Sifrol: Formula, Presentation, Indications, Action Mechanism, Dosage, Side Effects and Warnings

It belongs to a group of drugs called dopamine agonists.

Sifrol works with an effect similar to that of dopamine, which is a chemical in the brain necessary to control movement.

Chemical formula

  • C10H17N3S.
  • Active ingredient pramipexole.

Presentation

  • Tablets of 125 and 250 micrograms and 1 mg.

Indications

Sifrol is used for the treatment of the following diseases:

  • Parkinson’s disease: This is a progressive brain disorder that causes tremors, slow movements and muscle stiffness. Sifrol can be used alone or in combination with levodopa (another medicine used to treat Parkinson’s disease), at any stage of the disease.
  • The syndrome of restless legs of moderate to severe: It is a disorder in which the patient has uncontrollable impulses to move the extremities and stop uncomfortable, painful or strange sensations in the body, usually at night.

Sifrol is used when a specific cause of the disorder can not be identified.

Mechanism of action

The active substance in Sifrol, pramipexole, is a dopamine agonist (a substance that mimics the action of dopamine).

Dopamine is a messenger substance in the parts of the brain that control movement and coordination.

In patients with Parkinson’s disease, the cells that produce dopamine begin to die and the amount of dopamine in the brain decreases.

Then, the ability to control movements is lost.

Sifrol stimulates the brain as dopamine would, so patients can control their movements and have fewer signs and symptoms of Parkinson’s disease, such as tremors, stiffness and slowness of movement.

The way Sifrol works in restless leg syndrome is not completely understood. But it is believed that the syndrome is caused by problems with the deficiency of dopamine in the brain, and acts in the same way that it works as an agonist in Parkinson’s, and can be corrected with the treatment with Sifrol.

Dose

For the treatment of Parkinson’s disease, the initial dose is three tablets of 125 micrograms every 8 hours.

The following week, 250 mg every 8 hours and the third week 500 mg every 8 hours.

The dose should be increased every five to seven days until the symptoms are controlled without causing side effects that can not be tolerated.

The maximum daily dose is 4.5 mg.

For patients who have problems with the kidneys, sifrol should be administered less frequently.

In case the treatment should be interrupted for any reason, the dose should be gradually reduced.

For the treatment of restless leg syndrome, treatment should be administered once a day, two or three hours before bedtime.

The recommended initial dose is 125 micrograms, but, if necessary, it can be increased every four to seven days to further reduce symptoms, up to a maximum of 750 micrograms.

Sifrol tablets should be taken with water.

Prolonged-release tablets should not be chewed, divided or crushed, and should be taken at approximately the same time every day.

Side effects

The treatment of Sifrol as therapy for patients suffering from Parkinson’s disease or restless legs syndrome, can cause unwanted side effects in some people.

The following side effects have been reported: Occurrence of nausea, vomiting, constipation , diarrhea, dry mouth, drowsiness, tiredness, confusion or hallucinations such as seeing, feeling or hearing things that are not there, restlessness, dizziness, headache.

Dizziness when standing up, especially when getting up from a sitting or lying position, blurred vision, swelling in the hands, ankles or feet, uncontrollable shaking.

Difficulty sleeping or unusual dreams, gain or loss of weight, loss or gain of sexual impulse, forward flexion of the head and neck.

Some of these side effects are more common at the beginning of treatment and decrease or disappear over time.

If you notice any of the following serious side effects, you should go to the doctor immediately:

Memory loss or amnesia, fainting, signs of allergy such as rash or hives on the skin, swelling of the face, lips, tongue or other parts of the body, wheezing or shortness of breath, excessive sleepiness or sudden sleep during normal daily activities.

Compulsive behavior, such as gambling, hypersexuality, shopping, eating, the use of medications and repetitive activities without purpose, mental illnesses that cause severe suspicion such as paranoia.

Difficulty breathing or tightness in the chest, swelling of the feet or legs due to fluid accumulation or heart failure .

Warnings and contraindications

Hypersensitivity:

Sifrol should not be administered if the patient is hypersensitive to the active substance or to any of the excipients.

Kidney diseases:

In cases where Sifrol is prescribed in patients with Parkinson’s disease who suffer from renal insufficiency, the dose should be reduced since the elimination of the medication depends on renal function.

This decrease will depend on the results of laboratory monitoring of creatinine clearance.

Hallucinations:

Sifrol should be administered with caution, hallucinations, mainly visual ones, present as a side effect of treatment with dopamine agonists and levodopa.

Discinesia:

In the combined treatment with levodopa, for advanced Parkinson’s disease, dyskinesia may occur, during adjustment of the initial dose of Sifrol, should this occur, the dose of levodopa should be decreased.

Sudden onset of sleepiness and sleepiness:

Sifrol has been associated with episodes of drowsiness and sudden onset of sleep, during daily activities, in some cases with periods of unconsciousness.

Patients who have experienced drowsiness or an episode of sudden onset of sleep should refrain from driving vehicles, operating machinery or performing any activity that requires a state of alertness.

It can be considered a reduction of the dose or the completion of the therapy.

Disorders of impulse control and compulsive behaviors:

The onset of attitudes such as pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson’s disease, including Sifrol.

In addition, other behavioral symptoms of impulse control disorders may appear.

For these cases should be considered the reduction of the dose or the interruption of the treatment.

Patients with psychotic disorders:

Patients who present with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.

Ophthalmological monitoring:

It is recommended to perform ophthalmological monitoring at regular intervals or to report to the doctor if abnormalities occur in the vision.

Severe cardiovascular disease:

In case the patient suffers from severe cardiovascular diseases, care must be taken.

Regular control of blood pressure is recommended, especially at the beginning of treatment, due to the risk of the onset of hypotension associated with dopaminergic therapy.

Neuroleptic malignant syndrome:

The appearance of symptoms suggestive of neuroleptic malignant syndrome has been reported when abrupt withdrawal from therapy occurs.

Interactions

Sedatives and alcohol:

In view of the fact that Sifrol can produce these possible additive effects, caution should be exercised when patients are taking other sedative drugs or alcohol in combination with Sifrol.

Inhibitors and competitors of the active pathway of renal elimination:

Medications such as cimetidine, amantadine, mexiletine, zidovudine, cisplatin, quinine, and procainamide may interact with sifrol and result in reduced clearance of sifrol.

In these cases, a reduction in the dose of sifrol should be considered when these medicinal products are concomitantly administered with Sifrol.

Levodopa:

When Sifrol is administered in combination with levodopa, it is recommended that the dose of levodopa be reduced and the dose of other antiparkinson drugs kept constant while increasing the dose of Sifrol.

Antipsychotic medications:

The concomitant administration of antipsychotic medications with Sifrol should be avoided.

Pregnancy:

The effect of Sifrol on pregnancy has not been investigated in humans.

Sifrol should not be used when the patient is pregnant, unless the potential benefit to the patient justifies the potential risk to the fetus.

Lactation:

Treatment with sifrol inhibits the secretion of prolactin in humans.

The excretion of sifrol in breast milk has not been studied in women, however, if its use is unavoidable, it is advisable to inhibit lactation.

Fertility:

No studies have yet been conducted on the effect of Sifrol on human fertility.

In animal studies, as expected to be a dopamine agonist, Sifrol affected estrogen cycles and reduced female fertility.

But, these studies did not indicate harmful effects, direct or indirect with respect to male fertility.