Pramipexole Dihydrochloride

1 INDICATIONS AND USAGE

Indications & Usage Section

2 DOSAGE AND ADMINISTRATION

Dosage & Administration Section

3 DOSAGE FORMS AND STRENGTHS

Dosage Forms & Strengths Section

0.125 mg: white to off-white, round, flat, beveled edge uncoated tablets, debossed with ‘Y’ on one side ‘41’ on other side. Each tablet contains 0.125 mg pramipexole dihydrochloride monohydrate equivalent to 0.118 mg pramipexole dihydrochloride. 0.25 mg: white to off-white, oval, biconcave, beveled edge uncoated tablets, debossed with ‘Y’ and ‘42’ separated by score line on one side and plain with score line on other side. Each tablet contains 0.25 mg pramipexole dihydrochloride monohydrate equivalent to 0.235 mg pramipexole dihydrochloride. 0.5 mg: white to off-white, oval, biconcave, beveled edge uncoated tablets, debossed with ‘Y’ and ‘43’ separated by score line on one side and plain with score line on other side. Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.47 mg pramipexole dihydrochloride. 0.75 mg: white to off-white, oval, biconcave, beveled edge uncoated tablets, debossed with ‘Y’ on one side and ‘44’ on other side. Each tablet contains 0.75 mg pramipexole dihydrochloride monohydrate equivalent to 0.705 mg pramipexole dihydrochloride. 1 mg: white to off-white, round, flat, beveled edge uncoated tablets, debossed with ‘Y’ and ‘45’ separated by score line on one side and plain with score line on other side. Each tablet contains 1 mg pramipexole dihydrochloride monohydrate equivalent to 0.94 mg pramipexole dihydrochloride. 1.5 mg: white to off-white, round, flat, beveled edge uncoated tablets, debossed with ‘Y’ and ‘46’ separated by score line on one side and plain with score line on other side. Each tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride.

4 CONTRAINDICATIONS

Contraindications Section

None.

5 WARNINGS AND PRECAUTIONS

Warnings And Precautions Section

6 ADVERSE REACTIONS

Adverse Reactions Section

The following adverse reactions are discussed in greater detail in other sections of the labeling: Falling Asleep During Activities of Daily Living and Somnolence [ see Warnings and Precautions (5.1) ] Symptomatic Orthostatic Hypotension [ see Warnings and Precautions (5.2) ] Impulse Control/Compulsive Behaviors [ see Warnings and Precautions (5.3) ] Hallucinations and Psychotic-like Behavior [ see Warnings and Precautions (5.4) ] Dyskinesia [ see Warnings and Precautions (5.5) ] Postural Deformity [ see Warnings and Precautions (5.6 ) ] Rhabdomyolysis [ see Warnings and Precautions (5.8) ] Retinal Pathology [ see Warnings and Precautions (5.9) ] Events Reported with Dopaminergic Therapy [ see Warnings and Precautions (5.10) ] Withdrawal Symptoms [ see Warnings and Precautions (5.11) ]

7 DRUG INTERACTIONS

Drug Interactions Section

8 USE IN SPECIFIC POPULATIONS

Use In Specific Populations Section

10 OVERDOSAGE

Overdosage Section

There is no clinical experience with significant overdosage. One patient took 11 mg/day of pramipexole for 2 days in a clinical trial for an investigational use. Blood pressure remained stable although pulse rate increased to between 100 and 120 beats/minute. No other adverse reactions were reported related to the increased dose. There is no known antidote for overdosage of a dopamine agonist. If signs of central nervous system stimulation are present, a phenothiazine or other butyrophenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdosage has not been assessed. Management of overdose may require general supportive measures along with gastric lavage, intravenous fluids, and electrocardiogram monitoring.

11 DESCRIPTION

Description Section

Pramipexole dihydrochloride tablets contain pramipexole dihydrochloride (as a monohydrate). Pramipexole is a nonergot dopamine agonist. The chemical name of pramipexole dihydrochloride monohydrate is ( S )-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate. Its molecular formula is C 10 H 17 N 3 S·2HCl·H 2 O, and its molecular weight is 302.26. The structural formula is: Pramipexole dihydrochloride USP is a white or almost white, crystalline powder. Melting occurs in the range of 296°C to 301°C, with decomposition. Pramipexole dihydrochloride is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane. Pramipexole dihydrochloride tablets 0.125 mg: Each tablet contains 0.125 mg pramipexole dihydrochloride monohydrate equivalent to 0.118 mg pramipexole dihydrochloride USP. Pramipexole dihydrochloride tablets 0.25 mg: Each tablet contains 0.25 mg pramipexole dihydrochloride monohydrate equivalent to 0.235 mg pramipexole dihydrochloride USP. Pramipexole dihydrochloride tablets 0.5 mg: Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.47 mg pramipexole dihydrochloride USP. Pramipexole dihydrochloride tablets 0.75 mg: Each tablet contains 0.75 mg pramipexole dihydrochloride monohydrate equivalent to 0.705 mg pramipexole dihydrochloride USP. Pramipexole dihydrochloride tablets 1 mg: Each tablet contains 1 mg pramipexole dihydrochloride monohydrate equivalent to 0.94 mg pramipexole dihydrochloride USP. Pramipexole dihydrochloride tablets 1.5 mg: Each tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride USP. Inactive ingredients consist of colloidal silicon dioxide, corn starch, magnesium stearate, mannitol, and povidone.

12 CLINICAL PHARMACOLOGY

Clinical Pharmacology Section

13 NONCLINICAL TOXICOLOGY

Nonclinical Toxicology Section

14 CLINICAL STUDIES

Clinical Studies Section

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied Section

16.1 How Supplied Pramipexole Dihydrochloride tablets are available as follows: Pramipexole Dihydrochloride Tablets, 0.125 mg are white to off-white, round, flat, beveled edge uncoated tablets, debossed with ‘Y’ on one side ‘41’ on other side. NDC: 71335-1537-1: 30 Tablets in a BOTTLE NDC: 71335-1537-2: 60 Tablets in a BOTTLE 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Store in a safe place out of the reach of children. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

17 PATIENT COUNSELING INFORMATION

Information For Patients Section

Advise the patient to read the FDA-approved patient labeling (Patient Information) . Dosing Instructions Instruct patients to take pramipexole dihydrochloride tablets only as prescribed. If a dose is missed, advise patients not to double their next dose. Pramipexole dihydrochloride tablets can be taken with or without food. If patients develop nausea, advise that taking pramipexole dihydrochloride tablets with food may reduce the occurrence of nausea. Pramipexole is the active ingredient that is in both pramipexole dihydrochloride tablets and extended-release pramipexole tablets. Ensure that patients do not take both extended-release pramipexole and pramipexole dihydrochloride. Sedating Effects Alert patients to the potential sedating effects associated with pramipexole dihydrochloride tablets, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse reaction with potentially serious consequences, patients should neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient experience with pramipexole dihydrochloride tablets to gauge whether or not it affects their mental and/or motor performance adversely. Advise patients that if increased somnolence or new episodes of falling asleep during activities of daily living (e.g., conversations or eating) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their physician. Because of possible additive effects, advise caution when patients are taking other sedating medications or alcohol in combination with pramipexole dihydrochloride tablets and when taking concomitant medications that increase plasma levels of pramipexole (e.g., cimetidine) [ see Warnings and Precautions (5.1) ]. Postural (Orthostatic) Hypotension Advise patients that they may develop postural (orthostatic) hypotension, with or without symptoms such as dizziness, nausea, fainting or blackouts, and sometimes, sweating. Hypotension may occur more frequently during initial therapy. Accordingly, caution patients against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially at the initiation of treatment with pramipexole dihydrochloride tablets [ see Warnings and Precautions (5.2) ]. Impulse Control Symptoms Including Compulsive Behaviors Alert patients and their caregivers to the possibility that they may experience intense urges to spend money uncontrollably, intense urges to gamble, increased sexual urges, binge eating and/or other intense urges and the inability to control these urges while taking pramipexole dihydrochloride [ see Warnings and Precautions (5.3) ]. Hallucinations and Psychotic-like Behavior Inform patients that hallucinations and other psychotic-like behavior can occur. In patients with Parkinson’s disease, the elderly are at a higher risk than younger patients [ see Warnings and Precautions (5.4) ]. Withdrawal-Emergent Hyperpyrexia and Confusion Advise patients who have been prescribed a lower dose or who have been withdrawn from the drug to notify their healthcare provider if they have symptoms such as fever, muscular rigidity, or altered consciousness [ see Warnings and Precautions (5.10) ]. Withdrawal Symptoms Advise patients that withdrawal symptoms may occur during or after discontinuation or dose reduction of pramipexole dihydrochloride. Advise patients who have been prescribed a lower dose or who have been withdrawn from the drug to notify their healthcare provider if they have withdrawal symptoms such as apathy, anxiety, depression, fatigue, insomnia, sweating, or pain. Notify patients that in case of severe withdrawal symptoms, a trial re-administration of a dopamine agonist at the lowest effective dose may be considered [ see Warnings and Precautions (5.11) ]. Pregnancy Because the teratogenic potential of pramipexole has not been completely established in laboratory animals, and because experience in humans is limited, advise women to notify their physicians if they become pregnant or intend to become pregnant during therapy [ see Use in Specific Populations (8.1) ]. Lactation Because of the possibility that pramipexole may be excreted in breast milk, advise women to notify their physicians if they intend to breast-feed or are breast-feeding an infant [ see Use in Specific Populations (8.2) ]. Distributed by: Rising Health, LLC Saddle Brook, NJ 07663 Made in India Code: TS/DRUGS/22/2009 Revised: 08/2021

