A centrally acting antihypertensive drug called methyldopa (Aldomet) blocks the sympathetic output to the heart, blood vessels, and kidneys. It is regarded as the best treatment for pregnancy-related hypertension.

Methyldopa (Aldomet) Uses:

• Hypertension:

  • Used in the management of hypertension.

Note: According to the ACC/AHA [Whelton 2017], initial therapy of hypertension is not required.

Methyldopa Dose in Adults:

Methyldopa (Aldomet) Dose as an alternative agent in the treatment of Hypertension:

• Oral: Initial:
  • Maximum dose: 3,000 mg per day; typical dose range: 250 to 1,000 mg per day in 2 split doses; 250 to 1,000 mg 2 to 3 times per day; increase or decrease each dose every 2 days depending on response.
• Note: Limit the first daily dose of methyldopa to 500 mg when combined with other antihypertensives other than thiazide diuretics.
• IV :
  • Every six to eight hours, 250 to 1,000 mg; at most, 1,000 mg.

Methyldopa Dose in Childrens:

Note: .There is no methyldopate injectable available in the US.

Methyldopa (Aldomet) Dose in the treatment of Hypertension:

Note: Methyldopa is no longer recommended as a therapy choice for hypertension; alternative medications have taken its place.

• Children and Adolescents:

  • Oral: Initial: 10 mg per kg per day in two to four divided doses; titrate no more often than every two days until sufficient response to the daily maximum dose: 3,000 mg per day or 65 mg/kg per day, whichever is less.

Methyldopa (Aldomet) Dose in the treatment of Hypertensive crisis:

Note: Other medications have taken its place, and methyldopa is not recommended as a therapeutic choice by experts:

• Children and Adolescents:

  • IV: Initial: Every six to eight hours; titrate as necessary to a daily dose of 20 to 40 mg/kg/day in divided doses or higher if necessary up to the daily maximum dose: 3,000 mg per day, or 65 mg per kilogramme per day, whichever is less.

Methyldopa (Aldomet) Pregnancy Category:

• Methyldopa crosses over the placenta.
• Data available show that pregnancy use does not cause harm to fetal health and can improve fetal outcomes.
• The risk of birth abnormalities, low birthweight, stillbirths, preterm labour, and neonatal mortality can all be increased by chronic maternal hypertension.
• The severity and duration of maternal hypertension may have an impact on the actual fetal/neonatal risk.
• Untreated hypertension can also increase the risk of adverse maternal outcomes, myocardial injury, stroke, preeclampsia and gestational complications.
• Oral methyldopa can be used to treat chronic hypertension in pregnancy. However, adverse effects and reduced effectiveness may make it less attractive than other drugs.
• Pre-existing hypertension in women may be reintroduced to their medication during pregnancy, unless contraindications are present.

Methyldopa use during breastfeeding:

• Breast milk contains methyldopa.
• Methyldopa's relative infant dose (RID) is 1.2%. This was computed using the maximum amount of breast milk concentration and compared to a daily dose of 1,000 mg that was weight-adjusted for the mother.
• When the RID of medication falls below 10%, breastfeeding is generally acceptable.
• The RID of Methyldopa was calculated with a milk concentration 1.14 mg/mL.
• This gives an estimated daily infant dose via breastmilk of 0.1716mg/day.
• This was done after a 1-week-old patient was given oral methyldopa 1,000mg/day.
• The peak milk concentration was measured at 6 hours after administration.
• Additionally, methyldopa in the infant's serum was detected; no adverse effects were observed in this infant or in two other exposed infants.
• According to the World Health Organization and the American College of Obstetricians and Gynologists (ACOG), methyldopa can be used in conjunction with breastfeeding.
• Due to the risk of depression in the postnatal period, methyldopa administration has been linked to maternal depression.

Methyldopa (Aldomet) Dose in Kidney Disease:

• The manufacturer's labelling does not mention dosage changes, although the following ones have been suggested:
  • CrCl >50 mL/minute:
    • Administer every 8 hours.
  • CrCl 10 to 50 mL/minute:
    • Administer every 8 to 12 hours.
  • CrCl <10 mL/minute:
    • Administer every 12 to 24 hours.
• Intermittent hemodialysis:
  • Moderately dialyzable (with a 6-hour session, up to 60%): On days when you have hemodialysis, administer after.
• Peritoneal dialysis (PD):
  • Take every 12 to 24 hours.
• Continuous renal replacement therapy (CRRT):
  • Take every 8 to 12 hours.

Note: Since CRRT is primarily used when patients cannot tolerate intermittent hemodialysis due to hypotension, the use of antihypertensives in patients needing CRRT is generally not advised.

Methyldopa (Aldomet) Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling; use is contraindicated in patients with active hepatic disease.

