續上篇
3.5.1.J Dicumarol
3.5.1.J Dicumarol
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
3.5.1.K Fondaparinux
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
3.5.1.L Heparin
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
3.5.1.M Pentosan Polysulfate Sodium
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
3.5.1.N Phenindione
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
3.5.1.O Phenprocoumon
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
3.5.1.P Warfarin
1) Interaction Effect: reduced anticoagulant effectiveness
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
2) Summary: Coenzyme Q10 had no effect on the international normalized ratio (INR) in patients stable on warfarin in a randomized, double-blind, placebo-controlled, crossover trial (Engelsen et al, 2003a). Case reports associate coenzyme Q10 therapy with decreased INR in patients taking warfarin (Spigset, 1994a). Caution is advised if patients take coenzyme Q10 and warfarin.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Caution is advised if coenzyme Q10 and warfarin are taken together. Monitor the INR to determine continued therapeutic effect.
7) Probable Mechanism: similar chemical structure of coenzyme Q10 and vitamin K2
8) Literature Reports
a) Three patients were reported to have a decrease in the international normalized ratio (INR) after addition of ubidecarenone (coenzyme Q10) to their warfarin regimens. A 68-year-old man with a stable INR of 2 to 3.5 on warfarin had an INR of 1.31 after two weeks of taking ubidecarenone 30 mg daily. Ubidecarenone was discontinued and the INR subsequently remained therapeutic. A 72-year-old man developed a pulmonary embolism after three months of taking ubidecarenone. A 70-year-old woman stable on warfarin for several years had an INR of 1.42 after two weeks of taking ubidecarenone 30 mg daily. Her INR returned to the therapeutic range after discontinuation of ubidecarenone and a temporary increase in warfarin dosage (Spigset, 1994).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
b) Coenzyme Q10 did not affect the international normalized ratio (INR) in a randomized, double-blind, placebo-controlled, crossover trial of 24 patients stable on warfarin. Patients received coenzyme Q10 100 milligrams (mg) daily in addition to their regular warfarin therapy for four weeks, then crossed over to placebo after a two-week washout. The geometric mean warfarin dose remained the same and INR was unaffected during treatment (Engelsen et al, 2003).
4.0 Clinical Applications
Monitoring Parameters
Patient Instructions
Place In Therapy
Mechanism of Action / Pharmacology
Therapeutic Uses
4.1 Monitoring Parameters
A) Therapeutic
1) Laboratory Parameters
a) In patients with congestive heart failure, echocardiograms, impedance cardiography, chest X-ray, radionuclide ventriculography, and electrocardiograms should be performed periodically during coenzyme Q10 therapy.
b) Coenzyme Q10 blood levels of 2 to 2.5 mcg/mL have been associated with clinical efficacy in heart failure, although this requires confirmation. Normal (endogenous) blood levels are 0.7 to 1 mcg/mL.
b) Coenzyme Q10 blood levels of 2 to 2.5 mcg/mL have been associated with clinical efficacy in heart failure, although this requires confirmation. Normal (endogenous) blood levels are 0.7 to 1 mcg/mL.
2) Physical Findings
a) CONGESTIVE HEART FAILURE
1) Clinical signs and symptoms (eg, edema, pulmonary rales, dyspnea, cyanosis, liver enlargement)
B) Toxic
1) Laboratory Parameters
a) Liver function tests
2) Physical Findings
a) Blood pressure
b) Heart rate
b) Heart rate
4.2 Patient Instructions
A) Coenzyme Q10 (By mouth)
Coenzyme Q10
Used as a dietary supplement.
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to coenzyme Q10.
How to Use This Medicine:
Chewable Tablet, Liquid Filled Capsule
Used as a dietary supplement.
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to coenzyme Q10.
How to Use This Medicine:
Chewable Tablet, Liquid Filled Capsule
Your doctor will tell you how much of this medicine to use and how often. Do not use more medicine or use it more often than your doctor tells you to.
If you are using this medicine without a doctor's order, follow the instructions on the medicine label.
If you are using this medicine without a doctor's order, follow the instructions on the medicine label.
If a Dose is Missed:
Try not to miss any doses. However, because this is a dietary supplement, do not worry if you miss one or two doses.
How to Store and Dispose of This Medicine:
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine after you have finished your treatment. You will also need to throw away old medicine after the expiration date has passed.
