flumazenil contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.


• If Flumazenil accidentally spills on your skin, wash it off immediately with soap and water.


• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.


• If you miss a dose of Flumazenil, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Flumazenil.

Important safety information:

• Flumazenil may cause dizziness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Flumazenil. Using Flumazenil alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Avoid drinking alcohol or taking other medicines that cause drowsiness (eg, sedatives, tranquilizers) for at least 24 hours after receiving Flumazenil. Flumazenil will add to the effects of alcohol and other depressants. Ask your pharmacist if you have questions about which medicines are depressants.


• Although Flumazenil is given to reverse drowsiness, you may experience a return of drowsiness for up to 24 hours after Flumazenil is given. If you notice a return of drowsiness or experience shortness of breath, contact your doctor as soon as possible.


• Flumazenil is not recommended for use in CHILDREN younger than 1 year of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Flumazenil, discuss with your doctor the benefits and risks of using Flumazenil during pregnancy. It is unknown if Flumazenil is excreted in breast milk. If you are or will be breast-feeding while you are using Flumazenil, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Flumazenil:

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:

Abnormal or blurred vision; abnormal skin sensations; changes in vision; clumsiness; dizziness; dry mouth; feeling of a whirling motion; flushing; general body discomfort; headache; hot flashes; increased sweating; nausea; nervousness; pain at the injection site; restlessness; sleeplessness; sweating; tiredness; tremors; vomiting; weakness.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; change in behavior, mood, or emotions (eg, anxiety, depression); pounding in the chest; rapid deep breathing; seizures.

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: Flumazenil 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 agitation; anxiety; emotional or mood changes; increased sensitivity to pain or touch; seizures.

Proper storage of Flumazenil:

Flumazenil is usually handled and stored by a health care provider. If you are using Flumazenil at home, store Flumazenil as directed by your pharmacist or health care provider. Keep Flumazenil out of the reach of children and away from pets.

General information:

• If you have any questions about Flumazenil, please talk with your doctor, pharmacist, or other health care provider.


• Flumazenil is 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 Flumazenil. 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 Flumazenil resources

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

• Flumazenil Monograph (AHFS DI)


• Flumazenil Professional Patient Advice (Wolters Kluwer)


• flumazenil Concise Consumer Information (Cerner Multum)


• Romazicon Prescribing Information (FDA)

Compare Flumazenil with other medications

• Benzodiazepine Overdose
• Reversal of Sedation

Etopophos

Generic Name: etoposide phosphate (e TOE poe side FOS fate)

Brand Names: Etopophos

What is Etopophos (etoposide phosphate)?

Etoposide phosphate is a cancer medicine that interferes with the growth of cancer cells and slows their growth and spread in the body.

Etoposide phosphate is used to treat cancer of the lung or testicles.

Etoposide phosphate may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Etopophos (etoposide phosphate)?

Do not receive etoposide phosphate if you are pregnant. It could harm the unborn baby.

Before receiving etoposide phosphate, tell your doctor if you have kidney disease or a weak immune system.

Etoposide phosphate can lower the blood cells that help your body fight infections. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding or injury. Tell your doctor at once if you develop signs of infection.

Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Visit your doctor regularly.

Using etoposide phosphate may increase your risk of developing other types of cancer, such as leukemia. Talk with your doctor about your specific risk.

What should I discuss with my health care provider before using Etopophos (etoposide phosphate)?

You should not use this medication if you are allergic to etoposide.

To make sure you can safely receive etoposide phosphate, tell your doctor if you have any of these other conditions:

• kidney disease; or


• 
  

  a weak immune system (from disease or from taking certain medicines).

  
  

FDA pregnancy category D. Do not use etoposide phosphate if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. It is not known whether etoposide phosphate passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are being treated with etoposide phosphate.

Using etoposide phosphate may increase your risk of developing other types of cancer, such as leukemia. Talk with your doctor about your specific risk.

How is etoposide phosphate given?

