Apresoline

Name: Apresoline

Side Effects of Apresoline

Serious side effects have been reported with Apresoline. See the “Apresoline Precautions” section.

Common side effects of Apresoline include the following:

  • headache
  • anorexia
  • nausea/vomiting
  • diarrhea
  • palpitations
  • tachycardia
  • angina pectoris

This is not a complete list of Apresoline 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.

Apresoline Interactions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • MAO inhibitors such as tranylcypromine (Parnate), phenelzine (Nardil), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), and rasagiline (Azilect)
  • Other potent parenteral antihypertensive drugs, such as diazoxide (Proglycem)

This is not a complete list of Apresoline drug interactions. Ask your doctor or pharmacist for more information.

Apresoline and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Apresoline falls into category C. There are no well-controlled studies that have been done in pregnant women. Apresoline should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

What is Apresoline (hydralazine)?

Hydralazine is a vasodilator that works by relaxing the muscles in your blood vessels to help them dilate (widen). This lowers blood pressure and allows blood to flow more easily through your veins and arteries.

Hydralazine is used to treat high blood pressure (hypertension).

Hydralazine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Apresoline (hydralazine)?

You should not use this medication if you are allergic to hydralazine, or if you have coronary artery disease, or rheumatic heart disease affecting the mitral valve.

Before taking hydralazine, tell your doctor if you have kidney disease, lupus, angina pectoris (chest pain), or if you have ever had a stroke.

While taking hydralazine, 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.

Call your doctor at once if you have a serious side effect such as fast or pounding heartbeats, swelling, numbness or tingling, dark-colored urine, joint pain or swelling with fever, chest pain, weakness or tired feeling, and urinating less than usual or not at all.

To be sure this medication is helping your condition and is not causing harmful effects, your blood pressure will need to be checked often. You may also need occasional blood tests. Do not miss any scheduled appointments.

Keep using hydralazine as directed, even if you feel well. High blood pressure often has no symptoms, so you may not know when your blood pressure is high. You may need to use blood pressure medication for the rest of your life.

What should I avoid while taking Apresoline (hydralazine)?

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.

Apresoline (hydralazine) 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:

  • fast or pounding heartbeats;

  • swelling in your face, stomach, hands, or feet;

  • numbness, burning, pain, or tingly feeling;

  • feeling like you might pass out;

  • confusion, unusual thoughts or behavior;

  • pale skin, easy bruising;

  • painful or difficult urination;

  • dark-colored urine;

  • urinating less than usual or not at all; or

  • joint pain or swelling with fever, chest pain, weakness or tired feeling.

Less serious side effects may include:

  • nausea, vomiting, loss of appetite;

  • diarrhea, constipation;

  • headache;

  • dizziness;

  • anxiety;

  • muscle or joint pain;

  • runny or stuffy nose; or

  • mild itching or skin rash.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Before Using Apresoline

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 on the relationship of age to the effects of hydralazine have not been performed in the pediatric population. However, no pediatric-specific problems have been documented to date.

Geriatric

No information is available on the relationship of age to the effects of hydralazine in geriatric patients.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during 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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

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:

  • Angina (severe chest pain) or
  • Blood disease or
  • Heart attack, history of or
  • Heart rhythm problems or
  • Hypotension (low blood pressure) or
  • Peripheral neuritis (nerve problem) or
  • Stroke, history of or
  • Systemic lupus erythematosus—Use with caution. May make these conditions worse.
  • Coronary artery disease or
  • Mitral valvular rheumatic heart disease—Should not be used in patients with these conditions.
  • Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
  • Phenylketonuria—The oral solution contains aspartame, which can make this condition worse.

Apresoline - Clinical Pharmacology

Although the precise mechanism of action of hydralazine is not fully understood, the major effects are on the cardiovascular system. Hydralazine apparently lowers blood pressure by exerting a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle. Hydralazine, by altering cellular calcium metabolism, interferes with the calcium movements within the vascular smooth muscle that are responsible for initiating or maintaining the contractile state.

      The peripheral vasodilating effect of hydralazine results in decreased arterial blood pressure (diastolic more than systolic); decreased peripheral vascular resistance; and an increased heart rate, stroke volume, and cardiac output. The preferential dilatation of arterioles, as compared to veins, minimizes postural hypotension and promotes the increase in cardiac output. Hydralazine usually increases renin activity in plasma, presumably as a result of increased secretion of renin by the renal juxtaglomerular cells in response to reflex sympathetic discharge. This increase in renin activity leads to the production of angiotensin II, which then causes stimulation of aldosterone and consequent sodium reabsorption. Hydralazine also maintains or increases renal and cerebral blood flow.

      Hydralazine is rapidly absorbed after oral administration, and peak plasma levels are reached at 1-2 hours. Plasma levels of apparent hydralazine decline with a half-life of 3-7 hours. Binding to human plasma protein is 87% Plasma levels of hydralazine vary widely among individuals. Hydralazine is subject to polymorphic acetylation; slow acetylators generally have higher plasma levels of hydralazine and require lower doses to maintain control of blood pressure. Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine.

Warnings

In a few patients hydralazine may produce a clinical picture simulating systemic lupus erythematosus including glomerulonephritis. In such patients hydralazine should be discontinued unless the benefit-to-risk determination requires continued antihypertensive therapy with this drug. Symptoms and signs usually regress when the drug is discontinued but residua have been detected many years later. Long-term treatment with steroids may be necessary. (See PRECAUTIONS, Laboratory Tests.)

Precautions

General

Myocardial stimulation produced by Apresoline can cause anginal attacks and ECG changes of myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must, therefore, be used with caution in patients with suspected coronary artery disease.

      The “hyperdynamic" circulation caused by Apresoline may accentuate specific cardiovascular inadequacies. For example, Apresoline may increase pulmonary artery pressure in patients with mitral valvular disease. The drug may reduce the pressor responses to epinephrine. Postural hypotension may result from Apresoline but is less common than with ganglionic blocking agents. It should be used with caution in patients with cerebral vascular accidents

      In hypertensive patients with normal kidneys who are treated with Apresoline, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate. In some instances where control values were below normal, improved renal function has been noted after administration of Apresoline. However, as with any antihypertensive agent, Apresoline should be used with caution in patients with advanced renal damage.

      Peripheral neuritis, evidenced by paresthesia, numbness, and tingling, has been observed. Published evidence suggests an antipyridoxine effect, and that pyridoxine should be added to the regimen if symptoms develop.

The Apresoline tablets (100 mg) contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who are also hypersensitive to aspirin.

Information for Patient

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

Laboratory Tests

Complete blood counts and antinuclear antibody titer determinations are indicated before and periodically during prolonged therapy with hydralazine even though the patient is asymptomatic. These studies are also indicated if the patient develops arthralgia, fever, chest pain, continued malaise, or other unexplained signs or symptoms.

      A positive antinuclear antibody titer requires that the physician carefully weigh the implications of the test results against the benefits to be derived from antihypertensive therapy with hydralazine.

      Blood dyscrasias, consisting of reduction in hemoglobin and red cell count, leukopenia, agranulocytosis, and purpura have been reported. If such abnormalities develop, therapy should be discontinued.

Drug/Drug Interactions

MAO inhibitors should be used with caution in patients receiving hydralazine.

      When other potent parenteral antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure. Profound hypotensive episodes may occur when diazoxide injection and Apresoline are used concomitantly.

Drug/Food interactions

Administration of hydralazine with food results in higher plasma levels.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a lifetime study in Swiss albino mice, there was a statistically significant increase in the incidence of lung tumors (adenomas and adenocarcinomas) of both male and female mice given hydralazine continuously in their drinking water at a dosage of about 250 mg/kg per day (about 80 times the maximum recommended human dose). In a 2-year carcinogenicity study of rats given hydralazine by gavage at dose levels of 15, 30, and 60 mg/kg/day (approximately 5 to 20 times the recommended human daily dosage), microscopic examination of the liver revealed a small, but statistically significant, increase in benign neoplastic nodules in male and female rats from the high-dose group and in female rats from the intermediate-dose group. Benign interstitial cell tumors of the testes were also significantly increased in male rats from the high-dose group. The tumors observed are common in aged rats and a significantly increased incidence was not observed until 18 months of treatment, Hydralazine was shown to be mutagenic in bacterial systems (Gene Mutation and DNA Repair) and in one of two rat and one rabbit hepatocyte in vitro DNA repair studies. Additional in vivo and in vitro studies using lymphoma cells, germinal cells, and fibroblasts from mice, bone marrow cells from Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic potential for hydralazine.

      The extent to which these findings indicate a risk to man is uncertain. While long-term clinical observation has not suggested that human cancer is associated with hydralazine use, epidemiologic studies have so far been insufficient to arrive at any conclusions.

Pregnancy Category C

Animal studies indicate that hydralazine is teratogenic in mice at 20-30 times the maximum daily human dose of 200-300 mg and possibly in rabbits at 10-15 times the maximum daily human dose, but that it is nonteratogenic in rats. Teratogenic effects observed were cleft palate and malformations of facial and cranial bones.

      There are no adequate and well-controlled studies in pregnant women. Although clinical experience does not include any positive evidence of adverse effects on the human fetus, hydralazine should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.

Nursing Mothers

Hydralazine has been shown to be excreted in breast milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established in controlled clinical trials, although there is experience with the use of Apresoline in these patients. The usual recommended oral starting dosage is 0.75 mg/kg of body weight daily in four divided doses. Dosage may be increased gradually over the next 3-4 weeks to a maximum of 7.5 mg/kg or 200 mg daily.

How is Apresoline Supplied

Tablets 10 mg – round, pale yellow, dry-coated (imprinted CIBA 37)

      Bottles of 100 ........................... NDC 0083-0037-30

Tablets 25 mg – round, deep blue, dry-coated (imprinted CIBA 39)

      Bottles of 100 ........................... NDC 0083-0039-30

Tablets 50 mg – round, light blue, dry-coated (imprinted CIBA 73)

      Bottles of 100 ........................... NDC 0083-0073-30

Tablets 100 mg – round, peach, dry-coated (imprinted CIBA 101)

      Bottles of 100 ........................... NDC 0083-0101-30

Samples, when available, are identified by the word SAMPLE appearing on each tablet.

Do not store above 86ºF (30 C).

Dispense in tight, light-resistant container (USP).

666692                                          C95-14 (Rev. 5/95)

C I B A

Ciba-Geigy Corporation

Pharmaceuticals Division

Summit, New Jersey 07901

Apresoline HYDROCHLORIDE 
hydralazine hydrochloride tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0083-0037
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
hydralazine hydrochloride (hydralazine) hydralazine 10 mg
Inactive Ingredients
Ingredient Name Strength
Acacia  
D&C Yellow No. 10  
lactose  
magnesium stearate  
mannitol  
polyethylene glycol  
sodium starch glycolate  
starch  
stearic acid  
Product Characteristics
Color YELLOW (pale yellow) Score no score
Shape ROUND Size 1mm
Flavor Imprint Code CIBA;37
Contains     
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:0083-0037-30 100 TABLET, COATED (100 TABLET) in 1 BOTTLE
Apresoline HYDROCHLORIDE 
hydralazine hydrochloride tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0083-0039
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
hydralazine hydrochloride (hydralazine) hydralazine 25 mg
Inactive Ingredients
Ingredient Name Strength
Acacia  
FD&C Blue No. 1  
lactose  
magnesium stearate  
mannitol  
polyethylene glycol  
sodium starch glycolate  
starch  
stearic acid  
Product Characteristics
Color BLUE (deep blue) Score no score
Shape ROUND Size 1mm
Flavor Imprint Code CIBA;39
Contains     
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:0083-0039-30 100 TABLET, COATED (100 TABLET) in 1 BOTTLE
Apresoline HYDROCHLORIDE 
hydralazine hydrochloride tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0083-0073
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
hydralazine hydrochloride (hydralazine) hydralazine 50 mg
Inactive Ingredients
Ingredient Name Strength
Acacia  
FD&C Blue No. 1  
lactose  
magnesium stearate  
mannitol  
polyethylene glycol  
sodium starch glycolate  
starch  
stearic acid  
Product Characteristics
Color BLUE (light blue) Score no score
Shape ROUND Size 1mm
Flavor Imprint Code CIBA;73
Contains     
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:0083-0073-30 100 TABLET, COATED (100 TABLET) in 1 BOTTLE
Apresoline HYDROCHLORIDE 
hydralazine hydrochloride tablet, coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0083-0101
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
hydralazine hydrochloride (hydralazine) hydralazine 100 mg
Inactive Ingredients
Ingredient Name Strength
Acacia  
FD&C Yellow No. 5  
FD&C Yellow No. 6  
lactose  
magnesium stearate  
mannitol  
polyethylene glycol  
sodium starch glycolate  
starch  
stearic acid  
Product Characteristics
Color ORANGE (peach) Score no score
Shape ROUND Size 1mm
Flavor Imprint Code CIBA;101
Contains     
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:0083-0101-30 100 TABLET, COATED (100 TABLET) in 1 BOTTLE
Labeler - Ciba-Geigy Corporation
Revised: 05/2006   Ciba-Geigy Corporation

Hydralazine Levels and Effects while Breastfeeding

Summary of Use during Lactation

Limited milk level and infant serum level data and a long history of use in postpartum mothers indicate that hydralazine is an acceptable antihypertensive in nursing mothers, even those nursing newborns.

Drug Levels

Maternal Levels. In one case report, a mother taking oral hydralazine 50 mg 3 times daily for at least 8 weeks postpartum had hydralazine milk levels of about 130 mcg/L at 0.5 and 2 hours after a dose. In addition, milk contained an amount of acid-labile hydrazones with undefined pharmacologic activity. The authors estimated that a breastfed infant would receive a maximum of 13 mcg per feeding at this maternal dosage.[1]

Ten lactating women had blood and breastmilk samples analyzed within 24 hour after receiving a dose of hydralazine of between 10 and 40 mg in the first week postpartum. The analytic method measured hydralazine plus its pharmacologically active acid-labile metabolites. The average concentration of drugs in breastmilk was 240 nmol/L, which was about half of the simultaneous concentration in maternal plasma. The authors estimated that the daily dose to a breastfed infant would likely not exceed 25 mcg.[2]

Infant Levels. Two infants were breastfed after their mothers had received a dose of hydralazine between 10 and 40 mg during the first week postpartum., At 2 hours after feeding, infant serum drug concentration were 557 and 293 nmol/L. The analytic method measured hydralazine plus its pharmacologically active acid-labile metabolites. These values were much lower than those found in a 2 kg infant who was receiving hydralazine 6 mg/kg daily directly for coarctation of the aorta. Serum levels in this infant were 6230 nmol/L before a 4 mg dose, and 8050 and 8310 nmol/L at 2 and 4 hours after the dose, respectively. Two other infants who received sterilized (100 degrees C for 10 minutes) breastmilk from their mothers who were taking hydralazine had no detectable hydralazine in their serum 2 hours after receiving the breastmilk feeding. The authors showed that expressed milk concentrations from 2 mothers were 140 nmol/L before heating and <20 nmol/L after heating.[2]

Effects in Breastfed Infants

No adverse effects reported in one infant breastfed for 8 weeks.[1]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Enalapril, Hydrochlorothiazide, Methyldopa, Propranolol

References

1. Liedholm H, Wahlin-Boll E, Hanson A et al. Transplacental passage and breast milk concentration of hydralazine. Eur J Clin Pharmacol. 1982;21:417-9. PMID: 7200428

2. Lamont RF, Elder MG. Transfer of hydralazine across the placenta and into breast milk. J Obstet Gynaecol. 1986;7:47-8.

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