Methyldopa alternatives: What can I take instead of methyldopa?

Methyldopa doesn't work for everyone. Labetalol, nifedipine, hydralazine, clonidine, and furosemide are some methyldopa alternatives. Get the full list here.

By Marissa Walsh, Pharm.D., BCPS-AQ ID | Aug. 1, 2022

A diagnosis of hypertension—generally defined as systolic blood pressure greater than or equal to 140 mmHg or diastolic blood pressure greater than or equal to 90 mmHg—can be scary to hear. What may add to the fear and confusion of such a diagnosis are the number of medications available for the treatment of high blood pressure. There are several drug classes to manage hypertension with each containing many individual medications, and some people will require multiple medications from different drug classes.

A diagnosis of high blood pressure is also rarely isolated; many who suffer from hypertension carry other diagnoses, such as; diabetes, high cholesterol, and other cardiovascular conditions like heart failure, which in turn may require additional medications. Many antihypertensive medications have niche indications based on safety in certain patient populations and the benefits in the management of some of these other comorbid conditions. Selection of an antihypertensive is in no way a “one size fits all” approach. Careful consideration from healthcare professionals with an individualized approach to medication selection should always occur.

Methyldopa is an oral antihypertensive medication in the drug class known as alpha-2 adrenergic agonists; stimulation of these receptors results in a decrease in smooth muscle resistance in blood vessels and ultimately a decrease in blood pressure. Like most antihypertensives, methyldopa has a very specific patient population in which it is optimally employed, and this is in pregnant and postpartum women (including those breastfeeding). As with most medications in pregnancy, antihypertensives have not been evaluated in robust, randomized controlled clinical trials so much of the data is limited. One should weigh the risks of uncontrolled hypertension against the risks of antihypertensives and medications should be selected in conjunction with a healthcare professional. The risks of uncontrolled hypertension in pregnancy are real. Chronic maternal hypertension may increase the risk of poor fetal outcomes, including the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Untreated hypertension can also increase risks of adverse maternal outcomes, such as gestational diabetes, stroke, and delivery complications. Exposure to methyldopa has proven to be safe to the developing fetus and/or has minimal effect on a breastfeeding infant despite crossing over into breastmilk.

Methyldopa may be used in patients who have chronic hypertension during pregnancy (generally diagnosed prior to 20 weeks’ gestation), pregnancy-induced or gestational hypertension (diagnosed after 20 weeks gestation), and less commonly in those pregnant women that develop severe hypertension or other hypertensive disorders including preeclampsia, eclampsia, or HELPP syndrome (Hemolysis Elevated Liver Enzymes and Low Platelets). An injectable formulation of methyldopa is no longer available in the United States, and severe hypertension and the other scenarios that may require urgent blood pressure lowering with the use of intravenous formulations of medications.

What can I take in place of methyldopa?

There are a few options available for the treatment of hypertension in pregnancy and while breastfeeding. These alternative prescription medications include a similar medication to methyldopa known as clonidine, or other classes of blood pressure lowering medications such as the beta blocker labetalol, calcium channel blocker nifedipine, or the vasodilator hydralazine.

In pregnant women with other comorbid conditions, like heart failure, loop diuretics such as furosemide may be added to a patient’s hypertension regimen. Thiazide diuretics, like hydrochlorothiazide, may be risky to a developing fetus in the very beginning weeks of development; however, some experts will suggest continuing thiazides throughout pregnancy if initiated prior to pregnancy. Doses of hydrochlorothiazide less than or equal to 50 mg appear compatible with breastfeeding, whereas higher doses theoretically could decrease breastmilk volume. For patients on a thiazide diuretic prior to conception, if continued the dose may be decreased and the patient may require an additional agent added to their regimen to maintain adequate blood pressure control.

In patients with chronic hypertension after pregnancy, methyldopa or alternatives would likely be changed to first-line therapies based on national guidelines, but for those that are pregnant or trying to get pregnant the management of hypertension should be limited to use of specific antihypertensives with established fetal and infant safety profiles. Many first-line antihypertensive drugs outlined in hypertension management guidelines are contraindicated in pregnancy, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors, and aldosterone antagonists.

In pregnancy or while breastfeeding, alternative options to methyldopa may be more suitable for some women due to other comorbid conditions requiring medications given multiple drug interactions and/or its side effect profiles. Side effects of methyldopa include orthostatic hypotension, drowsiness and tiredness, skin rash, constipation, bone marrow depression, hemolytic anemia, abnormal liver function tests, edema, photosensitivity, and nasal congestion. Many experts also avoid methyldopa beyond pregnancy for management of hypertension since its use as been associated with depression, which may confuse a diagnosis of postpartum depression. This list of adverse effects and improved tolerance profiles of other antihypertensive drugs may yield better adherence by patients.

Compare methyldopa alternatives
Drug name	Uses	Dosage	Savings options
Methyldopa	Chronic hypertension, gestational hypertension	250 mg by mouth two to three times daily, increase every 2 days as needed up to a maximum total daily dose of 3000 mg	Methyldopa coupons
Labetalol	Chronic hypertension, gestational hypertension, severe hypertension, preeclampsia	100 mg by mouth twice daily, increase by 100 mg twice daily every 2 to 3 days as needed up to a maximum total daily dose of 2400 mg	Labetalol coupons
Nifedipine	Chronic hypertension, gestational hypertension, severe hypertension, preeclampsia	Immediate release: 10 mg by mouth one-time; may repeat 10 mg to 20 mg in 20 minutes if target blood pressure not achieved x 2 additional doses Extended release: 30 mg to 90 mg by mouth once daily, increase by 30 mg at 7 to 14 day intervals up to a maximum total daily dose of 120 mg	Nifedipine coupons
Hydralazine	Chronic hypertension, gestational hypertension, severe hypertension, preeclampsia	10 mg by mouth four times daily, increase by 10mg to 25 mg per dose every 2 to 5 days up to a maximum total daily dose of 200 mg	Hydralazine coupons
Clonidine	Chronic hypertension, gestational hypertension	Immediate release: 0.1mg by mouth twice daily, may increase dose by 0.1 mg per day at weekly intervals up to a maximum daily dose of 0.6 mg Transdermal patch: 0.1 mg/24-hour patch applied once every 7 days, may increase by 0.1 mg at 1 to 2 week intervals up to a maximum of 0.3 mg/24-hour patch	Clonidine coupons
Furosemide	Chronic hypertension accompanied by severe edema	20 mg once or twice daily	Furosemide coupons
Hydrochlorothiazide	Chronic hypertension	Limit dose up to a maximum total daily dose of 50 mg	Hydrochlorothiazide coupons

Other alternatives to methyldopa

Outside of pregnancy and/or breastfeeding, national guidelines should be followed for the management of hypertension. Medications for control of high blood pressure include:

Lotensin (benazepril)
Vasotec (enalapril)
Prinivil (lisinopril)
Accupril (quinapril)
Altace (rampiril)
Mavik (trandolapril)
Capten (captopril)
Monopril (fosinopril)
Univasc (moexpiril)
Aceon (perindopril)
Edarbo (azilsartan)
Atacand (candesartan)
Teveten (eprosartan)
Avapro (irbesartan)
Cozaar (losartan)
Diovan (valsartan)
Benicar (Olmesartan)
Micardis (telmisartan)
Norvasc (amlodipine)
Cardizem (diltiazem)
Plendil (felodipine)
Dynacirc (isradipine)
Cardene SR (nicardipine)
Calan (verapamil)
Lotrel (amlodipine and benazepril)
Diuril (chlorothiazide)
Demadex (torsemide)
Bumex (bumetanide)

Top 5 methyldopa alternatives

1. Labetalol

Labetalol is a type of beta blocker used to treat chronic hypertension during pregnancy and gestational hypertension. Labetalol does not reduce fetal blood flow and does not seem to cause growth restrictions, so is the preferred medication in the beta blocker drug class for use in hypertension in pregnancy. Low levels are transferred to breast milk, with no effects reported in infants. In severe hypertension or preeclampsia, an intravenous formulation of labetalol may be administered to quickly bring down blood pressure. A 2022 meta-analysis of randomized trials of antihypertensives for non-severe hypertension in pregnancy found that labetalol appeared to reduce proteinuria/preeclampsia compared with methyldopa and calcium channel blockers, although it is unknown if the absolute magnitude of this effect is clinically important. Common side effects which may limit its use include fatigue, dizziness, and headache.

