Captopril and hydrochlorothiazide

Serious side effects have been reported with captopril and hydrochlorothiazide. See the "Captopril and hydrochlorothiazide Precautions" section. 

Common side effects of captopril and hydrochlorothiazide include the following:

• skin reactions such as rash, itching, and sensitivity to the sun
• loss of taste
• low blood pressure (especially upon standing)
• fast heart beat
• chest pain
• a noticeably rapid, strong, or irregular heartbeat (palpitation)
• cough
• dizziness
• feeling like your surroundings are spinning or moving (vertigo)
• an eating disorder associated with low body weight (anorexia)
• nausea or vomiting
• cramping
• diarrhea or constipation
• headache

This is not a complete list of captopril and hydrochlorothiazide side effects. Ask your doctor or pharmacist for more information. 

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of captopril and hydrochlorothiazide, salt substitutes containing potassium should be avoided. 

• Take captopril and hydrochlorothiazide exactly as prescribed. 
• Captopril and hydrochlorothiazide comes in a tablet form and is usually taken by mouth once daily with or without food. 

Captopril

Reported incidences are based on clinical trials involving approximately 7000 patients.

Renal: About one of 100 patients developed proteinuria (see WARNINGS).

Each of the following has been reported in approximately 1 to 2 of 1000 patients and are of uncertain relationship to drug use: renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria, and urinary frequency.

Hematologic: Neutropenia/agranulocytosis has occurred (see WARNINGS). Cases of anemia, thrombocytopenia, and pancytopenia have been reported.

Dermatologic: Rash, often with pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 4 to 7 (depending on renal status and dose) of 100 patients, usually during the first four weeks of therapy. It is usually maculopapular, and rarely urticarial. The rash is usually mild and disappears within a few days of dosage reduction, short-term treatment with an antihistaminic agent, and/or discontinuing therapy; remission may occur even if captopril is continued. Pruritus, without rash, occurs in about 2 of 100 patients. Between 7 and 10 percent of patients with skin rash have shown eosinophilia and/or positive ANA titers. A reversible associated pemphigoid-like lesion, and photosensitivity, have also been reported.

Flushing or pallor has been reported in 2 to 5 of 1000 patients.

Cardiovascular: Hypotension may occur; see WARNINGS and PRECAUTIONS (DRUG INTERACTIONS) for discussion of hypotension with captopril therapy.

Tachycardia, chest pain, and palpitations have each been observed in approximately 1 of 100 patients.

Angina pectoris, myocardial infarction, Raynaud†s syndrome, and congestive heart failure have each occurred in 2 to 3 of 1000 patients.

Dysgeusia: Approximately 2 to 4 (depending on renal status and dose) of 100 patients developed a diminution or loss of taste perception. Taste impairment is reversible and usually self-limited (2 to 3 months) even with continued drug administration. Weight loss may be associated with the loss of taste.

Angioedema: Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported in approximately one in 1000 patients. Angioedema involving the upper airways has caused fatal airway obstruction. (See WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema and PRECAUTIONS: INFORMATION FOR PATIENTS.)

Cough: Cough has been reported in 0.5-2% of patients treated with captopril in clinical trials (see PRECAUTIONS: General: Captopril, Cough).

The following have been reported in about 0.5 -2% of patients but did not appear at increased frequency compared to placebo or other treatments used in controlled trials: gastric irritation, abdominal pain, nausea, vomiting, diarrhea, anorexia, constipation, aphthous ulcers, peptic ulcer, dizziness, headache, malaise, fatigue, insomnia, dry mouth, dyspnea, alopecia, paresthesias.

Other clinical adverse effects reported since the drug was marketed are listed below by body system. In this setting, an incidence or causal relationship cannot be accurately determined.

Body as a whole: anaphylactoid reactions (see WARNINGS: Captopril: Anaphylactoid and possibly related reactions and PRECAUTIONS: Hemodialysis).

General: asthenia, gynecomastia.

Cardiovascular: cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.

Dermatologic: bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis.

Gastrointestinal: pancreatitis, glossitis, dyspepsia.

Hematologic: anemia, including aplastic and hemolytic.

Hepatobiliary: jaundice, hepatitis, including rare cases of necrosis, cholestasis.

Metabolic: symptomatic hyponatremia.

Musculoskeletal: myalgia, myasthenia. Nervous/Psychiatric: ataxia, confusion, depression, nervousness, somnolence.

Respiratory: bronchospasm, eosinophilic pneumonitis, rhinitis.

Special Senses: blurred vision.

Urogenital: impotence.

As with other ACE inhibitors, a syndrome has been reported which may include: fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash or other dermatologic manifestations, eosinophilia and an elevated ESR.

