Aldomet

Centrally Acting Alpha Agonists

NOTE: When administering methyldopa concomitantly with other antihypertensive agents, the initial oral dosage should not exceed 500 mg/day PO, administered in divided doses. Tolerance to methyldopa may develop during the second or third month of therapy, and may require a dosage increase, or the addition of a thiazide diuretic in order to control blood pressure effectively.
 
 

Oral Administration

Any dosage increases of methyldopa should be made with the evening dose to minimize drowsiness.

Oral Liquid Formulations

Oral suspension: Shake methyldopa well prior to administration. Use a calibrated measuring device to administer dose.

Injectable Administration

Methyldopate hydrochloride is administered intravenously. Due to erratic absorption, intramuscular or subcutaneous injections are not recommended.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Intravenous infusion:
Adults: Add required dose of the commercial 50 mg/ml vial of methyldopate hydrochloride to 100 ml of D5W injection. Alternatively, dilute to 100 mg/10 ml using D5W injection.
Children: Dilute to a concentration of 1—20 mg/ml in D5W injection.
Infuse IV slowly over 30—60 minutes.

Severe

agranulocytosis / Delayed / 0-1.0
myocarditis / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
heart failure / Delayed / Incidence not known
cirrhosis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known

Moderate

choreoathetosis / Delayed / Incidence not known
depression / Delayed / Incidence not known
psychosis / Early / Incidence not known
hypotension / Rapid / Incidence not known
angina / Early / Incidence not known
edema / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
hemolysis / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
sialadenitis / Delayed / Incidence not known
constipation / Delayed / Incidence not known
colitis / Delayed / Incidence not known
hyperprolactinemia / Delayed / Incidence not known
ejaculation dysfunction / Delayed / Incidence not known
galactorrhea / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known

Mild

dizziness / Early / Incidence not known
headache / Early / Incidence not known
weakness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
drowsiness / Early / Incidence not known
nightmares / Early / Incidence not known
vertigo / Early / Incidence not known
fever / Early / Incidence not known
nausea / Early / Incidence not known
xerostomia / Early / Incidence not known
vomiting / Early / Incidence not known
diarrhea / Early / Incidence not known
flatulence / Early / Incidence not known
hyperkeratosis / Delayed / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
amenorrhea / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
orgasm dysfunction / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
nasal congestion / Early / Incidence not known
myalgia / Early / Incidence not known

Aldomet

Rx

Oral/parenteral antihypertensive; analog of 3,4 dihydroxyphenylalanine (DOPA)
Used most commonly for the treatment of hypertension during pregnancy
Less well tolerated in other patient populations; other antihypertensive classes have better tolerability for long-term treatment

For the treatment of hypertension. Oral dosage Adults

250 mg PO 2 to 3 times daily, initially. May increase dose every 2 days if further control is needed. Usual dosage: 250 to 2,000 mg/day in 2 to 4 divided doses. Max: 3,000 mg/day.

Children and Adolescents

10 mg/kg/day PO in 2 to 4 divided doses, initially. May increase dose every 2 days if further control is needed. Max: 65 mg/kg/day or 3,000 mg/day, whichever is less.

For the treatment of hypertensive emergency or hypertensive urgency. Intravenous dosage (methyldopate hydrochloride) Adults

250—500 mg IV, infused over 30—60 minutes every 6 hours. Maximum dosage is 4 g/day IV.

Geriatric

Lower doses may be needed (e.g., 250—1000 mg/day IV). Elderly patients are more likely to have an increased sensitivity to methyldopa effects (e.g., orthostatic hypotension, sedation) and arteriosclerotic disease, which may lead to syncope.

Children

20—40 mg/kg/day IV or 0.6—1.2 g/m2/day IV, given in divided doses every 6 hours. May increase dosage at intervals >= 2 days. Maximum dosage is 65 mg/kg/day IV or 3 g/day IV (whichever is less).

Hepatic Impairment

Methyldopa is contraindicated in patients with active hepatic disease, such as acute hepatitis and decompensated cirrhosis.

