What Is Pramipexole Dihydrochloride?

Praxox hydrochloride tablets are used to treat the signs and symptoms of idiopathic Parkinson's disease, either alone (without levodopa) or in combination with levodopa.

Drug Name: Praxol hydrochloride tablets

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Antiparkinsonian

Pramexol hydrochloride tablets ingredients

Chemical name of Praxox hydrochloride:
(S) -2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole dihydrochloride monohydrate = Pramexol hydrochloride monohydrate Chemical structure:

Molecular formula: C ₁₀ H ₁₇ N ₃ S · 2HCl · H ₂ O
Molecular weight: 302.3

Properties of pramipexole hydrochloride tablets

This product is a white tablet.

Pramexol hydrochloride indications

This product is used to treat the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa. For example, when the effect of levodopa gradually weakens or changes and fluctuations occur at the late stage of the disease (end-dose phenomenon or "switch" fluctuations), this product needs to be applied.

Specifications of pramipexole hydrochloride

(1) 0.25 mg (2) 1.0 mg

Dosage and dosage of pramipexole hydrochloride

Oral medication, swallowed with water, with or without food. three times a day.
Initial treatment:
The starting dose is 0.375 mg daily, and the dose is increased every 5-7 days. If the patient is tolerable, the dose should be increased to achieve maximum effect.
Weekly dose (mg) Total daily dose (mg)
1 3 × 0.125 0.375
2 3 × 0.25 0.75
3 3 × 0.5 1.50
If you need to increase the dose further, you should increase the dose once a week on a weekly basis, each time increasing the daily dose by 0.75 mg. The maximum daily dose is 4.5 mg.
However, it should be noted that when the daily dose is higher than 1.5 mg, the incidence of drowsiness increases (see [Adverse Reactions]).
Maintenance treatment:
The individual dose should be between 0.375 mg and 4.5 mg per day. In three important studies with increasing doses, drug efficacy was observed starting with a daily dose of 1.5 mg. Further dose adjustments should be made based on clinical response and tolerability. Approximately 5% of patients in clinical trials took less than 1.5 mg per day. When planning to reduce levodopa treatment, daily doses greater than 1.5 mg may be effective in patients with advanced Parkinson's disease. It is recommended to reduce the dosage of levodopa according to the individual response of the patient during the dosage and maintenance treatment of this product.
Treatment discontinuation:
Sudden discontinuation of dopaminergic therapy can lead to the development of malignant syndrome with neuroblockers. Therefore, pramipexole should be gradually stopped at a rate of 0.75 mg per day until the daily dose drops to 0.75 mg. After that, it should be reduced by 0.375 mg per day (see [Cautions]).
Medication for patients with impaired renal function:
Praxo's clearance depends on kidney function. The following dosage regimen is recommended for initial treatment:
Patients with creatinine clearance greater than 50 ml / min need not reduce their daily dose.
For patients with creatinine clearance between 20-50 ml / min, the initial daily dose of this product should be taken in two divided doses of 0.125 mg twice daily.
Patients with creatinine clearance below 20 ml / min. The daily dose of this product should be taken once, starting with 0.125 mg per day.
If renal function decreases during maintenance therapy, reduce the daily dose of this product by the same percentage as the decrease in creatinine clearance, for example, when creatinine clearance decreases by 30%.
The daily dose of this product is also reduced by 30%. If the creatinine clearance is between 20-50 ml / min, the daily dose should be taken in two doses; if the creatinine clearance is below 20 ml / min, the daily dose should be taken once.
Medication for patients with liver failure:
Dosage adjustments may not be necessary for patients with liver failure, as approximately 90% of the absorbed drug is excreted through the kidneys. However, the potential effects of liver dysfunction on the pharmacokinetics of this product have not been elucidated.

Adverse reactions of pramipexole hydrochloride

The following adverse events may be expected when using this product: abnormal dreaming, blurred consciousness, constipation, paranoia, dizziness, dyskinesia, fatigue, hallucinations, headache, hyperkinesia, hypotension, increased appetite (bulimia, excessive appetite), Insomnia, libido, nausea, peripheral edema, paranoia; pathological gambling, hypersexuality or other abnormal behaviors; drowsiness, weight gain, sudden onset of sleep; pruritus, rash, and other allergic symptoms.
Based on a pooled analysis of placebo-controlled trials, which included 1923 patients taking this product and 1354 patients taking placebo, the analysis showed that adverse events often occurred in both groups. 63% of patients taking this product and 52% of patients taking placebo have reported at least one adverse event.
Among patients with Parkinson's disease, the most common (5%) adverse drug events in the Praxo treatment group over the placebo group were nausea, dyskinesia, hypotension, dizziness, drowsiness, insomnia, constipation, hallucinations, headaches, fatigue. Incidence of drowsiness increased at daily doses above 1.5 mg (see [Dosage and Administration]). The most common adverse event when used with levodopa is dyskinesia. Hypotension may occur at the beginning of treatment, especially when the dose of this product increases too quickly.
Tables 1 and 2 show the frequency of adverse drug events in placebo-controlled clinical trials performed in patients with Parkinson's disease and patients with restless legs syndrome. The adverse drug events reported in the table are 1% when treated with this product, and are significantly higher in the treatment group of this product than in the control group, or are considered clinically relevant. However, the vast majority of common adverse drug events are mild to moderate, usually appear early in treatment, and most disappear even as treatment continues.
Table 1: Very common adverse drug events (1 / 10)

Table 2. Common adverse drug events (1 / 100 to <1/10)

This product is associated with drowsiness (8.6%) and uncommon excessive daytime sleepiness and sudden sleep onset (0.1%). See [Precautions].
This product may be associated with sexual desire disorder (increased (0.1%) or decreased (0.4%)).
Patients with Parkinson's disease treated with dopamine receptor agonists (including this product), especially at high doses, have reported symptoms of pathological gambling, increased libido, and hypersexuality. It is generally reversible with dose reduction or treatment discontinuation.

Contraindications of pramipexole hydrochloride

Allergic to this product's active ingredients or any excipients.

Precautions for pramipexole hydrochloride

When patients with Parkinson's disease with impaired renal function take this product, it is recommended to reduce the dosage by referring to [Usage and Dosage]. Hallucinations are a side effect of dopamine receptor agonists and levodopa treatment. Patients should be informed that hallucinations (mostly visual) may occur. For advanced Parkinson's disease, combined use of levodopa may cause dyskinesia during the initial dose of this product. If the above-mentioned side reactions occur, the amount of levodopa should be reduced.
This product is related to drowsiness and sudden sleep onset, especially for patients with Parkinson's disease. Sudden sleep episodes in daily activities, sometimes without consciousness or warning signs, are rarely reported. Patients must be informed of such side effects, and it is recommended that they drive the vehicle or operate the machine with caution during the application of this product. Patients who have experienced drowsiness and / or sudden sleep onset side effects must avoid driving or operating machines and should consider reducing the dose or discontinuing treatment. Due to possible additive effects, patients should use other sedatives or alcohol with caution when taking pramipexole (see Effects on the ability to drive and operate machines and [Adverse reactions]).
Pathological gambling, increased libido and hypersexuality have been reported in patients with Parkinson's disease who use dopamine receptor agonists, including this product. Therefore, patients and caregivers should be informed that behavior changes may occur. Consider reducing the dose / gradual discontinuation of treatment.
If the potential benefits outweigh the risks, patients with mental disorders should be treated with dopamine receptor agonists only.
Praxox should be avoided in conjunction with antipsychotics (see [Drug Interactions]).
Ophthalmic examinations should be performed regularly or when visual abnormalities occur.
Care should be taken with patients with severe cardiovascular disease. Since dopaminergic therapy is associated with the development of orthostatic hypotension, monitoring of blood pressure is recommended, especially in the early stages of treatment.
Symptoms of neuroleptic malignant syndrome have been reported when abrupt termination of dopaminergic therapy (see [Dosage and Administration]).
Impact on the ability to drive and operate the machine This product has a greater impact on the ability to drive and operate the machine.
Hallucinations or drowsiness may occur.
Patients taking this product with drowsiness and / or sudden onset of sleep must be advised to avoid driving a vehicle or engaging in activities that may impair themselves or others at risk of serious injury or death due to impaired alertness (e.g. when operating a machine) . Until this recurrent episode and lethargy symptoms have disappeared (see, [Drug Interactions] and [Adverse Reactions]).

Praxox hydrochloride tablets for pregnant and lactating women

The effects of pramipexole on human pregnancy and lactation have not been studied. It has no teratogenic effects on rats and rabbits, however, it is toxic to rat embryos at maternal toxic doses (see Preclinical Safety Data). This product is contraindicated during pregnancy, unless it is really needed, for example, when the potential benefits to the fetus outweigh the risks.
Since this product inhibits human prolactin secretion, it inhibits lactation. Whether this product can be secreted into women's milk has not been studied. Drug-related radioactivity in rat milk is higher than plasma.
Due to lack of human data, this product should not be applied during lactation. However, if its use is unavoidable, breastfeeding should be discontinued.

Pramexol hydrochloride tablets for children

There is no data on the safety and effectiveness of this product for children.

Pramexol hydrochloride tablets for the elderly

No special notice.

Pramipexole hydrochloride drug interactions

Praxox has a low degree of binding to plasma proteins (less than 20%), and almost no biotransformation occurs in men. Therefore, pramipexole cannot interact with other drugs that affect plasma protein binding, and it cannot be eliminated by biotransformation. Since anticholinergic drugs are mainly eliminated by biotransformation, although the interaction between pramipexole and anticholinergic drugs has not been studied, it is speculated that the possibility of this interaction is very limited. Praxo has no pharmacokinetic interactions with selegiline and levodopa.
Cimetidine can reduce the renal clearance of pramipexole by about 34%, possibly through inhibition of the renal tubular cation secretion transport system. Therefore, drugs that inhibit this active renal clearance pathway or clearance by this pathway, such as cimetidine and amantadine. May interact with pramipexole and result in reduced clearance of either or both drugs. When these drugs are used concurrently with this product, consideration should be given to reducing the pramipexole dose.
When this product is used in combination with levodopa, it is recommended that the dose of levodopa be reduced when increasing the dose of this product, while the dose of other anti-Parkinson's treatment drugs remain unchanged.
Due to possible additive effects, patients should take caution with other sedatives or alcohol while taking pramipexole.
Praxox should be avoided in conjunction with antipsychotics (see [Cautions]), for example, when antagonistic effects are expected.

