Consumer medicine information

Norprolac

Quinagolide hydrochloride

BRAND INFORMATION

Brand name

Norprolac

Active ingredient

Quinagolide hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Norprolac.

What is in this leaflet

This leaflet answers some common questions about Norprolac.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will provide.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Norprolac is taken for

Norprolac is used to treat people who have high blood levels of a hormone called prolactin. This condition is sometimes caused by a type of tumour called a prolactinoma.

Norprolac contains the active ingredient, quinagolide.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is only available with a doctor's prescription. It is not addictive.

There is not enough information to recommend its use in children.

Before you take Norprolac

When you must not take it

Do not take Norprolac if you have an allergy to:

  • quinagolide (the active ingredient) or any of the other ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not take this medicine if you have problems with your kidneys or liver. There is no experience with the use of this medicine in people whose kidney or liver function is impaired.

Do not take it after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

Before you start to take it

Tell your doctor if you have had any type of mental illness (e.g. schizophrenia). Your doctor may want to take special precautions while you are taking this medicine.

Tell your doctor if you are pregnant or intend to become pregnant. Your doctor can discuss with you the benefits and any risks of taking this medicine during pregnancy.

Tell your doctor if you are breast-feeding or intend to breast-feed. This medicine stops the production of breast milk due to its effect on prolactin. You will not be able to breast-feed while you are taking it.

Tell your doctor if you are lactose intolerant or you have an intolerance to some sugars. This medicine contains lactose.

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives. Your doctor will want to know if you are prone to allergies.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

It is possible that Norprolac and other medicines that affect prolactin may interfere with each other. This includes some medicines used to treat mental illness.

You may need different amounts of your medicines, or you may need to take different medicines. Your doctor and pharmacist have more information.

If you have not told your doctor about any of these things, tell him/her before you start taking this medicine.

How to take Norprolac

Follow all directions given to you by your doctor and pharmacist carefully. These instructions may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to take

You will usually begin treatment with the Norprolac starter pack. It contains 3 light pink 25 microgram tablets and 3 pale blue 50 microgram tablets. You will take the pink tablets once each day for 3 days, followed by the pale blue tablets once each day for 3 days.

After that, the dose you take each day may be slowly increased, depending on how well your prolactin levels are controlled. Packs of 75microgram tablets are available for this purpose.

How to take it

Take the tablet once each day at bedtime with some food. Taking it with food will help to prevent stomach upset.

How long to take it

Continue taking Norprolac for as long as your doctor recommends. Your doctor will check your progress to make sure the medicine is working and will discuss with you how long your treatment should continue.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take the next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the one that you missed. This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone number 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Norprolac. Do this even if there are no signs of discomfort or poisoning. Keep the telephone numbers for these places handy.

Some of the symptoms of an overdose may include nausea, vomiting, sleepiness, dizziness, light-headedness and hallucinations (seeing or hearing things that are not there).

While you are taking Norprolac

Things you must do

If you do not wish to become pregnant, you must use a reliable means of contraception. As your prolactin levels become lower, your menstrual periods may return to normal and you could become pregnant.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may want to do some tests from time to time.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Norprolac.

Tell any other doctor, dentist or pharmacist who treats you that you are taking this medicine.

Things you must not do

Do not give this medicine to anyone else even if their condition seems similar to yours.

Do not use it to treat any other complaints unless your doctor tells you to.

Things to be careful of

While you are taking Norprolac, be careful to get up slowly from a sitting or lying position. This medicine can make you dizzy, lightheaded or faint, especially when you first take it. This is because your blood pressure has suddenly dropped. Taking the dose at bedtime and being careful when standing up will help your body get used to the change in blood pressure and will reduce the risk of falling.

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how Norprolac affects you. Norprolac can make you dizzy, lightheaded or faint and it can also cause extreme sleepiness or mental changes in a few people. If you have any of these symptoms, do not drive or do anything else that could be dangerous.

Be careful when drinking alcohol while taking Norprolac. The combination may cause unwanted side effects. Your tolerance for alcohol may be lower than usual.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Norprolac. All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by these lists of possible side effects. You may not experience any of them. Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following side effects and they worry you:

  • nausea or vomiting
  • dizziness or light-headedness, especially on standing up
  • drowsiness or sleepiness (if you have extreme sleepiness, tell your doctor immediately)
  • headache
  • tiredness
  • mental changes such as confusion, changes in behaviour, hallucinations (seeing or hearing things that are not there)
  • loss of appetite
  • pain in the abdomen
  • constipation or diarrhoea
  • nasal congestion
  • muscular weakness.