Keep all medicine away from children and never share your medicine with anyone.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any leftover medicine after you have finished your treatment. You will also need to throw away old medicine after the expiration date has passed.
Keep all medicine away from children and never share your medicine with anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including over-the-counter medicines, vitamins, and herbal products.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breast feeding.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing.
If you notice these less serious side effects, talk with your doctor:
If you notice other side effects that you think are caused by this medicine, tell your doctor.
4.3 Place In Therapy
A) Coenzyme Q10 has shown promise in the treatment of several cardiovascular and noncardiovascular disorders, including congestive heart failure, hypertension, angina, and periodontal disease; there is some evidence of its efficacy as a myocardial preserving agent in heart surgery. However, the conflicting results of many studies underscore the need for well-designed trials with this agent, rigidly comparing it to placebo or other known-active agents in sufficiently large patient populations to provide meaningful statistical analysis of results; such studies are few.
B) One advantage of coenzyme Q10 is its apparent very low order of toxicity; this could enable it to be used in some conditions where efficacy is suggested based on currently available studies, but definitive conclusions regarding its ultimate role are awaiting results of further or ongoing investigations. The cost of therapy with coenzyme Q10 will be an important consideration if used in this "experimental" fashion, to be accepted or rejected pending further data; this application should of course also be limited to situations where traditional forms of therapy have failed or are intolerable. Of potential indications, the most experience with coenzyme Q10 has been in congestive heart failure, and its add-on use can be recommended in patients with class III or IV chronic heart failure who are responding poorly to conventional regimens (eg, digoxin, diuretics, angiotensin-converting enzyme inhibitors).
C) In addition to the need for well-controlled trials in other indications, further studies are needed to investigate the pharmacokinetics of coenzyme Q10 and its potential for drug interactions, and to determine optimal dose regimens in various conditions.
B) One advantage of coenzyme Q10 is its apparent very low order of toxicity; this could enable it to be used in some conditions where efficacy is suggested based on currently available studies, but definitive conclusions regarding its ultimate role are awaiting results of further or ongoing investigations. The cost of therapy with coenzyme Q10 will be an important consideration if used in this "experimental" fashion, to be accepted or rejected pending further data; this application should of course also be limited to situations where traditional forms of therapy have failed or are intolerable. Of potential indications, the most experience with coenzyme Q10 has been in congestive heart failure, and its add-on use can be recommended in patients with class III or IV chronic heart failure who are responding poorly to conventional regimens (eg, digoxin, diuretics, angiotensin-converting enzyme inhibitors).
C) In addition to the need for well-controlled trials in other indications, further studies are needed to investigate the pharmacokinetics of coenzyme Q10 and its potential for drug interactions, and to determine optimal dose regimens in various conditions.
4.4 Mechanism of Action / Pharmacology
A) MECHANISM OF ACTION
1) Coenzyme Q10 is a fat-soluble quinone which is synthesized intracellularly and participates in a variety of essential cellular processes. It is primarily found in the inner mitochondrial membrane, and highest concentrations in the human body are in the heart, liver, kidney, and pancreas; the total body content ranges from 0.5 to 1.5 g. Coenzyme Q10 is an essential coenzyme and has vitamin-like characteristics; it is structurally similar to vitamin K (Beyer, 1992; Langsjoen et al, 1988; Lampertico & Comis, 1993; Farah et al, 1984; Mortensen, 1993; Greenberg & Frishman, 1990a).
2) Coenzyme Q10 has a significant role in mitochondrial electron transfer and the synthesis of adenosine triphosphate (ATP). It serves as a mobile electron carrier in the mitochondrial electron-transfer process of respiration and oxidative phosphorylation. The coenzyme regulates NADH and succinyl dehydrogenases, and enables reversible interactions between the NADH dehydrogenase, succinate dehydrogenase, and cytochrome b-c1 portions of the mitochondrial electron transport chain. The oxidation-reduction cycling of coenzyme Q10 during electron transport has been observed directly. Coenzyme Q10 also may have direct membrane-stabilizing properties and be an antioxidant and free-radical scavenger; it has been demonstrated to scavenge lipid peroxidation-produced free radicals (Beyer, 1992; Lampertico & Comis, 1993; Matthews et al, 1993a; Greenberg & Frishman, 1990a; Permanetter et al, 1992).