2. Nifedipine

Long acting nifedipine is an oral calcium channel blocker that can be used to manage chronic hypertension during pregnancy or gestational hypertension. Short-acting oral nifedipine can be considered in pregnant women presenting with severe hypertension, to get her blood pressure down to a safe level quickly. This would be especially useful in a situation in which obtaining intravenous access for alternate fast-acting medications was difficult to obtain. While nifedipine is transferred to breast milk, it has been found to be unlikely to cause adverse effects in newborns. In the management of chronic hypertension with labetalol, short-acting nifedipine may be added if labetalol on its own is unable to achieve adequate blood pressure control.

3. Hydralazine

Hydralazine is a direct vasodilator that can be administered both by mouth and intravenously, so is a useful medication for management of chronic hypertension, gestational hypertension, as well as management of severe hypertension and/or preeclampsia. There is some human data to suggest risk when administered in the third trimester, so this medication is considered a second-line option by many experts. Also, because this medication can result in a phenomenon known as reflex tachycardia, oral hydralazine is generally not recommended to be used as monotherapy for management of chronic hypertension in pregnancy, but often is combined with methyldopa or labetalol if needed as an add-on therapy.

4. Clonidine

Like methyldopa, clonidine exhibits its blood pressure lowering effect by decreasing the ability of blood vessels to contract. Clonidine would mostly be used in the management of pregnant patients with non-severe hypertension. However, it also can cause many side effects, including a drop in blood pressure upon standing or walking, dry mouth, impotence, and drowsiness. Clonidine is associated with a phenomenon known as rebound hypertension, limiting its use. Given its availability as a transdermal patch, clonidine use would generally be considered an alternative option in those patients unable to take other antihypertensive medications during pregnancy by mouth.

5. Furosemide

Furosemide is a loop diuretic that may be used in addition to other antihypertensive drugs in the setting of non-severe hypertension with edema to achieve desired blood pressure control. It may be employed in the management of postpartum hypertension, and its use should be brief (generally no longer than a 5-day course). True edema in the postpartum setting may be difficult to determine based on prepartum versus postpartum weight difference, also contributing to its limited duration in this setting.

Natural alternatives to methyldopa

There are long-term considerations in women with gestational hypertension or in those who develop preeclampsia, including an increased risk factor of developing chronic hypertension and/or cardiovascular disease. Patients should be educated and encouraged to monitor and manage their blood pressure. In addition, lifestyle preventative strategies should be outlined and encouraged, including maintaining a healthy weight, consistent exercise, and dietary changes. The Dietary Approaches to Stop Hypertension, or DASH diet is an eating plan that has been found to lower blood pressure with its emphasis on fruits, vegetables, whole grains, healthier fats, and avoidance of foods high in sodium. A diet rich in certain vitamins and minerals, including potassium, magnesium, and calcium, have been shown to be essential in maintaining a health blood pressure. There is also some evidence to suggest that garlic supplementation may modestly reduce blood pressure readings in addition to other natural herbs, as well as drinking some varieties of teas. However, the risk of uncontrolled hypertension and its downstream cardiovascular effects are not something that should be managed without the oversight of a healthcare professional and assessment for the need of prescription medications in addition or in lieu of these more natural approaches.

How to switch to a methyldopa alternative

Abrupt discontinuation of methyldopa may be associated with a phenomenon known as rebound hypertension, so any switch to an alternative should be done as per the medical advice of a healthcare professional. Generally, methyldopa should be discontinued slowly by reducing the dose by one-third to one-half every two to three days. Alternative medications initiated would likely require a slow dose increase titration with close monitoring of blood pressure to make sure control is maintained without causing severe drops in blood pressure or seeing elevated blood pressures.