Zilxi Side Effects: What You Should Know Before Starting Treatment

Zilxi (Minocycline topical foam 1.5%) is a prescription medication used to treat the inflammatory bumps and pustules of rosacea in adults. Like any medication, it can cause side effects — though because it's applied to the skin rather than taken by mouth, many patients experience fewer systemic issues than they would with oral antibiotics.

This guide covers the common and serious side effects of Zilxi, who should use extra caution, and when to contact your doctor.

What Is Zilxi?

Zilxi is a topical foam containing Minocycline, a tetracycline-class antibiotic. It's applied once daily to the face to reduce the papules (red bumps) and pustules (pus-filled bumps) associated with rosacea. It was approved by the FDA and is manufactured by Journey Medical Corporation. For a full overview, see our guide on what Zilxi is and how it works.

Common Side Effects

In clinical trials, the most frequently reported side effects of Zilxi included:

• Diarrhea — This was the most common side effect, occurring in 1% or more of patients in clinical studies. While unexpected for a topical product, small amounts of Minocycline can be absorbed through the skin.
• Headache — Some patients reported headaches during treatment.
• Skin irritation at the application site — Redness, dryness, or mild burning at the site where the foam is applied.
• Nausea — Mild stomach upset was reported by some patients.

Most of these side effects are mild and tend to improve as your body adjusts to the medication. If any of them become bothersome or don't go away after the first few weeks, talk to your doctor.

Serious Side Effects

While serious side effects from Zilxi are uncommon — especially compared to oral Minocycline — they are possible because some of the drug is absorbed through the skin. Watch for:

• C. difficile-associated diarrhea — Severe, watery diarrhea that doesn't stop, stomach cramping, or bloody stools. This can occur weeks after starting any antibiotic, including topical ones. Seek medical attention immediately.
• Hepatotoxicity (liver injury) — Symptoms include yellowing of the skin or eyes (jaundice), dark urine, severe fatigue, or pain in the upper right abdomen.
• Autoimmune syndromes — Minocycline has been linked to drug-induced lupus, autoimmune hepatitis, and vasculitis. Symptoms may include joint pain, fever, rash, or unexplained swelling.
• Intracranial hypertension (pseudotumor cerebri) — Symptoms include severe headache, blurred vision, double vision, or vision loss. This risk is higher if you're also taking Isotretinoin (Accutane) or oral retinoids.
• Serious skin reactions — Stevens-Johnson syndrome, DRESS syndrome, and erythema multiforme are rare but potentially life-threatening. Seek emergency care for widespread skin rash with blistering, peeling, fever, or mouth sores.
• Photosensitivity — Increased sensitivity to sunlight, leading to severe sunburn. Use sunscreen and avoid prolonged sun exposure.
• Tissue hyperpigmentation — Minocycline can cause blue-gray discoloration of the skin, mucous membranes, or teeth. This is more common with long-term oral use but can occur with topical application.

Specific Populations

Some groups need extra caution with Zilxi:

• Pregnant women — Zilxi is not recommended during pregnancy. Tetracycline antibiotics may inhibit bone growth in the fetus and cause permanent tooth discoloration.
• Nursing mothers — Minocycline may be present in breast milk with oral use. Discuss the risks with your doctor before using Zilxi while breastfeeding.
• Children under 18 — Zilxi is not recommended for use in patients under 18 years old.
• Patients with kidney problems — Use with caution in patients with renal impairment, as Minocycline is partially excreted by the kidneys.
• Patients taking Isotretinoin — Do not use Zilxi with Isotretinoin (Accutane), as the combination increases the risk of intracranial hypertension. See our full guide on Zilxi drug interactions.

How to Manage Common Side Effects

Here are practical tips for dealing with the most common Zilxi side effects:

For Skin Irritation

• Apply a gentle, fragrance-free moisturizer after the Zilxi foam has fully absorbed.
• Avoid harsh cleansers, exfoliants, or other irritating skincare products.
• If irritation is severe, talk to your doctor about applying Zilxi every other day until your skin adjusts.

For Diarrhea or Nausea

• Stay hydrated and eat bland foods if you experience stomach issues.
• If diarrhea is severe, persistent, or bloody, stop using Zilxi and contact your doctor immediately — this could be a sign of C. difficile infection.

For Sun Sensitivity

• Apply a broad-spectrum sunscreen (SPF 30 or higher) every day, even on cloudy days.
• Wear a wide-brimmed hat and seek shade when possible.
• Avoid tanning beds.

For Headache

• Over-the-counter pain relievers like Acetaminophen (Tylenol) or Ibuprofen (Advil) can help with mild headaches.
• If headaches are severe, persistent, or accompanied by vision changes, contact your doctor right away — this could be a sign of intracranial hypertension.

When to Call Your Doctor

Contact your doctor or seek emergency care if you experience:

• Severe or bloody diarrhea
• Yellowing of your skin or eyes
• Severe headache with vision changes
• Widespread skin rash with blistering or peeling
• Joint pain, fever, or signs of an autoimmune reaction
• Blue-gray discoloration of your skin or gums

Final Thoughts

Most people tolerate Zilxi well, and serious side effects are uncommon with the topical foam formulation. The most common issues — mild diarrhea, headache, and skin irritation — are usually manageable and often improve with time.

That said, it's important to know the warning signs of serious reactions. If anything feels off, don't hesitate to contact your doctor. For more information about Zilxi, check out our guides on how Zilxi works and how to save money on your prescription.

Ready to fill your prescription? Find a pharmacy with Zilxi in stock near you on Medfinder.