Primaquine

Malaria is a serious and sometimes fatal illness caused by parasites. In most cases, it is caused by parasites carried by mosquitoes that enter the bloodstream through a bite. It is not generally considered incurable today, but prompt diagnosis and treatment are essential to help prevent complications. One of the medicines used to treat malaria is primaquine. It is widely used in areas where malaria is common, including parts of Africa and Asia, Central and South America, Haiti, and the Dominican Republic.

Learn more about primaquine, including its dosage, risks and side effects.

What is Primaquine?

Primaquine is a prescription medicine used to treat malaria spread through mosquito bites. It is a first-line treatment in countries where the risk of malaria is high. In the UK, doctors may prescribe it alongside other medicines such as chloroquine to help achieve the best treatment effect.

It belongs to a group of medicines called antimalarials (antiprotozoals). The World Health Organization (WHO) also includes it on its list of Essential Medicines.

Primaquine's Mechanism of Action

Primaquine's exact mechanism of action is not fully understood. However, it is thought to work by binding to and affecting protozoal deoxyribonucleic acid (DNA), producing reactive oxygen species, and interfering with the parasite's electron transport. Medical professionals note that the medicine is lethal to Plasmodium vivax and Plasmodium ovale (parasites that cause malaria in humans) once they reach the liver and blood cells.

After malaria parasites enter the human body, they break down red blood cells, especially haemoglobin. They split haemoglobin into two parts: haem and globin. Parasites cannot tolerate haem because it is toxic to them, so they produce certain chemicals to make the environment more favourable. When a person takes primaquine, it affects the parasites' ability to survive, especially by interfering with their mitochondria, which are responsible for energy production. Once this process is disrupted, the parasites die because they cannot survive without energy. In short, the medicine helps stop the infection and supports recovery.

It is not used on its own to treat malaria, but alongside other first-line medicines. Beyond that, primaquine's known mechanism is not suitable for preventing the disease.

What Is It Used for?

Today, the drug is approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of malaria.

In general, primaquine may be used for:

• treating malaria and helping prevent it from developing further or getting worse once a person is infected;
• treating Pneumocystis jiroveci pneumonia, a lung infection caused by a fungus that is common in people with acquired immunodeficiency syndrome (AIDS) and those taking immunosuppressive medicines.

A doctor may occasionally recommend other uses for primaquine when first-line treatments are unable to treat a particular condition. Only use it after discussing it with your healthcare professional.

Primaquine Dosage and Duration

Primaquine dosing is tailored to each person. Take it by mouth once daily with food to help prevent an upset stomach, or exactly as directed by your healthcare provider.

Primaquine is usually prescribed for 2 weeks after a person leaves an area with a high risk of malaria transmission. It is not suitable for long-term use, so treatment should not exceed 14 days. Do not stop taking primaquine without your doctor's approval, even if you feel better or do not notice any improvement. Your doctor may adjust the dose if needed to reduce the risk of side effects.

For Children

The recommended dose for children being treated for malaria is 0.5 mg/kg once daily for 2 weeks. The dose should not exceed 30 mg.

The recommended dose for children being treated for Pneumocystis pneumonia is 0.3 mg/kg once daily. The dose should not exceed 30 mg.

For Adults

The adult dose for treating malaria is 15 mg once daily for 2 weeks. It is recommended as a radical cure or to help prevent malaria relapse. It should be given alongside chloroquine.

The adult dose for treating Pneumocystis pneumonia is 30 mg once daily for 21 days. It should be taken alongside clindamycin or other recommended first-line medicines.

Please note that some patients may need a different dosing regimen depending on their current health condition.

During Pregnancy

It is not known whether this medicine can be used safely during pregnancy, so it is contraindicated. Based on animal studies, it has been linked to gene mutations, teratogenicity and harm to the fetus.

Tell your doctor if you are pregnant or planning to become pregnant while taking this medicine. Your doctor may advise you to avoid pregnancy because the fetus may be harmed or born with gene mutations.

You do not need to follow a special diet while taking this medicine unless your doctor advises otherwise. Do not increase or reduce the dose without speaking to your doctor, as it may become less effective or cause severe side effects or a worsening of your condition.

Symptoms of Overdose

Like any other medicine, it may cause serious side effects, including overdose if it is not taken as directed by a doctor.

Symptoms of overdose include:

• abdominal cramps;
• cardiac arrhythmia and QT interval prolongation;
• vomiting and nausea;
• epigastric distress;
• central nervous system and cardiovascular disturbances;
• cyanosis, methemoglobinaemia, moderate leukocytosis or leukopenia, and anaemia.

Note: this is not a full list of overdose symptoms, as they can vary from person to person.

If you think you may have taken too much, get emergency medical help straight away and call 999. If you simply feel unwell and your condition is not getting worse, sit or lie down. If your symptoms get worse and you cannot tolerate the pain, seek emergency help.

How Does It Interact With Other Drugs

This medicine may interact with a number of other medicines and substances. This is especially important for people who are already taking medicines for other health conditions. Herbal products and supplements may also affect how well it works. Pay particular attention to the following medicines, which are generally not recommended for use together.

Aurothioglucose

Primaquine is not recommended alongside aurothioglucose. This gold salt is typically used by intramuscular injection in the treatment of arthritis. It may be used for rheumatoid arthritis when first-line treatments are not effective enough or cause severe side effects.

If you are currently taking aurothioglucose, your doctor may change your treatment plan either by stopping the gold salt or by adjusting the doses of both medicines.

Levomethadyl

Levomethadyl is an opioid analgesic used to manage opioid dependence. It is a controlled drug that requires close supervision and caution. Do not take it with primaquine, as side effects may occur.

Carbamazepine

This anticonvulsant medicine is commonly prescribed to treat epilepsy and neuropathic pain. It may also be used to treat schizophrenia and bipolar disorder when first-line treatments are not effective or cause severe side effects. Primaquine should be avoided with carbamazepine.

Primaquine Side Effects

Common side effects of primaquine can range from mild to severe if the medicine is not taken as directed. Do not change the dose to increase the treatment effect, or because you do not feel any benefit, without speaking to your healthcare provider.

Gastrointestinal

The medicine may cause gastrointestinal effects, including acute intravascular haemolysis,

methemoglobinaemia, as well as immunosuppression through inhibition of lymphocyte proliferation. It may also cause an upset stomach, vomiting and nausea. These symptoms are usually temporary and may be managed with suitable medicines, but only after speaking to a doctor.

Hematologic

Its use may be linked to a sudden loss of red blood cells. This may lead to worsening health, with symptoms such as tiredness, changes in urine colour, changes in heartbeat, methemoglobinaemia and headache, among others.

Cardiac

You may experience a fast, slow or irregular heartbeat and other heart-related problems. Tell your doctor if you have a family history of heart disease or heart problems.

Nervous System

There is limited information confirming the effect of this medicine on the nervous system, although some people may experience tiredness or irritability. If you notice any changes in your nervous system or mental health, speak to your healthcare provider.

Skin and Soft Tissue

The medicine may rarely cause a severe allergic reaction. Skin-related side effects may include rash, itching, swelling and trouble breathing.

Note: some side effects are temporary and may settle as your body gets used to the medicine. However, long-term effects can occur and should be discussed with a doctor straight away.

Warnings

Before starting treatment with this medicine in the UK, speak to your healthcare provider to get the right dose and instructions for you. Some important warnings include the following.

Allergy

Allergic reactions to this medicine and its ingredients are possible, but rare. Symptoms may include itching, rash, trouble breathing and dizziness, among others. Give your doctor your full medical history, and make sure you mention any allergies to other medicines or foods.

Alcohol Interaction

It is not recommended to take this medicine with alcohol because it may cause dizziness or marked drowsiness. If you have taken primaquine with alcohol, do not drive or operate heavy machinery, as this could lead to injury or death. Both substances can greatly affect alertness. Tell your doctor if you use marijuana as well, as it should be avoided while taking this medicine.

For People With Certain Health Conditions

Certain health conditions may mean this medicine is not suitable for you. In particular, this includes immune system conditions such as rheumatoid arthritis and lupus. It also includes blood disorders such as anaemia, low white blood cell counts, haemolytic anaemia and methemoglobinaemia.

This medicine may also affect heart rhythm, so tell your doctor about your current heart health. You should also share any relevant family medical history.

Pregnant Women

This medicine should not be used during pregnancy or while breastfeeding. It may harm the fetus. It is strongly recommended to avoid pregnancy during and after treatment by using reliable contraception.

As it is not known whether this medicine passes into breast milk, breastfeeding mothers should not take it either.

You should also avoid grapefruit products, especially grapefruit juice, as they may affect how well this medicine works or increase side effects.

This is not a full list of all warnings and precautions. Discuss all relevant medical details with your healthcare provider for your own safety. Please also refer to the Medicines and Healthcare products Regulatory Agency (MHRA) prescribing information for this medicine to learn more.

Pros and Cons of Primaquine

Like other medicines, primaquine has benefits and drawbacks that should usually be discussed with your healthcare provider.

If you want to know more about the dosing regimen, especially for your own situation, speak to your doctor. If you notice any side effects or changes in your usual state of health, speak to your doctor to help prevent your condition from getting worse. Do not diagnose or treat yourself with this medicine based on online instructions, guidelines or comments from other patients who have had malaria or Pneumocystis pneumonia. This may be dangerous and could lead to overdose or even fatal events.