Fetal/Neonatal Morbidity and Mortality

See WARNINGS: Captopril: Fetal/Neonatal Morbidity and Mortality.

Hydrochlorothiazide

Gastrointestinal System: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, and sialadenitis.

Central Nervous System: dizziness, vertigo, paresthesias, headache, and xanthopsia.

Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia.

Cardiovascular: orthostatic hypotension.

Hypersensitivity: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis; cutaneous vasculitis), fever, respiratory distress including pneumonitis, and anaphylactic reactions.

Other: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, and transient blurred vision.

Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.

Altered Laboratory Findings

Serum Electrolytes: Hyperkalemia: small increases in serum potassium, especially in patients with renal impairment (see PRECAUTIONS: Captopril).

Hyponatremia: particularly in patients receiving a low sodium diet or concomitant diuretics.

BUN/Serum Creatinine: Transient elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with renovascular hypertension may occur. Rapid reduction of longstanding or markedly elevated blood pressure can result in decreases in the glomerular filtration rate and, in turn, lead to increases in BUN or serum creatinine.

Hematologic: A positive ANA has been reported.

Liver Function Tests: Elevations of liver transaminases, alkaline phosphatase, and serum bilirubin have occurred.

Read the entire FDA prescribing information for Capozide (Captopril and Hydrochlorothiazide)

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Captopril and hydrochlorothiazide combination is used to treat high blood pressure (hypertension). High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys resulting in a stroke, heart failure, or kidney failure. Hypertension may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled .

Captopril works by blocking an enzyme in the body that is necessary to produce a substance that causes blood vessels to tighten. As a result, the blood vessels relax. Hydrochlorothiazide works by helping reduce the amount of salt and water in the body by acting on the kidneys to increase the flow of urine. Both of these medicines lower blood pressure and increase the supply of blood and oxygen to the heart .

captopril and hydrochlorothiazide is available only with your doctor's prescription .

In addition to the use of captopril and hydrochlorothiazide, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that captopril and hydrochlorothiazide will not cure your high blood pressure but it does help control it. Therefore, you must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

It is best to take captopril and hydrochlorothiazide on an empty stomach at least 1 hour before eating any food .

Dosing

The dose of captopril and hydrochlorothiazide 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 captopril and hydrochlorothiazide. 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 (tablets):
  • For high blood pressure:
    • Adults—1 or 2 tablets once a day.
    • Children—Use and dose must be determined by your doctor .

Missed Dose

If you miss a dose of captopril and hydrochlorothiazide, 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.

Storage

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

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Use captopril and hydrochlorothiazide as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take 1 hour before meals.
• Take this medicine at the same time of day.
• To gain the most benefit, do not miss doses.
• Keep taking captopril and hydrochlorothiazide as you have been told by your doctor or other health care provider, even if you feel well.
• This medicine may cause you to pass urine more often. To keep from having sleep problems, try to take before 6 pm.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Captopril

Anaphylactoid and Possibly Related Reactions

Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors, including captopril, may be subject to a variety of adverse reactions, some of them serious.

Head and neck angioedema

Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been seen in patients treated with ACE inhibitors, including captopril. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Emergency therapy, including but not necessarily limited to subcutaneous administration of a 1:1000 solution of epinephrine, should be promptly instituted.

Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of treatment; some cases required medical therapy. (See PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Captopril.)

Intestinal angioedema

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Anaphylactoid reactions during desensitization

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid reactions during membrane exposure

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Neutropenia/Agranulocytosis

Neutropenia (< 1000/mm3) with myeloid hypoplasia has resulted from use of captopril. About half of the neutropenic patients developed systemic or oral cavity infections or other features of the syndrome of agranulocytosis.

The risk of neutropenia is dependent on the clinical status of the patient:

  In clinical trials in patients with hypertension who have normal renal function (serum creatinine less than 1.6 mg/dL and no collagen vascular disease), neutropenia has been seen in one patient out of over 8,600 exposed.   In patients with some degree of renal failure (serum creatinine at least 1.6 mg/dL) but no collagen vascular disease, the risk of neutropenia in clinical trials was about 1 per 500, a frequency over 15 times that for uncomplicated hypertension. Daily doses of captopril were relatively high in these patients, particularly in view of their diminished renal function. In foreign marketing experience in patients with renal failure, use of allopurinol concomitantly with captopril has been associated with neutropenia but this association has not appeared in U.S. reports.   In patients with collagen vascular diseases (e.g., systemic lupus erythematosus, scleroderma) and impaired renal function, neutropenia occurred in 3.7 percent of patients in clinical trials.   While none of the over 750 patients in formal clinical trials of heart failure developed neutropenia, it has occurred during the subsequent clinical experience. About half of the reported cases had serum creatinine > 1.6 mg/dL and more than 75 percent were in patients also receiving procainamide. In heart failure, it appears that the same risk factors for neutropenia are present.

The neutropenia has usually been detected within three months after captopril was started. Bone marrow examinations in patients with neutropenia consistently showed myeloid hypoplasia, frequently accompanied by erythroid hypoplasia and decreased numbers of megakaryocytes (e.g., hypoplastic bone marrow and pancytopenia); anemia and thrombocytopenia were sometimes seen.

In general, neutrophils returned to normal in about two weeks after captopril was discontinued, and serious infections were limited to clinically complex patients. About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors.

Evaluation of the Hypertensive or Heart Failure Patient Should Always Include Assessment of Renal Function.

If captopril is used in patients with impaired renal function, white blood cell and differential counts should be evaluated prior to starting treatment and at approximately two-week intervals for about three months, then periodically.

In patients with collagen vascular disease or who are exposed to other drugs known to affect the white cells or immune response, particularly when there is impaired renal function, captopril should be used only after an assessment of benefit and risk, and then with caution.

All patients treated with captopril should be told to report any signs of infection (e.g., sore throat, fever). If infection is suspected, white cell counts should be performed without delay.

Since discontinuation of captopril and other drugs has generally led to prompt return of the white count to normal, upon confirmation of neutropenia (neutrophil count < 1000/mm3) the physician should withdraw captopril and closely follow the patient's course.

Proteinuria

Total urinary proteins greater than 1 g per day were seen in about 0.7 percent of patients receiving captopril. About 90 percent of affected patients had evidence of prior renal disease or received relatively high doses of captopril (in excess of 150 mg/day), or both. The nephrotic syndrome occurred in about one-fifth of proteinuric patients. In most cases, proteinuria subsided or cleared within six months whether or not captopril was continued. Parameters of renal function, such as BUN and creatinine, were seldom altered in the patients with proteinuria.

Hypotension

Excessive hypotension was rarely seen in hypertensive patients but is a possible consequence of captopril use in salt/volume-depleted persons (such as those treated vigorously with diuretics), patients with heart failure or those patients undergoing renal dialysis. (See PRECAUTIONS, Drug Interactions.)

Fetal/Neonatal Morbidity and Mortality

ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.

The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE-inhibitor exposure.

These adverse effects do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of captopril as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.

If oligohydramnios is observed, captopril should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. While captopril may be removed from the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the circulation of neonates or children. Peritoneal dialysis is not effective for removing captopril; there is no information concerning exchange transfusion for removing captopril from the general circulation.

When captopril was given to rabbits at doses about 0.8 to 70 times (on a mg/kg basis) the maximum recommended human dose, low incidences of craniofacial malformations were seen. No teratogenic effects of captopril were seen in studies of pregnant rats and hamsters. On a mg/kg basis, the doses used were up to 150 times (in hamsters) and 625 times (in rats) the maximum recommended human dose.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Hydrochlorothiazide

Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

In general, lithium should not be given with diuretics (see PRECAUTIONS, Drug Interactions, Captopril and Hydrochlorothiazide).

Captopril and Hydrochlorothiazide tablets USP are available as follows:

Captopril and Hydrochlorothiazide tablets USP, 25 mg/15 mg are available as white, round tablets debossed "93" and "176" on the upper surface and quadrisected on the lower surface in bottles of 100 with desiccant/carbon canisters.

Captopril and Hydrochlorothiazide tablets USP, 25 mg/25 mg are available as tan, round tablets debossed "93" and "177" on the upper surface and quadrisected on the lower surface in bottles of 100 with desiccant/carbon canisters.

Captopril and Hydrochlorothiazide tablets USP, 50 mg/15 mg are available as white, oval tablets debossed "93" and "181" on the bisected side in bottles of 100 with desiccant/carbon canisters.

Captopril and Hydrochlorothiazide tablets USP, 50 mg/25 mg are available as tan, oval tablets debossed "93" and "182" on the bisected side in bottles of 100 with desiccant/carbon canisters.

Store at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature].

Dispense in a tight container as defined in the USP, with a child-resistant closure (as required).

Keep bottles tightly closed.

Protect from moisture.

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. H 5/2009

• Angiotensin-Converting Enzyme (ACE) Inhibitor
• Antihypertensive
• Diuretic, Thiazide

Reduce initial daily dose and titrate slowly (1- to 2-week intervals) with smaller increments. Slowly back titrate to determine the minimum effective dose once the desired therapeutic effect has been reached. Hydrochlorothiazide is contraindicated in patients with anuria.