ROPIX – Uses, Side Effects, Precautions and

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Composition:
Ropix 0.25mg
Each film-coated tablet contains:

Ropinirole as HCI………………0.25mg

(USP Specifications)

Ropix 1mg
Each film-coated tablet contains:

Ropinirole as HCI…………….1mg

(USP Specifications)

Ropix 2mg
Each film-coated tablet contains:

Ropinirole as HCI……………….2mg

(USP Specifications)

Description:
ROPIX Ropinirole hydrochloride) is an orally administered non-ergoline dopamine agonist. It is the
hydrochloride salt of 4-2-(dipropylamino) ethyl]-1,3-dihydro- 2H-indol-2-one monohydrochloride and has
an empirical formula of C16H24N20oHCI. The molecular weight is 296.84(260.38 as the free base).

Clinical Pharmacology:
Mechanism e pf Action: ROPIX is a non-ergoline dopamine agonist with high relative in vitro specificity
and full intrinsic activity at the D2 and D5 dopamine receptor subtypes, binding with higher affinity to D3
than to D2 or D4 receptor subtypes. Ropinirole has moderate in vitro affinity for opioid receptors.
Ropinirole and its metabolites have negligible in vitro affinity for dopamine D1, 5-HT1, 5 HT2,
benzodiazepine, GABA, muscarinic, alpha-1, alpha2-, and beta-adrenoreceptors.

Parkinson’s Disease:
The precise mechanism of action of ROPIX as a treatment for Parkinson’s disease is unknown, although it
is believed to be due to stimulation of postsynaptic dopamine D2-type receptors within the caudate-
putamen in the brain, this conclusion is supported by studies that show that ropinirole improves motor
function in various animal models of Parkinson’s disease. In particular, ropinirole attenuates the motor
deficits induced by lesioning the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-
methyl-4-phenyl-1,2,3,6-tetrahydroPyridine (MPTP) in primates. The relevance of D3 receptor binding in
Parkinson’s disease is unknown.

Restless Legs Syndrome (RLS):

The precise mechanism of action of ROPIX as a treatment for Restless Legs Syndrome (also known as
Ekbom Syndrome) is unknown Although the pat E pathophysiology of RLS is largely unknown,
neuropharmacological evidence suggests primary dopaminergic system Involvement. Positron emission
tomography (PET) studies suggest that mild striatal presynaptic dopaminergic dysfunction may be
involved in the pathogenesis of RLS.

Indications:
ROPINIROLE is used to treat Parkinson’s disease. People with Parkinson’s disease have low levels of
dopamine in some parts of their brains. Ropinirole has effects similar to those of natural dopamine, so it
helps to reduce the symptoms of Parkinson’s disease. ROPINIROLE is used to treat the symptoms of
moderate to severe Restless Legs Syndrome (RLS). Restless legs syndrome (RLS) is also called Ekbom
syndrome. People with restless legs syndrome have an irresistible urge to move their legs, and
sometimes their arms and other parts of their bodies. Usually, they have unpleasant sensations in their
limbs – sometimes described as ‘crawling’ or bubbling’ – which can begin as soon as they Sit or lie down,
and are relieved only by movement. So, they often have problems with sitting still and especially with
sleeping, ROPNIROLE Relieves the unpleasant sensations, and so reduces the urge to move the legs and
other limbs.

