When should you not take hydralazine after 6 p.m.?

In this article:

• What is the "6 p.m. rule"?
• How your body responds to hydralazine
• Implementing the 6 p.m. rule
• Lifestyle adjustments
• The bottom line

In this article

• What is the "6 p.m. rule"?
• How your body responds to hydralazine
• Implementing the 6 p.m. rule
• Lifestyle adjustments
• The bottom line

Hydralazine is a medication that’s most commonly used to treat high blood pressure and some types of heart failure. It may also be used to treat high blood pressure and preeclampsia in pregnant women.

As with many other meds, it’s important to take hydralazine consistently to experience its benefits. The specific timing also matters. If you receive a prescription for hydralazine, especially if it’s combined with a diuretic to eliminate excess fluid, your healthcare provider may advise you to avoid taking it at night. Here’s what you need to know about the ideal timing of your hydralazine doses.

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Why the “6 p.m. rule” matters for hydralazine users

Hydralazine is a generic medication that is also sold under the brand name Apresoline. It belongs to a class of drugs known as vasodilators, which are sometimes used to treat hypertension and heart failure. Vasodilators open, or dilate, blood vessels to allow blood to flow more easily through them, which decreases blood pressure.

Although hydralazine is an older antihypertensive medication that’s not considered a first-line treatment, it can help some people. Hydralazine is available in tablets and an oral liquid, but an intravenous version is also available for hypertensive emergencies.

Sometimes, healthcare professionals will also recommend that patients take hydralazine in combination with another drug. For example, a patient might take a pill that combines hydralazine with hydrochlorothiazide, which is a diuretic.

“Because hydralazine can cause fluid retention or a fast heartbeat, it’s often paired with a beta blocker and sometimes a diuretic to help balance those effects,” says Dr. Erika Alexander, Pharm.D., a clinical pharmacist with MOBE.

According to Dr. Jonathan Newsome, Pharm.D., professor of clinical sciences at High Point University’s Fred Wilson School of Pharmacy, the “6 p.m. rule” primarily applies to people who are taking a diuretic along with their hydralazine.

As Dr. Erika Gray, Pharm D, and chief medical officer at ToolBox Genomics notes, a possible side effect of hydralazine is increased urination, especially when combined with a diuretic. Taking it at night can lead to nighttime awakenings and trips to the bathroom. 

The dosage amount matters, too. Some patients may only need to take hydralazine once daily when used in combination with a diuretic. Once-a-day dosing may make it easier to abide by the 6 p.m. rule. In this case, experts often recommend taking hydralazine in the morning at the same time each day.

However, Dr. Newsome notes that many people taking oral hydralazine need to take it three or four times daily, depending on their particular health condition. In fact, most people do take several doses per day.

If that’s the case for you, chances are that your healthcare provider will recommend spacing your doses out throughout the day. They may also recommend that you try to avoid taking your last dose too close to bedtime. 

“It’s not a hard rule, but timing adjustments are often reasonable,” says Dr. Erika Alexander, Pharm.D..

Another reason to avoid taking hydralazine at night is the possibility of having chest pain, a fast or irregular heartbeat, or blood pressure that drops too low while sleeping.

“If these symptoms occur at night when one is sleeping because the medication was taken later in the day, (they) may not realize they are having these side effects and will not be able to let their doctor know,” Dr. Gray says.

She adds that the peak effect of hydralazine usually occurs about one or two hours after taking it, and that’s when the blood-pressure-lowering effects will be strongest, as well as when side effects are more likely to occur.

“Taking hydralazine before 6 p.m. can allow the drug to reach its peak and for side effects like increased urination to occur before bedtime,” Dr. Gray says.

How your body responds to hydralazine

As a direct-acting vasodilator, hydralazine relaxes the smooth muscles in the arterioles, which are the small branches of arteries that lead into the capillaries. Then the blood vessels widen, making it easier for the heart to pump blood through them. This helps lower the blood pressure.

However, hydralazine can cause an increase in heart rate in some people because the body senses the drop in blood pressure and activates the body’s “fight or flight” response. This might include heart palpitations. Since it can tend to stimulate the sympathetic nervous system, hydralazine is not usually a first-line treatment for hypertension.

According to the 2025 guidelines for the treatment of high blood pressure, published in the Journal of the American College of Cardiology (JACC), direct vasodilators, including both hydralazine and minoxidil, are typically considered alternatives to first-line treatments for hypertension. Hydralazine can be used if a first-line agent isn’t sufficient or if a person doesn’t tolerate the first-line treatment very well. It can also be used as an add-on.

Sometimes, people taking hydralazine will experience unwanted side effects. Some of the most common, yet less serious, effects include diarrhea, nausea, and weight loss.

However, some side effects are more serious and may include:

• Pain in the chest, arm, back, or jaw
• Tightness, heaviness, or discomfort in the chest
• Rapid heart rate or irregular heartbeat
• Nausea
• Shortness of breath
• Sweating
• Low blood counts

If you do experience any side effects that concern you, contact your healthcare provider and seek medical attention. Don’t stop taking the medication, however, until you’ve spoken with your provider for medical advice.

According to Dr. Alexander, you want to avoid a “prescribing cascade” where you begin taking another medication to address side effects from another medication.

“Staying in touch with your care team and reviewing all your meds regularly helps prevent that,” she says.

Implementing the 6 p.m. rule

Most people who take combination hydralazine and diuretic tablets notice that they have to urinate more or more frequently, especially at first, according to the Mayo Clinic. While that effect usually lessens over time, it’s possible to minimize the effect on an otherwise good night’s sleep by taking the medication strategically.

“If a patient is taking hydralazine three times daily, then they should separate the doses by eight hours,” Dr. Newsome says. “If they are taking hydralazine four times daily, then they should attempt to separate the doses by six hours.”

He acknowledges that it can be tricky to achieve the correct timing. “If so, patients should attempt to separate the doses as evenly as possible during the waking hours,” he says.

Ideally, if you take multiple doses per day, try to take the last dose by 6 p.m. However, discuss the specific timing with your healthcare provider, as everyone’s situation is unique.

“Using a pill box or other reminders will be helpful since taking a medication more than once daily can be hard for some patients,” Dr. Alexander says.

Lifestyle adjustments to complement your hydralazine therapy

Healthcare experts typically encourage people undergoing treatment for high blood pressure to also consider embracing some lifestyle changes.

“This medicine helps, but blood pressure control always works best alongside health habits,” says Dr. Alexander. “I encourage patients to stay active, manage their weight, and limit salt intake.”

To manage high blood pressure, the Centers for Disease Control and Prevention (CDC) recommends the following strategies:

• Check your blood pressure regularly.
• Carefully manage other health conditions, such as diabetes, depression, or anxiety.
• Aim for a healthy weight to reduce stress on your heart.
• Exercise and find ways to incorporate physical activity into your daily life.
• Eat heart-healthy foods, including fruits, vegetables, and whole grains.
•  Quit smoking, as smoking damages blood vessels and raises blood pressure.

The bottom line

Before taking any medication, including hydralazine, let your healthcare provider know if you are pregnant, breastfeeding, or have a history of certain health conditions such as heart disease or heart attack, kidney disease, liver disease, or systemic lupus erythematosus (SLE).

According to the Cleveland Clinic, hydralazine may interact with certain antidepressant medications and other high blood pressure medications, so it’s also important to let your healthcare provider know about any supplements or other meds that you’re currently taking so you can avoid potential drug interactions.

When using any prescription or over-the-counter medication, it’s essential to read the directions carefully and follow them closely. Ask your healthcare provider if they have any guidance on the best time to take hydralazine to minimize side effects, including disruptions to your sleep.