Norprolac^® (Tablets) Instructions for Use

Marketing Authorization Holder

Ferring Pharmaceuticals B.V. (Netherlands)

Manufactured By

Novartis Pharmaceuticals UK Ltd. (United Kingdom)

ATC Code

G02CB04 (Quinagolide)

Active Substance

Quinagolide (Rec.INN registered by WHO)

Dosage Forms

	Norprolac®	Tablets 25 mcg: 3 pcs. and Tablets 50 mcg: 3 pcs. (starter pack)
		Tablets 75 mcg: 30 pcs.
		Tablets 150 mcg: 30 pcs.

Dosage Form, Packaging, and Composition

The “Starter pack” includes: 3 tablets of 25 mcg + 3 tablets of 50 mcg.

Tablets of pale pink color with specks, round, flat, with beveled edges, printed with “NORPROLAC” around the perimeter on one side, and “25” on the other side (3 pcs. per pack).

Excipients: colloidal anhydrous silica, magnesium stearate, hypromellose, corn starch, microcrystalline cellulose, lactose, red iron oxide.

Tablets of bluish color with specks, round, flat, with beveled edges, printed with “NORPROLAC” around the perimeter on one side, and “50” on the other side (3 pcs. per pack).

Excipients: colloidal anhydrous silica, magnesium stearate, hypromellose, corn starch, microcrystalline cellulose, lactose, indigo carmine.

Tablets of whitish color, round, flat, with beveled edges, printed with “NORPROLAC” around the perimeter on one side, and “75” on the other side.

Excipients: colloidal anhydrous silica, magnesium stearate, hypromellose, corn starch, microcrystalline cellulose, lactose.

10 pcs. – blister packs (3) – cardboard cartons.

Tablets of whitish color, round, flat, with beveled edges, printed with “NORPROLAC” around the perimeter on one side, and “150” on the other side.

Excipients: colloidal anhydrous silica, magnesium stearate, hypromellose, corn starch, microcrystalline cellulose, lactose.

10 pcs. – blister packs (3) – cardboard cartons.

Clinical-Pharmacological Group

Dopamine receptor agonist. Inhibitor of prolactin secretion

Pharmacotherapeutic Group

Dopamine receptor agonist

Pharmacological Action

Inhibitor of prolactin secretion, a selective agonist of dopamine D₂ receptors. It has a pronounced inhibitory effect on prolactin secretion by the anterior pituitary gland, without reducing normal levels of other pituitary hormones. In some patients, the decrease in prolactin secretion may be accompanied by a short-term slight increase in plasma growth hormone levels, but the clinical significance of this phenomenon is not yet known. Norprolac^® is effective when administered orally once daily for hyperprolactinemia, reducing the severity of clinical manifestations such as galactorrhea, oligomenorrhea, amenorrhea, infertility, and decreased libido.

A clinically significant decrease in blood prolactin levels occurs 2 hours after oral administration of the drug, reaches a maximum after 4-6 hours, and lasts about 24 hours. A direct dependence of the duration of action of Norprolac^® on its dose was established, while no such dependence was found for the prolactin-lowering effect. The maximum effect was noted after a single dose of 50 mcg. A further increase in dose does not lead to an increase in the severity of the effect, but increases its duration.

It has been established that long-term use of Norprolac^® leads to regression or inhibition of the growth of prolactin-producing pituitary micro- and macroadenomas.

Pharmacokinetics

Absorption

After oral administration, Quinagolide is rapidly and completely absorbed from the gastrointestinal tract. Plasma concentration values measured for quinagolide and its metabolites by a non-selective radioimmunoassay (RIA) method were close to the quantification limit and cannot serve as a source of reliable information.

Distribution

After a single oral administration of the radiolabeled drug, the apparent V_d is about 100 L. Plasma protein binding is about 90%.

Metabolism

Quinagolide is extensively metabolized during the “first pass” through the liver. Quinagolide and its N-desethylated analogue, which have biological activity, are found in the blood in small amounts. Their inactive conjugates with sulfuric and glucuronic acids circulate in the blood in more significant amounts.

Excretion

More than 95% is excreted from the body as metabolites in feces and urine in approximately equal amounts. The main metabolites found in urine are sulfate and glucuronide conjugates of quinagolide and its N-desethylated and N,N-didesethylated analogues. Unconjugated forms of these three substances were found in feces.

The T_1/2 of unchanged quinagolide after a single dose is 11.5 hours; at steady state – 17 hours.

Indications

• Hyperprolactinemia (idiopathic or caused by prolactin-secreting pituitary micro- or macroadenoma).

ICD codes

Dosage Regimen

The optimal dose for adults is selected individually depending on the degree of reduction in prolactin levels and drug tolerance. Therapy should be started with tablets from the Norprolac^® “starter pack”, taking into account the possibility of orthostatic hypotension due to dopaminergic stimulation.

For the first 3 days, the drug is prescribed at a dose of 25 mcg/day; for the next 3 days – at a dose of 50 mcg/day. Starting from the 7th day, the recommended dose is 75 mcg/day.

If necessary, a further gradual increase in the dose (no more than once a week) is carried out until the optimal therapeutic effect is achieved. The maintenance dose ranges from 75 to 150 mcg/day.

The need to use a daily dose of 300 mcg and above arises only in 1/3 of patients, while the dose is gradually increased by 75-150 mcg at intervals of at least 4 weeks until a satisfactory therapeutic effect is achieved or until drug tolerance decreases (a break in administration may be required).

The tablets are taken once a day, at night, with a small amount of food.

Adverse Reactions

From the digestive system frequently (>10%) – nausea, vomiting; rarely (1-10%) – anorexia, abdominal pain, constipation, diarrhea.

From the CNS frequently (>10%) – headache, dizziness and weakness; rarely (1-10%) – insomnia; in some cases – acute psychosis (which disappeared after discontinuation of the drug).

From the cardiovascular system rarely (1-10%) – edema, flushing, orthostatic hypotension (which can lead to severe weakness or fainting).

Other rarely (1-10%) – nasal congestion.

Adverse reactions described with the use of Norprolac^® are characteristic of treatment with dopamine receptor agonists, usually do not lead to drug withdrawal and tend to disappear with continued treatment.

Frequent adverse reactions (>10%) occur mainly in the first few days of using the drug or when increasing the dose (in this case, they pass very quickly). If necessary, domperidone can be prescribed for several days 1 hour before taking Norprolac^® to prevent nausea and vomiting.

Contraindications

• Impaired liver function;
• Impaired renal function;
• Hypersensitivity to the drug.

Use in Pregnancy and Lactation

Experience with the use of Norprolac^® during pregnancy is limited. If pregnancy occurs, Norprolac^® should be discontinued, except in cases where continuation of therapy is vitally necessary. No increase in the frequency of spontaneous abortions was observed after discontinuation of Norprolac^®. If pregnancy occurs in a patient with a pituitary adenoma and Norprolac^® is discontinued, careful monitoring of the patient throughout the pregnancy is indicated.

Experimental studies have not established embryotoxic or teratogenic effects of Norprolac^®.

Since Norprolac^® suppresses lactation, breastfeeding is generally not possible. If lactation persists, breastfeeding should be discontinued (because it is not known whether Quinagolide is excreted in breast milk).

Treatment with Norprolac^® may restore fertility. Women of childbearing age who do not wish to become pregnant during treatment with Norprolac^® should use reliable methods of contraception.

Use in Hepatic Impairment

Contraindicated in impaired liver function.

Use in Renal Impairment

Contraindicated in impaired renal function.

Pediatric Use

There is no experience with the use of Norprolac^® in children.

Geriatric Use

There is no experience with the use of Norprolac^® in elderly patients.

Special Precautions

During the first days of treatment with Norprolac^® and when increasing the dose, blood pressure should be regularly monitored in lying and standing positions, due to the possibility of orthostatic hypotension and fainting.

Several cases of acute psychosis have been reported with the use of Norprolac^® (including in patients with no history of mental illness), which usually resolved after discontinuation of the drug. Particular caution should be exercised when prescribing Norprolac^® to patients with a history of mental disorders.

Concomitant use of alcohol may worsen the tolerability of Norprolac^®.

There is no experience with the use of Norprolac^® in elderly patients.

Use in pediatrics

There is no experience with the use of Norprolac^® in children.

Effect on ability to drive vehicles and operate machinery

Patients engaged in potentially hazardous activities should exercise caution, as sometimes, especially in the first days of using Norprolac^®, arterial hypotension and a decrease in the speed of motor and mental reactions may occur.

Overdose

Acute overdose of Norprolac^® tablets has not been described.

Possible symptoms include severe nausea, vomiting, headaches, dizziness, drowsiness, arterial hypotension, collapse, hallucinations.

Treatment: if necessary, symptomatic therapy is carried out.

Drug Interactions

No interactions of Norprolac^® with other drugs have been reported to date. There is a theoretical possibility of a decrease in the prolactin-inhibiting effect of Norprolac^® when it is co-administered with drugs that have a pronounced antidopaminergic effect (for example, neuroleptics), so caution should be exercised when using these drugs concomitantly.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 3 years.

Pharmacy dispensing conditions

The drug is dispensed by prescription.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.