Pharmacokinetics:
Absorption, Distribution, Metabolism, and Elimination: The pharmacokinetics of ropinirole are similar in
Parkinson’s disease patients and Patients with Restless Legs Syndrome. Ropinirole is rapidly absorbed
after oral administration, reaching peak concentration in approximately 1-2 hours. In clinical studies,
over 88% of a radiolabeled dose was recovered in urine and the absolute bioavailability was 55%,
indicating a First-pass effect. Relative bioavailability from a tablet compared to an oral solution is 85%.
Food does not affect the extent of absorption of Ropinirole, although its Tmax is increased by 2.5 hours
and its Cmax is decreased by approximately 25% when the drug is taken with a high-fat meal. The
clearance of ropinirole after oral administration to patients is 47 L/hr (cv = 4586) and its elimination half-
life is approximately 6 hours. Ropinirole is extensively metabolized by the liver to inactive metabolites
and displays linear kinetics over the therapeutic dosing Range of 1 to 8 mg 3 times daily. Steady-state
concentrations are expected to be achieved within 2 days of dosing; Accumulation upon Multiple dosing
is predictive of single dosing. Ropinirole is widely distributed throughout the body, with an apparent
volume of Distribution of 7.5 L/kg (cy =32%). It is up to 40% bound to plasma proteins and has a blood-
to-plasma ratio of 1:1. The major metabolic Pathways are N-despropylation and hydroxylation to form
the inactive N-despropyl and hydroxy metabolites. In vitro studies indicate that the major cytochrome
P450 isozyme involved in the metabolism of ropinirole is CYP1A2, an enzyme known to be stimulated by
smoking & Omeprazole, and inhibited by, for example, fluvoxamine, mexiletine, and the older
fluoroquinolones such as ciprofloxacin and norfloxacin. The N-despropyl metabolite is converted to
carbamyl glucuronide, carboxylic acid, and N-despropyl hydroxy metabolites. The hydroxy Metabolite of
ropinirole is rapidly glucuronidated. Less than 10% of the administered dose is excreted as an unchanged
drug in urine. 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%).

Population Subgroups:
Because therapy with ROPIX IS initiated at a low dose and gradually titrated upward according to clinical
tolerability to obtain the optimum Therapeutic effect, adjustment of the initial dose based on gender,
weight, or age is not necessary.

Age:
Oral clearance of ropinirole is reduced by 30% in patients above 65 years of age compared to younger
patients. Dosage adjustment is not necessary for the elderly (above 65 years), as the dose of ropinirole is
to be individually titrated to clinical response.

Gender:
Female and male patients showed similar oral clearance.

Race:
The influence of race on the pharmacokinetics of ropinirole has not been evaluated.

Cigarette Smoking:
Smoking is expected to increase the clearance of ropinirole since CYPLA2 Is known to be induced by
smoking. In a study of patients with RLS, Smokers (n + 7) had an approximately 30% lower Cmax and a
38% lower AUC than did nonsmokers (n + 11) when those parameters were normalized for dose.

Renal impairment:
Based on population pharmacokinetic analysis, no difference was observed in the pharmacokinetics of
ropinirole in patients with moderate renal impairment (creatinine clearance between 30 to 50 ml/min.)
compared to an age-matched population with creatinine clearance above S0 mL/min. Therefore, no
dosage adjustment is necessary for moderately renal-impaired patients. The use of ROPDC in patients
with severe renal impairment has not been studied. The effect of hemodialysis on drug removal is not
known, but because of the relatively high apparent volume of distribution of ropinirole (525 L), the
removal of the drug by hemodialysis is unlikely.

Hepatic impairment:
The pharmacokinetics of ropinirole have not been studied in hepatically impaired patients. These
patients may have Higher plasma levels and lower clearance of the drug than patients with normal
hepatic function. The drug should be titrated with caution in this population.

Other Diseases:
Population pharmacokinetic analysis revealed no change in the oral clearance of ropinirole in patients
with concomitant diseases such as Hypertension, depression, osteoporosis/arthritis, and insomnia
compared to patients with Parkinson’s disease only

Do Not take ROPINIROLE:

 If you are allergic to the active ingredient. Ropinirole, or any of the other ingredients of
ROPINIROLE
 If you have serious liver disease
 If you have a serious kidney disease
 Tell your doctor if you think any of these may apply to you.

Side Effects:
Nausea, vomiting constipation, dizziness, drowsiness, weakness, unusual sweating, headache, and dry
mouth may occur If these effects persist or worsen, notify your doctor promptly and remember that this
medication has been prescribed because your doctor has judged that the benefit to you is greater than
the risk of side effects. Many people using this medication do not have serious side effects. You may also
develop sudden drops in blood pressure, which can cause dizziness, nausea, and fainting. This is more
likely when you are first starting the medication or when your dose is increased, or when you get up
suddenly. To lower your risk, get up slowly from a sitting or lying position. This medication may also raise
your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Tell
your doctor right away if you have any serious side effects, including difficulty moving or walking,
mental/mood changes (such as confusion, agitation, hallucinations), muscle cramps/spasms, decreased
sexual ability, unusual strong urges (such as increased gambling, increased sexual urges), swelling of the
legs happen.

