Pramipexole

Products

Pramipexole is commercially available in tablet and sustained-release tablet form (Sifrol, Sifrol ER, generics). It has been approved in many countries since 1997; generics were released in 2010 and entered the market in January 2011. Sifrol ER sustained-release tablets were relaunched by the original manufacturer in 2010.

Structure and properties

Pramipexole (C10H17N3S, Mr = 211.30 g/mol) is a nonergoline dopamine agonist and a tetrahydrobenzothiazole derivative. It is present in drugs as pramipexole dihydrochloride monohydrate, i.e., pramipexole – 2 HCl – H2O, a white crystalline powder that is readily soluble in water. Pramipexole is a racemate and is commercially available in the form of the pure -enantiomer. Therapeutic use of the -enantiomer dexpramipexole is being investigated in other indications.

Effects

Pramipexole (ATC N04BC05) has dopaminergic and neuroprotective properties. The effects are due to binding to dopamine receptors, especially D3 dopamine receptors of the D2 receptor family. Unlike other dopamine agonists, it is relatively selective.

Indications

For symptomatic treatment of Parkinson’s disease as monotherapy or in combination with levodopa and for symptomatic treatment of restless legs syndrome. Other potential indications are mentioned in the literature (eg, bipolar affective disorder, depression), but pramipexole has not yet been approved for this purpose.

Abuse

Because of its psychotropic and libido-increasing properties, pramipexole can be abused as an aphrodisiac.

Dosage

According to the SmPC. Pramipexole has a medium-long half-life of 8-12 hours and is taken with water three times daily, independent of meals, for the treatment of Parkinson’s disease. The sustained-release tablets need to be administered only once daily due to the delayed release of the active ingredient. For the treatment of restless legs syndrome, pramipexole is taken as non-retarded tablets 2-3 hours before bedtime.

Contraindications

  • Hypersensitivity

For complete precautions, see the drug label.

Interactions

Pramipexole is poorly metabolized and there are no known interactions via CYP450. Nevertheless, there is some potential for pharmacokinetic drug-drug interactions because pramipexole is eliminated and secreted by the kidney as an organic cation (Figure). Other organic cations may competitively inhibit renal secretion of pramipexole and increase plasma concentrations to a relevant extent. These include nitrogen compounds such as amantadine, cimetidine, diltiazem, quinidine, quinine, ranitidine, triamterene, verapamil, digoxin (no N compound), procainamide, and trimethoprim. Additive effects are possible with other antiparkinsonian and central depressant drugs.

Adverse effects

A very common adverse effect is drowsiness, which may occasionally lead to sudden falling asleep. Therefore, driving and operating heavy machinery should be avoided during treatment. Alcohol and centrally depressant medications may additionally increase this side effect. Dizziness, movement disorders, headache, low blood pressure (occasionally with brief loss of consciousness), amnesia, and nausea are also very common. Dopamine agonists are known to cause behavioral changes. These include libido disturbances, hypersexuality, delusions, paranoia, gambling addiction, shopping addiction, and binge eating. Other possible side effects include insomnia, confusion, unusual dreams, restlessness, visual disturbances, indigestion, edema, fatigue, weight gain or loss, pneumonia, breathing disorders, and hypersensitivity reactions.