Fixed Combinations of Lily-of-the-Valley herb and Squill

Fixed combinations of lily-of-the-valley herb and squill.

Fixed combinations consisting of:

• Lily-of-the-valley herb corresponding to DAB 10;
• squill corresponding to DAB 10;
• as well as their preparations.  

The leading glycoside of lily-of-the-valley leaf is convallatoxin; of squill, proscillaridin A.

The actions of cardiac glycosides on the heart are:

1. positive inotropic (increasing contractile strength and velocity while delaying relaxation);
2. negative chronotropic (decreasing the time or rate of contraction);
3. negative dromotropic (decreasing stimulus conduction);
4. positive bathmotropic (increasing stimulation of the ventricular muscle).  

Pharmacokinetics

Convallatoxin:

• For convallatoxin an absorption rate of 10 percent and a subsidence rate of 40 - 50 percent are given.  The absorption rate is believed to be increased by saponins contained in the herb.  No information is available concerning its metabolism in humans.  A renal/biliary excretion is assumed.  Binding to plasma proteins lies between 16 and 23 percent.  

Recent investigations, particularly for the substance reacting in combination, are not available.

Proscillaridin A:

• Proscillaridin A is absorbed at a rate of 20 - 30 percent; the half-life value is 45 - 50 hours.  The plasma protein binding is about 85 percent.  Proscillaridin A is eliminated after biliary conjugation with glucuronic and sulfuric acid.  There is evidence for an entero-hepatic circulation.  Recent information pertaining to the substance in the combination is not available.  Pharmacodynamic and pharmacokinetic studies with the fixed combination of lily-of-the-valley herb and squill are not available.  
• A "sub-additive" effect on guinea pigs is described for the toxicity of proscillaridin A and convallatoxin.  The transferability of these data to the herbs is not clear.
• Pertaining to the cumulative effect and pharmacokinetics affecting patients at risk, e.g., patients with kidney insufficiency, there are no data available for the herbs and their fixed combination.  

Clinical Data

Preparations of the fixed combination of lily-of-the-valley and squill are used for mild and moderate forms of heart insufficiency, also for diminished kidney capacity, geriatric heart, chronic cor pulmonale, continuation of digitalis therapy (interval treatment), hypertonia, neurocirculatory disturbances, such as tachycardia, feeling of oppression, as a diuretic with mainly cardiac target, and for functional heart symptoms.

There is no useful information available for the claimed uses.  The effectiveness for the claimed applications is not documented.

Not to be used in case of therapy with digitalis glycosides, digitalis intoxication, hypercalcemia, potassium deficiency, bradycardia, ventricular tachycardia.

Since no investigations for the use by children are available, the application is contraindicated.

Caution if conduction disturbances exist and i.v.  calcium therapy is applied.

Side effects that may occur: nausea, vomiting, gastric disturbances, irregular pulse and cardiac dysrhythmia.

Increase in effectiveness, and thus also side effects, occurs with simultaneous administration of quinidine, calcium, saluretics, laxatives and long-term therapy with glucocorticoids.  One case report exists of an Adam-Stokes seizure.  More information is not available.

Positive monographs are available for the individual herbs.

Sufficiently validated information concerning the dosage of the herb in the combination products, as well as the ratio of the herbs to each other, is not available.  Because of the inadequate pharmacodynamic and pharmacokinetic study, as well as inadequate clinical study pertaining to the fixed combination, effectiveness and safety of preparations of lily-of-the-valley herb and squill cannot be evaluated.

Without further investigation, the risk of the combination cannot be evaluated.  Cardiac glycosides have a comparatively narrow therapeutic range, making respective investigations necessary, especially if a prolonged therapy is required.  The risks are not biased to the fixed combination as compared to the individual herbs.  No scientific information is available for the effectiveness of this medicinal combination.