3) An endogenous deficiency of coenzyme Q10 has been suggested in a variety of disorders/conditions, including cancer, congestive heart failure, hypertension, chronic hemodialysis, mitochondrial disease, and periodontal disease (Greenberg & Frishman, 1990a; Matthews et al, 1993a; Lockwood et al, 1994; Ogasahara et al, 1986; Triolo et al, 1994).
4) When given with alpha-tocopherol in mice, coenzyme Q10 has reduced liver damage following intraperitoneal injection of endotoxin; survival was enhanced and reduced levels of hepatic lipid peroxidation products (and preserved levels of ATP) were reported in treated animals (Zimmerman, 1991).
2) Coenzyme Q10 has a significant role in mitochondrial electron transfer and the synthesis of adenosine triphosphate (ATP). It serves as a mobile electron carrier in the mitochondrial electron-transfer process of respiration and oxidative phosphorylation. The coenzyme regulates NADH and succinyl dehydrogenases, and enables reversible interactions between the NADH dehydrogenase, succinate dehydrogenase, and cytochrome b-c1 portions of the mitochondrial electron transport chain. The oxidation-reduction cycling of coenzyme Q10 during electron transport has been observed directly. Coenzyme Q10 also may have direct membrane-stabilizing properties and be an antioxidant and free-radical scavenger; it has been demonstrated to scavenge lipid peroxidation-produced free radicals (Beyer, 1992; Lampertico & Comis, 1993; Matthews et al, 1993a; Greenberg & Frishman, 1990a; Permanetter et al, 1992).
3) An endogenous deficiency of coenzyme Q10 has been suggested in a variety of disorders/conditions, including cancer, congestive heart failure, hypertension, chronic hemodialysis, mitochondrial disease, and periodontal disease (Greenberg & Frishman, 1990a; Matthews et al, 1993a; Lockwood et al, 1994; Ogasahara et al, 1986; Triolo et al, 1994).
4) When given with alpha-tocopherol in mice, coenzyme Q10 has reduced liver damage following intraperitoneal injection of endotoxin; survival was enhanced and reduced levels of hepatic lipid peroxidation products (and preserved levels of ATP) were reported in treated animals (Zimmerman, 1991).
B) EFFECTS IN CARDIOVASCULAR DISEASE
1) The most extensive studies of coenzyme Q10 have been in the area of cardiovascular disease, most specifically for its purported benefit in preventing cellular damage during myocardial ischemia and reperfusion (Greenberg & Frishman, 1990a; Rengo et al, 1993; Mortensen, 1993). Numerous potential therapeutic mechanisms for coenzyme Q10 in cardiovascular diseases have been advanced. The most notable of these are: (1) correction of a coenzyme Q10 deficiency state; (2) direct free-radical scavenging activity via semiquinone species; (3) direct membrane-stabilizing properties due to phospholipid protein interactions; (4) and correction of a mitochondrial "leak" of electrons during oxidative respiration (Greenberg & Frishman, 1990a; Mortensen, 1993; Rengo et al, 1993; Greenberg & Frishman, 1988). Lending support to coenzyme Q10 deficiency, one study reported significantly lower coenzyme Q10 myocardial tissue levels in patients with advanced heart failure (New York Heart Association (NYHA) classes III and IV) compared to those with less advanced failure (classes I and II) (Mortensen, 1993). Blood levels of coenzyme Q10 were also significantly higher in normal subjects than in patients with cardiac disease in another report (Greenberg & Frishman, 1990a).
2) Other potential mechanisms suggested for coenzyme Q10 in patients with cardiovascular disease include effects on prostaglandin metabolism, inhibition of intracellular phospholipases, and stabilization of the integrity of calcium-dependent slow channels (Greenberg & Frishman, 1990a).
3) In vitro and animal studies have indicated the ability of coenzyme Q10 to protect the myocardium against functional and structural changes induced by ischemia and reperfusion (Zimmerman, 1991; Mortensen, 1993; Farah et al, 1984; Colucci et al, 1986), suggesting a role for the drug in heart surgery, and results of other experimental data suggest that the coenzyme may have a role in protecting the heart from functional damage elicited by doxorubicin (Farah et al, 1984; Folkers et al, 1977; Greenberg & Frishman, 1990a). Coenzyme Q10 has blunted blood pressure increases induced by desoxycorticosterone and saline in unilaterally nephrectomized rats (Greenberg & Frishman, 1990a).
