Consumer medicine information

Primacin Tablets

Primaquine

BRAND INFORMATION

Brand name

Primacin

Active ingredient

Primaquine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Primacin Tablets.

What is in this leaflet

Please read this leaflet carefully before you start taking Primacin.

This leaflet answers some common questions about Primacin . It does not contain all the available information. The most up-to-date Consumer Medicine Information can be downloaded from www.ebs.tga.gov.au.

Reading this leaflet 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 Primacin against the benefits this medicine is expected to have for you.

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

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

What Primacin is used for

Primacin contains primaquine phosphate. It works by killing the malarial parasite at different stages of its life cycle, both in the blood and in the liver.

Primacin is used to treat the vivax and ovale forms of malaria following an attack. It is also used to aid in the treatment of falciparum malaria.

Your doctor may have prescribed this medicine for another reason.

Ask your doctor if you have any questions about why it has been prescribed for you.

Primacin is only available with a doctor's prescription.

Primacin is not addictive.

Before you take Primacin

Primacin is not suitable for everyone.

When you must not take it

Do not take Primacin if you:

  • have severe glucose-6-phosphate (G6PD) deficiency
    You may not know if you have this deficiency but your doctor can do a quick blood test to check.
  • are pregnant
  • have rheumatoid arthritis or lupus erythematosus
  • are taking quinacrine hydrochloride to treat malaria
  • are taking other medicines that affect your red blood cells or bone marrow.

Do not take Primacin if you are allergic to any medicine containing primaquine or other 8-aminoquinolines or any of the ingredients listed at the end of this leaflet.

Do not take it after the expiry date (‘Expiry’) printed on the pack. If you take it after the expiry date has passed, it may not work as well.

Do not take it if the packaging is torn or shows signs of tampering.

If you are not sure whether you should start taking Primacin, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if you have allergies to any other medicines, foods, preservatives or dyes. Primacin tablets contain small amounts of lactose and wheat starch (gluten), which can cause an allergic reaction in some people.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • NADH methaemoglobin reductase deficiency
  • heart disease
  • irregular heartbeat
  • slow heart rate
  • low potassium or magnesium levels in the blood
  • a recent attack of malaria that was treated with quinacrine hydrochloride.

Do not take this medicine if you are pregnant or intend to become pregnant. The safety of the use of this medicine in women who are pregnant or may become pregnant has not been established.

Do not breastfeed if you are taking this medicine. There is no information on the safe use of this medicine during breastfeeding.

Use with caution if you are over 65 years old. Elderly persons are more sensitive to the effects of the medicine.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Primacin.

Taking other medicines

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

Tell any healthcare professional who is prescribing a new medicine for you that you are taking Primacin.

Some medicines and Primacin may interfere with each other. These include:

  • proguanil, which is used to treat malaria
  • medicines that reduce the ability of your bone marrow to produce red blood cells and platelets, such as medicines used in chemotherapy
  • some medicines used to treat irregular heartbeat
  • ketoconazole, used to treat fungal infections.

The above medicines may be affected by Primacin, or may affect how well it works. You may need different amounts of Primacin, or take it at different times, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Primacin.

How to take Primacin

Read the label carefully and follow all directions given to you by your doctor and pharmacist. They may differ from the information contained in this leaflet.

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

How much to take

The treatment and dose will depend upon the area where you were infected with malaria. In South East Asia and the Pacific region close to Australia (Papua New Guinea, Vanuatu, Solomon Islands), there are malaria parasites that are more resistant to treatment. If your stay has been in one of these areas, the treatment may include an increased dose of Primacin, or the use of Primacin over a longer period of time.

The treatment is usually one of the following:

For adults

  • 15 mg daily for 14 days
  • up to 30 mg daily for 14 days in areas where resistant malaria strains occur or where treatment has failed with lower doses
  • treatment may be extended to 21 days in most of South East Asia and the Pacific region, and other medicines to treat malaria may be given at the same time as Primacin
  • if you have G6PD deficiency: up to 45 mg once weekly for 8 weeks
  • if you have falciparum malaria: 45 mg as a single dose.

For children

  • 0.3 mg/kg/day
  • if your child has falciparum malaria: 0.7 - 1.0 mg/kg/day.

Your doctor will tell you how much Primacin you should take or give to your child.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take. This depends on your condition and whether or not you are taking any other medicines.

If you take the wrong dose, Primacin may not work as well and your problem may not improve.

Swallow Primacin whole with a full glass of water.

When to take it

Take it at about the same time each day with a meal. Primacin must be taken regularly. Taking it at the same time each day will have the best effect. It will also help you to remember when to take it. Make sure that you take Primacin with food, or an upset stomach may occur.

How long to take it

Continue taking the medicine for as long as your doctor tells you to. Primacin helps to control your condition, but may not cure it.