PATIENT INFORMATION

SPL PATIENT PACKAGE INSERT SECTION

Pramipexole Dihydrochloride Tablets (pram" i pex' ole dye hye" droe klor' ide) Read this Patient Information before you start taking pramipexole dihydrochloride tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What are pramipexole dihydrochloride tablets? Pramipexole dihydrochloride tablets are a prescription medicine used to treat: signs and symptoms of Parkinson's disease (PD) moderate to severe primary Restless Legs Syndrome (RLS) It is not known if pramipexole dihydrochloride tablets are safe and effective in children. What should I tell my doctor before taking pramipexole dihydrochloride tablets? Before taking pramipexole dihydrochloride tablets, tell your doctor if you: feel sleepy during the day from a sleep problem other than Restless Legs Syndrome have low blood pressure, or if you feel dizzy or faint, especially when getting up from sitting or lying down have trouble controlling your muscles (dyskinesia) have kidney problems drink alcohol. Alcohol can increase the chance that pramipexole dihydrochloride tablets will make you feel sleepy or fall asleep when you should be awake. have any other medical conditions are pregnant or plan to become pregnant. It is not known if pramipexole dihydrochloride tablets will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if pramipexole dihydrochloride passes into your breast milk. You and your doctor should decide if you will take pramipexole dihydrochloride tablets or breastfeed. You should not do both. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. The combination of pramipexole dihydrochloride tablets and other medicines may affect each other and may cause side effects. Pramipexole dihydrochloride tablets may affect the way other medicines work, and other medicines may affect how pramipexole dihydrochloride tablet works. Especially tell your doctor if you take: medicines called neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide. Pramipexole dihydrochloride tablets may not work as well if you take these medicines. pramipexole dihydrochloride extended-release tablets. Pramipexole is the active ingredient in both pramipexole dihydrochloride tablets and pramipexole dihydrochloride extended-release tablets. If you are taking pramipexole dihydrochloride extended-release tablets, you should not take pramipexole dihydrochloride tablets. any other medicines that make you sleepy or may increase the effects of pramipexole dihydrochloride tablets, such as cimetidine (Tagamet). Ask your doctor for a list of these medicines if you are not sure. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I take pramipexole dihydrochloride tablets? Take pramipexole dihydrochloride tablets exactly as your doctor tells you to take them. Your doctor will tell you how much pramipexole dihydrochloride to take and when to take it. Do not take more or less pramipexole dihydrochloride tablets than your doctor tells you to. Your doctor may change your dose if needed. Pramipexole dihydrochloride tablets can be taken with or without food. Taking pramipexole dihydrochloride tablets with food may lower your chances of getting nausea. If you take more pramipexole dihydrochloride tablets than your doctor recommends, call your doctor or go to the nearest hospital emergency room right away. If you miss a dose, do not double your next dose . Skip the dose you missed and take your next regular dose. Do not stop taking pramipexole dihydrochloride tablets without talking to your doctor first. If your doctor tells you to stop taking pramipexole dihydrochloride tablets, you should ask your doctor for specific instructions on how to safely discontinue taking pramipexole dihydrochloride tablets. If you stop pramipexole dihydrochloride tablets you may have withdrawal symptoms (see “withdrawal symptoms” under “What are the possible side effects of