Pramipexole hydrochloride overdose

No clinical experience with drug overdose. Anticipated events may be events related to the pharmacodynamic characteristics of dopamine receptor agonists, including nausea, vomiting, hyperkinesia, hallucinations, agitation, and hypotension. There is no clear antidote for overdose of dopamine receptor agonists. If there are symptoms of central nervous system excitement, neurosuppressive drugs may be needed for treatment. Overdose may require general supportive measures, as well as measures such as gastric lavage, intravenous infusion, administration of activated carbon and ECG monitoring.

Pharmacology and toxicology of pramipexole hydrochloride

Pharmacodynamic properties Praxox is a dopamine receptor agonist. It binds to the D2 subfamily of dopamine receptors with high selectivity and specificity, and has complete intrinsic activity. It has a preferential affinity for the D3 receptors.
Praxox reduces dyskinesias in Parkinson's patients by activating dopamine receptors in the striatum. Animal tests have shown that pramipexole inhibits dopamine synthesis, release and regeneration.
The mechanism of action of pramipexole for restless leg syndrome is unclear. Neuropharmacological evidence suggests a possible connection with the dopaminergic system.
A dose-dependent decrease in prolactin was observed in volunteers.
Clinical trials in patients with Parkinson's disease This product can reduce the symptoms and signs of patients with idiopathic Parkinson's disease.
Controlled clinical trials included approximately 2,100 patients with Heohn-Yahr stage I-IV. Of these, approximately 900 patients are receiving advanced levodopa combined with motor complications.
In early and late Parkinson's disease controlled clinical trials, the efficacy of this product was maintained for about six months. In open follow-up trials that lasted more than 3 years, there was no decrease in efficacy. In a two-year controlled double-blind clinical trial, the use of pramipexole as the initial treatment significantly slowed and reduced the incidence of motor complications compared with levodopa as the initial treatment. It is necessary to balance the effect of delaying motor complications of pramipexole and the more significant improvement of levodopa on motor function (measured by the average change in UPDRS score). The overall incidence of hallucinations and drowsiness is higher in the pramipexole group However, there are no significant differences during the maintenance phase. These factors should be considered when starting pramipexole in patients with Parkinson's disease.
Preclinical safety data. Repeated dose toxicity tests have shown functional effects of pramipexole, mainly involving the central nervous system and female reproductive system, and may be caused by enlarged pramipexole pharmacodynamic effects.
Mini-pig experiments have recorded reductions in diastolic blood pressure, systolic blood pressure, and heart rate, and experiments in monkey rats and rabbits have investigated the potential effects of pramipexole on reproductive function. Praxox has no teratogenic effects on rats and rabbits, but has toxic effects on rat embryos at maternal toxic doses. Because of the selectivity of animal populations and limited research parameters, the effects of pramipexole on pregnancy and male fertility have not been fully elucidated.
Praxox is not genotoxic. In a carcinogenicity experiment, the presence of testicular mesenchymal hyperplasia and adenomas in male rats can be explained by the prolactin inhibition of pramipexole. However, the findings have no clinical relevance to male humans. The same experiment also showed that at 2 mg / kg (salt) and higher doses, Praxox was associated with retinal degeneration in rats, but in carcinogenic experiments in pigmented rats, 2-year-old mice or other populations studied Did not find the same.

Pharmacokinetics of pramipexole hydrochloride

Praxox is absorbed quickly and completely. The absolute bioavailability is above 90%. Maximum plasma concentrations occur between 1-3 hours after taking the drug. Taking it with food does not decrease the extent of pramipexole absorption, but it does reduce its rate of absorption. Praxox exhibits linear dynamics, with small differences in plasma levels between patients.
In humans, pramipexole has a low degree of plasma protein binding (less than 20%) and a large volume of distribution (400 I). It was observed that the concentration of the drug in rat brain tissue was very high (approximately 8 times the plasma concentration).
Praxox is poorly metabolized in men.
Excretion from the kidney in its original form is the main clearance route for pramipexole. About 90% of the 14C-labeled drugs are excreted through the kidneys, and less than 2% of the drugs in the stool. The total clearance of pramipexole is approximately 500 ml / min, and the renal clearance is approximately 400 ml / min.
Praxo clearance half-life (t _1/2 ) in young and old people ranges from 8-12 hours.

Pramexol hydrochloride tablets storage

Sealed and stored in a dark place below 30 ° C. Keep out of reach of children.

Packaging of pramipexole hydrochloride tablets

Aluminum foil, 10 pieces, 30 pieces / box

Expiration date of pramipexole hydrochloride

36 months

Praxox Hydrochloride Tablets

Import Drug Registration Standard] X20110060 ^[1]