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Pramipexole Dihydrochloride

FDA Drug Information • Also known as: Pramipexole Dihydrochloride, Pramipexole Dihydrochloride Extended-Release

Brand Names
Pramipexole Dihydrochloride, Pramipexole Dihydrochloride Extended-Release
Route
ORAL
Dosage Form
TABLET
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Pramipexole dihydrochloride extended-release tablets contain pramipexole dihydrochloride (as a monohydrate). Pramipexole is, a non-ergot dopamine agonist. The chemical name of pramipexole dihydrochloride monohydrate is (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate. Its empirical 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 monohydrate USP is a white to almost white crystalline powder. Melting occurs in the range of 296°C to 301°C, with decomposition. Pramipexole dihydrochloride monohydrate USP is freely soluble in water, soluble in methanol, slightly soluble in alcohol, practically insoluble in methylene chloride. Pramipexole Dihydrochloride Extended-Release Tablets 0.375 mg: Each extended-release tablet contains 0.375 mg pramipexole dihydrochloride monohydrate equivalent to 0.352 mg pramipexole dihydrochloride. Pramipexole Dihydrochloride Extended-Release Tablets 0.75 mg: Each extended-release tablet contains 0.75 mg pramipexole dihydrochloride monohydrate equivalent to 0.705 mg pramipexole dihydrochloride. Pramipexole Dihydrochloride Extended-Release Tablets 1.5 mg: Each extended-release tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride. Pramipexole Dihydrochloride Extended-Release Tablets 2.25 mg: Each extended-release tablet contains 2.25 mg pramipexole dihydrochloride monohydrate equivalent to 2.12 mg pramipexole dihydrochloride. Pramipexole Dihydrochloride Extended-Release Tablets 3 mg: Each extended-release tablet contains 3 mg pramipexole dihydrochloride monohydrate equivalent to 2.82 mg pramipexole dihydrochloride. Pramipexole Dihydrochloride Extended-Release Tablets 3.75 mg: Each extended-release tablet contains 3.75 mg pramipexole dihydrochloride monohydrate equivalent to 3.53 mg pramipexole dihydrochloride. Pramipexole Dihydrochloride Extended-Release...

What Is Pramipexole Dihydrochloride Used For?

1 INDICATIONS AND USAGE Pramipexole dihydrochloride extended-release tablets are indicated for the treatment of Parkinson’s disease. Pramipexole dihydrochloride is a non-ergot dopamine agonist indicated for the treatment of Parkinson’s disease (PD)(1)

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

  • Pramipexole dihydrochloride extended-release tablets are taken once daily, with or without food (2.1)
  • Tablets must be swallowed whole and must not be chewed, crushed, or divided (2.1)
  • Starting dose is 0.375 mg given once daily (2.2)
  • Dose may be increased gradually, not more frequently than every 5 to 7 days, first to 0.75 mg per day and then by 0.75 mg increments up to a maximum recommended dose of 4.5 mg per day. Assess therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment (2.2)
  • Patients may be switched overnight from immediate-release pramipexole tablets to pramipexole dihydrochloride extended-release tablets at the same daily dose. Dose adjustment may be needed in some patients (2.3)
  • Pramipexole dihydrochloride extended-release tablets should be discontinued gradually (2.2) 2.1 General Dosing Considerations Pramipexole dihydrochloride extended-release tablets are taken orally once daily, with or without food. Pramipexole dihydrochloride extended-release tablets must be swallowed whole and must not be chewed, crushed, or divided. If a significant interruption in therapy with pramipexole dihydrochloride extended-release tablets has occurred, re-titration of therapy may be warranted. 2.2 Recommended Dosage The starting dose is 0.375 mg given once per day. Based on efficacy and tolerability, dosages may be increased gradually, not more frequently than every 5 to 7 days, first to 0.75 mg per day and then by 0.75 mg increments up to a maximum recommended dose of 4.5 mg per day. In clinical trials, dosage was initiated at 0.375 mg/day and gradually titrated based on individual therapeutic response and tolerability. Doses greater than 4.5 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment [see Clinical Studies (14)]. Due to the flexible dose design used in clinical trials, specific dose-response information could not be determined [see Clinical Studies (14)]. Pramipexole dihydrochloride extended-release tablets may be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose may be reduced by 0.375 mg per day [see Warnings and Precautions (5.10, 5.11)]. Recommended Dosage in Patients with Renal Impairment In patients with moderate renal impairment (creatinine clearance between 30 and 50 mL/min), pramipexole dihydrochloride extended-release tablets should initially be taken every other day. Caution should be exercised and careful assessment of therapeutic response and tolerability should be made before increasing to daily dosing after one week, and before any additional titration in 0.375 mg increments up to 2.25 mg per day. Dose adjustment should occur no more frequently than at weekly intervals. Pramipexole dihydrochloride extended-release tablets have not been studied in...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS 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)] Most common adverse reactions (incidence ≥5% and greater than placebo): · Early PD without levodopa: somnolence, nausea, constipation, dizziness, fatigue, hallucinations, dry mouth, muscle spasms, and peripheral edema (6.1) · Advanced PD with levodopa: dyskinesia, nausea, constipation, hallucinations, headache, and anorexia (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice. During the premarketing development of pramipexole dihydrochloride extended-release tablets, patients with early Parkinson’s disease were treated with pramipexole dihydrochloride extended-release tablets, placebo, or immediate-release pramipexole tablets. In addition, a randomized, double-blind, parallel group trial was conducted in 156 early Parkinson’s disease patients (Hoehn & Yahr Stages I to III) to assess overnight switching of immediate-release pramipexole tablets to pramipexole dihydrochloride extended-release tablets. In this latter study, concomitant treatment with stable doses of levodopa, monoamine oxidase B inhibitor (MAOB-I) drugs, anticholinergics, or amantadine, individually or in combination, was allowed. In a third trial, advanced Parkinson’s disease patients received pramipexole dihydrochloride extended-release tablets, placebo, or immediate-release pramipexole tablets as adjunctive therapy to levodopa. Early Parkinson’s Disease The most common adverse reactions (≥5% and more frequent than placebo) after 33 weeks of treatment with pramipexole dihydrochloride extended-release tablets in the trial of early Parkinson’s disease patients were somnolence, nausea, constipation, dizziness, fatigue, hallucinations, dry mouth, muscle spasms, and peripheral edema. Twenty four of 223 (11%) patients treated with pramipexole dihydrochloride extended-release tablets for 33 weeks discontinued treatment due to adverse reactions compared to 4 of 103 (4%) patients who received placebo and approximately 20 of 213 (9%) patients who received immediate-release pramipexole tablets. The adverse reaction most commonly causing discontinuation of treatment with pramipexole dihydrochloride extended-release tablets was nausea (2%). Table 1 lists adverse reactions that occurred with a frequency of at least 2% with pramipexole dihydrochloride extended-releasetablets and were more frequent than with placebo during 33 weeks of treatment in a double-blind, placebo-controlled study in early Parkinson’s disease. In this study, patients did not receive concomitant levodopa; however, levodopa was permitted as rescue medication. Table 1: Adverse-Reactions in a 33-Week Double-Blind, Placebo-Controlled Trial with Pramipexole Dihydrochloride Extended-Release Tablets in Early Parkinson’s Disease Body System /...

