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Active ingredient: Ropinirole - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Dopamine Agonists
  • Antiparkinson Agents
  • Antidyskinetics
  • Central Nervous System Agents

Dosage Forms

  • Tablet (0.25 mg, 0.5 mg, 1 mg, 2 mg, 4 mg or 5 mg)

Brands / Synonyms

Requip; Requip XL; Ropinirol [INN-Spanish]; Ropinirole HCl; Ropinirole hydrochloride; Ropinirolum [INN-Latin]

Indications

For the treatment of the signs and symptoms of idiopathic Parkinson's disease. Also used for the treatment of restless legs syndrome.

Pharmacology

Ropinirole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The relevance of D3 receptor binding in Parkinson's disease is unknown. The mechanism of ropinirole-induced postural hypotension is presumed to be due to a D2 -mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance.

Mechanism of Action

Ropinirole binds the dopamine receptors D3 and D2. Although the precise mechanism of action of ropinirole as a treatment for Parkinson's disease is unknown, it is believed to be related to its ability to stimulate these receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that ropinirole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum.

Absorption

Absolute bioavailability is 55%, indicating a first pass effect. Food does not affect the extent of absorption.

Toxicity

Symptoms of overdose include agitation, chest pain, confusion, drowsiness, facial muscle movements, grogginess, increased jerkiness of movement, symptoms of low blood pressure (dizziness, light-headedness)upon standing, nausea, and vomiting.

Biotrnasformation / Drug Metabolism

Hepatic. Ropinirole is extensively metabolized to inactive metabolites via N -despropylation and hydroxylation pathways, largely by the P450 isoenzyme CYP1A2. N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%).

Contraindications

Requip is contraindicated for patients known to have hypersensitivity to the product.

Drug Interactions

P 450 Interaction:    In vitro metabolism studies showed that CYP1A2 was the major enzyme responsible for the metabolism of ropinirole. There is thus the potential for substrates or inhibitors of this enzyme when coadministered with ropinirole to alter its clearance. Therefore, if therapy with a drug known to be a potent inhibitor of CYP1A2 is stopped or started during treatment with Requip , adjustment of the Requip dose may be required.

L-dopa:   Co-administration of carbidopa + L-dopa (Sinemet® 10/100 mg b.i.d.) with ropinirole (2.0 mg t.i.d.) had no effect on the steady-state pharmacokinetics of ropinirole (n=28 patients). Oral administration of Requip 2.0 mg t.i.d. increased mean steady state C max of L-dopa by 20% but its AUC was unaffected (n=23 patients).

Digoxin:   Co-administration of Requip (2.0 mg t.i.d.) with digoxin (0.125-0.25 mg q.d.) did not alter the steady-state pharmacokinetics of digoxin in 10 patients.

Theophylline:    Administration of theophylline (300 mg b.i.d., a substrate of CYP1A2) did not alter the steady-state pharmacokinetics of ropinirole (2 mg t.i.d.) in 12 patients with Parkinson's disease. Ropinirole (2 mg t.i.d.) did not alter the pharmacokinetics of theophylline (5 mg/kg i.v.) in 12 patients with Parkinson's disease.

Ciprofloxacin:   Co-administration of ciprofloxacin (500 mg b.i.d.), an inhibitor of CYP1A2, with ropinirole (2 mg t.i.d.) increased ropinirole AUC by 84% on average, and C max by 60% (n=12 patients).

Estrogens:   Population pharmacokinetic analysis revealed that estrogens (mainly ethinylestradiol: intake 0.6-3 mg over 4-month to 23-year period) reduced the oral clearance of ropinirole by 36% in 16 patients. Dosage adjustment may not be needed for Requip in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with Requip , then adjustment of the Requip (ropinirole hydrochloride) dose may be required.

Dopamine Antagonists:   Since ropinirole is a dopamine agonist, it is possible that dopamine antagonists, such as neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of Requip . Patients with major psychotic disorders, treated with neuroleptics, should only be treated with dopamine agonists if the potential benefits outweigh the risks.

Population analysis showed that commonly administered drugs, e.g., selegiline, amantadine, tricyclic antidepressants, benzodiazepines, ibuprofen, thiazides, antihistamines, and anticholinergics did not affect the oral clearance of ropinirole.

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