Medopexol

Uses

Medopexol is used for:

• The treatment of Parkinson's diseases, used alone or as an adjunct to levodopa with dopa decarboxylase inhibitor
• Moderate to severe restless legs syndrome

Medopexol is also used to associated treatment for these conditions: Bipolar Disorder (BD), Moderate restless legs syndrome (RLS), Parkinson's Disease (PD), Severe restless legs syndrome (RLS)

How Medopexol works

The exact mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown at this time. It is thought, however, that the ability of pramipexole to cause stimulation of the dopamine receptors in the striatum of the brain, a region that receives a vast array of neurological input and is responsible for a wide variety of functions, may be involved. Studies performed in animals show that pramipexole influences striatal neuronal transmission rates following activation of dopamine receptors .

Medopexol is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D2 subfamily of dopamine receptors in vitro, binding selectively and dopamine D2 receptors and showing a preference for the dopamine D3 receptor subtype rather than other subtypes . The clinical significance of this binding specificity is unknown , .

Dosage

Medopexol dosage

The recommended dose of Medopexol is as following-

Parkinson's disease: 

• Initial dose: 88 micrograms 3 times daily, dose doubled every 5-7 days if tolerated to 350 micrograms 3 times daily; further increased if necessary by 180 micrograms 3 times daily at weekly intervals
• Maximum dose: 3.3 mg daily in 3 divided doses. During pramipexole dose titration and maintenance Levodopa dose should be reduced.

Restless legs syndrome: 

• Initial dose: 88 micrograms once daily 2-3 hours before bedtime, dose doubled every 4-7 days if necessary to 350 micrograms daily.
• Maximum dose: 540 micrograms daily

Side Effects

The common side effects are dizziness, dyskinesia, nausea, hypotension, abnormal dreams, confusion, constipation, delusion, hallucinations, headache, hyperkinesia, increased eating (binge eating, hyperphagia), insomnia, libido disorders, nausea, peripheral oedema, paranoia, pathological gambling, hypersexuality and other abnormal behaviour, somnolence, weight increase, sudden onset of sleep, pruritus and rash and other hypersensitivity.

Toxicity

LD50

Rat Oral LD 50 >800 mg/kg .

Carcinogenicity, mutagenicity, impact on fertility

Medopexol was not found to be carcinogenic in 2-year studies on mice and rats at 0.3, 2.2, and 11 times the maximum recommended human dose (MRHD). No increased incidence of tumors was observed . No mutagenicity was detected in various assays, including the Ames test. Finally, pramipexole given to rat models at a dose of 2.5 mg/kg/day (5 times the maximum recommended human dose), increased estrus cycles and inhibited implantation of a fertilized ovum. Decreased levels of prolactin, a hormone necessary for implantation and maintenance of early pregnancy, were measured . The significance of these findings in humans is unknown.

Pregnancy

This drug is considered a pregnancy category C drug, showing teratogenic effects in animals. Currently, there no studies of pramipexole in human pregnancy. Animal reproduction studies are not always predictive of human response. This drug should only be used in pregnancy if the potential benefit outweighs the possible fetal risks .

Nursing

Whether pramipexole is excreted in human milk is unknown. A decision should be made regarding the administration pramipexole during nursing, or whether to discontinue it during nursing, as many drugs are excreted in human milk. The potential exists for risk to the infant if pramipexole is, in fact, excreted in the milk .

Precaution

Caution should be taken in patients with psychotic disorder, ophthalmologic monitoring is recommended at regular intervals, severe cardiovascular disease and renal impairment.

Interaction

Medopexol is the only dopamine agonist not appreciably metabolized by the P450 system which minimizes about possible drug-drug interactions. Cimetidine and amantadine may reduce the renal clearance of pramipexole. Sedating medicinal products or alcohol in combination with pramipexole may cause additive effects.

Food Interaction

• Take with or without food. Food decreases the risk of GI side effects.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Medopexol Drug Interaction

Moderate: duloxetine, pregabalin, acetaminophen / hydrocodone, cetirizineUnknown: aspirin, aspirin, celecoxib, apixaban, omega-3 polyunsaturated fatty acids, furosemide, atorvastatin, metoprolol, metoprolol, esomeprazole, albuterol, budesonide / formoterol, levothyroxine, cyanocobalamin, ascorbic acid, cholecalciferol

Medopexol Disease Interaction

Major: hypotension, neuroleptic malignant syndrome, psychosis, renal function disorders

Volume of Distribution

This drug is extensively distributed in the body with a volume of distribution of approximately 500 L .

Elimination Route

The bioavailability of pramipexole is higher than 90%, indicating a high level of absorption .

Half Life

About 8.5-12 hours .

Clearance

Renal clearance is about 400 mL/min, indicating heavy secretion by the renal tubules .

Elimination Route

The main route of pramipexole elimination, with 90% of a pramipexole dose found in the urine, almost entirely as unchanged drug .

Pregnancy & Breastfeeding use

The effect of pramipexole on pregnancy and lactation has not been investigated in humans so it should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Medopexol inhibits secretion of prolactin in humans. The excretion of pramipexole into breast milk has not been studied in women so it should not be used during breast-feeding. However, if its use is unavoidable then breast-feeding should be discontinued.

Contraindication

Medopexol is contraindicated in patients with known Hypersensitivity to the active substance or to any of the excipients.

Special Warning

Renal Impairment-

Restless leg syndrome: 

• CrCl 20-60: Increase titration interval to 14 days.

Parkinson's disease:

• CrCl <20: 125 mcg once daily. Max: 1.5 mg/day.
• CrCl 20-50: 125 mcg bid. Max: 2.25 mg/day.

Hepatic Impairment: No dosage adjustment needed.

Use in children: Medopexol is not recommended for children below 18 years of age

Acute Overdose

There is no clinical experience with massive overdose. Symptoms of overdose are nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension. There is no established antidote. If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.

Storage Condition

Store in a cool and dry place. Protect from light.

Innovators Monograph

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