Dopegyt^® (Tablets) Instructions for Use

Marketing Authorization Holder

Egis Pharmaceuticals PLC (Hungary)

ATC Code

C02AB02 (Methyldopa (racemic mixture))

Active Substance

Methyldopa (Rec.INN registered by WHO)

Dosage Form

Dopegyt®

Tablets 250 mg: 50 pcs.

Dosage Form, Packaging, and Composition

Tablets white or greyish-white, round, flat, with a bevel, engraved with “DOPEGYT” on one side, odorless or almost odorless.

Excipients: corn starch – 45.7 mg, ethylcellulose – 8.8 mg, talc – 6 mg, sodium carboxymethyl starch – 3.5 mg, stearic acid – 3 mg, magnesium stearate – 1 mg.

50 pcs. – brown glass bottles (1) with a PE cap with first-opening control and a bellows-shaped cushion – cardboard packs.

Clinical-Pharmacological Group

Stimulator of central alpha₂-adrenergic receptors. Antihypertensive drug

Pharmacotherapeutic Group

Centrally acting antihypertensive agent

Pharmacological Action

Centrally acting antihypertensive agent. Alpha-methylnorepinephrine, a metabolite of methyldopa formed in the CNS, stimulates postsynaptic α-adrenoceptors of medullary neurons, leading to inhibition of the vasomotor center and a reduction in descending sympathetic impulses.

It exerts an antihypertensive effect mainly due to a decrease in total peripheral resistance and, to some extent, a reduction in cardiac output and heart rate. It increases glomerular filtration rate and renal blood flow. It causes a sedative effect.

Pharmacokinetics

After oral administration, absorption from the gastrointestinal tract is variable and averages 50%. Protein binding is low, less than 20%. It is converted to alpha-methylnorepinephrine in central adrenergic neurons. It is metabolized in the liver to form a sulfate conjugate.

The T_1/2 of alpha-methylnorepinephrine is 1.7 hours; in anuria, it is 3.6 hours. It is excreted by the kidneys. Approximately 70% of the absorbed active substance is excreted in the urine as a mono-O-sulfate metabolite and unchanged. The unabsorbed portion of the active substance is excreted through the intestines.

Indications

Arterial hypertension.

ICD codes

Dosage Regimen

For oral administration in adults, the initial dose is 250 mg 2-3 times/day. The single dose is increased by 125 mg every 2-3 days until the optimal antihypertensive effect is achieved, which is usually observed at a daily dose of 1 g. To reduce the severity of the sedative effect, the evening dose is increased first. Once a stable antihypertensive effect is achieved, the dose is gradually reduced to the minimum effective dose. In case of renal impairment, the single dose should be reduced.

For children, the initial dose is 10 mg/kg/day in 2-4 divided doses.

Maximum daily doses for oral administration: for adults – 2 g, for children – 65 mg/kg.

Adverse Reactions

From the cardiovascular system: orthostatic hypotension, bradycardia, peripheral edema, flushing of the upper body; rarely – myocarditis, pericarditis.

From the digestive system: dry mouth, nausea, vomiting, diarrhea, impaired liver function, increased activity of hepatic transaminases, jaundice.

From the central nervous system: drowsiness, lethargy, sluggishness, parkinsonian syndrome, unsteady gait, headache, dizziness.

From the hematopoietic system: rarely – hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia.

From the musculoskeletal system: myalgia, arthralgia.

From the endocrine system: gynecomastia, hyperprolactinemia, galactorrhea.

Allergic reactions: fever, skin rash, toxic epidermal necrolysis.

From the reproductive system: amenorrhea, impotence, decreased libido.

Other: nasal congestion.

Contraindications

Acute liver diseases, impaired liver function, severe renal impairment, collagen and allergic diseases, parkinsonism, depression, pheochromocytoma, severe coronary and cerebral atherosclerosis, concurrent use of ethanol and agents causing CNS depression, hypersensitivity to methyldopa.

Use in Pregnancy and Lactation

Adequate and well-controlled studies on the safety of methyldopa use during pregnancy have not been conducted. Methyldopa crosses the placental barrier.

Methyldopa is excreted in breast milk; therefore, if use during lactation is necessary, the ratio of the intended therapeutic benefit for the mother to the potential risk for the child should be carefully weighed.

In experimental studies, no adverse effects on the fetus were identified.

Use in Hepatic Impairment

Contraindicated in acute liver diseases, impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

For children, the initial dose is 10 mg/kg/day in 2-4 divided doses.

Geriatric Use

When used in elderly and senile patients, the daily dose should be increased strictly gradually, as a sharp decrease in blood pressure is possible.

Special Precautions

Use with caution in hepatitis, history of acute left ventricular failure, diencephalic syndrome. Methyldopa should not be used concurrently with MAO inhibitors and with levodopa.

In patients with renal impairment, the daily dose of methyldopa should be reduced. When used in elderly and senile patients, the daily dose should be increased strictly gradually, as a sharp decrease in blood pressure is possible.

It should be considered that after discontinuation of methyldopa, the antihypertensive effect ceases relatively quickly; an increase in blood pressure usually occurs within 48 hours.

During treatment, liver function and peripheral blood picture should be monitored. The urine of patients taking methyldopa may darken upon standing. With long-term (more than 6 months) use of methyldopa at a daily dose of more than 1 g, a positive direct Coombs test is possible. If a positive direct Coombs test appears, it is first necessary to determine whether hemolytic anemia is present. If anemia is present, methyldopa should be discontinued. The blood picture may normalize on its own; sometimes the use of corticosteroids is required.

Alcohol consumption is not recommended during treatment.

Effect on ability to drive vehicles and operate machinery

Patients taking methyldopa should refrain from potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Drug Interactions

With concurrent use with beta-blockers, orthostatic hypotension is possible.

There is a possibility of developing arterial hypertension, which is caused by alpha-methylnorepinephrine formed from methyldopa acting on unblocked alpha-adrenoceptors of blood vessels and the heart.

With concurrent use with oral hormonal contraceptives, a decrease in the antihypertensive effect of methyldopa is possible.

With concurrent use with MAO inhibitors, both arterial hypotension and severe hypertension with psychomotor agitation are possible.

With concurrent use with anesthetic agents (including halothane, sodium thiopental, diethyl ether), collapse is possible.

With concurrent use with tranquilizers, an enhancement of the antihypertensive effect is possible.

With concurrent use with tricyclic antidepressants, a decrease in the antihypertensive effect and the occurrence of tachycardia, agitation, and headaches are possible.

With concurrent use with indomethacin, other NSAIDs, anorectic drugs (except for fenfluramine), and sympathomimetics, the antihypertensive effect of methyldopa is reduced.

With concurrent use with haloperidol, sedative effects, depression, dementia, confusion, and dizziness are possible.

With concurrent use with digoxin, bradycardia is possible.

With concurrent use with ferrous sulfate, ferrous gluconate, the effectiveness of methyldopa is reduced.

With concurrent use with levodopa, an enhancement of the antiparkinsonian effect is possible, due to inhibition of peripheral dopa decarboxylase as a result of methyldopa’s action, leading to an increase in the concentration of levodopa in the CNS. In addition, an additive hypotensive effect is observed.

There are reports of lithium intoxication with concurrent use with lithium carbonate.

With concurrent use with trifluoperazine, a case of paradoxical increase in blood pressure has been described.

With concurrent use with fenfluramine, the antihypertensive effect of methyldopa is enhanced.

With concurrent use with chlorpromazine, the antihypertensive effect is enhanced.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.