2) Other potential mechanisms suggested for coenzyme Q10 in patients with cardiovascular disease include effects on prostaglandin metabolism, inhibition of intracellular phospholipases, and stabilization of the integrity of calcium-dependent slow channels (Greenberg & Frishman, 1990a).
3) In vitro and animal studies have indicated the ability of coenzyme Q10 to protect the myocardium against functional and structural changes induced by ischemia and reperfusion (Zimmerman, 1991; Mortensen, 1993; Farah et al, 1984; Colucci et al, 1986), suggesting a role for the drug in heart surgery, and results of other experimental data suggest that the coenzyme may have a role in protecting the heart from functional damage elicited by doxorubicin (Farah et al, 1984; Folkers et al, 1977; Greenberg & Frishman, 1990a). Coenzyme Q10 has blunted blood pressure increases induced by desoxycorticosterone and saline in unilaterally nephrectomized rats (Greenberg & Frishman, 1990a).
C) REVIEW ARTICLES
1) The role of coenzyme Q10 as an antioxidant and in free radical generation has been reviewed (Beyer, 1992).
2) Reviews on the potential use of coenzyme Q10 in cardiovascular disease, including summaries of clinical trials, are available (Prepping, 1999; Greenberg & Frishman, 1990a; Mortensen, 1993).
2) Reviews on the potential use of coenzyme Q10 in cardiovascular disease, including summaries of clinical trials, are available (Prepping, 1999; Greenberg & Frishman, 1990a; Mortensen, 1993).
4.5 Therapeutic Uses
Angina
Cardiotoxicity - Doxorubicin adverse reaction
Chronic obstructive pulmonary disease
Congestive heart failure
Diabetes mellitus
Drug-related alopecia - Warfarin adverse reaction
Hypercholesterolemia; Adjunct
Hypertension
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke
Male infertility
Migraine; Prophylaxis
Operation on heart
Parkinson's disease
Periodontal disease
Pulmonary fibrosis
Ventricular arrhythmia
4.5.A Angina
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Increased exercise time, but frequency of anginal attacks not always reduced
3) Adult:
a) The ability of oral coenzyme Q10 to protect the ischemic myocardium is suggested in small double-blind studies involving patients with stable angina pectoris (Mortensen, 1993a; Greenberg & Frishman, 1990b; Kamikawa et al, 1985b; Hiasa et al, 1984). With doses of 150 to 600 milligrams daily, coenzyme Q10, compared to placebo, has significantly prolonged exercise duration and reduced exercise-induced ischemic ST-segment depression. However, anginal symptoms and nitroglycerin consumption were not reduced significantly in one study (Kamikawa et al, 1985b). Additional, larger controlled trials are required to evaluate the potential place in therapy of oral coenzyme Q10 in angina.
b) Intravenous coenzyme Q10 (1.5 milligram/kilogram once daily for 7 days) was effective in increasing mean exercise time in chronic stable angina patients in one double-blind study. Blood pressure, heart rate, and the double-product were not altered significantly by coenzyme Q10 or placebo (Greenberg & Frishman, 1990b).
c) The mechanism of action of coenzyme Q10 in stable angina may be related to enhanced adenosine triphosphate (ATP) resynthesis, direct membrane protection, and/or a reduction of free radical species (Greenberg & Frishman, 1990b).
b) Intravenous coenzyme Q10 (1.5 milligram/kilogram once daily for 7 days) was effective in increasing mean exercise time in chronic stable angina patients in one double-blind study. Blood pressure, heart rate, and the double-product were not altered significantly by coenzyme Q10 or placebo (Greenberg & Frishman, 1990b).
c) The mechanism of action of coenzyme Q10 in stable angina may be related to enhanced adenosine triphosphate (ATP) resynthesis, direct membrane protection, and/or a reduction of free radical species (Greenberg & Frishman, 1990b).
4.5.B Cardiotoxicity - Doxorubicin adverse reaction
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive; Pediatric, Evidence is inconclusive
Recommendation: Adult, Class III; Pediatric, Class III
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Potential role in prevention of DOXORUBICIN-INDUCED CARDIOTOXICITY, but data are limited and conflicting
3) Adult:
a) Preliminary clinical studies suggest a potential role for coenzyme Q10 in the prevention of CARDIOTOXICITY induced by doxorubicin. Less severe depression of the ejection fraction was observed in cancer patients receiving coenzyme Q10 combined with doxorubicin in one prospective study (Greenberg & Frishman, 1990b). Increases in the systolic time interval (indicative of reduced cardiac dysfunction) induced by doxorubicin were reduced with the addition of daily coenzyme Q10 50 milligrams (Cortes et al, 1978), but this was not a randomized study. Beneficial effects of coenzyme Q10 in this setting may be related to inhibition of lipid peroxidation initiated by doxorubicin, scavenging of doxorubicin induced free radicals, and/or correction of a deficiency of coenzyme Q10.
