Apresazide

Patients should be informed of possible side effects and advised to take the medication regularly and continuously as directed.

In the U.S.

• Apresazide

Available Dosage Forms:

• Capsule
• Tablet

Therapeutic Class: Vasodilator/Thiazide Combination

Pharmacologic Class: Diuretic

Chemical Class: Thiazide

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 hydralazine and hydrochlorothiazide combination in the pediatric population. Safety and efficacy have not been established .

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of hydralazine and hydrochlorothiazide combination in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults. However, dizziness or lightheadedness or symptoms of too much potassium loss may be more likely to occur in the elderly, who are usually more sensitive to the effects of this medicine. Also, this medicine may reduce tolerance to cold temperatures in elderly patients.

Pregnancy

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.

• Dofetilide

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.

• Aceclofenac
• Acemetacin
• Acetyldigoxin
• Amphetamine
• Amtolmetin Guacil
• Arsenic Trioxide
• Aspirin
• Benzphetamine
• Bromfenac
• Bufexamac
• Celecoxib
• Choline Salicylate
• Clonixin
• Cyclophosphamide
• Deslanoside
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Diclofenac
• Diflunisal
• Digitalis
• Digitoxin
• Digoxin
• Dipyrone
• Droperidol
• Droxicam
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Flecainide
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Ibuprofen
• Indomethacin
• Ketanserin
• Ketoprofen
• Ketorolac
• Levomethadyl
• Lisdexamfetamine
• Lithium
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Methamphetamine
• Methotrexate
• Metildigoxin
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Ouabain
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Proglumetacin
• Propyphenazone
• Proquazone
• Proscillaridin
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sotalol
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Valdecoxib

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.

• Aminolevulinic Acid
• Bepridil
• Carbamazepine
• Cholestyramine
• Ginkgo
• Gossypol
• Licorice
• Topiramate

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. 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 may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Enteral Nutrition
• food

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:

• Gout (history of)
• Hyperuricemia (high uric acid in the blood) or—Hydrochlorothiazide may increase the amount of uric acid in the blood, which can lead to gout .

• Heart or blood vessel disease or
• Stroke (recent)—Lowering blood pressure may make problems resulting from these conditions worse.

• Hypochloremia (low chloride in the blood) or
• Hypokalemia (low potassium in the blood)
• Hypomagnesemia (low magnesium in the blood) or
• Hyponatremia (low sodium in the blood) or
• Parathyroid disease or
• Systemic lupus erythematosus (history of)—Use with caution. This medicine may make these conditions worse .

• Kidney disease—Hydrochlorothiazide may worsen this condition. Also, the blood pressure lowering effects may be increased because of slower removal of hydralazine from the body.

• Liver disease—If hydrochlorothiazide causes loss of too much water from the body, liver disease can become much worse.

• Sympathectomy—Use with caution. The effects of this medicine may be increased .

• Type 2 diabetes mellitus—Hydrochlorothiazide may change the amount of diabetes medicine needed .

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. 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.

In addition to the use of the medicine your doctor has prescribed, 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 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 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.

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 oral dosage forms (capsules):
  • For high blood pressure:
    • Adults—1 capsule two times a day.
    • 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.

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.

Applies to hydralazine / hydrochlorothiazide: oral capsule, oral tablet

Along with its needed effects, hydralazine / hydrochlorothiazide 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 as soon as possible if any of the following side effects occur while taking hydralazine / hydrochlorothiazide:

• Dryness of mouth
• increased thirst
• irregular heartbeats
• mood or mental changes
• muscle cramps or pain
• weak pulse

• Confusion
• convulsions
• decreased mental activity
• irritability
• muscle cramps
• unusual tiredness or weakness

• Blisters on skin
• chest pain
• general feeling of discomfort or illness or weakness
• joint pain
• numbness, tingling, pain, or weakness in hands or feet
• skin rash or itching
• sore throat and fever
• swelling of the lymph glands

• Lower back or side pain
• severe stomach pain with nausea and vomiting
• unusual bleeding or bruising
• yellow eyes or skin

Some side effects of hydralazine / hydrochlorothiazide 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:

• Diarrhea
• fast or irregular heartbeat
• headache
• loss of appetite
• nausea or vomiting

• Constipation
• decreased sexual ability
• dizziness or lightheadedness, especially when getting up from a lying or sitting position
• increased sensitivity of skin to sunlight
• redness or flushing of face
• shortness of breath with exercise or work
• stuffy nose
• watering or irritated eyes

In general, hydralazine has been used extensively and safely for the treatment of maternal hypertension during pregnancy. There are reports of neonatal asymptomatic and symptomatic thrombocytopenia and maternal and fetal lupus-like toxicity associated with the maternal use of hydralazine, but there are no reports of associated teratogenicity. Among 50,282 mother-child pairs monitored in the Collaborative Perinatal Project, 136 pairs had been exposed to hydralazine during pregnancy. Of the 136 pairs, 8 malformed children were observed (3.8 were expected from the population studied), yielding a standardized relative risk of 2.09. Underlying preeclampsia makes implication of drug therapy alone difficult. Of 50,282 mother-child pairs in the Collaborative Perinatal Project, 233 pairs were exposed to thiazide or related diuretics during the first trimester. An increased risk of malformations was found for thiazide diuretics. Use of thiazides after the first trimester does not seem to carry this risk. Thiazide diuretics may, however pose metabolic risks to the mother and fetus (hyponatremia, hypokalemia, thrombocytopenia, hyperglycemia), and may have a direct effect on smooth muscle, resulting in inhibition of labor. Data from the Michigan Medicaid Birth Defects Study (MMBDS) failed to reveal an association between the use of hydralazine and congenital abnormalities (written communication, Franz Rosa, MD, Food and Drug Administration, 1994). The MMBDS is a retrospective study of 229,101 completed pregnancies between 1985 and 1992, of which 40 were exposed to hydralazine at some time during the first trimester and 341 were exposed to the drug at any time during pregnancy. These data do not support an association between hydralazine and birth defects. Data from the MMBDS has revealed an association between the use of hydrochlorothiazide (HCTZ) and congenital abnormalities. Between 1985 and 1992, 567 of 229,101 completed pregnancies were exposed to HCTZ at some time during the first trimester, and 1,173 were exposed to the drug at any time during pregnancy. Of the 567 pregnancies, there were 24 total and 7 cardiovascular birth defects (22 and 6 were expected, respectively). There were no observations of cleft palate, spina bifida, limb reduction, or hypospadias. The one instance of polydactyly did not achieve statistical significance. These data are consistent with an association between the use of HCTZ and birth defects, although other factors, including underlying disease(s) of the mother are not accounted for. Cases of neonatal thrombocytopenia associated with antepartum administration of thiazide diuretics have been reported.

Hydralazine-hydrochlorothiazide (HCTZ) has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of teratogenicity after doses 20 to 30 times the maximum recommended daily human dose (on a per kg basis) were given to mice. Teratogenicity was possibly related to hydralazine after doses 10 to 15 times the maximum recommended daily human dose (on a per kg basis) were given to rabbits. There are no controlled data in human pregnancy, but retrospective reviews have shown an increased risk of malformations associated with thiazide diuretics. Hydralazine-HCTZ should only be given during pregnancy when benefit outweighs risk.