Side effects of Methyldopa (Aldomet):

• Cardiovascular:

  • Bradycardia
  • Cardiac Failure
  • Exacerbation Of Angina Pectoris
  • Myocarditis
  • Orthostatic Hypotension
  • Paradoxical Pressor Response (Intravenous Use)
  • Pericarditis
  • Peripheral Edema
  • Prolonged Carotid Sinus Syncope
  • Vasculitis

• Central Nervous System:

  • Bell’s Palsy
  • Cerebrovascular Insufficiency (Symptoms)
  • Choreoathetosis
  • Decreased Mental Acuity
  • Depression
  • Dizziness
  • Drug Fever
  • Headache
  • Nightmares
  • Paresthesia
  • Parkinson’s Disease
  • Sedation

• Dermatologic:

  • Skin Rash
  • Toxic Epidermal Necrolysis

• Endocrine & Metabolic:

  • Amenorrhea
  • Decreased Libido
  • Gynecomastia
  • Hyperprolactinemia
  • Weight Gain

• Gastrointestinal:

  • Abdominal Distention
  • Colitis
  • Constipation
  • Diarrhea
  • Flatulence
  • Glossalgia
  • Melanoglossia
  • Nausea
  • Pancreatitis
  • Sialadenitis
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Breast Hypertrophy
  • Impotence
  • Lactation

• Hematologic & Oncologic:

  • Bone Marrow Depression
  • Eosinophilia
  • Granulocytopenia
  • Hemolytic Anemia
  • Leukopenia
  • Positive ANA Titer
  • Positive Direct Coombs Test
  • Thrombocytopenia

• Hepatic:

  • Abnormal Hepatic Function Tests
  • Hepatic Disease (Hepatitis)
  • Jaundice

• Neuromuscular & Skeletal:

  • Arthralgia
  • Lupus-Like Syndrome
  • Myalgia
  • Positive Rheumatoid Factor
  • Weakness

• Renal:

  • Increased Blood Urea Nitrogen

• Respiratory:

  • Nasal Congestion

• Miscellaneous:

  • Positive LE Cell Preparation

Contraindications to Methyldopa (Aldomet):

• hypersensitivity to methyldopa and/or any formulation ingredient
• previously connected hepatic problems with methyldopa usage;
• Active hepatic Disease (eg, active Cirrhosis, acute Hepatitis)
• Concurrent use of MAO inhibitors

Warnings and precautions

• Edema

  • You may experience weight gain or clinical edema. If this happens, discontinue the treatment. Concomitant diuretic therapy may be used to control mild edema.

• Hematologic effects

  • There have been a few isolated reports of reversible thrombocytopenia or granulocytopenia.
  • Hemolytic anaemia is uncommon; 10% to 20% of patients get positive Coombs testing. Between 6 and 12 months of treatment, this is possible.
  • Do not use methyldopa-induced Coombs negative hemolytic anemia during therapy.
  • It could take weeks or months before the Coombs test returns to normal.

• Hepatic effects

  • Occasionally may lead to deadly hepatic neoplasms and other hepatic disorders.
  • If you have fever, jaundice, or abnormal liver function tests, stop using the drug and don't restart it.

• Sedation

  • Sedation normally lasts only a short while and can happen when a dose is being started or increased.

• Cerebrovascular disease

  • Stop using if symptoms appear in people with severe cerebrovascular disease.

• Hepatic impairment

  • Patients with a history or impairment of the liver should be cautious.

• Pheochromocytoma:

  • Patients with pheochromocytoma should not use this product.

• Renal impairment

  • Patients with impaired renal function should be cautious. You may need to take smaller doses.
  •  

Methyldopa: Drug Interaction

Monitoring parameters:

• Blood pressure (standing and sitting/lying down),
• CBC,
• liver enzymes
• Coombs test 
• blood pressure monitor required during IV administration

The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults:

• Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%:
  • Target blood pressure less than 130 per 80 mm Hg is necessary.
• Confirmed hypertension without markers of increased ASCVD risk:
  • Target blood pressure <130/80 mm Hg may be reasonable

How to administer Methyldopa (Aldomet)?

• IV: For 30 to 60 minutes, infuse.
• Oral: To reduce sedation, give fresh dosage increases in the evening.

Mechanism of action of Methyldopa (Aldomet):

• Alpha-methyl-norepinephrine, a fake neurotransmitter that stimulates central alpha-adrenergic receptors, causes a reduction in sympathetic outflow to the heart, kidneys, and peripheral vasculature.

The onset of action:

• Peak effect: Hypotensive: Oral, IV:
  • Single-dose: Within 3 to 6 hours;
  • Multiple-dose: 48 to 72 hours

Duration:

• Oral:
  • Single-dose: 12 to 24 hours,
  • Multiple-dose: 24 to 48 hours;
• IV: 10 to 16 hours

Absorption: Oral:

• Incomplete due to presystemic gut metabolism.

Protein binding:

• 10 percent to 15 percent.

Metabolism:

• Intestinal and hepatic

Bioavailability:

• ~42 percent.

Half-life elimination:

• Neonates: 10 to 20 hours;
• Adults: 1.5 to 2 hours;
• End-stage renal disease: Prolonged.

Time to peak, plasma:

• Oral: 2 to 4 hours.

Excretion:

• Urine (~70 percent as parent drug and metabolites);
• excretion complete within 36 hours

International Brand Names of Methyldopa:

• Adamet
• Adopal
• Aldin
• Aldomet
• Aldomet Forte
• Aldomet-Forte
• Aldometil
• Aldopa
• Alfamed
• Alfamet
• Alphadopa
• Bekanta
• Domecin
• Domepa
• Dopaflex
• Dopagyt
• Dopamed
• Dopamet
• Dopanore
• Doparine
• Dopatab
• Dopatab M
• Dopegyt
• Dopress
• Emdopa
• Fidopa
• Hy-po-tone
• Hydopa
• Hypolag
• Hypotens
• Kadomet
• Matilda
• Medopa
• Medoram
• Mefpa
• Methoplain
• Metildopa
• Metpata
• Normopress
• Pharmet
• Presinol
• Presinol 500
• Prodopa
• Rivapress
• Sardopa
• Sembrina
• Siamdopa
• Stridopa

Methyldopa Brand Names in Pakistan: