BiDil

BiDil is the brand name of a combination medicine that contains the drugs hydralazine and isosorbide dinitrate.

It's used to treat heart failure in African Americans — a population that's more likely to develop the condition at a younger age and die earlier, compared with other racial or ethnic groups.

Hydralazine is a vasodilator. It works by relaxing veins and arteries, which makes it easier for the heart to pump blood.

Isosorbide dinitrate belongs to a group of drugs called nitrates. It works by widening blood vessels, which makes it easier for blood to flow through them and for the heart to pump.

BiDil was the first prescription drug approved to treat a single racial group, which caused some controversy in the medical community.

The Food and Drug Administration (FDA) approved BiDil in 2005. It's marketed by Arbor Pharmaceuticals, LLC.

BiDil Warnings

Before starting treatment with BiDil, tell your doctor if you have, or have ever had:

• Low blood pressure
• Heart disease
• Pulmonary arterial hypertension (high blood pressure in the lungs)
• Lupus (an autoimmune disease characterized by inflammation and a variety of symptoms)
• Allergies to any medication

Not drinking enough liquids, or losing fluids (due to diarrhea, sweating, or vomiting) while taking BiDil may cause low blood pressure or fainting. Talk to your doctor about how much you should drink each day.

Some medicines — such as those used to treat erectile dysfunction and pulmonary arterial hypertension — can cause serious side effects if they're used along with BiDil.

Tell your doctor if you're taking any of the following medications:

• Viagra or Revatio (sildenafil)
• Stendra (avanafil)
• Cialis (tadalafil)
• Levitra (vardenafil)
• Adempas (riociguat)

You may experience headaches while taking BiDil. This symptom will usually go away.

Don't stop taking BiDil without first talking to your doctor.

Pregnancy and BiDil

It's not known whether BiDil could harm a fetus if taken during pregnancy.

Tell your doctor if you're pregnant, or might become pregnant, before taking this medicine.

It's also not known whether BiDil passes into breast milk. Tell your doctor if you're breastfeeding a baby.

Common Side Effects of BiDil

Tell your doctor if the following side effects become severe or don't go away:

• Headache
• Mild dizziness

Serious Side Effects of BiDil

Let your doctor know immediately if you experience any of the following serious side effects:

• Fast heart rate
• Shortness of breath that worsens
• Chest pain or pressure
• Pain that spreads to your jaw or shoulder
• Severe nausea or sweating
• Unexplained fever or a general ill feeling
• Skin rash
• Prolonged weakness or fatigue
• Joint pain or swelling
• Numbness or tingling in your hands or feet
• Feeling like you might pass out
• Signs of anaphylaxis, which may include hives, difficulty breathing, or swelling of the face, lips, tongue, or throat

BiDil comes as a tablet to take by mouth.

Each tablet contains 20 milligrams (mg) of isosorbide dinitrate and 37.5 mg of hydralazine.

Your dose will depend on your medical condition and response to treatment.

Follow the instructions on your prescription label carefully. Don't take more BiDil than is recommended.

Don't stop taking BiDil without first talking to your doctor.

BiDil Overdose

Symptoms of a BiDil overdose may include:

• Severe dizziness
• Warmth or tingling under the skin
• Confusion
• Throbbing headache
• Chest pain
• Fast heartbeats

If you suspect an overdose, contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at 800-222-1222.

Missed Dose of BiDil

If you miss a dose of BiDil, take it as soon as you remember.

But if it's almost time for your next scheduled dose, skip the missed dose and continue with your regular medication schedule.

Don't take extra medicine to make up for a missed dose.

• Arbor Pharmaceuticals, Inc.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You should not stop using hydralazine and isosorbide dinitrate suddenly. Stopping suddenly may make your condition worse.

Store at room temperature away from moisture, heat, and light.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. 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.

Drinking alcohol with this medicine can cause side effects.

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

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of isosorbide dinitrate and hydralazine combination in the elderly. However, elderly patients are more likely to have age-related liver or kidney problems, which may require caution and an adjustment in the dose for patients receiving isosorbide dinitrate and hydralazine combination.

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.

• Avanafil
• Riociguat
• Sildenafil
• Tadalafil
• Vardenafil

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:

• Allergic reaction to nitrates, history of—Should not be used in patients with these condition.

• Hypertrophic cardiomyopathy (a heart disease) or
• Hypotension (low blood pressure)—Use with caution. May make these conditions worse.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.
• Very bad headache.
• Very bad dizziness or passing out.
• Chest pain or pressure or a fast heartbeat.
• Fever.
• A burning, numbness, or tingling feeling that is not normal.
• Feeling very tired or weak.

Pregnancy

Pregnancy Category C:

There are no studies using BiDil in pregnant women.

Isosorbide dinitrate has been shown to cause a dose-related increase in embryo-toxicity (excess mummified pups) in rabbits at 70 mg/kg (12 times the MRHD of BiDil on a body surface area basis).

Hydralazine hydrochloride is teratogenic in mice at 66 mg/kg and possibly in rabbits at 33 mg/kg (2 and 3 times the MRHD of BiDil on a body surface area basis). There are no animal studies assessing the teratogenicity of BiDil.

A meta-analysis of randomized controlled trials comparing hydralazine hydrochloride with other antihypertensive agents for severe hypertension in pregnancy found that hydralazine hydrochloride was associated with significantly more maternal hypotension, placental abruption, caesarean sections and oliguria, with more adverse effects on fetal heart rate and with lower Apgar scores.

A combination of propranolol and hydralazine hydrochloride was administered to 13 patients with long-standing hypertension during 15 pregnancies. These pregnancies resulted in 14 live births and one unexplained stillbirth. The only neonatal complications were two cases of mild hypoglycemia. Hydralazine hydrochloride and its metabolites have been detected using a non-selective assay in maternal and umbilical plasma in patients treated with the drug during pregnancy.

Isosorbide dinitrate has been used for effective acute and sub-chronic control of hypertension in pregnant women, but there are no studies using it in a chronic regimen and assessing its effects on pregnant women and/or the fetus.

Nursing Mothers

No studies have been performed with BiDil. It is not known if either hydralazine or isosorbide dinitrate is excreted in human milk.

Pediatric Use

The safety and effectiveness of BiDil in children have not been established.

Geriatric Use

Clinical studies of BiDil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function, and of concomitant disease or other drug therapies.

Isosorbide dinitrate, its active metabolites, and hydralazine may be eliminated more slowly in elderly patients.

Renal Impairment

There are no studies of renal impairment using BiDil. No dose adjustment is required for hydralazine or isosorbide dinitrite [see Clinical Pharmacology (12.3)].

Dialyzability of hydralazine has not been determined. Dialysis is not an effective method for removing isosorbide dinitrate or its metabolite isosorbide-5-mononitrate from the body.

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of hydralazine alone has not been determined. Isosorbide dinitrate concentrations increase in patients with cirrhosis. There are no studies of hepatic impairment using BiDil.

Take BiDil exactly as directed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You should not stop using BiDil suddenly. Stopping suddenly may make your condition worse.

Store at room temperature away from moisture, heat, and light.

Get emergency medical help if you have signs of an allergic reaction to BiDil: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

This medicine can cause headaches, especially when you first start using it. These headaches may gradually become less severe as you continue to use the medicine. Do not stop taking BiDil. Call your doctor before using any headache pain medication.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• numbness or tingling in your hands or feet;

• joint pain or swelling;

• fever, chest pain, general ill feeling;

• fast heart rate;

• shortness of breath that is worse than usual; or

• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating.

Some side effects may be more likely in older adults.

Common BiDil side effects may include:

• headache; or

• dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Common side effects of BiDil include: dizziness, headache, and nausea. Other side effects include: hypotension, and paresthesia. See below for a comprehensive list of adverse effects.