Warnings and precautions:

Tell your doctor or pharmacist before you start taking ROPINIROLE if you:

 Are pregnant or think you may be pregnant

 Are breastfeeding
 Are under 18 years old
 Have liver disease
 Have a serious heart complaint
 Have a serious mental health problem
 Have experienced any unusual urges and /or behaviors (such as excessive gambling or
excessively sexual behavior)
 Have an intolerance to some sugars (such as lactase)
 Other medicines and ROPINIROLE

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines,
including any herbal medicines or other medicines you obtained without a prescription. Remember to
tell your doctor or pharmacist if you begin taking a new medicine while you are taking ROPINIROLE.

Remember to tell your doctor if you start taking any other medicine while taking ROPINIROLE.

Some medicines can affect the way ROPINIROLE works, or make it more likely that you will have side
effects. ROPINIROLE can also affect how some other medicines work. These medicines include:

 The anti-depressant fluvoxamine

 Medication for other mental health problems, for example, sulpiride
 Metoclopramide, which is used to treat nausea and heartburn
 HRT (hormone replacement therapy)
 The antibiotics ciprofloxacin or enoxacin.
 Any other drug, which blocks dopamine in the brain.
 Cimetidine, used in the treatment of stomach ulcers.
 Any other medicine for Parkinson’s disease.

Talk to your doctor if you think any of these may apply to you. If you and your doctor decide that you can
take this medicine, your doctor will probably ask you to have extra check-ups while you are taking it.

You will require additional blood tests if you are taking these medicines with ROPINIROLE:

Vitamin K antagonists (used to reduce blood clotting) such as Warfarin (coumadin).

Taking ROPINIROLE with food and drink:

If you take this medicine with food, you may be less likely to feel sick (nauseous) or be sick (vomit). So, it
may be best to take it with food if you can.

Pregnancy and breast-feeding:

  If you are pregnant or breastfeeding, think you may be pregnant or planning to have a baby, ask
your doctor or pharmacist for advice before taking any medicine.
 ROPINIROLE is not recommended if you are pregnant unless your doctor advises that the benefit
to you of taking it is greater than the risk to your unborn baby.
 ROPINIROLE is not recommended if you are breastfeeding, as it can affect your milk production.
 Tell your doctor immediately if you are pregnant, if you think you might be pregnant, or if you
are planning to become pregnant. Your doctor will also advise you if you are breastfeeding or
planning to do so. Your doctor may advise you to stop taking ROPINIROLE.

Overdosage:
In the Parkinson’s disease program, there have been patients who accidentally or intentionally took
more than their prescribed dose of Ropinirole. The largest overdose reported in the Parkinson’s disease
clinical trials was 435 mg taken over 7 days (62.1 mg/day). Of patients who received a dose greater than
24 mg/day, reported symptoms included adverse events commonly reported during dopaminergic
therapy (nausea, dizziness), as well as visual hallucinations, hyperhidrosis, claustrophobia, chorea,
palpitations, asthenia, and nightmares. Additional symptoms reported for doses of 24 mg or less or
overdoses of the unknown amount included vomiting. Increased coughing, fatigue, syncope, vasovagal
syncope, dyskinesia, agitation, chest pain, orthostatic hypotension, somnolence, and confusional state.

Overdose Management:
It is anticipated that the symptoms of overdose with ROPIX will be related to its dopaminergic activity.
general supportive measures are recommended. Vital signs should be maintained, if necessary. Removal
of any unabsorbed material (e.g., by Gastric lavage) should be considered.

Instructions:
 Store in a cool & dry place.
 Protect from heat, light & moisture.
 Keep all medicines out of reach of the children.
 You to stop taking ROPINIROLE
 To be sold on prescription of a registered medical Practitioner only.

Presentation:
Ropix is available in 0.25mg, 1mg 2mg 21’s blister.

Ropix (Ropinirole as HCI)

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