Etoposide phosphate is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. The medicine is sometimes given slowly through an IV infusion, and can take up to 3-1/2 hours to complete.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when etoposide phosphate is injected.

Etoposide phosphate is usually given for 4 or 5 days in a row every 3 to 4 weeks. Follow your doctor's instructions.

Etoposide phosphate can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill.

Your blood may need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Visit your doctor regularly.

Etoposide phosphate is used together with other cancer medications. Read the medication guide or patient instructions provided with each of your medications.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your etoposide phosphate injection.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving Etopophos (etoposide phosphate)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Etopophos (etoposide phosphate) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  fever, chills, body aches, flu symptoms, sores in your mouth and throat;

  
  


• 
  

  easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  
  


• 
  

  pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

  
  


• 
  

  pain, burning, irritation, or skin changes where the injection was given;

  
  


• 
  

  feeling like you might pass out; or

  
  


• 
  

  severe nausea and vomiting.

  
  

Less serious side effects may include:

• 
  

  mild nausea, vomiting, stomach pain, loss of appetite;

  
  


• 
  

  constipation, diarrhea;

  
  


• 
  

  dizziness, feeling tired or weak;

  
  


• 
  

  temporary hair loss; or

  
  


• 
  

  mild skin rash.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Etopophos (etoposide phosphate)?

Before you receive etoposide phosphate, tell your doctor if you are using cyclosporine (Neoral, Sandimmune, Gengraf).

There may be other drugs that can interact with etoposide phosphate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Etopophos resources

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

• Etopophos Prescribing Information (FDA)


• Etopophos Advanced Consumer (Micromedex) - Includes Dosage Information


• Etopophos MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Etopophos with other medications

• Cancer
• Hodgkin's Lymphoma
• Ovarian Cancer
• Small Cell Lung Cancer
• Testicular Cancer

Where can I get more information?

• Your doctor or pharmacist can provide more information about etoposide phosphate.

See also: Etopophos side effects (in more detail)

Victrelis

Generic Name: boceprevir (Oral route)

boe-SE-pre-vir

Commonly used brand name(s)

In the U.S.

• Victrelis

Available Dosage Forms:

• Capsule

Pharmacologic Class: Protease Inhibitor

Uses For Victrelis

Boceprevir is used in combination with injectable peginterferon alfa (Pegasys®, Pegintron®) and ribavirin (Copegus®, Rebetol®) to treat chronic hepatitis C infection. These medicines are used in patients with compensated liver disease (including cirrhosis), who have not been treated before or who have received other medicines but did not work well. Boceprevir is a direct-acting antiviral agent that treats hepatitis C infection.

This medicine is available only with your doctor's prescription.

Before Using Victrelis

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of boceprevir in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of boceprevir have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related liver problems, which may require caution in patients receiving boceprevir.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Alfuzosin


• Carbamazepine


• Cisapride


• Colchicine


• Dihydroergotamine


• Drospirenone


• Ergonovine


• Ergotamine


• Lovastatin


• Methylergonovine


• Midazolam


• Phenobarbital


• Phenytoin


• Pimozide


• Rifampin


• Sildenafil


• Simvastatin


• St John's Wort


• Tadalafil


• Triazolam

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alprazolam


• Amiodarone


• Bepridil


• Budesonide


• Dexamethasone


• Digoxin


• Efavirenz


• Ethinyl Estradiol


• Flecainide


• Fluticasone


• Itraconazole


• Posaconazole


• Propafenone


• Quinidine


• Rifabutin


• Ruxolitinib


• Salmeterol


• Sirolimus


• Sunitinib


• Vardenafil


• Voriconazole

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ketoconazole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood or bone marrow problems (e.g., anemia, neutropenia)—Use with caution. May make these conditions worse.

Proper Use of Victrelis

To help clear up your infection completely, boceprevir must be taken together with peginterferon alfa and ribavirin for the full time of treatment, even if you begin to feel better after a few days. Also, it is important to keep the amount of medicine in your body at a steady level. To help keep the amount constant, boceprevir must be used on a regular schedule.

Take this medicine with a meal or light snack.

Do not change or suddenly stop using this medicine without checking first with your doctor.

This medicine should come with a Medication Guide. Read and follow the information carefully. Ask your doctor if you have any questions. Ask your pharmacist for the Medication Guide if you do not have one.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  
  • For hepatitis C virus infection, in combination with peginterferon alfa and ribavirin:
    
    • Adults—800 milligrams (mg) (four 200-mg capsules) three times a day with food. Each dose should be taken 7 to 9 hours apart.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose or forget to use it, and it is less than 2 hours before your next regular dose, wait until then to take the medicine and skip the missed dose. If you miss a dose and it is more than 2 hours before your next regular dose, go ahead and take the missed dose and take the next regular dose as scheduled. If you have any questions about this, ask your pharmacist or doctor.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Victrelis

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine together with peginterferon alfa and ribavirin while you are pregnant can harm your unborn baby. These medicines may also cause birth defects if the father is using it when his sexual partner becomes pregnant. If a pregnancy occurs while you are using these medicines, tell your doctor right away.

To make sure you are not pregnant, your doctor may ask you to have a pregnancy test before you start using this medicine. You must have a negative pregnancy test before you will be allowed to use this medicine with ribavirin. Two forms of birth control must be used during treatment and for 6 months after treatment ends. You should test for pregnancy every month while you are using this medicine, and for 6 months after your treatment ends.

Birth control pills may not work while you are using this medicine. To keep from getting pregnant, use two other forms of birth control. Other forms of birth control include condoms, diaphragms, or contraceptive foams or jellies.

Do not use this medicine together with the following medicines: alfuzosin (Uroxatral®), cisapride (Propulsid®), drospirenone (Yasmin®, Yaz®), oral midazolam (Versed®), pimozide (Orap®), rifampin (Rifadin®, Rimactane®), sildenafil (Revatio®), St. John's wort, tadalafil (Adcirca®), triazolam (Halcion®), certain medicines to lower cholesterol (such as lovastatin, simvastatin, Mevacor®, or Zocor®), medicines to treat seizures (such as carbamazepine, phenobarbital, phenytoin, Dilantin®, or Tegretol®), or ergot medicines (such as dihydroergotamine, ergonovine, ergotamine, methylergonovine, DHE 45®, Ergomar®, Ergotrate®, or Methergine®). Using boceprevir with any of these medicines can cause very serious medical problems.

Check with your doctor right away if you have back, leg, or stomach pains; bleeding gums; chills; dark urine; difficulty with breathing; fever; general body swelling; headache; loss of appetite; nausea or vomiting; nosebleeds; pale skin; sore throat; unusual tiredness or weakness; or yellowing of the eyes or skin. These could be symptoms of a blood disorder called anemia.

Birth control pills may not work while you are using this medicine. To keep from getting pregnant, use two other forms of birth control. Other forms of birth control include condoms, diaphragms, or contraceptive foams or jellies.

Using this medicine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets in the blood, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.


• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in the urine or stools; or pinpoint red spots on your skin.


• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.


• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.


• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.


• Avoid contact sports or other situations where bruising or injury could occur.

Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests.

This medicine will not keep you from giving hepatitis C to other people. Follow your doctor's instructions about how to prevent the spread of this infection.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Victrelis Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Black, tarry stools


• chills


• cough


• difficult or labored breathing


• fever


• lower back or side pain


• painful or difficult urination


• pale skin


• shortness of breath


• sore throat


• tightness in the chest


• troubled breathing with exertion


• ulcers, sores, or white spots in the mouth


• unusual bleeding or bruising


• unusual tiredness or weakness


• wheezing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Change in taste


• decreased appetite


• diarrhea


• difficulty with moving


• dizziness


• dry mouth


• dry skin


• hair loss or thinning of the hair


• irritability


• lack or loss of strength


• loss of taste


• muscle pain or stiffness


• nausea


• pain in the joints


• rash


• sleeplessness


• trouble sleeping


• unable to sleep


• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.