If you feel chilly or have a fever following return from a malaria area, see your doctor even if you have taken a course of tablets. Relapses may occur in some people.

Continue taking the tablets until you finish the pack or until your doctor tells you to stop.

If you are unsure whether you should stop taking Primacin, talk to your doctor or pharmacist.

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.

Do not try to make up for missed doses by taking more than one dose at a time. This may increase the chance of getting an unwanted side effect.

If there is still a long time to go before your next dose, take it as soon as you remember, and then go back to taking it as you would normally.

If you miss more than one dose, consult your doctor.

If you are not sure what to do, ask your doctor or pharmacist.

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

While you are taking Primacin

Things you must do

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Primacin. Likewise, tell any other doctors, dentists and pharmacists who are treating you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked. Your doctor may do tests to check the levels of cells in your blood or check how your heart is working.

See your doctor if you feel that your condition is not improving or is getting worse.

Things you must not do

Do not give your medicine to anyone else, even if they have the same condition as you. This medicine is only intended for the person it has been prescribed for.

Do not take Primacin to treat any other complaints unless your doctor tells you to.

Do not stop taking Primacin or change the dosage without checking with your doctor.

In case of overdose

If you take too much

Immediately telephone your doctor, or the Poisons Information Centre (telephone 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 Primacin.

Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include:

  • abdominal cramps, vomiting or burning pain in the upper abdomen
  • irregular heartbeat, slow or increased heart rate
  • dark-coloured urine
  • feeling tired, weak, dizzy, confused or sick
  • pale or bluish hue to your skin
  • headache
  • shortness of breath
  • fever
  • pain, tingling or weakness in your arms or legs
  • sore mouth and gums, mouth ulcers or bleeding gums.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Primacin. Like all medicines, Primacin may occasionally cause side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • abdominal cramps and pains
  • nausea
  • vomiting
  • dizziness
  • headache
  • rash
  • itching of the skin.

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • dark-coloured urine
  • irregular heartbeat or slow heart rate
  • feeling tired, weak, confused or sick
  • pale or bluish hue to your skin
  • shortness of breath
  • fever
  • pain, tingling or weakness in your arms or legs
  • sore mouth and gums, mouth ulcers or bleeding gums.

These may be serious side effects. You may need urgent medical attention.

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • serious allergic reaction (swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing).

These are very serious side effects; you may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some patients.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After taking Primacin

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep Primacin in a cool dry place where the temperature stays below 25°C.

Do not store it or any other medicine in the bathroom, near a sink, or on a window sill. Do not leave it in the car. Heat and damp can destroy some medicines.

Keep it and any other 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.

Do not keep Primacin past its expiry date.

Disposal

Return any unused medicine and any medicine past its expiry date (as shown on the labelling) to your pharmacy.

Product description

What it looks like

Primacin is available in bottles with child-resistant closures of 28 or 56 tablets. The tablets are round, flat, orange uncoated tablets.

Ingredients

Active ingredient:

7.5 mg primaquine base as 13.2 mg primaquine phosphate

Inactive ingredients:

  • lactose
  • wheat starch
  • purified talc
  • gelatine
  • povidone
  • magnesium stearate
  • glycerol.

Sponsor details

Distributed in Australia by:

Boucher & Muir Pty Ltd
Level 9, 76 Berry Street
North Sydney NSW 2060

AUST R 226430

Date of preparation

This leaflet was prepared on 27 February 2017.




Published by MIMS June 2017

BRAND INFORMATION

Brand name

Primacin

Active ingredient

Primaquine

Schedule

S4

 

1 Name of Medicine

Primaquine phosphate.

6.7 Physicochemical Properties

Chemical structure.


Molecular formula: C15H21N3O,2H3PO4.
Molecular weight: 455.3.
Chemical name: (4RS)-N4-(6-Methoxyquinolin-8-yl) pentane-1,4-diamine bisphosphate.
Primaquine phosphate is an orange crystalline powder and melts at about 200°C with decomposition. It is soluble in water and practically insoluble in ethanol.

CAS number.

63-45-6.

2 Qualitative and Quantitative Composition

Each Primacin tablet contains 7.5 mg primaquine base as 13.2 mg primaquine phosphate.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Primacin tablets are orange tablets, 6 mm diameter, flat without breakline or logo.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Primaquine is an antimalarial agent. It is used as a schizontocide for the treatment of the hypnozoite stage (in the liver) of malaria. Primaquine is effective against exoerythrocytic stages of Plasmodium vivax and Plasmodium ovale and against the primary exoerythrocytic stages of Plasmodium falciparum. It is also effective against the sexual forms (gametocytes) of plasmodia, especially P. falciparum, disrupting transmission of the disease by eliminating the reservoir from which the mosquito carrier is infected. Primaquine is more active against tissue forms and gametes than asexual blood forms of plasmodia. The precise mechanism of action is not known. There is some in vitro evidence that some of the antiparasitic effect may be due to the binding and inhibition of entry of the parasite to the hepatoma cell.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Primaquine is rapidly absorbed (Tmax about 2 hours) from the gastrointestinal tract and the concentration of the drug in the body is dose dependent. Oral bioavailability studies (not performed with this product) shows that primaquine is rapidly and almost completely absorbed.

