The P-I-E-N-O Parkinsn's List Drug Database

alpha-methyldopa / AldometTM AldoprenTM
HydopaTM NudopaTM

BLOOD PRESSURE: LOW RISK

Description: Methyldopa is an oral and parenteral antihypertensive agent. An analog of 3,4-dihydroxyphenylalanine (DOPA), methyldopa originally was developed to inhibit DOPA carboxylase, an enzyme critical for the biosynthesis of catecholamines. Methyldopa was later discovered to have antihypertensive activity, but more recently, its use as an antihypertensive agent has declined due to adverse side effects and an increased potential for organ toxicity. Methyldopa received FDA approval in December 1962.

Mechanism of Action: After crossing the blood-brain barrier, methyldopa is decarboxylated to produce ›-methylnorepinephrine. This metabolite stimulates central inhibitory ›-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. Serum prolactin levels can increase during administration.

Pharmacokinetics: Methyldopa is administered orally and intravenously. 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; onset of hypotensive effect occurs no sooner after parenteral administration of methyldopa due to delayed hydrolysis of the intravenous formulation. 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. Renal impairment slows excretion and increases the half-life of the drug to approximately 4-6 hours. Unabsorbed drug is excreted in the feces.

CONTRAINDICATIONS/PRECAUTIONS: Because of the risk of hemolytic anemia, patients receiving methyldopa should have a hemoglobin, hematocrit, or red blood cell count assessed before and during therapy. Positive Coombs' tests occur in 10-20% of patients receiving methyldopa therapy, and this usually reverses within weeks to months following discontinuance of the drug. If there is evidence of anemia or a positive Coombs' test during therapy, hemolysis should be ruled out. Methyldopa should be used with caution in patients with a history of hemolytic anemia or autoimmune disease. If hemolytic anemia is present, the drug should be discontinued.

Hepatic function also should be determined periodically to detect methyldopa-induced hepatic changes. Methyldopa should be used cautiously in patients who have a history of hepatic disease resulting from methyldopa therapy. The drug is contraindicated in patients with active hepatic disease such as cirrhosis or hepatitis. Methyldopa is relatively contraindicated in patients with pheochromocytoma. Methyldopa may interfer with laboratory tests for catecholamines. Methyldopa may also cause pressor responses in patients with a pheochromocytoma.

Methyldopa should be used cautiously in patients with renal impairment because the accumulation of the sulfate conjugate, leading to toxicity. Lower doses of methyldopa may be required.

Methyldopa should be used cautiously in patients receiving other antihypertensive agents because additive effects could occur (see Drug Interactions).

Methyldopa should be used cautiously in patients with severe coronary insufficiency, cardiac disease, or cerebrovascular disease because drug-induced hypotension can be hazardous to patients with these conditions.

Methyldopa can cause sedation, so patients should be warned that impaired physical coordination and/or reduced mental alertness can affect their ability to operate machinery or drive a vehicle. Methyldopa should be used cautiously in patients with preexisting mental status changes. Methyldopa should be used with caution in patients with a history of major depression. Parkinson's disease may be exacerbated with in patients receiving methyldopa. Methyldopa has rarely been associated with causing choreoathetotic movements and therefore it should be used with caution in patients with severe bilateral cerebrovascular disease.

Some preparations of methyldopa or methyldopate hydrochloride contain sulfites and should be used with caution in patients with a known sulfite hypersensitivity. Use in these patients could precipitate severe allergic reactions including life- threatening asthmatic attacks or anaphylaxis.

DRUG INTERACTIONS: The concomitant administration of methyldopa with diuretics or other antihypertensive agents can result in additive hypotensive effects. This can be therapeutically advantageous, but dosages must be adjusted accordingly.

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 bulk of evidence does not support this. Nevertheless, dosages of methyldopa may need to be increased in patients who begin concurrent antidepressant therapy.

Administration of monoamine oxidase inhibitors (MAOIs) with methyldopa has resulted in headaches, severe hypertension, and hallucinations. Data describing this interaction are limited. In addition, other reports describe safe use of these agents in combination.

Additive hypotensive effects can occur when methyldopa is administered concurrently with general anesthetics; reduced dosages of methyldopa may be required during heavy sedation.

