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Methyldopa and hydrochlorothiazide: Drug information

Methyldopa and hydrochlorothiazide: Drug information
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For additional information see "Methyldopa and hydrochlorothiazide: Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Appropriate use:

This fixed combination drug is not indicated for initial therapy of hypertension. Hypertension requires therapy titrated to the individual patient. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management. The treatment of hypertension is not static, but must be reevaluated as conditions in each patient warrant.

Brand Names: Canada
  • Apo-Methazide
Pharmacologic Category
  • Alpha2-Adrenergic Agonist;
  • Antihypertensive;
  • Diuretic, Thiazide
Dosing: Adult
Hypertension

Hypertension:

Note: Dose must be individualized, as determined by titration of individual components. Once the patient has been successfully titrated, methyldopa/hydrochlorothiazide combination tablets may be substituted.

Oral: Replacement therapy: Methyldopa 250 mg/hydrochlorothiazide 15 mg 2 to 3 times daily or methyldopa 250 mg/hydrochlorothiazide 25 mg twice daily; alternatively, methyldopa 500 mg/hydrochlorothiazide 30 mg once daily or methyldopa 500 mg/hydrochlorothiazide 50 mg once daily. Avoid use of hydrochlorothiazide doses >50 mg/day. When initiating therapy in patients who are already taking other antihypertensive agents (other than thiazides), limit the initial dose of methyldopa to ≤500 mg/day in divided doses.

Note: Tolerance to methyldopa may occur, usually after 2 to 3 months of therapy; administration of additional separate doses of methyldopa (as a single agent) may be needed or replace the combination tablet with single agents to facilitate dose titration.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (use is contraindicated with anuria). The following adjustments have been recommended for hydrochlorothiazide (Ref):

Altered kidney function:

CrCl ≥10 mL/minute: No dosage adjustment necessary. The diuretic effect of hydrochlorothiazide is diminished with CrCl <30 mL/minute, but small, short-term studies suggest hypertensive benefit may be preserved (Ref). Switching to a loop diuretic may be considered if BP is no longer controlled or if management of fluid overload is required (Ref). Methyldopa is largely excreted by the kidney; as kidney function declines patients may require smaller doses to maintain target BP and avoid hypotension (Ref).

CrCl <10 mL/minute: Use not recommended due to lack of efficacy of the hydrochlorothiazide component (Ref).

Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref); use not recommended due to lack of efficacy of the hydrochlorothiazide component (Ref).

Peritoneal dialysis: Use not recommended due to lack of efficacy of the hydrochlorothiazide component (Ref).

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use is contraindicated in patients with active hepatic disease, such as acute hepatitis and active cirrhosis.

Acute hepatotoxicity during treatment: Abnormalities in LFTs (eg, alkaline phosphatase, transaminases, bilirubin, prothrombin time), fever, or jaundice may occur while taking methyldopa; this may represent cholestasis or hepatitis and hepatocellular injury; if any of these occur, stop therapy and do not reinitiate.

Dosing: Older Adult

Avoid use (Ref).

Adverse Reactions

See individual agents.

Contraindications

Hypersensitivity to methyldopa, hydrochlorothiazide, sulfonamide-derived drugs, or any component of the formulation; active hepatic disease (eg, acute hepatitis, active cirrhosis); hepatic disorders previously associated with use of methyldopa; concurrent use of MAO inhibitors; anuria.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged.

Warnings/Precautions

Concerns related to adverse effects:

• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia can occur with hydrochlorothiazide.

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz 1997).

• Hematologic effects: Rare cases of reversible granulocytopenia and thrombocytopenia have been reported with methyldopa. May rarely produce hemolytic anemia; positive Coombs' test occurs in 10% to 20% of patients usually occurring between 6 and 12 months of therapy; perform CBC periodically. If Coombs'-positive hemolytic anemia occurs during therapy, discontinue use and do not reinitiate; Coombs’ test may not revert back to normal for weeks to months following discontinuation.

• Hepatic effects: Methyldopa may rarely produce liver disorders including fatal hepatic necrosis; use with caution in patients with previous liver disease or dysfunction.

• Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma.

• Neuromuscular effects: Patients with severe bilateral cerebrovascular disease have exhibited involuntary choreoathetotic movements with methyldopa (rare); discontinue use if these symptoms develop.

• Ocular effects: Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

• Photosensitivity: Photosensitization may occur with hydrochlorothiazide.

• Sedation: Usually transient, sedation may occur with initiation or whenever the methyldopa dose is increased.

• Skin cancer, nonmelanoma: Prolonged use (≥3 years) may increase the risk for squamous cell carcinoma up to 4 times and increase the risk for basal cell carcinoma up to 1.25 times compared to patients not treated with hydrochlorothiazide (Pedersen 2018; Pottegård 2017).

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Bariatric surgery: Dehydration: Avoid diuretics in the immediate postoperative period after bariatric surgery; electrolyte disturbances and dehydration may occur. Diuretics may be resumed, if indicated, once oral fluid intake goals are met (Ziegler 2009).

• Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Hepatic impairment: Use hydrochlorothiazide with caution in patients with severe hepatic dysfunction. In progressive or severe liver disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy/coma.

• Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia.

• Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported.

• Hypokalemia: Use hydrochlorothiazide with caution in patients with hypokalemia; correct before initiating therapy.

• Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

• Renal impairment: Cumulative effects of hydrochlorothiazide may develop, including azotemia, in patients with impaired renal function. Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia. The active metabolites of methyldopa accumulate in uremia.

• Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Fixed-dose therapy is not indicated as the initial treatment for hypertension.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:

Methyldopa 250 mg and hydrochlorothiazide 15 mg

Methyldopa 250 mg and hydrochlorothiazide 25 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Methyldopa-hydroCHLOROthiazide Oral)

250-15 mg (per each): $1.83

250-25 mg (per each): $2.16

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: To minimize sedation associated with methyldopa, start dosage increases in the evening.

Use: Labeled Indications

Hypertension: Management of hypertension

Medication Safety Issues
Sound-alike/look-alike issues:

Aldoril may be confused with Aldomet, Elavil

Older Adult: High-Risk Medication:

Beers Criteria: Central alpha-agonists (methyldopa) are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older (independent of diagnosis or condition) due to high risk of CNS adverse effects and risk of bradycardia and orthostatic hypotension associated with central alpha blockers; not recommended as routine treatment for hypertension (Beers Criteria [AGS 2023]).

Beers Criteria: Diuretics (hydrochlorothiazide) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Clinically Relevant Anticholinergic Effects: May increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Ajmaline: Sulfonamides may increase adverse/toxic effects of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor

Alcohol (Ethyl): May increase orthostatic hypotensive effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Allopurinol: Thiazide and Thiazide-Like Diuretics may increase hypersensitivity effects of Allopurinol. Risk C: Monitor

Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification

Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid

Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor

Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Angiotensin-Converting Enzyme Inhibitors: Thiazide and Thiazide-Like Diuretics may increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Arsenic Trioxide: Thiazide and Thiazide-Like Diuretics may increase hypotensive effects of Arsenic Trioxide. Thiazide and Thiazide-Like Diuretics may increase QTc-prolonging effects of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the thiazide and thiazide-like diuretics. Risk D: Consider Therapy Modification

Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Beta-Blockers: May increase rebound hypertensive effects of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Alpha2-Agonists may increase AV-blocking effects of Beta-Blockers. Sinus node dysfunction may also be enhanced. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider Therapy Modification

Beta2-Agonists: May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Bile Acid Sequestrants: May decrease absorption of Thiazide and Thiazide-Like Diuretics. Management: Separate administration of bile acid sequestrants and oral thiazide diuretics by at least 4 hours. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. Risk D: Consider Therapy Modification

Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor

Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid

Calcium Salts: Thiazide and Thiazide-Like Diuretics may increase serum concentration of Calcium Salts. Risk C: Monitor

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor

Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification

COMT Inhibitors: May increase serum concentration of COMT Substrates. Risk C: Monitor

Corticosteroids (Systemic): May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

CycloPHOSphamide: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of CycloPHOSphamide. Specifically, granulocytopenia may be enhanced. Risk C: Monitor

Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor

Dexketoprofen: May increase adverse/toxic effects of Sulfonamides. Risk C: Monitor

Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor

Diacerein: May increase therapeutic effects of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor

Diazoxide Choline: May increase adverse/toxic effects of Thiazide and Thiazide-Like Diuretics. Specifically, the hyperglycemic and hyperuricemic effects may be increased. Risk C: Monitor

Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Diazoxide: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of Diazoxide. Risk C: Monitor

Dichlorphenamide: Thiazide and Thiazide-Like Diuretics may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor

Dofetilide: HydroCHLOROthiazide may increase QTc-prolonging effects of Dofetilide. HydroCHLOROthiazide may increase serum concentration of Dofetilide. Risk X: Avoid

DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor

EPINEPHrine (Systemic): Diuretics may increase arrhythmogenic effects of EPINEPHrine (Systemic). Diuretics may decrease vasopressor effects of EPINEPHrine (Systemic). Risk C: Monitor

Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid

Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification

Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor

Haloperidol: May increase adverse/toxic effects of Methyldopa. Risk C: Monitor

Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Iobenguane Radiopharmaceutical Products: Methyldopa may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer methyldopa until at least 7 days after each iobenguane dose. Risk X: Avoid

Ipragliflozin: May increase adverse/toxic effects of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Risk C: Monitor

Iron Preparations: May decrease serum concentration of Methyldopa. Management: Consider separating doses of methyldopa and orally administered iron preparation by 2 or more hours. Monitor for decreased efficacy of methyldopa if an oral iron preparation is initiated/dose increase, or increased efficacy if discontinued/dose decreased. Risk D: Consider Therapy Modification

Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid

Isocarboxazid: May increase hypotensive effects of Diuretics. Risk X: Avoid

Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor

Ivabradine: Thiazide and Thiazide-Like Diuretics may increase arrhythmogenic effects of Ivabradine. Risk C: Monitor

Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor

Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor

Levosulpiride: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of Levosulpiride. Risk X: Avoid

Licorice: May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Lithium: Thiazide and Thiazide-Like Diuretics may decrease excretion of Lithium. Management: Reduce the lithium dose if coadministered with thiazide or thiazide-like diuretics. Monitor serum lithium levels during coadministration with thiazide and thiazide-like diuretics. Risk D: Consider Therapy Modification

Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Mecamylamine: Thiazide and Thiazide-Like Diuretics may increase adverse/toxic effects of Mecamylamine. Management: Consider avoiding the use of mecamylamine and thiazide diuretics. If combined, mecamylamine prescribing information suggests reducing the mecamylamine dose by 50% in order to avoid excessive hypotension. Risk D: Consider Therapy Modification

Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor

Methenamine: Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Methenamine. Risk C: Monitor

Methotrexate: HydroCHLOROthiazide may increase nephrotoxic effects of Methotrexate. Risk C: Monitor

Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor

Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor

Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Mirtazapine: May decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Risk D: Consider Therapy Modification

Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Monoamine Oxidase Inhibitors: May increase adverse/toxic effects of Methyldopa. Risk X: Avoid

Multivitamins/Fluoride (with ADE): May increase hypercalcemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease serum concentration of Methyldopa. Management: Consider separating doses of these products by more than 2 hours to minimize this interaction; however, the success of this action appears limited. Monitor for decreased therapeutic effects of methyldopa with concurrent use. Risk D: Consider Therapy Modification

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor

Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Neuromuscular-Blocking Agents (Nondepolarizing): Thiazide and Thiazide-Like Diuretics may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor

Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor

Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification

Opioid Agonists: May increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor

Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Palopegteriparatide: Thiazide and Thiazide-Like Diuretics may increase therapeutic effects of Palopegteriparatide. Thiazide and Thiazide-Like Diuretics may decrease therapeutic effects of Palopegteriparatide. Risk C: Monitor

Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor

Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor

Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Piperacillin: May increase hypokalemic effects of Diuretics. Risk C: Monitor

Polyethylene Glycol-Electrolyte Solution: Diuretics may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor

Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification

Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid

Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor

Promazine: Thiazide and Thiazide-Like Diuretics may increase QTc-prolonging effects of Promazine. Risk X: Avoid

Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Reboxetine: May increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Riluzole: Methyldopa may increase adverse/toxic effects of Riluzole. Specifically, the risk of hepatotoxicity may be increased. Management: Consider alternatives to methyldopa in patients receiving treatment with riluzole due to the potential for additive hepatotoxicity. Risk D: Consider Therapy Modification

Selective Serotonin Reuptake Inhibitor: May increase hyponatremic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Serotonin/Norepinephrine Reuptake Inhibitor: May decrease therapeutic effects of Alpha2-Agonists. Risk C: Monitor

Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification

Sodium Phosphates: Diuretics may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor

Sotagliflozin: HydroCHLOROthiazide may decrease therapeutic effects of Sotagliflozin. Sotagliflozin may decrease serum concentration of HydroCHLOROthiazide. Risk C: Monitor

Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor

TiZANidine: Alpha2-Agonists may increase hypotensive effects of TiZANidine. Risk X: Avoid

Topiramate: Thiazide and Thiazide-Like Diuretics may increase hypokalemic effects of Topiramate. Thiazide and Thiazide-Like Diuretics may increase serum concentration of Topiramate. Risk C: Monitor

Toremifene: Thiazide and Thiazide-Like Diuretics may increase hypercalcemic effects of Toremifene. Risk C: Monitor

Tricyclic Antidepressants: May decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider Therapy Modification

Triptorelin: Hyperprolactinemic Agents may decrease therapeutic effects of Triptorelin. Risk X: Avoid

Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor

Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor

Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may increase hypercalcemic effects of Vitamin D Analogs. Risk C: Monitor

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. See individual agents.

Breastfeeding Considerations

Methyldopa and hydrochlorothiazide are excreted into breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. See individual agents.

Monitoring Parameters

Blood pressure; serum electrolytes, BUN, creatinine; CBC; liver enzymes (periodically during the first 6 to 12 weeks or when unexplained fever occurs); Coombs test (direct) (may obtain prior to initiation and at 6 and 12 months).

Mechanism of Action

Methyldopa stimulates central alpha-adrenergic receptors by a false transmitter that results in a decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature.

Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Hydromet;
  • (BR) Brazil: Hydromet;
  • (CO) Colombia: Hydromet;
  • (EC) Ecuador: Hydromet;
  • (FI) Finland: Dopamet comp | Hydromet | Levomet comp. | Medopasal comp | Sembrina comp;
  • (GB) United Kingdom: Hydromet;
  • (GR) Greece: Hydromet | Rabemylon;
  • (ID) Indonesia: Tensifort;
  • (IT) Italy: Medozide;
  • (LB) Lebanon: Hydromet;
  • (MX) Mexico: Hydromet-25;
  • (PR) Puerto Rico: Aldoril | Methyldopa/hctz;
  • (SE) Sweden: Dopamet comp;
  • (TW) Taiwan: Hydromet;
  • (VE) Venezuela, Bolivarian Republic of: Hydromet
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  19. Refer to manufacturer's labeling.
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