NORPROLAC 0.075 MG TABLETS

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) – 1986

The medicine is dispensed with a doctor’s prescription only

Norprolac

®

Norprolac

®

25 mcg

50 mcg

Tablets

Tablets

Composition:

Composition:

Each tablet contains:

Each tablet contains:

Quinagolide 25 mcg

Quinagolide 50 mcg

Lactose 90 mg

Lactose 90 mg

Norprolac

®

Norprolac

®

75 mcg

150 mcg

Tablets

Tablets

Composition:

Composition:

Each tablet contains:

Each tablet contains:

Quinagolide 75 mcg

Quinagolide 150 mcg

Lactose 87 mg

Lactose 174 mg

Inactive ingredients – see section 6 “Further Information”.

Read this leaflet carefully in its entirety before using the medicine.

This leaflet contains concise information about the medicine. If you have further

questions, refer to the doctor or pharmacist.

This medicine has been prescribed for the treatment of your ailment. Do

not pass it on to others. It may harm them, even if it seems to you that their

ailment is similar.

1. WHAT IS THE MEDICINE INTENDED fOR?

The medicine inhibits prolactin secretion.

Therapeutic group: Dopamine D

-receptor agonist.

2. BEfORE USING THE MEDICINE

Do not use the medicine if:

- Do not breastfeed while taking the medicine.

- Do not use this medicine if there is a known sensitivity to any of the

medicine’s ingredients.

- Do not use this medicine in cases of impaired liver or kidney function.

Special warnings regarding use of the medicine

- Consult with the doctor before beginning treatment if you are pregnant.

- Consult with the doctor before beginning treatment if you suffer or have

suffered in the past from: low blood pressure, psychotic disturbances.

- During treatment with this medicine, blood pressure tests should be

performed.

- If you are sensitive to any type of food, inform your doctor before taking the

medicine.

- Inform your doctor if you or any of your family members notice that you are

developing urges or cravings to behave in ways that are unusual for you, or

if you cannot resist the impulse or temptation to carry out certain activities

that could harm yourself or others. These behaviors are called impulse

control disorders and can include pathological gambling, excessive eating,

spending, an abnormally high sex drive or an increase in the frequency of

sexual thoughts. Your doctor may need to check your treatment.

If you are taking, or have recently taken, other medicines, including

non-prescription medicines and food supplements, tell the doctor or

pharmacist. Especially, inform the doctor or pharmacist if you are taking:

- Anti-psychotic medications.

Use of the medicine and alcohol consumption: Do not drink wines or

alcoholic beverages while under treatment with the medicine.

Pregnancy and breastfeeding: If you are pregnant or breastfeeding, consult

the doctor or pharmacist before using the medicine.

Driving and operating machinery: Use of this medicine may impair alertness

and therefore, requires caution when driving a car, operating dangerous

machinery and in any other activity that requires alertness.

Important information about some of the ingredients of the medicine:

The medicine contains the ingredient lactose. Inform the doctor if you have a

sensitivity to this ingredient.

3. HOW SHOULD yOU USE THE MEDICINE?

Always use according to the doctor’s instructions.

Check with the doctor or pharmacist if you are uncertain.

The dosage and manner of treatment will be determined by the doctor only.

The usual dosage is generally:

The treatment normally begins with a dose of 25 mcg once daily for the first

three days followed by 50 mcg once daily for the next three days. From day

7, the dose is 75 mcg although it is possible to increase the amount until

reaching the optimal dosage. The usual dosage is 75-150 mcg daily. Some

patients will require a daily dose of 300 mcg or more.

Do not exceed the recommended dose.

Directions for use:

- Do not chew! Swallow the medicine with a little water.

- Do not crush or halve the tablet.

- Take the medicine at bedtime with a little food.

If you accidentally took an overdose, or if a child has accidentally swallowed

the medicine, refer immediately to a doctor or proceed to a hospital emergency

room, and bring the package of the medicine with you.

If you forgot to take this medicine at the required time, take a dose as

soon as you remember but under no circumstances should two doses be

taken together!

Be sure to adhere to the treatment as recommended by the doctor.

Even if there is an improvement in your health, do not stop treatment with the

medicine without consulting the doctor or pharmacist.

Do not take medicines in the dark! Check the label and the dose each time

you take medicine. Wear glasses if you need them.

If you have further questions regarding use of the medicine, consult a doctor

or pharmacist.

4. SIDE EffECTS

As with any medicine, use of Norprolac

may cause side effects in some

users. Do not be alarmed by the list of side effects. You may not suffer from

any of them.

Stop treatment and consult the doctor immediately in case of weakness

and fainting as a result of a decrease in blood pressure (rare).

Consult the doctor as soon as possible in the case of inability to resist the

impulse to perform an action that could be harmful, which may include:

Strong impulse to gamble compulsively despite personal or family

consequences.

Altered or increased sexual interest or behavior, for example, an increased

sexual drive.

Uncontrollable excessive shopping and spending.

Binge eating (eating large amounts of food in a short time period) or

compulsive eating (eating more food than normal and more than is needed

to satisfy your hunger).

Additional side effects:

- Side effects that occur frequently: vomiting, nausea, headache, dizziness,

fatigue, loss of appetite, abdominal pain, constipation or diarrhea, edema,

flushing.

- Side effects that occur rarely: sleepiness, reversible psychosis.

If any of the side effects worsen or if you suffer from a side effect not mentioned

in the leaflet, consult with the doctor.

5. HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine, and any other medicine, should be kept

in a safe place out of the reach of children and/or infants in order to avoid

poisoning.

Do not induce vomiting unless explicitly instructed to do so by the doctor.

Do not use the medicine after the expiry date (exp. date) appearing on the

package. The expiry date refers to the last day of that month.

Store at a temperature that does not exceed 25°C, in the original packaging,

protect from light and moisture.

6. fURTHER INfORMATION

In addition to the active ingredient, the medicine also contains:

Hypromellose, Lactose monohydrate, Maize starch, Microcrystalline cellulose,

colloidal Silica anhydrous, Magnesium stearate.

Norprolac

25 mcg: round light pink tablets, with NORPROLAC written

circularly on one side and “25” written on the other side. Supplied in a pack

of 3 tablets.

Norprolac

50 mcg: round light blue tablets, with NORPROLAC written

circularly on one side and “50” written on the other side. Supplied in a pack

of 3 tablets.

Norprolac

75 mcg: round white tablets, with NORPROLAC written circularly

on one side and “75” written on the other side. Supplied in a pack of 30

tablets.

Norprolac

150 mcg: round white tablets, with NORPROLAC written circularly

on one side and “150” written on the other side. Supplied in a pack of 30

tablets.

License holder and address:

Ferring Pharmaceuticals Ltd., 8 Hashita St., Industrial Park, Caesarea

3890000.

Manufacturer and address: Pharmaceutical Company Jelfa SA, Poland.

Importer and address:

A. Lapidot Pharmaceuticals Ltd., 8 Hashita St., Industrial Park, Caesarea

3890000.

This leaflet was checked and approved by the Ministry of Health on

March 23, 2014.

Registration numbers of the medicine in the National Drug Registry of

the Ministry of Health:

mcg – 133 50 28204

mcg – 133 51 28205

mcg – 133 52 28206

150 mcg – 133 53 28207

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Norprolac 25 microgram + 50 microgram tablets

Norprolac 75 microgram tablets

Norprolac 150 microgram tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

1 tablet 25 micrograms contains: 25 micrograms of quinagolide as

quinagolide hydrochloride.

1 tablet 50 micrograms contains: 50 micrograms of quinagolide as

quinagolide hydrochloride.

1 tablet 75 micrograms contains: 75 micrograms of quinagolide as

quinagolide hydrochloride.

1 tablet 150 micrograms contains: 150 micrograms of quinagolide as

quinagolide hydrochloride.

For excipients, see 6.1.

3.

PHARMACEUTICAL FORM

Tablet 25 micrograms: Light pink with isolated pigment spots, circular,

flat, bevelled edge, 7 mm in diameter.

Inscriptions: “NORPROLAC” circular on one side and “25” linear on

the other side.

Tablet 50 micrograms: Light blue with isolated pigment spots, circular,

flat, bevelled edge, 7 mm in diameter.

Inscriptions: “NORPROLAC” circular on one side and “50” linear on

the other side.

Tablet 75 micrograms: White, circular, flat, bevelled edge, 7 mm in

diameter.

Inscriptions: “NORPROLAC” circular on one side and “75” linear on

the other side.

Tablet 150 micrograms: White, circular, flat, bevelled edge, 9 mm in

diameter.

Inscriptions: “NORPROLAC” circular on one side and “150” linear on

the other side.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Second line treatment of hyperprolactinaemia (idiopathic or due to

prolactin-secreting micro- or macroadenoma) and its clinical manifestation

(galactorrhoea, oligomenorrhoea, infertility, reduced libido).

4.2

Posology and method of administration

Since dopaminergic stimulation may lead to symptoms of orthostatic

hypotension, the dosage of Norprolac should be initiated gradually with

the aid of the titration pack, and given once daily in the evening with

food. The optimal dose must be titrated individually on the basis of the

prolactin-lowering effect and tolerability.

Adults

With the titration pack treatment begins with 25 micrograms/day for the

first 3 days, followed by 50 micrograms/day for a further 3 days. From

day 7 onwards, the recommended dose is 75 micrograms/day.

When required, the daily dose may be increased in steps of 75 micrograms

at intervals not shorter than one week until the optimal individual

response is attained. The usual maintenance dosage is 75 micrograms/day

or 150 micrograms/day. Single patients may require daily doses of

300 micrograms or higher. In such cases, the daily dosage may be

increased in steps of 75 micrograms to 150 micrograms at intervals

not shorter than 4 weeks until satisfactory therapeutic effectiveness is

achieved or reduced tolerability limits further increases in the dose.

Elderly

Experience with the use of Norprolac in elderly patients is not

available.

Children

Experience with the use of Norprolac in children is not available.

4.3

Contraindications

Severely impaired hepatic or renal function. Hypersensitivity to the active

substance or to any of the excipients.

4.4

Special warnings and special precautions for use

Hyperprolactinaemia may be physiological (pregnancy, lactation) as well

as be due to other causes among others tumours in hypothalamus or

pituitary gland and a number of drugs. Therefore, it is important that

the specific cause for hyperprolactinaemia is explained as far as possible

and that causal therapy is initiated.

Since orthostatic hypotension may result in syncope in rare cases, it is

recommended to check blood pressure both lying and standing during

the first days of therapy and following dosage increases. Moreover,

orthostatic blood pressure changes with reflex increases in heart rate

might be relevant for patients with severe heart diseases.

In women suffering from prolactin-related fertility disorders, fertility may

be restored by treatment with Norprolac. Women of child-bearing age

who do not wish to conceive should therefore be advised to practice a

reliable method of contraception.

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 in patients who have had psychotic episodes in their

previous history.

To date, no data are available on the use of Norprolac in patients with

impaired renal or hepatic function.

Norprolac has been associated with somnolence. Other dopamine agonists

have been associated with sudden sleep onset episodes, particularly

in patients with Parkinson’s disease. Patients must be informed of this

and advised to be cautious 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.

No interaction studies have been performed with quinagolide and

caution is therefore recommended if Norprolac is combined with other

medicinal products (see section 4.5).

Patients with rare hereditary problems of galactose intolerance, the

Lapp lactase deficiency or glucose-galactose malabsorption should not

take this medicine.

The tolerability of Norprolac may be reduced by alcohol.

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.

4.5

Interaction with other medicinal products and other forms

of interaction

No interaction studies have been performed and 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-HT

and 5-HT

receptors is some

100 times lower than that for D

receptors, an interaction between

Norprolac and 5-HT

receptors is unlikely. However, care should be

taken when using the medicaments interfering with these receptors

concomitantly.

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 combined with other medicinal products, in particular with drugs

known to be potent inhibitors of drug-metabolising enzymes.

The tolerability of Norprolac may be reduced by alcohol.

4.6

Pregnancy and lactation

Pregnancy: Animal data provide no evidence that Norprolac has any

embryotoxic or teratogenic potential, but clinical experience in pregnant

women is limited.

In patients wishing to conceive, Norprolac should be discontinued when

pregnancy is confirmed, unless there is a medical reason for continuing

therapy. No increased incidence of abortion has been observed following

withdrawal of the drug at this point.

If pregnancy occurs in the presence of a pituitary adenoma and Norprolac

treatment has been stopped, close supervision throughout pregnancy

is essential.

Lactation: Breast-feeding is usually not possible since Norprolac suppresses

lactation. If lactation should continue during treatment, breast-feeding

cannot be recommended because it is not known whether quinagolide

passes into human breast milk.

4.7

Effects on ability to drive and use machines

Treatment with Norprolac may, in some patients, impair the ability to react

during the first days of treatment. This has to be taken into consideration

when sharpened alertness is demanded, e.g., when driving. Patients

being treated with Norprolac and presenting with somnolence and/or

sudden sleep onset episodes 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 these episodes

or the somnolence have ceased.

See also section 4.4.

4.8

Undesirable effects

Most adverse reactions are dose-dependent and transient. The adverse

reactions are seldom sufficiently serious to require discontinuation of

treatment.

