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  1. Pharmacology. Extracts of the milk thistle plant have been used since ancient times to treat a variety of hepatic and biliary disorders, including cholestasis, jaundice, cirrhosis, acute and chronic hepatitis, and primary malignancies, and to protect the liver against toxin-induced injury. The extract of the ripe seeds and leaves contains 70–80% silymarin, a flavanolignan mixture of which silibinin is the most biologically active constituent. The hypothesized mechanism of action is twofold: alteration of hepatocyte cell membrane permeability, preventing toxin penetration; and increased ribosomal protein synthesis, promoting hepatocyte regeneration.

    Although the efficacy of silibinin has not been established in controlled studies in humans, it has been associated with reduced liver damage when administered intravenously in the treatment of amatoxin mushroom poisoning. Competitive inhibition of amatoxin entry via the membrane transport system for bile salts has been demonstrated. Silibinin also appears to inhibit tumor necrosis factor (TNF) release in the injured liver, thus slowing the process of amatoxin-induced apoptosis. There is recent evidence that a continuous infusion of silibinin can effectively suppress viral load in patients with hepatitis C.

    Silymarin also is reported to have antifibrotic, anti-inflammatory, and antioxidant activity and may have therapeutic efficacy in the treatment of prostate and skin cancer. There is preliminary evidence that milk thistle constituents may also protect against the nephrotoxic effects of drugs such as acetaminophen, cisplatin, and vincristine.

  2. Indications

    1. Intravenous silibinin is approved across Europe for the prevention and treatment of fulminant hepatic failure following ingestion of amatoxin-containing mushrooms. An FDA-sanctioned clinical trial has recently made the drug available in the United States as well.

    2. Although this indication is unproven, silibinin may be effective as adjuvant therapy in cases of acute hepatic injury caused by acetaminophen toxicity, and potentially other chemical- and drug-induced liver diseases.

  3. Contraindications. None reported.

  4. Adverse effects are few and generally mild.

    1. Nausea, diarrhea, abdominal fullness or pain, flatulence, and anorexia may occur in users of oral preparations.

    2. Mild warmth and a flushing sensation are commonly reported during intravenous infusion.

    3. Milk thistle is a member of the Asteraceae (daisy) family and can cause an allergic reaction in ragweed-sensitive individuals, including rash, urticaria, pruritus, and anaphylaxis.

    4. Use in pregnancy. FDA Category B. Insufficient reliable information is available (See Introduction in Section III).

  5. Drug or laboratory interactions. Although milk thistle has been shown to induce slight cytochrome P-450 enzyme inhibition in vitro, significant drug interactions with milk thistle extract have not been demonstrated in humans.

  6. Dosage and method of administration

    1. Intravenous dosing for amatoxin mushroom poisoning is 20–50 mg/kg/d by continuous infusion or in four divided doses administered over 2 hours each.

    2. Oral doses used in published studies have ranged from 280–800 mg/d of standardized silymarin. A typical dose used for chronic hepatitis is 420 mg/d in two or three oral doses.

  7. Formulations

    1. Oral. In the United States, milk thistle extracts are available as over-the-counter dietary supplements (eg, Thisilyn). Oral formulations include Legalon (standardized to contain 70% silibinin) and Silipide (silibinin complexed with phosphatidylcholine, which has a higher oral bioavailability). ...

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