Renal Impairment

CrCl > 50 ml/min: No dosage adjustment is needed.
CrCl 10—50 ml/min: Administer the indicated dosage every 8—12 hours.
CrCl < 10 ml/min: Administer the indicated dosage every 12—24 hours.
 
Intermittent hemodialysis
Methyldopa is significantly removed (about 60% of dose) is removed during a six hour hemodialysis session; a supplemental dose of 250 mg PO or IV is recommended following dialysis (see Patients with renal impairment for maintenance dosage).

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Patients should be monitored for loss of blood pressure control.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetaminophen; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Acetazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Acrivastine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Aldesleukin, IL-2: (Moderate) Antihypertensive agents may potentiate the hypotension seen with aldesleukin, IL-2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alfentanil: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Alprazolam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and central-acting antihypertensive agents may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving central-acting adrenergic agents should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amlodipine; Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Amoxapine: (Moderate) Amoxapine, as a cyclic antidepressant, can block the action of methyldopa, preventing or significantly reducing the expected antihypertensive effects. Avoid use of amoxapine concurrently with methyldopa when possible.
Amphetamine; Dextroamphetamine Salts: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving methyldopa and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Apomorphine: (Moderate) Use of central-acting adrenergic agents and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aripiprazole: (Minor) Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Articaine; Epinephrine: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with methyldopa can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzodiazepines: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Benzphetamine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of methyldopa. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
Bupivacaine; Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including methyldopa. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure. In addition, the prolactin-lowering effect of cabergoline may be diminished by medications that increase prolactin levels such as methyldopa. Monitor for reduced response to cabergoline.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and central-acting adrenergic agents. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbidopa; Levodopa; Entacapone: (Moderate) Drugs known to be metabolized by catechol-O-methyltransferase, such as methyldopa, should be administered cautiously in patients receiving COMT inhibitors. Concomitant use may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure. Additive sedation and hypotension can occur. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Carbonic anhydrase inhibitors: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Celecoxib; Tramadol: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and methyldopa. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with methyldopa should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Concurrent use of cetirizine/levocetirizine with methyldopa should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlordiazepoxide: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Chlordiazepoxide; Amitriptyline: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Chlordiazepoxide; Clidinium: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpheniramine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Chlorpromazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Clonazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Clorazepate: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Phenylephrine; Promethazine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and central-acting adrenergic agents use. Concomitant use may result in additive hypotension.
COMT inhibitors: (Moderate) Drugs known to be metabolized by catechol-O-methyltransferase, such as methyldopa, should be administered cautiously in patients receiving COMT inhibitors. Concomitant use may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure. Additive sedation and hypotension can occur. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Degarelix: (Major) Avoid coadministration of degarelix with methyldopa due to the risk of reduced efficacy of degarelix. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog.
Desloratadine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as methyldopa, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents. Diazoxide can enhance the hyperglycemic, hyperuricemic and antihypertensive effects of thiazide diuretics.
Diclofenac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diclofenac; Misoprostol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as methyldopa. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diflunisal: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with methyldopa can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dobutamine: (Major) Sympathomimetics, such as dobutamine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Dopamine: (Major) Sympathomimetics, such as dopamine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Duloxetine: (Moderate) Monitor blood pressure during concomitant duloxetine and central-acting adrenergic agent use. Concomitant use increases the risk for hypotension, including orthostatic hypotension and syncope. Consider reducing the duloxetine dose or discontinuing duloxetine if symptomatic orthostatic hypotension, falls, or syncope occur during treatment.
Entacapone: (Moderate) Drugs known to be metabolized by catechol-O-methyltransferase, such as methyldopa, should be administered cautiously in patients receiving COMT inhibitors. Concomitant use may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure. Additive sedation and hypotension can occur. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by methyldopa, Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by methyldopa, Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
Epoprostenol: (Moderate) The concomitant administration of epoprostenol with other antihypertensive agents can result in additive hypotensive effects. This can be therapeutically advantageous, but dosages must be adjusted accordingly.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and methyldopa for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Etodolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and methyldopa. Concurrent use may result in additive CNS depression.
Fenoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Fentanyl: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ferric Maltol: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Fexofenadine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Fluphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Flurazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Flurbiprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of methyldopa and gabapentin. Concurrent use may result in additive CNS depression.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Goserelin: (Major) Avoid coadministration of goserelin with methyldopa due to the risk of reduced efficacy of goserelin. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Guaifenesin; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Guaifenesin; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Haloperidol: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Histrelin: (Major) Avoid coadministration of histrelin with methyldopa due to the risk of reduced efficacy of histrelin. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Hydrocodone; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Ibritumomab Tiuxetan: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal in

sufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Famotidine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Indomethacin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Iron Salts: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Iron: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Isocarboxazid: (Contraindicated) The manufacturer of methyldopa contraindicates its use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations. A paradoxical pressor effect has been noted with methyldopa use. Data describing this interaction are limited.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Isoproterenol: (Major) Sympathomimetics can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Ketoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ketorolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and methyldopa. Concurrent use may result in additive CNS depression.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and methyldopa. Dosage adjustments of lemborexant and methyldopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Leuprolide: (Major) Avoid coadministration of leuprolide with methyldopa due to the risk of reduced efficacy of leuprolide. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with methyldopa due to the risk of reduced efficacy of leuprolide. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with methyldopa should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levodopa: (Moderate) Monitor blood pressure during concomitant use of levodopa and central-acting adrenergic agents due to risk for additive hypotension.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Levorphanol: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
Linezolid: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
Lisdexamfetamine: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving methyldopa and lisdexamfetamine. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents.
Lithium: (Moderate) Patients receiving lithium and methyldopa concomitantly can develop lithium toxicity. Interestingly, lithium levels may appear to be in the therapeutic range while signs of lithium toxicity are evident. Therefore, plasma lithium concentrations are not an accurate indicator of lithium toxicity in patients receiving concurrent methyldopa therapy.
Lofexidine: (Major) Lofexidine is a central alpha-2 adrenergic agonist, and its effects can be additive to other medications in the same class. Monitor for excessive hypotension, bradycardia, and sedation during coadministration. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Loratadine; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Lorazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Lumateperone: (Moderate) Monitor for excessive sedation, somnolence, and orthostatic hypotension during coadministration of lumateperone and methyldopa. Concurrent use may result in additive CNS depression or orthostasis.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Maprotiline: (Moderate) Maprotiline, as a cyclic antidepressant, can block the action of methyldopa, preventing or significantly reducing the expected antihypertensive effects. Avoid use of maprotiline concurrently with this antihypertensive drug when possible.
Meclofenamate Sodium: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Mefenamic Acid: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Meperidine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methadone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like methyldopa. Close monitoring of blood pressure is advised.
Methazolamide: (Moderate) The concomitant administration of diuretics with other antihypertensive agents can result in additive hypotensive effects. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Methylphenidate Derivatives: (Moderate) Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including methyldopa. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate derivatives.
Midazolam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Midodrine: (Major) Sympathomimetics can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Monoamine oxidase inhibitors: (Contraindicated) The manufacturer of methyldopa contraindicates its use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations. A paradoxical pressor effect has been noted with methyldopa use. Data describing this interaction are limited.
Morphine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Nabilone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of nabilone and methyldopa. Concurrent use may result in additive CNS depression.
Nabumetone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen; Esomeprazole: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen; Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Clonidine has been shown to inhibit niacin-induced flushing. The interaction is harmless unless niacin augments the hypotensive actions of clonidine.
Nitrates: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant central-acting adrenergic agent and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Norepinephrine: (Major) Sympathomimetics, such as norepinephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oliceridine: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opiate Agonists: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opicapone: (Moderate) Drugs known to be metabolized by catechol-O-methyltransferase, such as methyldopa, should be administered cautiously in patients receiving COMT inhibitors. Concomitant use may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure. Additive sedation and hypotension can occur. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Oxaprozin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Oxazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Oxycodone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by methyldopa. If these drugs are used together, closely monitor for changes in blood pressure.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and central-acting adrenergic agents who are susceptible to hypotension.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perphenazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Perphenazine; Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with methyldopa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phendimetrazine: (Major) Sympathomimetics can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Phenelzine: (Contraindicated) The manufacturer of methyldopa contraindicates its use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations. A paradoxical pressor effect has been noted with methyldopa use. Data describing this interaction are limited.
Phenothiazines: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Phentermine: (Major) Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as methyldopa. Concomitant use of phentermine with methyldopa may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Phentermine; Topiramate: (Major) Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as methyldopa. Concomitant use of phentermine with methyldopa may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Piroxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Polysaccharide-Iron Complex: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of methyldopa and pregabalin. Concurrent use may result in additive CNS depression.
Pretomanid: (Major) Avoid coadministration of pretomanid with methyldopa, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Prochlorperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Dextromethorphan: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Promethazine; Phenylephrine: (Major) Sympathomimetics, such as phenylephrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved. (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Pseudoephedrine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Pseudoephedrine; Triprolidine: (Major) Sympathomimetics, such as pseudoephedrine, can antagonize the antihypertensive effects of methyldopa when administered concomitantly. Blood pressure should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Quazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rasagiline: (Moderate) Orthostatic hypotension has been reported during administration of rasagiline; caution is advised during concurrent use with antihypertensive agents. Patients receiving rasagiline in combination with an antihypertensive should be instructed to rise slowly from a sitting position, and to report syncope, and changes in heart rate or blood pressure to their health care provider. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious hypertensive reactions with agents affecting catecholamine release (e.g., guanabenz, reserpine, guanethidine) are unlikely.
Remifentanil: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Remimazolam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and methyldopa. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Selegiline: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Coadministration of methyldopa with iron salts or polysaccharide-iron complex is not recommended. If iron supplementation is necessary, administer a methyldopa dose at least 2 hours prior to the iron supplement. Iron salts have been reported to dramatically reduce the oral absorption of methyldopa. Several studies demonstrate decreased bioavailability of methyldopa when coadministered with ferrous sulfate or ferrous gluconate. This interaction may result in decreased antihypertensive effect of methyldopa.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and methyldopa. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Sulindac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Sumatriptan; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Tapentadol: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Temazepam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thioridazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. Concurrent administration of thiothixene and methyldopa has been reported to cause dementia in some cases. The clinical importance of this interaction has not been established.
Tizanidine: (Major) The use of tizanidine with other alpha 2-adrenergic agonists (such as central-acting adrenergic agonist antihypertensive agents) should be avoided because hypotensive effects may be cumulative. Tizanidine is an alpha 2-adrenergic agonist that can produce hypotension. Syncope has been reported in the postmarketing setting.
Tolbutamide: (Minor) Methyldopa may potentiate the hypoglycemic effects of tolbutamide by impairing the drug's metabolism.
Tolcapone: (Moderate) Drugs known to be metabolized by catechol-O-methyltransferase, such as methyldopa, should be administered cautiously in patients receiving COMT inhibitors. Concomitant use may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure. Additive sedation and hypotension can occur. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tolmetin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Tramadol: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tramadol; Acetaminophen: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tranylcypromine: (Contraindicated) The manufacturer of methyldopa contraindicates its use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations. A paradoxical pressor effect has been noted with methyldopa use. Data describing this interaction are limited.
Triazolam: (Moderate) Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly.
Tricyclic antidepressants: (Moderate) Many references caution against the combined use of tricyclic antidepressants (TCAs) and methyldopa. Although reports exist of loss of blood pressure control when TCAs are added to methyldopa, the interaction is not well documented. Nevertheless, if use of these drugs together is not avoidable, monitor the patient's blood pressure for the desired response.
Trifluoperazine: (Moderate) Monitor blood pressure and for unusual drowsiness or excessive sedation during concomitant central-acting adrenergic agent and phenothiazine use. Concomitant use increases the risk for additive hypotension and CNS depression.
Triptorelin: (Major) Avoid coadministration of triptorelin with methyldopa due to the risk of reduced efficacy of triptorelin. Methyldopa can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
Valdecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion ma y have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as methyldopa. Use together may increase the pressor and antidiuretic effects of vasopressin.
Vincristine Liposomal: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

Aldomet/Methyldopa Oral Tab: 250mg, 500mg
Methyldopate Hydrochloride Intravenous Inj Sol: 1mL, 50mg

Adults

3 g/day PO or 4 g/day IV.

Elderly

1 g/day PO or IV.

Adolescents

65 mg/kg/day or 3 g/day PO or IV, whichever is less.

Children

65 mg/kg/day or 3 g/day PO or IV, whichever is less.

Mechanism of Action: After crossing the blood-brain barrier, methyldopa is decarboxylated to produce alpha-methylnorepinephrine. This metabolite stimulates central inhibitory alpha-adrenergic receptors, thereby reducing peripheral resistance and lowering blood pressure. Although cardiac output and heart rate are not believed to be affected, conflicting data from studies of long-term therapy and the use of methyldopa in patients with congestive heart failure suggest that cardiac output may be decreased and peripheral resistance unaffected. Methyldopa also may act as a false transmitter, thereby exerting a direct effect on peripheral sympathetic nerves. Blood pressure decreases are greatest when the patient is standing but are also significant when the patient is supine. Postural hypotension has been reported in patients receiving methyldopa.Methyldopa can cause sodium and fluid retention, and tolerance can develop during long-term therapy. As an antihypertensive, reduces LVH and does not worsen glucose tolerance, but does exert detrimental effects on serum lipids. Serum prolactin levels can increase during methyldopa administration.

Methyldopa is administered orally and intravenously.  Methyldopa appears to cross the blood-brain barrier as well as the placenta. The drug distributes in breast milk, but the quantity is probably not clinically significant. Antihypertensive effects last 12—24 hours. Methyldopa is eliminated biphasically, with 95% excreted during the initial phase (plasma half-life of 2 hours) and the rest excreted much more slowly. Unabsorbed drug is excreted in the feces.

Oral Route

Roughly 50% of an oral dose of methyldopa is absorbed across the GI tract, with maximal antihypertensive effects occurring 4—6 hours after administration. Plasma levels of methyldopa have no correlation with hypotensive effect.

Intravenous Route

Plasma levels of methyldopa have no correlation with hypotensive effect; onset of hypotensive effect occurs no sooner after parenteral administration of methyldopa due to delayed hydrolysis of the intravenous formulation.

Pregnancy

Methyldopa (oral) has long been the antihypertensive medication of choice in pregnancy due to a long record of safety and efficacy. Published reports of the use of methyldopa during all trimesters indicate that the possibility of fetal harm is remote. In five studies, three of which were controlled, involving 332 pregnant hypertensive women, treatment with oral methyldopa was associated with an improved fetal outcome. The majority of these women were in the third trimester when methyldopa therapy was begun. There are no well-controlled studies of the use of methyldopa in pregnant women in the first trimester of pregnancy. In one study, maternal receipt of methyldopa beginning at 16 to 20 weeks of pregnancy resulted in infants whose average head circumference was slightly reduced at birth compared to infants of untreated mothers; however follow up of 195 (97.5%) of the infants born to these methyldopa-treated pregnant women failed to uncover any significant adverse developmental effect on the pediatric patients at 4 years or 7 years of age versus those who were not exposed during gestation.

Although caution in use is advised historically by the manufacturers ; methyldopa has been studied during maternal use during lactation and appears to distribute minimally into breast milk; the quantity is not considered to be clinically significant. The American Academy of Pediatrics considers methyldopa to be generally compatible with breast-feeding, due to the lack of adverse events reported in nursing infants. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.