Sympathomimetics, such as cocaine, dobutamine, dopamine, norepinephrine, epinephrine, metaraminol, methoxamine, phenylephrine, phenylpropanolamine, and ephedrine, 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.

Methyldopa can potentiate the hypoglycemic effects of tolbutamide by impairing the drug's metabolism.

Iron salts have been reported to dramatically reduce the oral absorption of methyldopa.

Methyldopa can cause psychosis if administered concomitantly with levodopa. Additive hypotensive effects also could occur.

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.

ADVERSE REACTIONS: The most frequently reported adverse effect of methyldopa therapy is drowsiness. This usually occurs within the first 48-72 hours of administration and may subside with continued therapy. Larger doses produce sedation, decreased mental acuity, lapses of memory, and impaired ability to concentrate. Nightmares, vertigo, headache, weakness, and asthenia also have been reported, generally occurring during early treatment.

Orthostatic hypotension can occur with methyldopa administration. Sinus bradycardia, worsening angina, and myocarditis have been reported, as well as congestive heart failure and carotid sinus hypersensitivity. Sodium and fluid retention can occur, producing edema, and can often be alleviated with concomitant thiazide diuretic therapy.

Patients receiving methyldopa can develop a positive Coombs' test. This is usually not clinically important, but hemolysis with anemia has occurred on rare occasions, causing death in two patients. If hemolysis is present, methyldopa therapy should be discontinued. Methyldopa has also been associated with thrombocytopenia.

Methyldopa-induced fever can occur within 3 weeks of initiating therapy. This may be associated with eosinophilia and/or elevated hepatic enzymes. Hepatocellular injury, cirrhosis, hepatitis, and cholestasis have been reported. If methyldopa is the source of these abnormalities, temperature and liver function will usually return to baseline a few months after discontinuance of the drug.

Adverse GI effects can occur with methyldopa therapy and include diarrhea, nausea/vomiting, xerostomia (dry mouth), distension, constipation, "black" tongue, and pancreatitis.

Adverse dermatological effects of methyldopa therapy include rash, urticaria, and hyperkeratosis.

Prolactin levels are increased in patients receiving methyldopa therapy, and adverse effects, including breast enlargement, gynecomastia, lactation, and amenorrhea, can occur. Impotence, libido decrease, ejaculation dysfunction (delayed or no ejaculation), orgasm dysfunction, nasal congestion, interstitial nephritis, blurred vision, nocturia, and azotemia also have been reported during methyldopa therapy.

PATIENT INFORMATION:

What do methyldopa tablets do?

METHYLDOPA (AldometTM ) is an antihypertensive. Methyldopa affects nerve centers in the brain that control blood vessels. As blood vessels relax, methyldopa relieves high blood pressure (hypertension). Methyldopa is not a cure and has to be used regularly. Generic methyldopa tablets are available.

What should my doctor, dentist, or pharmacist know before I take methyldopa?

They need to know if you have any of these conditions:

How should I take this medicine?

Take methyldopa tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What other medicines can interact with methyldopa?

Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.

What side effects may I notice from taking methyldopa?

Serious side effects with methyldopa include:

Call your doctor as soon as you can if you get any of these side effects.

Minor side effects with methyldopa include:

Let your doctor know about these side effects if they do not go away or if they annoy you.

What do I need to watch for while I take methyldopa?

Visit your doctor for regular checks on your progress. Check your heart rate and blood pressure regularly while you are taking methyldopa. Ask your doctor what your heart rate should be and when you should contact him or her. If you get a fever, especially in the first few months, call your doctor. Do not treat yourself.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how methyldopa affects you. To avoid dizzy or fainting spells, do not stand or sit up quickly, especially if you are an older person. Alcohol can make you more drowsy and dizzy. Avoid alcoholic drinks.

Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.

Iron can stop the absorption of methyldopa. Do not take methyldopa with iron preparations or multiple vitamins containing iron. If you have to take iron, make sure that there are at least 2 hours between iron and methyldopa doses.

Where can I keep my medicine?

Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30C (59 and 86F). Keep container tightly closed. Throw away any unused medicine after the expiration date.

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