Clindesse Side Effects: What to Expect and When to Call Your Doctor

Clindesse is a single-dose intravaginal antibiotic cream used to treat bacterial vaginosis (BV). Because it's administered locally in the vagina as a single application, most patients tolerate it well. However, side effects do occur, and some are important to recognize. Here's a clear rundown of what to expect, based on clinical trial data and FDA labeling.

How Clindesse Works and Why Side Effects Occur

Clindesse (clindamycin phosphate 2%) is a lincosamide antibiotic that works by inhibiting bacterial protein synthesis. It kills or stops the growth of the anaerobic bacteria that cause BV. While the drug is applied locally (intravaginally), small amounts are absorbed systemically — about 5% of the dose reaches the bloodstream. This minimal systemic absorption is sufficient to cause side effects beyond the vaginal area in some patients.

Common Side Effects of Clindesse (≥2% in Clinical Trials)

In placebo-controlled clinical trials involving 368 Clindesse-treated patients, the following adverse reactions occurred in 2% or more of patients at a higher rate than placebo:

Vaginal yeast infection / fungal vaginosis: 14% — The most common side effect. Clindamycin kills the bacteria causing BV but can also disrupt the normal vaginal flora, allowing Candida (yeast) to overgrow. If you develop itching, thick white discharge, or irritation after using Clindesse, see your doctor — an antifungal treatment may be needed.

Headache: 7% — Mild to moderate headache is one of the most common non-vaginal side effects reported. Usually self-limiting.

Back pain: 5% — Reported in clinical trials, though the causal relationship is not always clear.

Constipation: 2% — Likely related to systemic absorption of clindamycin.

Urinary tract infection (UTI): 2% — Reported at a higher rate in the Clindesse group than placebo in trials.

Local Vaginal Side Effects

In addition to the yeast infection risk, Clindesse can cause local vaginal reactions including:

Vaginal itching, burning, or irritation

Vaginal discharge (may be related to the cream itself or to the treatment response)

Vaginal pain or discomfort

Serious Side Effects to Watch For

While rare with intravaginal clindamycin, serious reactions can occur and should be treated as medical emergencies:

Severe allergic reaction (anaphylaxis): Signs include rash, hives (urticaria), swelling of the face/lips/tongue/throat, difficulty breathing, or dizziness. Stop use immediately and seek emergency care.

Clostridioides difficile-associated diarrhea (CDAD): Any antibiotic — including intravaginal clindamycin — can trigger C. difficile colitis by disrupting gut flora. While rare with topical use, CDAD has been reported. If you develop severe or persistent diarrhea (with or without blood/mucus) during or up to 2 months after treatment, contact your doctor immediately.

Erythema multiforme: A rare skin reaction that can manifest as target-shaped lesions on the skin and mucous membranes. Reported with clindamycin formulations; seek care if you notice unusual skin changes.

Important Safety Notes

Condom/diaphragm compatibility: Clindesse's cream base contains mineral oil, which weakens latex and rubber. Do not use latex condoms or diaphragms for at least 5 days after using Clindesse. Polyurethane condoms may also be less reliable for up to 7 days after treatment.

Pregnancy: Clindesse is not recommended during pregnancy (insufficient safety data). If you are pregnant, tell your doctor so they can prescribe an appropriate alternative.

C. diff history: Clindesse is contraindicated in patients with a history of C. difficile-associated diarrhea. Inform your provider of your C. diff history before starting treatment.

When Should You Call Your Doctor?

Call your doctor or seek care if you experience:

Signs of a new yeast infection (thick white discharge, intense itching)

Symptoms of a UTI (burning urination, frequency, urgency, cloudy urine)

Diarrhea — especially watery, bloody, or mucus-containing diarrhea — during or up to 2 months after treatment

Any signs of allergic reaction (hives, swelling, trouble breathing)

BV symptoms that don't improve within 1 week of treatment

Also see: Clindesse Drug Interactions: What to Avoid and What to Tell Your Doctor.

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