    • Drug Interactions

    7 DRUG INTERACTIONS Dopamine antagonists: May diminish the effectiveness of pramipexole (7.1) 7.1 Dopamine Antagonists Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of pramipexole dihydrochloride extended-release tablets.

    Contraindications

    4 CONTRAINDICATIONS None. None (4)

    Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of pramipexole dihydrochloride extended-release tablets in pregnant women. No adverse developmental effects were observed in animal studies in which pramipexole was administered to rabbits during pregnancy. Effects on embryofetal development could not be adequately assessed in pregnant rats; however, postnatal growth was inhibited at clinically relevant exposures [see Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of pramipexole (0.1, 0.5, or 1.5 mg/kg/day) to pregnant rats during the period of organogenesis resulted in a high incidence of total resorption of embryos at the highest dose tested. This increase in embryolethality is thought to result from the prolactin-lowering effect of pramipexole; prolactin is necessary for implantation and maintenance of early pregnancy in rats but not in rabbits or humans. Because of pregnancy disruption and early embryonic loss in this study, the teratogenic potential of pramipexole could not be adequately assessed in rats. The highest no-effect dose for embryolethality in rats was associated with maternal plasma drug exposures (AUC) approximately equal to those in humans receiving the maximum recommended human dose (MRHD) of 4.5 mg/day. There were no adverse effects on embryo-fetal development following oral administration of pramipexole (0.1, 1, or 10 mg/kg/day) to pregnant rabbits during organogenesis (plasma AUC up to approximately 70 times that in humans at the MRHD). Postnatal growth was inhibited in the offspring of rats treated with pramipexole (0.1, 0.5, or 1.5 mg/kg/day) during the latter part of pregnancy and throughout lactation. The...

    Overdosage

    10 OVERDOSAGE 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.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Pramipexole Dihydrochloride Extended-Release Tablets are available as follows: 0. 375 mg: white to off white, round, biconvex, uncoated extended-release tablets debossed with ‘401’ on one side and ‘ER’ on other side. NDC 62332-154-30 bottle of 30 tablets 0.75 mg: white to off white, round, biconvex, uncoated extended-release tablets debossed with ‘402’ on one side and ‘ER’ on other side. NDC 62332-155-30 bottle of 30 tablets 1.5 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘403’ on one side and ‘ER’ on other side. NDC 62332-156-30 bottle of 30 tablets 2.25 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘413’ on one side and ‘ER’ on other side. NDC 62332-157-30 bottle of 30 tablets 3 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘404’ on one side and ‘ER’ on other side. NDC 62332-158-30 bottle of 30 tablets 3.75 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘414’ on one side and ‘ER’ on other side. NDC 62332-160-30 bottle of 30 tablets 4.5 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘405’ on one side and ‘ER’ on other side. NDC 62332-159-30 bottle of 30 tablets 16.2 Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from exposure to high humidity. Store in a safe place out of the reach of children.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.