The following side effects have also been reported in patients taking drugs like Norprolac:

  • compulsive behaviour such as gambling, increase in sex drive, increased libido, compulsive spending and buying or compulsive eating.

This possible behaviour may have serious financial and social consequences.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may have other side effects not yet known or mentioned in this leaflet.

After using Norprolac

Storage

  • keep your medicine in the original container until it is time to take it
  • store it in a cool dry place
  • do not store it or any other medicine in the bathroom or near a sink
  • do not leave it in the car or on window sills.

Keep the medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Maintenance packs of Norprolac contain 30 tablets:

  • off-white 75 microgram tablets marked with "NORPROLAC" on one side and "75" on the other side

Ingredients

Norprolac tablets contain 75 micrograms of the active ingredient, quinagolide (as the hydrochloride salt). They also contain:

  • magnesium stearate
  • silica colloidal anhydrous
  • hypromellose
  • maize starch
  • microcrystalline cellulose
  • lactose monohydrate.

Sponsor

Norprolac is supplied in Australia by:

Ferring Pharmaceuticals Pty Ltd
Suite 2, Level 1, Building 1
20 Bridge Street
Pymble, NSW 2073

This leaflet was prepared in July 2020

Australian Registration Number:

75 microgram AUST R 48991

DOCS#15656-v8A

Published by MIMS May 2023

BRAND INFORMATION

Brand name

Norprolac

Active ingredient

Quinagolide hydrochloride

Schedule

S4

 

1 Name of Medicine

Quinagolide (as hydrochloride).

2 Qualitative and Quantitative Composition

Tablets containing 25, 50, 75 or 150 microgram (0.025, 0.050, 0.075 or 0.150 mg) quinagolide as hydrochloride.
Norprolac Tablets also contain the following inactive excipients: silica, magnesium stearate, hypromellose, starch-maize, cellulose, lactose monohydrate, iron oxide red (25 microgram tablet only), indigo carmine (50 microgram tablet only).

3 Pharmaceutical Form

Oral tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Hyperprolactinaemia (idiopathic or originating from a prolactin-secreting pituitary microadenoma or macroadenoma) associated with its clinical manifestations such as galactorrhoea, oligomenorrhoea, amenorrhoea, infertility and reduced libido.

4.2 Dose and Method of Administration

Norprolac tablets should be taken once a day at bedtime with some food. The optimal dose must be titrated individually on the basis of the prolactin lowering effect and tolerability.
With the 'starter pack', treatment begins with 25 microgram/day for the first three days, followed by 50 microgram/day for a further three days. From day 7 onwards, the recommended dose is 75 microgram/day. If necessary, the daily dose may then be increased stepwise at intervals not shorter than one week until the optimal individual response is attained.
The usual maintenance dosage is 75 to 150 microgram/day. Daily doses of 300 microgram or higher doses are required in less than one-third of the patients. In such cases, the daily dosage may be increased in steps of 75 to 150 microgram at intervals not shorter than four weeks.
There is no evidence of reduced tolerability or altered dosage requirements in elderly patients.

4.3 Contraindications

Hypersensitivity to the drug.
For procedure during pregnancy, see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy.
Impaired hepatic or renal function.

4.4 Special Warnings and Precautions for Use

Fertility may be restored by the treatment with Norprolac. Women of childbearing age who do not wish to conceive should, therefore, be advised to practice a reliable method of contraception.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Impulse control disorders.

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Norprolac. Dose reduction/ tapered discontinuation should be considered if such symptoms develop.
Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson's disease.

Psychiatric disturbances.

In a few cases, including patients with no previous history of mental illness, treatment with Norprolac has been associated with the occurrence of acute psychosis, usually reversible upon discontinuation.
Particular caution is required when Norprolac is given to patients with a history of psychotic disorders.

Hypotension.

Since, especially during the first days of treatment, hypotensive reactions may occasionally occur and result in reduced alertness, patients should be cautious when driving a vehicle or operating machinery. Since orthostatic hypotension may result in syncope, it is recommended that blood pressure be checked both lying and standing during the first days of therapy and following dosage increases.

CNS effects.

Norprolac has been associated with somnolence. Other dopamine agonists have been associated with episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with Norprolac. Patients who have experienced somnolence must not drive or operate machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Fibrotic complications.

