Health Canada's review of the available information has established a link between use of the dopamine agonists pramipexole, quinagolide, or ropinirole and the risk of dopamine agonist withdrawal syndrome (DAWS). DAWS may occur after reducing the dose of or discontinuing dopamine agonists, and includes symptoms such as apathy, anxiety, depression, fatigue, sweating, panic attacks, insomnia, irritability, and pain. The Canadian product information for pramipexole has been updated to include a warning on the risk of DAWS. Health Canada will work with the manufacturers of quinagolide and ropinirole to update the product information to include a warning on the risk of DAWS. At this time, there is not enough information to establish a link between other dopamine agonists that were assessed as part of this safety review (ie, apomorphine, bromocriptine, cabergoline, pergolide [no longer marketed], and rotigotine) and DAWS. As a precaution, Health Canada will work with the manufacturers of these dopamine agonists to include the potential risk of DAWS in the product information.
Further information is available at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00269.
Hyperprolactinemia: Oral:
Initial: 0.025 mg once daily for 3 days followed by 0.05 mg once daily for 3 days (starter pack)
Maintenance (beginning on day 7): 0.075 mg once daily; if needed, a further stepwise titration may occur at intervals of ≥1 week; usual maintenance range: 0.075 to 0.15 mg/day; if higher doses are needed, titrate in increments of 0.075 to 0.15 mg/day at intervals ≥4 weeks up to a maximum of 0.9 mg/day
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Use in contraindicated.
Use in contraindicated.
Refer to adult dosing.
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Norprolac: 0.025 mg [DSC], 0.05 mg [DSC], 0.075 mg [DSC], 0.15 mg [DSC]
Not available in the US
Oral: Administer once daily with snack at bedtime. Nausea and vomiting may be alleviated by premedicating with a peripheral dopamine antagonist.
Note: Not approved in the US
Hyperprolactinemia: Treatment of hyperprolactinemia (idiopathic or due to a prolactin-secreting pituitary microadenoma or macroadenoma)
Quinagolide may be confused with quinapril
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Nausea, vomiting
Nervous system: Dizziness, fatigue, headache
1% to 10%:
Cardiovascular: Edema (2%), hypotension (1%)
Gastrointestinal: Abdominal distress (3%), abdominal pain (3%), anorexia (2%), constipation (3%), dyspepsia (2%)
Nervous system: Insomnia (2%), malaise (1%), sedated state (3%)
Neuromuscular & skeletal: Asthenia(3%)
Respiratory: Nasal congestion (2%)
Ophthalmic: Eye disease (2%)
<1%:
Cardiovascular: Flushing, palpitations, syncope
Endocrine & metabolic: Weight gain
Gastrointestinal: Diarrhea
Genitourinary: Mastalgia
Nervous system: Acute psychosis, drowsiness, emotional lability, lack of concentration
Neuromuscular & skeletal: Limb pain
Frequency not defined:
Endocrine & metabolic: Increased creatinine phosphokinase in blood specimen, increased serum potassium, increased serum triglycerides
Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, neutropenia
Hepatic: Increased serum bilirubin, increased serum transaminases
Postmarketing: Nervous system: Withdrawal syndrome (dopamine agonist withdrawal syndrome [DAWS]) (Health Canada 2021)
Hypersensitivity to quinagolide or any component of the formulation; hepatic or renal impairment
Concerns related to adverse effects:
• CNS depression: May cause CNS depression (eg, sudden sleep onset and somnolence) particularly in patients with Parkinson disease which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). Use with other agents known to induce somnolence or sleep may be expected to potentiate these risks. Dose reduction or therapy discontinuation may be needed if sudden onset of sleep develops.
• Fertility changes: Use caution in women of childbearing age; restoration of fertility may occur; patients not wanting to conceive should implement a reliable method of birth control.
• Gastrointestinal distress: Use may be associated with frequent (but transient) nausea and vomiting early in therapy; during initial therapy, premedication with a peripheral dopamine antagonist may alleviate these effects and improve tolerance.
• Hypotension: Hypotensive episodes along with syncope may occur with the onset of therapy; monitor blood pressure early in therapy.
• Impulse control disorders: Monitor for development of impulse control disorders (eg, pathological gambling, increased libido, hypersexuality, compulsive spending, or binge and compulsive eating). Consider dose reduction or tapered discontinuation if symptoms develop.
Disease-related concerns:
• Psychosis: Use with caution in patients with prior psychotic disorders; the onset of acute psychosis has rarely been observed with use of quinagolide (reversible upon discontinuation).
Other warnings/precautions:
• Radiotherapy/Surgery: Treatment with quinagolide may not exclude the need for radiation and/or surgical intervention if appropriate.
None known.
Alcohol (Ethyl): May enhance the adverse/toxic effect of Quinagolide. Risk C: Monitor therapy
Antipsychotic Agents: May diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Blood Pressure Lowering Agents: Quinagolide may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromopride: May diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Pipamperone [INT]: Quinagolide may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of Quinagolide. Risk X: Avoid combination
Sulpiride: Quinagolide may diminish the therapeutic effect of Sulpiride. Sulpiride may diminish the therapeutic effect of Quinagolide. Risk X: Avoid combination
Fertility may be restored with treatment; contraception should be used by females of reproductive potential who do not wish to conceive.
Discontinue use with confirmed pregnancy unless medically necessary to continue. No increase in the incidence of abortion has been seen upon discontinuation of the drug during pregnancy. The reinstitution of therapy may be necessary in patients who display symptoms of tumor enlargement (headaches, visual field changes).
By inhibiting prolactin secretion, quinagolide suppresses lactation.
Prolactin levels; blood pressure; sedation, mental changes
Selective dopamine D2 receptor agonist that exerts a direct inhibitory effect on cells (lactotrophs) in the anterior pituitary gland which synthesize and secrete prolactin; not an ergot alkaloid
Onset of action: 2 hours; maximum effect: 4 to 6 hours
Duration: >24 hours
Absorption: Rapid
Distribution: Vd: 100 L
Protein binding: ~90%
Metabolism: Hepatic; via conjugation (glucuronide and sulfate)
Bioavailability: 4%
Half-life elimination: 11.5 hours; steady state: 17 hours
Time to peak, serum: 30 to 60 minutes
Excretion: Urine (50%); feces (40%); >95% as metabolites