pramipexole dihydrochloride tablets?” ). What should I avoid while taking pramipexole dihydrochloride tablets? Do not drink alcohol while taking pramipexole dihydrochloride tablets. It can increase your chance of having serious side effects. See “What are the possible side effects of pramipexole dihydrochloride tablets?” Do not drive a car, operate a machine, or do other dangerous activities until you know how pramipexole dihydrochloride tablets affect you. Sleepiness caused by pramipexole dihydrochloride tablets can happen as late as 1 year after you start your treatment. What are the possible side effects of pramipexole dihydrochloride tablets? Pramipexole dihydrochloride tablets may cause serious side effects, including: falling asleep during normal daily activities. Pramipexole dihydrochloride tablets may cause you to fall asleep while you are doing daily activities such as driving, talking with other people, or eating. Some people taking the medicine in pramipexole dihydrochloride tablets have had car accidents because they fell asleep while driving. Some patients did not feel sleepy before they fell asleep while driving. You could fall asleep without any warning. Tell your doctor right away if you fall asleep while you are doing activities such as talking, eating, driving, or if you feel sleepier than normal for you. low blood pressure when you sit or stand up quickly. You may have: dizziness nausea fainting sweating Sit and stand up slowly after you have been sitting or lying down. unusual urges. Some people who take certain medicines to treat Parkinson’s disease or RLS, including pramipexole dihydrochloride tablets, have reported problems, such as gambling, compulsive eating, compulsive buying, and increased sex drive. If you or your family members notice that you are developing unusual urges or behaviors, talk to your doctor. hallucinations and other psychotic-like behavior (seeing visions, hearing sounds or feeling sensations that are not real, confusion, excessive suspicion, aggressive behavior, agitation, delusional beliefs and disorganized thinking). The chances of having hallucinations or other psychotic-like changes are higher in people taking pramipexole dihydrochloride tablets for Parkinson’s disease who are elderly (age 65 or older). If you have hallucinations or other psychotic-like changes, talk with your doctor right away. uncontrolled sudden movements (dyskinesia). If you have new dyskinesia or your existing dyskinesia gets worse tell your doctor. posture changes. Talk with your doctor if you have posture changes you cannot control. These may include your neck bending forward, bending forward at the waist, or tilting sideways when you sit, stand, or walk. withdrawal symptoms . Pramipexole dihydrochloride tablets is a dopamine agonist medicine. Dopamine agonist medicines, including pramipexole dihydrochloride tablets, can cause withdrawal symptoms as your dose is slowly lowered (tapered) or when treatment with pramipexole dihydrochloride tablets is stopped. Tell your doctor right away if you get any of the following withdrawal symptoms: fever confusion severe muscle stiffness feeling like you do not care about things you usually care about (apathy) anxiety depression fatigue insomnia sweating pain After you have stopped taking pramipexole dihydrochloride tablets, your doctor may need to restart you at a low dose of pramipexole dihydrochloride tablets if you get severe withdrawal symptoms. The most common side effects in people taking pramipexole dihydrochloride tablets for Restless Legs Syndrome are nausea and headache. The most common side effects in people taking pramipexole dihydrochloride tablets for Parkinson’s disease are: nausea dizziness insomnia constipation muscle weakness abnormal dreams confusion memory probl...

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Pramipexole Dihydrochloride 0.125mg Tab