Distribution.

It is widely distributed and the mean apparent Vd range across studies is 260-300 L. It is extensively distributed in body tissues.

Metabolism.

Primaquine is rapidly metabolised after an oral dose, mainly by the liver, with an elimination half-life ranging from 4.3 to 7.4 hours. The principle metabolite is carboxyprimaquine which has a longer half-life and accumulates over a 14 day course of 15 mg primaquine/day.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Prevention of relapses (radical cure) of malaria caused by P. vivax and P. ovale.
Adjunctive therapy in the treatment of gametocytemia due to P. falciparum in patients resident in areas receptive to malaria.

4.3 Contraindications

Hypersensitivity to primaquine or other 8-aminoquinolines.
Hypersensitivity to other ingredients in Primacin tablets.
Severe glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Pregnant women.
Acutely ill patients with any serious systemic diseases characterised by a tendency to granulocytopenia, such as rheumatoid arthritis or lupus erythematosus.
Patients receiving concurrently other potentially haemolytic medicines or depressants of myeloid elements of the bone marrow.

4.4 Special Warnings and Precautions for Use

Primaquine was first used as an anti-malarial agent in humans in the late 1940's and early 1950's. It has not been subject to the systematic long term safety testing in animals that would be expected of a drug developed more recently.

Haemolytic anaemia and G6PD deficiency.

Primaquine may cause severe haemolytic anaemia in individuals with G6PD deficiency. Due to the risk of haemolytic anaemia in patients with G6PD deficiency, G6PD testing has to be performed prior to the administration of primaquine. Due to the limitations of G6PD tests, physicians need to be aware of residual risk of haemolysis, and adequate medical support and follow-up to manage haemolytic risk should be available.
Primaquine should not be prescribed for patients with severe G6PD deficiency (see Section 4.3 Contraindications).
There is limited evidence that adults with moderately reduced G6PD deficiency may be able to tolerate 45 mg once weekly for 8 weeks. In case of mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine. If primaquine administration is considered, baseline haematocrit and haemoglobin must be checked before treatment, and close haematological monitoring (e.g. at day 3 and 8) is required. Adequate medical support to manage haemolytic risk should be available.
When G6PD status is unknown and G6PD testing is not available, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine. Risk factors for G6PD deficiency or favism must be assessed. Baseline haematocrit and haemoglobin must be checked before treatment and close haematological monitoring (e.g. at day 3 and 8) is required. Adequate medical support to manage haemolytic risk should be available.
Discontinue the use of primaquine phosphate promptly if signs suggestive of haemolytic anaemia occur (darkening of the urine, marked fall of haemoglobin or erythrocyte count).
Haemolytic reactions (moderate to severe) may occur in individuals with G6PD deficiency and in individuals with a family or personal history of favism. Areas of high prevalence of G6PD deficiency are Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia and Oceania. People from these regions have a greater tendency to develop haemolytic anaemia while receiving primaquine and related drugs, due to a congenital deficiency of erythrocytic G6PD.

Methaemoglobinaemia and NADH methaemoglobin reductase deficiency.

Primaquine may cause methaemoglobinaemia in individuals with NADH methaemoglobin reductase deficiency. Patients should be observed carefully and treatment stopped if signs of methaemoglobinaemia are observed.

Blood monitoring.

Anaemia, methaemoglobinaemia and leukopenia have been observed following administration of large doses of primaquine. Primaquine taken at daily doses of 120 mg/day, higher than recommended for Primacin tablets, has been associated with neutropenia and agranulocytosis.
It is advisable to perform routine blood examinations, particularly blood cell counts and haemoglobin determinations, during therapy.
If primaquine phosphate is prescribed for an individual who has shown a previous idiosyncratic reaction to primaquine phosphate as manifested by haemolytic anaemia, methaemoglobinaemia or leukopenia, or for an individual with a family or personal history of haemolytic anaemia or NADH methaemoglobin reductase deficiency, the person should be observed closely.
In all patients, primaquine phosphate should be discontinued immediately if marked darkening of the urine or sudden decrease in haemoglobin concentration or leukocyte count occurs.

Potential prolongation of QT interval.

