Avoid in individuals with a known allergy or hypersensitivity to podophyllum.

Podophyllum applied on the skin for genital warts and oral hairy leukoplakia appears to be well-tolerated. Generally mild adverse effects include burning sensation, bad or altered taste, and mild pain to severe irritation in topical application. Adverse effects from ingestion by mouth may include gastrointestinal discomfort (diarrhea and abdominal pain).

Systemic absorption of podophyllum resin may result in tachycardia (increased heart rate), hypotension (low blood pressure), hallucinations, confusion, dizziness, and convulsions. These symptoms may be delayed in onset and prolonged in duration. Podophyllum may also cause nausea, vomiting, bloody-watery diarrhea, and a diminished number of neutrophils in the blood (neutropenia). Use cautiously in patients with Crohn's disease or irritable bowel syndrome (IBS).

Podophyllum toxicity may cause muscle paralysis, ataxia (loss of coordination), urinary retention, renal (kidney) failure, and hypotonia (decreased muscle tone). Chronic use of podophyllym as a cathartic (relieves constipation) may cause abnormally low potassium concentrations in the blood (hypokalemia) and metabolic alkalosis.

Podophyllotoxin solution (Wartec®) may cause sweaty palms and feet or rash. Alopecia (hair loss) and gastrointestinal toxicity (nausea, vomiting, stomatitis) has occurred in about 20-30% of patients given recommended dosages of etoposide, a semi-synthetic derivative of podophyllotoxin. Patients receiving oral CPH 82 for rheumatoid arthritis reported gastrointestinal discomfort (diarrhea and abdominal pain).

Use cautiously in patients with cardiovascular, muscular, and neurologic disorders, renal (kidney) insufficiency, liver insufficiency, hypertension (high blood pressure), arrhythmia (abnormal heart rate), or psychosis.

Avoid in patients with gallbladder disease or gallstones. Podophyllum is believed to stimulate the production of bile in the gallbladder.

Podophyllum is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence. Documented cases of birth defects and fetal deaths have been associated with podophyllum used during pregnancy.

Various doses have been studied with varying degrees of safety and efficacy. For rheumatoid arthritis, 300 milligrams of CPH 82, composed of two purified semisynthetic lignan glycosides of Podophyllum emodi, has been taken daily and used safely for up to 12 weeks.

When used topically and appropriately, podophyllum has been used safely for up to five weeks. For genital warts, 5 milliliters of 0.5% podophyllin applied on the affected area twice daily, three days a week for five weeks has been used; a 2% podophyllin preparation has also been applied topically to the affected area twice daily, three days a week for five weeks. For HIV-related hairy leukoplakia, topical podophyllum resin 25% solution for 30 days has been used.

There is no proven safe or effective dose for podopyllum in children.

Podophyllum toxicity may cause additive hypotension (low blood pressure) if administered with antihypertensive medications.

Podophyllum interrupts cellular mitosis at metaphase. Podophyllum may interact with drugs that have a similar mechanism, such as paclitaxel, vincristine. Additionally, anticancer agents may cause neutropenia (diminished number of neutrophils in the blood). Concurrent use of podophyllum and antineoplastic agents may cause further bone marrow suppression.

Podophyllum toxicity may cause a worsening of extrapyramidal symptoms that may occur with antipsychotic agents. Caution is advised when taking podophyllum with other agents that could potentiate these symptoms.

Although not well studied in humans, degenerative changes were observed in the liver after ingestion of podophyllum. Caution is advised when taking podophyllum with other potentially liver damaging agents due to the increased risk of liver damage.

Podophyllum has been historically used as a laxative. Concurrent use of podophyllum and other laxatives may result in an additive effect and cause dehydration and electrolyte disturbances (usually fluid depletion and accumulation of electrolytes).

Podophyllum toxicity may cause additive hypotension (low blood pressure) if administered with antihypertensive (blood pressure lowering) herbs and supplements.

Podophyllum may interrupt mitosis and prevent cell division. Additionally, anticancer agents may cause neutropenia (shortage of white blood cells). Concurrent use of podophyllum and anticancer agents may cause an increase in neutropenia (shortage of white blood cells).

Podophyllum toxicity may cause a worsening of extrapyramidal symptoms and neurologic side effects that may occur with some antipsychotic agents. Caution is advised when taking podophyllum with herbs or supplements that could potentiate these symptoms.

Although not well studied in humans, degenerative changes were observed in the liver after ingestion of podophyllum. Caution is advised when taking podophyllum with other potentially liver damaging herbs due to the increased risk of liver damage.

Podophyllum has been historically used as a laxative. Concurrent use of podophyllum and other laxatives may result in an additive effect and cause dehydration and electrolyte disturbances.