Hydralazine and hydrochlorothiazide

Hypertension (see boxed WARNING).

In the U.S.

• Apresazide

Available Dosage Forms:

• Capsule
• Tablet

Therapeutic Class: Vasodilator/Thiazide Combination

Pharmacologic Class: Diuretic

Chemical Class: Thiazide

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

Hydralazine works by relaxing blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload. The hydrochlorothiazide is a type of medicine known as a thiazide diuretic and helps reduce the amount of water in the body by acting on the kidneys to increase the flow of urine.

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

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 hydralazine and hydrochlorothiazide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to hydralazine and hydrochlorothiazide 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, hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide. Also, hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide, 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 hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide, 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 hydralazine and hydrochlorothiazide. 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. hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide may be increased .

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

hydralazine and hydrochlorothiazide 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 hydralazine and hydrochlorothiazide.

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 hydralazine 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.

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 hydralazine 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 hydralazine 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 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 hydralazine 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.

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.

Hydralazine HCl and hydrochlorothiazide is an antihypertensive-diuretic combination available as capsules for oral administration. Hydralazine HCl and hydrochlorothiazide capsules of 25 mg/25 mg contain 25 mg of Hydralazine hydrochloride USP and 25 mg of hydrochlorothiazide USP; capsules of 50 mg/50 mg contain 50 mg of hydralazine hydrochloride USP and 50 mg of hydrochlorothiazide USP; and capsules of 100 mg/50 mg contain 100 mg of hydralazine hydrochloride USP and 50 mg of hydrochlorothiazide USP.

Each capsule also contains the following inactive ingredients: Corn starch, crospovidone, gelatin, lactose monohydrate, pharmaceutical glaze, sodium starch glycolate, stearic acid, talc, and titanium dioxide. In addition, the 25 mg/25 mg capsule contains ammonium hydroxide, ethylene glycol monoethyl ether, propylene glycol and synthetic black iron oxide; the 50 mg/50 mg capsule contains FD&C Blue #1, FD&C Red #40, FD&C Yellow #6, synthetic red iron oxide and pharmaceutical shellac; and the 100 mg/50 mg capsule contains D&C Red #28, D&C Yellow #10, FD&C Blue #1,FD&C Blue #2, FD&C Red #40, propylene glycol and synthetic black iron oxide.

Hydralazine hydrochloride is 1-hydrazinophthalazine monohydrochloride, and its structural formula is:

Hydralazine hydrochloride USP is a white to off-white, odorless crystalline powder. It is soluble in water, slightly soluble in alcohol, and very slightly soluble in ether. It melts at about 275°C, with decomposition, and has a molecular weight of 196.64.

Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, and its structural formula is:

Hydrochlorothiazide USP is a white, or practically white, practically odorless crystalline powder. It is freely soluble in sodium hydroxide solution, inn-butylamine, and in dimethylformamide; sparingly soluble in methanol; slightly soluble in water; and insoluble in ether, in chloroform, and in dilute mineral acids. Its molecular weight is 297.75.

Hypertension (see boxed WARNING).

Acute Toxicity

Oral LD50’s in rats (mg/kg): hydralazine, 173 and 187; hydrochlorothiazide, 2750.

Signs and Symptoms

Hydralazine: Signs and symptoms of overdosage include hypotension, tachycardia, headache, and generalized skin flushing.

Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia and profound shock.

Hydrochlorothiazide: The most prominent feature of poisoning is acute loss of fluid and electrolytes.

Cardiovascular: Tachycardia, hypotension, shock.

Neuromuscular:Weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness.

Digestive: Nausea, vomiting, thirst.

Renal:Polyuria, oliguria or anuria (due to hemoconcentration).

Laboratory Findings: Hypokalemia, hyponatremia, hypochloremia, alkalosis; increased BUN (especially in patients with renal insufficiency).

Combined Poisoning: Signs and symptoms may be aggravated or modified by concomitant intake of antihypertensive medication, barbiturates, curare, digitalis (hypokalemia), corticosteroids, narcotics, or alcohol.

Treatment

There is no specific antidote.

The gastric contents should be evacuated, taking adequate precautions against aspiration and for protection of the airway. An activated charcoal slurry may be instilled if conditions permit. Dialysis may not be effective for elimination of hydralazine HCl and hydrochlorothiazide because of its plasma protein binding (seeCLINICAL PHARMACOLOGY).

These manipulations may have to be omitted or carried out after cardiovascular status has been stabilized, since they might precipitate cardiac arrhythmias or increase the depth of shock.

Support of the cardiovascular system is of primary importance in suspected hydralazine overdosage. Shock should be treated with plasma expanders. The patient’s legs should be kept raised and lost fluid and electrolytes (potassium, sodium) should be replaced. If possible, vasopressors should not be given, but if a vasopressor is required, care should be taken not to precipitate or aggravate cardiac arrhythmia. Tachycardia responds to beta blockers. Digitalization may be necessary, and renal function should be monitored and supported as required.