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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Arrhythmia. Although there has been interest in using oral lily-of-the-valley for arrhythmia, there is insufficient reliable information about the clinical effects of lily-of-the-valley for this purpose.
• Heart failure. Although there has been interest in using oral lily-of-the-valley for heart failure, there is insufficient reliable information about the clinical effects of lily-of-the-valley for this purpose. More evidence is needed to rate lily-of-the-valley for these uses.

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There is insufficient reliable information available about the effectiveness of star of Bethlehem.

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POSSIBLY UNSAFE ...when the standardized extract is used orally (2,12). Medical supervision and monitoring may reduce the risk for serious safety events; however, botanical cardiac glycosides are generally not recommended for use. Poor oral absorption of the cardiac glycosides in lily-of-the-valley can reduce the risk of poisoning (18), but the number of glycosides and their varied properties makes therapeutic use difficult (7).

LIKELY UNSAFE ...when the whole plant is ingested. Lily-of-the-valley is considered poisonous (12).

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally for self-medication (12). Avoid using.

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LIKELY UNSAFE ...when used orally. Star of Bethlehem contains toxic cardiac glycosides (15330,15331,15332,15333). Ingestion of star of Bethlehem could result in serious adverse effects including cardiac arrhythmia and death.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally. Star of Bethlehem contains toxic cardiac glycosides (15330,15331,15332,15333). Ingestion of star of Bethlehem could result in serious adverse effects.

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CORTICOSTEROIDS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, using lily-of-the-valley with prolonged corticosteroid therapy can cause cardiac glycoside toxicity.  Details Lily-of-the-valley contains cardiac glycosides (2). Concomitant, long-term corticosteroid use can increase the risk of cardiac glycoside toxicity due to potassium depletion and electrolyte imbalance.

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = D Using lily-of-the-valley with digoxin can cause cardiac glycoside toxicity.  Details Lily-of-the-valley contains cardiac glycosides (2). Use of the cardiac glycoside digoxin and lily-of-the-valley concomitantly increases the risk of cardiac glycoside toxicity.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using lily-of-the-valley with diuretics can increase the risk of cardiac glycoside toxicity.  Details Lily-of-the-valley contains cardiac glycosides. Concomitant use of potassium depleting diuretics and lily-of-the-valley can increase the risk of cardiac glycoside toxicity due to potassium depletion and electrolyte imbalance (506).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, lily-of-the-valley can increase levels of lithium and increase toxicity.  Details Lily-of-the-valley is thought to have diuretic properties (18). Theoretically, due to these potential diuretic effects, lily-of-the-valley might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

MACROLIDE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using lily-of-the-valley with macrolide antibiotics can increase the risk of cardiac glycoside toxicity.  Details Macrolide antibiotics appear to increase the gastrointestinal absorption of oral digoxin. Theoretically, concomitant use of macrolide antibiotics might increase the absorption of the cardiac glycosides found in lily-of-the-valley (17).

QUININE Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, using lily-of-the-valley with quinine can increase the risk of cardiac glycoside toxicity.  Details Quinine may reduce the clearance of oral digoxin. Theoretically, concomitant use of quinine with lily-of-the-valley might reduce the clearance of cardiac glycosides found in lily-of-the-valley and increase the risk of toxicity (506).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using lily-of-the-valley with stimulant laxatives can increase the risk of cardiac glycoside toxicity.  Details Lily-of-the-valley contains cardiac glycosides. The overuse of stimulant laxatives can increase the risk of cardiac glycoside toxicity with lily-of-the-valley due to potassium depletion (19).

TETRACYCLINE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, using lily-of-the-valley with tetracycline antibiotics might increase the risk of cardiac glycoside toxicity.  Details Tetracycline antibiotics appear to increase the gastrointestinal absorption of oral digoxin, a cardiac glycoside. Theoretically, concomitant use of tetracycline antibiotics might increase the absorption of the cardiac glycosides found in lily-of-the-valley (17).

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CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking star of Bethlehem with prolonged corticosteroid therapy might increase the risk of toxicity.  Details Star of Bethlehem contains cardiac glycosides (15330,15331). Concomitant use of corticosteroids with star of Bethlehem can increase the therapeutic and adverse effects of long-term corticosteroid use due to potassium depletion and electrolyte imbalance.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking star of Bethlehem in combination with digoxin might have additive effects and increase the risk of toxicity.  Details Star of Bethlehem contains cardiac glycosides with effects similar to digoxin (15330,15331).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking diuretics with star of Bethlehem might increase the risk of toxicity.  Details Star of Bethlehem contains cardiac glycosides (15330,15331). Theoretically, concomitant use of potassium-depleting diuretics and star of Bethlehem can increase the risk of cardiac glycoside toxicity due to potassium depletion (506).

MACROLIDE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking macrolide antibiotics with star of Bethlehem might increase the risk of cardiac glycoside toxicity.  Details Star of Bethlehem contains cardiac glycosides (15330,15331). Macrolide antibiotics appear to increase the gastrointestinal absorption of oral digoxin. Theoretically, concomitant use of macrolide antibiotics might increase the absorption of the cardiac glycosides found in star of Bethlehem and increase the risk of adverse effects (17).

QUININE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking quinine with star of Bethlehem might increase the risk of cardiac glycoside toxicity.  Details Star of Bethlehem contains cardiac glycosides (15330,15331). Quinine may reduce the clearance of oral digoxin. Theoretically, concomitant use of quinine might reduce the clearance of cardiac glycosides found in star of Bethlehem and increase the risk of adverse effects (2).

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, excessive use of stimulant laxatives with star of Bethlehem might increase the risk of toxicity.  Details Star of Bethlehem contains cardiac glycosides (15330,15331). Excessive use of stimulant laxatives can cause diarrhea, resulting in potassium depletion. This might increase the risk of cardiac glycoside toxicity.

TETRACYCLINE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking tetracycline antibiotics with star of Bethlehem might increase the risk of cardiac glycoside toxicity.  Details Star of Bethlehem contains cardiac glycosides similar to digitalis (15330,15331). Tetracycline antibiotics appear to increase the gastrointestinal absorption of oral digoxin. Theoretically, concomitant use of tetracycline antibiotics might increase the absorption of the cardiac glycosides found in star of Bethlehem and increase the risk of adverse effects (17).

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General ...When used orally without the supervision of a healthcare professional, lily-of-the-valley is unsafe.
Serious Adverse Effects (Rare):
Orally, lily-of-the-valley can cause cardiac arrhythmias.

Cardiovascular ...Orally, lily-of-the-valley can cause cardiac arrhythmias, due to the numerous cardiac glycosides it contains (2). In one case report, an 87-year-old female was admitted to the hospital with bradycardia, cardiac repolarization abnormalities, and elevated blood pressure after the consumption of 2 sprigs of lily-of-the-valley. The patient was discharged after 24 hours monitoring. (115496).

Gastrointestinal ...Orally, lily-of-the-valley can cause nausea and vomiting (2).

Neurologic/CNS ...Orally, lily-of-the-valley can cause headache and stupor (18). Visual color disturbances can also occur (18).

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General ...Star of Bethlehem contains cardiac glycosides, which can cause serious adverse effects.
Serious Adverse Effects (Rare):
Orally: Star of Bethlehem contains toxic cardiac glycosides that can cause cardiac arrhythmia and death.

Cardiovascular ...Orally, the cardiac glycosides in star of Bethlehem can cause cardiac arrhythmias (2).

Gastrointestinal ...Orally, the cardiac glycosides in star of Bethlehem can cause nausea and vomiting (2).

Neurologic/CNS ...Orally, the cardiac glycosides in star of Bethlehem can cause headache and stupor (18). Visual color disturbances can also occur (18).

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