MedDRA

Organ Class

Very common

(>10%)

Common

(1-10%)

Rare

(0.01-0.1%)

Metabolism

and nutrition

disorders

Anorexia

Psychiatric

disorders

Insomnia

Reversible acute

psychosis

Nervous system

disorders

Dizziness,

headache

Somnolence

Vascular

disorders

Orthostatic

hypotension

Respiratory,

thoracic and

mediastinal

disorders

Nasal

congestion

Gastrointestinal

disorders

Nausea,

vomiting

Abdominal

pain,

constipation,

diarrhoea

Musculoskeletal,

connective

tissue and bone

disorders

Muscular

weakness

General

disorders and

administration

site conditions

Fatigue

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 special precautions for use’).

Orthostatic hypotension reported following use of Norprolac, rarely can

result in syncope.

The risk of hypersensitive reactions could not be excluded.

4.9

Overdose

Limited experience of overdose. It would be expected to cause nausea,

vomiting, headache, dizziness, drowsiness, hypotension, hallucinations.

Treatment of overdose should be symptomatic. If justified, stomach

wash-out or carbon.

5.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Dopamine receptor agonist, prolactin

inhibitors

ATC code: G02CB04.

Quinagolide is a selective dopamine D

-receptor agonist. Quinagolide

exerts an inhibitory effect on the secretion of prolactin, but does not

reduce normal levels of other pituitary hormones. Reduction of the

prolactin level occurs within 2 hours after ingestion, reaches a maximum

within 4 to 6 hours and is maintained for about 24 hours. The duration

is dose-dependent.

Long-term treatment with Norprolac was found to reduce the

size or limit the growth of prolactin-secreting pituitary macro- and

microadenomas.

5.2

Pharmacokinetic properties

Since intravenous studies have not been possible to perform, information

on absolute bioavailability, clearance and volume of distribution is lacking.

Quinagolide is rapidly absorbed. The influence of concomitant food intake

on absorption has not been studied. Maximal plasma concentration

(about 10 picogram/ml at steady-state) was reached after 30 minutes

when 75 micrograms quinagolide was given. The protein binding of the

substance is approximately 90% and is non-specific. The elimination

half-life is about 11 hours (single dose) and 17 hours at steady-state. The

metabolism of quinagolide is extensive. Quinagolide and its N-desethyl

analogue occur in small amounts in the blood, about one tenth of the

total radioactivity. The N-desethyl analogue has pharmacological effect

similar to the parent substance but is less potent and probably does not

contribute to the clinical effect. The sulphate and 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 faeces the unconjugated

forms of the three components were found.

The pharmacokinetics has not been studied in elderly patients or in

patients with impaired hepatic or renal function.

5.3

Preclinical safety data

In comprehensive in vitro and in vivo mutagenic studies performed with

quinagolide, there was no evidence of a mutagenic effect. Carcinogenicity

studies showed an increase in tumours of the female mouse reproductive

tract and of benign Leydig cell adenomas in rats. These findings are the

consequences of the central dopaminergic effects of the long-lasting

inhibition of prolactin in rodents with a specific hormonal physiology

different to man. Consequently, these effects are not regarded as relevant

to clinical use.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

1 tablet 25 micrograms contains: lactose monohydrate, red iron

oxide (E172), microcrystalline cellulose, maize starch, hypromellose,

magnesium stearate, anhydrous colloidal silica.

1 tablet 50 micrograms contains: lactose monohydrate, indigo carmine

lake (E132), microcrystalline cellulose, maize starch, hypromellose,

magnesium stearate, anhydrous colloidal silica.

1 tablet 75 micrograms contains: lactose monohydrate, microcrystalline

cellulose, maize starch, hypromellose, magnesium stearate, anhydrous

colloidal silica.

1 tablet 150 micrograms contains: lactose monohydrate, microcrystalline

cellulose, maize starch, hypromellose, magnesium stearate, anhydrous

colloidal silica.

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

5 years in blister.

6.4

Special precautions for storage

Do not store above 25°C.

Store in the original package in order to protect from light and

moisture.

6.5

Nature and contents of container

Pack sizes:

Titration package 25+50 micrograms, 3+3 tablets

Packed in a blister of ALU/PVC/PVDC which is sealed in a moisture-proof

aluminium bag.

75 micrograms 30 tablets

150 micrograms 30 tablets

Packed in blisters of ALU/ALU

6.6

Instructions for use and handling and disposal

No special requirements.

7.

MANUFACTURER

Ferring GmbH, Germany

8.

LICENSE HOLDER

Ferring Pharmaceuticals Ltd.,

8, Hashita Street, Industrial Park Caesarea 38900,

ISRAEL

The format of this leaflet was determined by the Ministry of Health and

its content was checked and approved in March 2014

NORP TAB PHY SH 060414