Norprolac is a non-ergot derived dopaminergic agent. Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis and cardiac valvulopathy have been reported in some patients treated with ergot derived dopaminergic agents in high doses for Parkinson's disease. While these complications may resolve when the drug is discontinued, complete resolution does not always occur. No increased risk has been reported with use of ergot derived dopamine agonists in hyperprolactinaemia patients, where a much lower dose is used. These fibrotic complications are believed to be related to the ergoline structure of these compounds. Association with non-ergot derived dopamine agonists is not established. No case of any fibrotic complication associated with Norprolac has been reported.

Impaired renal or hepatic function.

To date, no data are available on the use of Norprolac in patients with impaired renal or hepatic function (see Section 4.3 Contraindications).

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions between Norprolac and other drugs have so far been reported. On theoretical grounds, a reduction of the prolactin lowering effect could be expected when drugs (e.g. neuroleptic agents) with strong dopamine antagonistic properties are used concomitantly.
As the potency of quinagolide for 5-HT1 and 5-HT2 receptors is around 100 times lower than that for D2 receptors, an interaction between Norprolac and 5-HT1A receptors is unlikely. However, care should be taken with concomitant use of medication interfering with these receptors.
Due to limited data available with respect to the enzyme(s) involved in the metabolism of quinagolide, potential pharmacokinetic interactions are difficult to predict. Data are also lacking regarding the potential for quinagolide to affect the pharmacokinetics of other medicinal products, e.g. via enzyme inhibition. Caution is therefore recommended if Norprolac is used with other medicinal products, in particular with drugs known to be substrates, inducers or inhibitors of drug metabolising enzymes.
The tolerability of Norprolac may be reduced by alcohol.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.4 Special Warnings and Precautions for Use.
(Category B3)
Reproductive studies performed in pregnant rats at oral doses up to 1 mg/kg per day have revealed no evidence of embryotoxicity or teratogenicity to quinagolide. Although in pregnant rabbits treated with oral doses of up to 3 mg/kg per day there was a slight increase in the incidence of anomalies in foetuses and litters, the incidence of the individual anomalies do not indicate a teratogenic potential of quinagolide. There were no adequate or well controlled studies in female patients.
In patients wishing to conceive, Norprolac should be discontinued when pregnancy is confirmed, unless there is a medical reason for continuing therapy.
If pregnancy occurs in the presence of a pituitary adenoma and Norprolac treatment has been stopped, close supervision throughout pregnancy is essential. In patients who show symptoms of tumour enlargement (e.g. visual field deterioration or headache), Norprolac treatment may be reinstituted or surgery may be appropriate.
Owing to its inhibitory effect on prolactin secretion, Norprolac suppresses lactation. Therefore, mothers receiving the drug cannot breastfeed.

4.7 Effects on Ability to Drive and Use Machines

Patients being treated with Norprolac and presenting with somnolence must be advised not to drive or engage in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until somnolence has resolved (see Section 4.4 Special Warnings and Precautions for Use).
Since, especially during the first days of treatment, hypotensive reactions may occur and result in decreased alertness, particular care should be exercised when driving a vehicle or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

The adverse reactions reported with the use of Norprolac are characteristic for dopamine receptor agonist therapy. They occur predominantly during the first few days of treatment, are usually not sufficiently serious to require discontinuation of treatment and tend to disappear when treatment is continued.
The most frequent side effects (> 10%) are nausea, vomiting, headache, dizziness and fatigue. If necessary, nausea and vomiting may be prevented by the intake of a peripheral dopaminergic antagonist such as domperidone for a few days, at least one hour before the ingestion of Norprolac.
Less frequent side effects (1 to 10%) include anorexia, abdominal pain, constipation or diarrhoea, insomnia, nasal congestion, hypotension and muscular weakness. Since, on rare occasions, orthostatic hypotension may result in syncope, it is recommended to check blood pressure during the first days of therapy.
In a few isolated cases, treatment with Norprolac has been associated with the occurrence of acute psychosis, reversible upon discontinuation.
In rare cases (< 0.1%) Norprolac is associated with somnolence.

Impulse control disorders.

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Norprolac. (See Section 4.4 Special Warnings and Precautions for Use, Impulse control disorders.)
Patients treated with dopamine agonists for treatment of Parkinson's disease, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Acute overdose with Norprolac tablets has not been reported. It would be expected to cause severe nausea, vomiting, headache, dizziness, drowsiness, hypotension and possibly collapse. Hallucinations could also occur.
Treatment would be symptomatic. Metoclopramide could be indicated for the treatment of emesis or hallucinations.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

The most meaningful information on the pharmacokinetic behaviour of quinagolide and its active metabolites can be derived from pharmacodynamic studies in which the reduction in plasma prolactin levels, a reliable marker of drug activity, has been quantified. The results indicate that, with the recommended therapeutic dosage, a clinically significant prolactin lowering effect occurs within two hours after ingestion, reaches a maximum within four to six hours and is maintained for about 24 hours.
A definite dose response relationship could be established for the duration, but not for the magnitude, of the prolactin lowering effect which, with a single oral dose of 50 microgram, was close to maximum. Higher doses did not result in a considerably greater effect but prolonged its duration.

Mechanism of action.

Norprolac is a selective dopamine D2-receptor agonist. Unlike the other dopamine receptor agonists presently available, Norprolac is not an ergot or ergoline compound. Owing to its dopaminergic action, the drug exerts a strong inhibitory effect on the secretion of the anterior pituitary hormone prolactin, but does not reduce normal levels of other pituitary hormones such as luteinising hormone, follicle stimulating hormone, thyrotropin or corticotropin.
As a specific inhibitor of prolactin secretion with a favourable tolerability profile and a prolonged duration of action, Norprolac has been shown to be effective and suitable for once a day oral treatment for patients presenting with hyperprolactinaemia and its clinical manifestations. This includes patients who have not responded adequately to other dopamine agonist therapy.
Long-term treatment with Norprolac was found to reduce the size or limit the growth of prolactin secreting pituitary macroadenomas.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

After oral administration of radiolabelled drug, quinagolide is rapidly and well absorbed. Plasma concentration values obtained by a nonselective radioimmunoassay (RIA), measuring quinagolide together with some of its metabolites, were close to the limit of quantification and gave no reliable information.

Distribution.

The apparent volume of distribution of quinagolide after single oral administration of radiolabelled compound was calculated to be approximately 100 L. The protein binding of quinagolide is approximately 90% and is nonspecific.

Metabolism and excretion.

Quinagolide is extensively metabolised during its first pass. For the parent drug, a terminal half-life of 11.5 hours has been calculated under single dose conditions and of 17 hours at steady state. In blood, quinagolide and its N-desethyl analogue are the biologically active but minor components. Their inactive sulphate or glucuronide conjugates represent the major circulating metabolites. In urine, the main metabolites are the glucuronide and sulphate conjugates of quinagolide and the N-desethyl and N,N-bidesethyl analogues. In the faeces, the unconjugated forms of the three components were found. Studies performed with 3H-labelled quinagolide revealed that more than 95% of the drug is excreted as metabolites. About equal amounts of total radioactivity are found in faeces and urine.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been conducted.

Carcinogenicity.

A 2 year study in rats showed that dietary administration of quinagolide at doses of 0.01 to 0.2 mg/kg/day increased the incidence of benign Leydig cell tumours in males and reduced the incidence of mammary gland adenomas and adenocarcinomas and pituitary carcinoma in females and of pituitary adenomas in both sexes. A 90 week study in mice showed that dietary administration at 0.1 and 0.4 mg/kg/day increased the incidences of reproductive tract mesoderm derived tumours, such as leiomyoma and leiomyosarcoma, and stromal polyp and stromal sarcoma. The carcinogenic effects in rats and mice may involve endocrine mechanisms resulting from disturbances of the hypothalamic pituitary gonadal axis secondary to inhibition of prolactin secretion and not predictive of a risk in humans. Gene mutation, cytogenetic and DNA damage assays suggest that quinagolide does not possess mutagenic activity.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Starter pack.

3 tablets 25 microgram (light pink, "Norprolac" on one side, "25" on the other).
3 tablets 50 microgram (pale blue, "Norprolac" on one side, "50" on the other).

Maintenance pack.

50 microgram, packs of 30 (as above).
75 microgram, packs of 30 (off-white, "Norprolac" on one side, "75" on the other).
150 microgram, packs of 30 (off-white, "Norprolac" on one side, "150" on the other).
Not all strengths/pack sizes are being distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Quinagolide hydrochloride is (3α, 4aα, 10aβ)-±-N,N-diethyl-N'- (1,2,3,4,4a,5,10,10a- octahydro-6- hydroxy-1-propylbenzo(g) quinolin-3-yl)- sulfamide hydrochloride. It is present in Norprolac as the racemate.

Chemical structure.


CAS number.

94424-50-7.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes