The Potential Side Effects of Primaquine: What You Need to Know

Primaquine is a medication used to prevent malaria relapses, especially in cases caused by Plasmodium vivax and Plasmodium ovale. It’s often prescribed after other antimalarials like chloroquine to kill dormant liver parasites that can wake up weeks or months later. But while it’s effective, it’s not without risks. Many people take it without knowing what could go wrong - and that’s where things get dangerous.

What primaquine does - and why it’s not just another pill

Primaquine works by targeting the dormant forms of malaria parasites hiding in your liver. Unlike other antimalarials that only attack the blood stage, primaquine clears out the hidden reservoirs. That’s why it’s critical for travelers returning from places like Southeast Asia, South America, or parts of Africa where these parasite types are common. But here’s the catch: it only works if your body can process it correctly - and not everyone can.

The biggest risk: hemolytic anemia in G6PD-deficient people

The most serious side effect of primaquine is hemolytic anemia - a condition where red blood cells break down too fast. This doesn’t happen to everyone. It only affects people with a genetic condition called glucose-6-phosphate dehydrogenase (G6PD) deficiency. About 400 million people worldwide have this, mostly of African, Mediterranean, or Southeast Asian descent. In the UK, it’s less common but still present, especially among communities with ancestry from those regions.

If you’re G6PD deficient and take primaquine, your red blood cells can’t handle the oxidative stress the drug causes. They burst, leading to fatigue, dark urine, jaundice, and in severe cases, kidney failure or shock. This isn’t a rare reaction - it’s the leading reason primaquine causes hospitalizations. That’s why doctors are supposed to test your G6PD levels before prescribing it. If they don’t, you’re at risk.

Other common side effects you might not expect

Even if you’re not G6PD deficient, primaquine can still cause unpleasant reactions. The most frequent ones include:

• Nausea and vomiting - especially if taken on an empty stomach
• Stomach cramps or bloating
• Dizziness or lightheadedness
• Headaches
• Heartburn or indigestion

These usually show up within the first few days of starting the drug and often fade as your body adjusts. Taking it with food helps reduce stomach upset. But if vomiting is severe or you can’t keep the pill down, contact your provider - you might need a different treatment.

Less common but serious reactions

Some side effects are rare but require immediate attention:

• Dark or tea-colored urine - a sign of red blood cell breakdown
• Yellowing of the skin or eyes (jaundice)
• Unexplained fever or chills
• Rapid heartbeat or shortness of breath
• Severe skin rash or blistering

If you notice any of these, stop taking primaquine and seek medical help right away. These could signal a serious reaction beyond simple side effects. In rare cases, primaquine has been linked to methemoglobinemia - a condition where your blood can’t carry oxygen properly. Symptoms include bluish lips or skin, confusion, and fatigue. It’s more likely in people with certain enzyme disorders or those taking other drugs like sulfonamides or nitrites.

Who should never take primaquine?

Primaquine isn’t safe for everyone. You should avoid it if:

• You’ve been tested and have G6PD deficiency
• You’re pregnant - it can harm the fetus, especially in the first trimester
• You’re breastfeeding and your baby has unknown G6PD status
• You have a history of severe allergic reactions to primaquine or similar drugs
• You have active systemic infections like sepsis or severe liver disease

Even if you’ve taken primaquine before without issues, don’t assume it’s safe every time. Your health can change. A new medication, an infection, or even a change in diet can alter how your body handles the drug.

What to do before and during treatment

Before starting primaquine, make sure your doctor has:

1. Ordered a G6PD blood test - don’t rely on family history alone
2. Reviewed all your current medications - some interact badly with primaquine
3. Asked about your ancestry and past reactions to drugs

During treatment:

• Take the pill with food to reduce nausea
• Drink plenty of water - staying hydrated helps your kidneys flush out byproducts
• Watch for signs of anemia or jaundice - check your urine color daily
• Don’t skip doses - incomplete treatment can lead to drug resistance

Keep a small notebook. Write down any new symptoms, no matter how small. Even mild dizziness or a strange taste in your mouth could be an early warning.

What happens if you miss a dose or take too much?

If you miss a dose, take it as soon as you remember - unless it’s close to your next scheduled dose. Then skip the missed one. Never double up. Taking too much primaquine increases the risk of severe toxicity, especially if you’re undiagnosed with G6PD deficiency.

Overdose symptoms include vomiting, confusion, seizures, and breathing trouble. If you think you’ve taken too much, call emergency services immediately. There’s no antidote, but supportive care - like oxygen, IV fluids, and blood transfusions - can save your life.

How primaquine compares to other radical cure options

Primaquine isn’t the only drug used to prevent relapses. Tafenoquine is a newer alternative that works in a single dose. But it has the same G6PD risk and is more expensive. It’s also not approved for pregnant women or children under 16. For most people, primaquine remains the standard because it’s cheaper, widely available, and well-studied over decades.

Still, if you have mild G6PD deficiency, your doctor might prescribe a lower dose of primaquine over a longer period - sometimes up to 14 days - to reduce risk. This is called “low-dose primaquine” and is used in places like Thailand and Brazil with good success.

Real-world examples: What went wrong

In 2023, a traveler returning from Cambodia developed severe anemia after taking primaquine. He had no family history of G6PD deficiency and assumed he was fine. The test came back positive only after he was hospitalized. His case wasn’t unique. A study from the UK Health Security Agency found that 1 in 5 patients prescribed primaquine in 2022 had no prior G6PD testing - and 12% of them developed moderate to severe hemolysis.

Another case involved a woman in Leeds who took primaquine after a trip to India. She had mild nausea but ignored it. Two days later, her urine turned dark. She waited another day before seeing a doctor. By then, her hemoglobin had dropped dangerously low. She needed a blood transfusion. Her story highlights a dangerous myth: “If I feel okay, it’s fine.” Side effects can sneak up fast.

When to get help - and what to tell your doctor

Don’t wait for symptoms to get bad. If you’re on primaquine and notice:

• Unusual tiredness that doesn’t go away
• Dark urine
• Yellow eyes or skin
• Shortness of breath during normal activity

Call your doctor or go to urgent care. Tell them: “I’m taking primaquine and I’m worried about side effects.” That phrase alone will trigger the right checks - G6PD levels, liver enzymes, hemoglobin count.

Many doctors don’t ask about ancestry or drug history unless prompted. Be your own advocate. Bring a list of all medications, supplements, and recent travel. Don’t assume they know what you’ve been through.

Final thoughts: Primaquine is powerful - but not risk-free

Primaquine saves lives by stopping malaria from coming back. But it’s not a benign pill. It’s a tool that needs careful handling. The risks are real, predictable, and preventable - if you get tested, listen to your body, and speak up.

If your doctor skips the G6PD test, ask why. If you feel off after starting the drug, don’t brush it off. Your health isn’t worth gambling with.

If you’re planning travel to a malaria zone, talk to your doctor at least 4-6 weeks ahead. Don’t wait until you’re packing your bags. Primaquine isn’t something to rush into. It’s a medication that demands respect - and a little caution goes a long way.