Aldoril

Name: Aldoril

Uses

This medication is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This product contains 2 medications: methyldopa and hydrochlorothiazide. Methyldopa works by relaxing blood vessels so blood can flow more easily. Hydrochlorothiazide is a "water pill" (diuretic). It increases the amount of urine you make, especially when you first start the medication. It also helps to relax the blood vessels so that blood can flow more easily.These medications are used together when 1 drug alone is not controlling your blood pressure. Your doctor may direct you to start taking the individual medications first, and then switch you over to this combination product if this is the best dose combination for you.

Warnings

Methyldopa

It is important to recognize that a positive Coombs test, hemolytic anemia, and liver disorders may occur with methyldopa therapy. The rare occurrences of hemolytic anemia or liver disorders could lead to potentially fatal complications unless properly recognized and managed. Read this section carefully to understand these reactions.

With prolonged methyldopa therapy, 10 to 20 percent of patients develop a positive direct Coombs test which usually occurs between 6 and 12 months of methyldopa therapy. Lowest incidence is at daily dosage of 1 g or less. This on rare occasions may be associated with hemolytic anemia, which could lead to potentially fatal complications. One cannot predict which patients with a positive direct Coombs test may develop hemolytic anemia.

Prior existence or development of a positive direct Coombs test is not in itself a contraindication to use of methyldopa. If a positive Coombs test develops during methyldopa therapy, the physician should determine whether hemolytic anemia exists and whether the positive Coombs test may be a problem. For example, in addition to a positive direct Coombs test there is less often a positive indirect Coombs test which may interfere with cross matching of blood.

Before treatment is started it is desirable to do a blood count (hematocrit, hemoglobin, or red cell count) for a baseline or to establish whether there is anemia. Periodic blood counts should be done during therapy to detect hemolytic anemia. It may be useful to do a direct Coombs test before therapy and at 6 and 12 months after the start of therapy.

If Coombs-positive hemolytic anemia occurs, the cause may be methyldopa and the drug should be discontinued. Usually the anemia remits promptly. If not, corticosteroids may be given and other causes of anemia should be considered. If the hemolytic anemia is related to methyldopa, the drug should not be reinstituted.

When methyldopa causes Coombs positivity alone or with hemolytic anemia, the red cell is usually coated with gamma globulin of the IgG (gamma G) class only. The positive Coombs test may not revert to normal until weeks to months after methyldopa is stopped. Should the need for transfusion arise in a patient receiving methyldopa, both a direct and an indirect Coombs test should be performed. In the absence of hemolytic anemia, usually only the direct Coombs test will be positive. A positive direct Coombs test alone will not interfere with typing or cross matching. If the indirect Coombs test is also positive, problems may arise in the major cross match and the assistance of a hematologist or transfusion expert will be needed.

Occasionally, fever has occurred within the first three weeks of methyldopa therapy, associated in some cases with eosinophilia or abnormalities in one or more liver function tests, such as serum alkaline phosphatase, serum transaminases (SGOT, SGPT), bilirubin, and prothrombin time. Jaundice, with or without fever, may occur with onset usually within the first two to three months of therapy. In some patients the findings are consistent with those of cholestasis. In others the findings are consistent with hepatitis and hepatocellular injury.

Rarely, fatal hepatic necrosis has been reported after use of methyldopa. These hepatic changes may represent hypersensitivity reactions. Periodic determination of hepatic function should be done particularly during the first 6 to 12 weeks of therapy or whenever an unexplained fever occurs. If fever, abnormalities in liver function tests, or jaundice appear, stop therapy with methyldopa. If caused by methyldopa, the temperature and abnormalities in liver function characteristically have reverted to normal when the drug was discontinued. Methyldopa should not be reinstituted in such patients.

Rarely, a reversible reduction of the white blood cell count with a primary effect on the granulocytes has been seen. The granulocyte count returned promptly to normal on discontinuance of the drug. Rare cases of granulocytopenia have been reported. In each instance, upon stopping the drug, the white cell count returned to normal. Reversible thrombocytopenia has occurred rarely.

Hydrochlorothiazide

Use 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.

Thiazides may add to or potentiate the action of other antihypertensive drugs.

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.

Lithium generally should not be given with diuretics (see PRECAUTIONS: DRUG INTERACTIONS).

Uses For Aldoril

Methyldopa and hydrochlorothiazide combination is used to treat high blood pressure (hypertension).

High blood pressure adds to the workload 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. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Methyldopa works by controlling nerve impulses along certain nerve pathways. As a result, it relaxes blood vessels so that blood passes through them more easily. Hydrochlorothiazide helps reduce the amount of water in the body by increasing the flow of urine. These actions help to lower blood pressure.

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

Proper Use of Aldoril

In addition to the use of the medicine your doctor has prescribed, appropriate treatment for your high blood pressure may include weight control and care in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which factors 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 this medicine 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.

This medicine may cause you to have an unusual feeling of tiredness when you begin to take it. You may also notice an increase in the amount of urine or in your frequency of urination. After taking the medicine for a while, these effects should lessen. In general, to keep the increase in urine from affecting your sleep:

  • If you are to take a single dose a day, take it in the morning after breakfast.
  • If you are to take more than one dose a day, take the last dose no later than 6 p.m., unless otherwise directed by your doctor.

However, it is best to plan your dose or doses according to a schedule that will least affect your personal activities and sleep. Ask your health care professional to help you plan the best time to take this medicine.

To help you remember to take your medicine, try to get into the habit of taking it at the same time each day.

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 treating high blood pressure:
    • For oral dosage form (tablets):
      • Adults: Two to four tablets a day, taken as a single dose or in divided doses.
      • Children: 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.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

TABLETS Aldoril® (METHYLDOPA-HYDROCHLOROTHIAZIDE)

WARNING

This fixed combination drug is not indicated for initial therapy of hypertension. Hypertension requires therapy titrated to the individual patient. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management. The treatment of hypertension is not static, but must be re-evaluated as conditions in each patient warrant.

Indication and usage

Hypertension (see box warning).

Contraindications

Aldoril is contraindicated in patients:

  • with active hepatic disease, such as acute hepatitis and active cirrhosis
  • with liver disorders previously associated with methyldopa therapy (see WARNINGS)
  • with anuria
  • with hypersensitivity to methyldopa, or to hydrochlorothiazide or other sulfonamide-derived drugs
  • on therapy with monoamine oxidase (MAO) inhibitors.

Overdosage

Acute overdosage may produce acute hypotension with other responses attributable to brain and gastrointestinal malfunction (excessive sedation, weakness, bradycardia, dizziness, lightheadedness, constipation, distention, flatus, diarrhea, nausea, vomiting).

In the event of overdosage, symptomatic and supportive measures should be employed. When ingestion is recent, gastric lavage or emesis may reduce absorption. When ingestion has been earlier, infusions may be helpful to promote urinary excretion. Otherwise, management includes special attention to cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function and cerebral activity.

Sympathomimetic drugs [e.g., levarterenol, epinephrine, ARAMINE1 (Metaraminol Bitartrate)] may be indicated. Methyldopa is dialyzable. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

The oral LD50 of methyldopa is greater than 1.5 g/kg in both the mouse and the rat. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.

Aldoril Dosage and Administration

DOSAGE MUST BE INDIVIDUALIZED, AS DETERMINED BY TITRATION OF THE INDIVIDUAL COMPONENTS (see box warning). Once the patient has been successfully titrated, Aldoril may be substituted if the previously determined titrated doses are the same as in the combination. The usual starting dosage is one tablet of Aldoril 15 two or three times a day or one tablet of Aldoril 25 two times a day. Alternatively, one tablet of Aldoril D30 or Aldoril D50 once daily may be used. Hydrochlorothiazide doses greater than 50 mg daily should be avoided.

Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone. The usual daily dosage of methyldopa is 500 mg to 2 g. To minimize the sedation associated with methyldopa, start dosage increases in the evening. The maximum recommended daily dose of methyldopa is 3 g.

Occasionally tolerance to methyldopa may occur, usually between the second and third month of therapy. Additional separate doses of methyldopa or replacement of Aldoril with single entity agents is necessary until the new effective dose ratio is re-established by titration. If Aldoril does not adequately control blood pressure, additional doses of other agents may be given. When Aldoril is given with antihypertensives other than thiazides, the initial dosage of methyldopa should be limited to 500 mg daily in divided doses and the dose of these other agents may need to be adjusted to effect a smooth transition.

Since both components of Aldoril have a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours. This is not complicated by an overshoot of blood pressure.

Since methyldopa is largely excreted by the kidney, patients with impaired renal function may respond to smaller doses. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses. (See PRECAUTIONS, Geriatric Use.)

Hydrochlorothiazide / methyldopa Pregnancy Warnings

Animal studies have failed to reveal evidence of fetal harm. In humans, treatment with methyldopa has revealed improved fetal outcome as well as reduced infant average head circumference (0.4 cm). There are no controlled data in the first trimester of human pregnancy; there are no controlled data for hydrochlorothiazide in the second and third trimesters. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if clearly needed. US FDA pregnancy category: C

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