Description and Composition of Timeldopa
Table of Contents
Timeldopa is a phenylalanine derivative and an aromatic amino acid decarboxylase inhibitor with antihypertensive activity. It contains methyldopa as its active pharmaceutical ingredient and other excipients in sufficient quantities. It is a prodrug that is metabolized in the central nervous system into alpha-methylnorepinephrine, a potent alpha-2 adrenergic agonist.
Mechanism of Actions and Pharmacology of Timeldopa
How does methyldopa work?
The exact mechanism of antihypertensive action of methyldopa is unknown. However, it is thought to involve stimulation of central alpha-adrenergic receptors by a metabolite, alpha-methylnorepinephrine, thus inhibiting sympathetic outflow to the heart, kidneys and peripheral vasculature. Reduced peripheral resistance and plasma renin activity levels may also contribute to its effect.
Pharmacokinetics of Timeldopa
Absorption of methyldopa from the gastrointestinal tract is variable but averages approximately 50%.
Methyldopa – Low (less than 20%)
Its sulphate conjugate – Moderate
It is extensively metabolised and is converted to alpha-methyinorepinephrine in central adrenergic neurons; methyldopate hydrochloride is hydrolysed to methyldopa.
Sulphate conjugation occurs to a greater extent after orat than after intravenous administration
Normal – Alpha: 1.7 hours
Anuric – Alpha: 3.6 hours
Time to peak effect:
Single dose – 4 to 6 hours
Multiple doses – 2 to 3 days
Duration of action:
Single dose – 12 to 24 hours
Multiple doses – 24 to 48 hours
Renal, approximately 70% of absorbed drug is excreted in urine as methyldopa and its mono-O-sulfate metabolite.
Unabsorbed oral methyldopa is excreted unchanged in the feces
Indications and Uses of Timeldopa
Methyldopa is used in treatment of:
- Moderate to severe hypertension.
- Gestational hypertension (or pregnancy-induced hypertension)
Contraindication of Timeldopa
When should one not take methyldopa?
Not recommended for patients with acute liver disease or phaeochromocytoma
- Evidence of hemolytic anaemia is an indication for discontinuing the drug.
- Positive Coombs’ tests may indicate an incompatible cross-match when transfusion is required and an indirect Coombs test should be carried out
- Safety for use in pregnancy and lactation has not been established.
- Caution if any kind of surgery or dialysis is required.
Pregnancy and Lactation
Is methyldopa to be taken in pregnancy or by breastfeeding women?
Safety for use in pregnancy and lactation has not been established. It is however used after first trimester in the treatment of pregnancy induced hypertension and preeclampsia.
Side Effects of Timeldopa
What are the side effects of methyldopa?
- Dry mouth
Other side effects other than those listed above can occur.
Report to your healthcare provider if you experience severe side effects while taking this drug.
Concurrent use with the following drugs is not recommended.
- Monoamine oxidase (MAO) inhibitors,
Concurrent use with the following drugs requires careful monitoring
- General anaesthetics
- Tachycardia or bradycardia,
- Extra-pyramidal signs
Treat overdosage by emesis or gastric lavage, if appropriate; and IV 1-2 mg benztropine if extrapyramidal signs are present
Dosage and Adminstration
What is the dosage of methyldopa?
Initial – Oral, 250 mg two or three times a day for two days, the dosage then being adjusted as directed.
Maintenance – Oral, 500 mg to 2 g a day, divided into two to four doses, not exceeding 3 g daily.
Oral, initially 10 mg per kg of body weight daily, divided into two to four doses, the dosage then being adjusted as directed, not exceeding 65 mg per kg of body weight or 3 g daily, whichever is less.
Chemical structure of Timeldopa
Store below 25°C. Protect from light. Keep all medicines away from the reach of children.
- Dopatab drug leaflet: Hovid brand of methyldopa