Daptomycin Side Effects: What You Should Know

Daptomycin (brand name Cubicin) is a powerful IV antibiotic used to treat serious bacterial infections like MRSA bacteremia, complicated skin infections, and endocarditis. Like all antibiotics, it comes with potential side effects — some mild and manageable, others that need immediate medical attention.

This guide covers the most common and serious side effects of Daptomycin based on FDA labeling, so you know what to watch for during your treatment.

What Is Daptomycin?

Daptomycin is a cyclic lipopeptide antibiotic that works by disrupting bacterial cell membranes. It's administered intravenously (IV) and is only effective against gram-positive bacteria — including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). For a deeper dive, read our guide on what Daptomycin is and how it's used.

Common Side Effects

The following side effects are reported frequently in clinical trials and are generally mild to moderate. They often improve as your body adjusts to the medication:

• Diarrhea — One of the most common side effects. Stay hydrated and let your doctor know if it becomes severe or persistent.
• Headache — Usually mild and manageable with over-the-counter pain relievers (with your doctor's approval).
• Nausea and vomiting — May occur during or shortly after infusion. Eating a light meal beforehand can help.
• Constipation — Less common than diarrhea but still reported.
• Injection site reactions — Redness, swelling, or pain at the IV site. Let your nurse or infusion team know if this happens.
• Insomnia — Some patients report difficulty sleeping during treatment.
• Rash — Mild skin rashes have been reported. If a rash spreads or is accompanied by other symptoms, contact your doctor immediately.
• Limb pain — Aching in the arms or legs may occur.
• Elevated CPK levels — Creatine phosphokinase (CPK) is a muscle enzyme. Mild elevations are common and don't always cause symptoms, but they need monitoring.

Serious Side Effects

These side effects are less common but can be dangerous. Contact your doctor or seek emergency care if you experience any of the following:

Myopathy and Rhabdomyolysis

This is the most well-known serious risk of Daptomycin. Myopathy means muscle damage, and rhabdomyolysis is a severe form where muscle breakdown products can damage your kidneys.

Watch for:

• Unexplained muscle pain, tenderness, or weakness
• Dark or brown-colored urine
• Elevated CPK levels on blood tests (your doctor should check weekly)

If you're taking statins (like Atorvastatin or Simvastatin), your doctor should temporarily stop them during Daptomycin therapy to reduce this risk. Learn more in our Daptomycin drug interactions guide.

Eosinophilic Pneumonia

This is a rare but serious lung reaction that the FDA has specifically warned about.

Watch for:

• New or worsening cough
• Fever
• Difficulty breathing or shortness of breath

If you develop these symptoms during Daptomycin treatment, contact your doctor immediately. This condition usually resolves after stopping the medication, but it requires prompt attention.

Important: Daptomycin should never be used to treat pneumonia — it is inactivated by lung surfactant and won't work for lung infections.

Peripheral Neuropathy

Some patients experience tingling, numbness, or burning sensations in their hands or feet. Report any new nerve symptoms to your doctor.

Clostridioides difficile-Associated Diarrhea (CDAD)

Like many antibiotics, Daptomycin can disrupt your gut bacteria and lead to a C. difficile infection. This causes severe, watery diarrhea that may be bloody.

Watch for:

• Watery diarrhea (more than 3 times per day)
• Abdominal cramping or pain
• Fever
• Blood or mucus in stool

Anaphylaxis and Hypersensitivity

Severe allergic reactions are rare but possible. Signs include hives, swelling of the face or throat, difficulty breathing, and a rapid heartbeat. This is a medical emergency — call 911.

Renal Impairment

Daptomycin can affect kidney function, especially if combined with other nephrotoxic medications. Your doctor should monitor your kidney function with regular blood tests.

Side Effects in Specific Populations

Children

Daptomycin is approved for pediatric use in children 1 year and older. It is not recommended for children under 12 months due to the risk of effects on the muscles and nervous system.

Elderly Patients

Older adults may be more susceptible to side effects, particularly renal impairment. Dose adjustments may be necessary if kidney function is reduced.

Patients with Kidney Problems

If your creatinine clearance is less than 30 mL/min (including dialysis patients), your doctor will adjust the dosing schedule — typically giving Daptomycin every 48 hours instead of daily.

Pregnant or Breastfeeding Women

Daptomycin is FDA Pregnancy Category B. It should only be used during pregnancy if clearly needed. Discuss risks and benefits with your doctor.

How to Manage Side Effects

Here are some practical tips for dealing with Daptomycin side effects:

• Stay hydrated — This helps with diarrhea, nausea, and kidney protection.
• Keep all lab appointments — Weekly CPK monitoring is essential. Don't skip blood draws.
• Report muscle symptoms immediately — Unexplained muscle pain or weakness needs prompt evaluation.
• Avoid strenuous exercise — Heavy physical activity can raise CPK levels and make it harder to monitor for myopathy.
• Tell your doctor about all medications — Especially statins and other drugs that affect muscles or kidneys.
• Don't stop treatment early — Even if you feel better, completing the full course is critical to prevent resistance. If side effects are intolerable, talk to your doctor about alternatives to Daptomycin.

Final Thoughts

Most people tolerate Daptomycin well, especially with proper monitoring. The key is knowing what to watch for — particularly muscle symptoms and breathing problems — and communicating with your medical team throughout treatment.

If you're having trouble finding Daptomycin in stock for your treatment, Medfinder can help you locate pharmacies with availability near you.