Due to potential for QT prolongation, monitor electrocardiogram (ECG) when using primaquine in patients with cardiac disease, long QT syndrome, a history of ventricular arrhythmias, uncorrected hypokalaemia and/or hypomagnesaemia, or bradycardia (< 50 bpm) and during concomitant administration with QT interval prolonging agents.

Lactose intolerance.

Primaquine tablets contain lactose monohydrate as an excipient and should be used with caution in patients sensitive to lactose monohydrate.

Use in hepatic impairment.

See Section 4.4 Special Warnings and Precautions for Use, Use in the elderly.

Use in renal impairment.

See Section 4.4 Special Warnings and Precautions for Use, Use in the elderly.

Use in the elderly.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other therapy.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

See Section 4.8 Adverse Effects (Undesirable Effects).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Because quinacrine hydrochloride appears to potentiate the toxicity of antimalarial compounds which are structurally related to primaquine, the use of quinacrine in patients receiving primaquine is contraindicated. Similarly, primaquine should not be administered to patients who have received quinacrine recently, as toxicity is increased.
The interaction of primaquine and proguanil has not been assessed in vivo.
Other 8-aminoquinolines (pamaquine and pentaquine) administered with proguanil have resulted in 5-10 fold increases in 8-aminoquinoline concentration.
Drugs known to suppress bone marrow and drugs known to cause haemolysis should not be administered with primaquine.
Caution is advised when primaquine is used concomitantly with other medicines that prolong the QT interval.
Ketoconazole reduced metabolism of primaquine in an in vitro study using human liver microsomes. The effects of ketoconazole and other drugs metabolised by the cytochrome P450 system on primaquine metabolism have not been assessed in vivo.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
Safe usage of primaquine phosphate in pregnancy has not been established. Primaquine is contraindicated in pregnant women. Even if a pregnant woman is G6PD normal, the fetus may not be.
 No studies have been carried out in relation to the safe use of primaquine during lactation. It is not known whether primaquine is excreted in human milk. Because many medicines are excreted in human milk and because of the potential for serious adverse effects in nursing infants from primaquine, a decision should be made whether to discontinue nursing or discontinue primaquine, taking into account the importance of primaquine to the mother.

4.8 Adverse Effects (Undesirable Effects)

Gastrointestinal disorders.

Common: abdominal cramps and pains, nausea, vomiting, epigastric distress. Gastrointestinal symptoms are dose related.

Blood and lymphatic system disorders.

Haemolytic anaemia in individuals with G-6-PD deficiency or following administration of large doses of primaquine.
Methaemoglobinaemia in individuals with NADH methaemoglobin reductase deficiency or following administration of large doses of primaquine. Evidence of increased methaemoglobin concentration on laboratory testing may be observed more commonly.
Leukopenia has been observed following administration of large doses of primaquine. Neutropenia and agranulocytosis have been observed in subjects taking very high doses of primaquine (120 mg daily for 14 days).

Cardiac disorders.

Cardiac arrhythmia, QT interval prolongation.

Nervous system disorders.

Common: dizziness, headache.

Skin and subcutaneous disorders.

Rash, pruritus.

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 www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Primaquine should be taken with food.

Radical treatment.

(a) 15 mg daily for 14 days.
(b) Up to 30 mg daily for 14 days in areas where resistant malaria strains occur or where treatment has failed with lower doses.
(c) The WHO advises that the treatment period of 21 days should be employed to achieve radical cure in most of South East Asia and the Pacific regions. Other antimalarial agents may be used concomitantly.
(d) For patients with G6PD deficiency: up to 45 mg once weekly for 8 weeks with monitoring for the development of haemolysis.
(e) Paediatric dose: 0.3 mg/kg/day.
(f) For the reduction of gametocytes of P. falciparum: 45 mg as a single dose for adults and 0.7 to 1.0 mg/kg for children.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Symptoms of overdosage of primaquine phosphate include abdominal cramps, vomiting, burning epigastric distress, central nervous system and cardiovascular disturbances, including cardiac arrhythmia and QT interval prolongation, cyanosis, methaemoglobinaemia, moderate leukocytosis or leukopenia, and anaemia. The most striking symptoms are granulocytopenia and acute haemolytic anaemia in sensitive persons. Acute haemolysis occurs, but patients recover completely if the dosage is discontinued.
For all overdoses in general, the mainstay of treatment is supportive and symptomatic care.
Treatment may be conducted according to an acute oral overdose protocol, including use of activated charcoal. Activated charcoal may reduce absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
Prompt measures should be taken to counteract depressant effects on the cardiovascular and respiratory systems.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

6 Pharmaceutical Particulars

6.1 List of Excipients

Primacin tablets contain lactose monohydrate (53.6 mg), wheat starch, povidone, gelatin, glycerol, magnesium stearate and purified talc as excipients.

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

HDPE bottles with PP child-resistant closure of 28 and 56 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes