Quinagolide

G02C - Other gynecologicals ATC G02CB04 Small molecule approved 2004 Natural product

JFDA label: Norprolac Tab

Mechanism of Action

Agonist of D(2) dopamine receptor — Dopamine D2 receptor agonist

Target	Action	Gene / class
D(2) dopamine receptor efficacy	AGONIST	DRD2

Indications

Approved

Hyperprolactinemia

Contraindications

Source: Lexicomp

Hypersensitivity to quinagolide or any component of the formulation Absolute
hepatic or renal impairment Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (5)

Common Edema · flushing · hypotension · palpitations · syncope

Nervous system disorders (8)

Very Common Dizziness · fatigue · headache

Common emotional lability · insomnia · lack of concentration · malaise · Sedation

Renal and urinary disorders (1)

Common Mastalgia

Metabolism and nutrition disorders (1)

Common Weight gain

Gastrointestinal disorders (8)

Very Common Nausea · vomiting

Common abdominal distress · abdominal pain · anorexia · Constipation · diarrhea · dyspepsia

Musculoskeletal and connective tissue disorders (2)

Common limb pain · Weakness

Respiratory, thoracic and mediastinal disorders (1)

Common Nasal congestion

Dosing

Source: Lexicomp

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

Refer to adult dosing.

Use in contraindicated.

Warnings & Precautions

Source: Lexicomp

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). Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Radiotherapy/Surgery

Treatment with quinagolide may not exclude the need for radiation and/or surgical intervention if appropriate.

Pregnancy & Lactation

Pregnancy

Adverse events have not been observed in animal reproduction studies. Fertility may be restored with treatment. 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).

Lactation

By inhibiting prolactin secretion, quinagolide suppresses lactation.

Monitoring

Clinical pearl	Prolactin levels; blood pressure; sedation, mental changes

Chemistry & Properties

Formula	C20H33N3O3S
Molecular weight	395.57 g/mol
IUPAC name	(3S,4aS,10aR)-3-(diethylsulfamoylamino)-6-hydroxy-1-propyl-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinoline
CAS	87056-78-8
PubChem CID	3086401
InChIKey	`GDFGTRDCCWFXTG-UHFFFAOYSA-N`
logP	2.14 (XLogP 3.1)
Polar surface area	72.88 Å²
H-bond acceptors / donors	4 / 2
Drug-likeness (QED)	0.74
Lipinski violations	0

SMILES

CCCN1CC(NS(=O)(=O)N(CC)CC)CC2Cc3c(O)cccc3CC21

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	0.668 h
Volume of distribution	1.207 L/kg
Protein binding	92.2%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Norprolac Tab	Tablet 25 (as Hcl) mcg	3 tab	Petra Drug Store	2.420