4) Pediatric:
a) One study involving children with malignancies reported no effect of coenzyme Q10 on elevated lipid peroxide levels induced by doxorubicin chemotherapy (Horino et al, 1983).
4.5.C Chronic obstructive pulmonary disease
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Possible improvement in pulmonary function, but data is limited and not reliable
3) Adult:
a) Therapy with coenzyme Q10 appears to improve pulmonary function and exercise performance in patients with chronic lung disease (Fujimoto et al, 1993). The effects of CoQ10 treatment (ie ventilatory capacity, arterial oxygen (PaO2), and exercise performance) were evaluated in 21 patients with CHRONIC OBSTRUCTIVE LUNG DISEASE (COPD) and 9 patients with IDIOPATHIC PULMONARY FIBROSIS (IPF). Patients were given 90 milligrams daily for 8 weeks. Patients with hypoxemia at rest tended to have lower CoQ10 levels, (0.56 micrograms/milliliter (mcg/mL) for COPD patients and 0.45 mcg/mL for IPF patients) and those with exercise-induced hypoxemia also had reduced levels. After 8 weeks of treatment, the blood levels of CoQ10 had risen from 0.33 mcg/mL at baseline to 0.90 mcg/mL (P less than 0.01). Ventilatory capacity had also risen from 2.54 to 2.71 liters, the PaO2 increased from 74.5 to 81.5 torr (P less than 0.05), and the treadmill time increased from 12 to 14 minutes (P less than 0.02), respectively. Under these low level conditions, some organs, including the heart, liver, and skeletal muscles, may become hypoxic. During treatment, however, there was no significant difference in oxygen consumption compared to baseline. Heart rate during exercise was significantly decreased and PaO2 was significantly improved. Another result of CoQ10 administration was improved oxygen transport to muscles during exercise, due to the improved PaO2 and increased cardiac output. This study suggests that CoQ10 has a favorable effect on the energy production of exercising muscles in patients with chronic lung diseases who have hypoxemia at rest or during exercise.
b) Coenzyme Q10 50 milligrams daily was superior to placebo in increasing maximal oxygen consumption and expired volume in patients with chronic obstructive pulmonary disease (COPD) in a double-blind study (Satta et al, 1991). However, deficiencies were apparent in this study (eg, interpretation of results with respect to statistical analysis) and its results require confirmation.
b) Coenzyme Q10 50 milligrams daily was superior to placebo in increasing maximal oxygen consumption and expired volume in patients with chronic obstructive pulmonary disease (COPD) in a double-blind study (Satta et al, 1991). However, deficiencies were apparent in this study (eg, interpretation of results with respect to statistical analysis) and its results require confirmation.
4.5.D Congestive heart failure
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Used as an adjunct to conventional therapy
Most studies somewhat deficient
Possible clinical benefit includes reduced need for hospitalization and improved quality of life
Generally more effective in patients with more severe heart failure and lower endogenous levels of the enzyme
Most studies somewhat deficient
Possible clinical benefit includes reduced need for hospitalization and improved quality of life
Generally more effective in patients with more severe heart failure and lower endogenous levels of the enzyme
3) Adult:
a) Numerous open studies, some involving over 1000 patients, have reported clinical benefits of short-term (one to four weeks) and long-term (3 months to 6 years) therapy with oral coenzyme Q10 in doses of 50 to 100 milligrams daily when added to conventional therapy, including digitalis, diuretics, and angiotensin-converting enzyme inhibitors, in patients with chronic CONGESTIVE HEART FAILURE (CHF) (Lampertico & Comis, 1993b; Mortensen, 1993a; Langsjoen et al, 1990b; Baggio et al, 1993a; Greenberg & Frishman, 1990b; Langsjoen et al, 1988a; Ishiyama et al, 1976a). Most placebo-controlled studies support these findings, demonstrating a significant improvement in left-ventricular ejection fraction, stroke volume, clinical symptoms, and functional status during therapy with add-on coenzyme Q10 100 to 150 milligrams daily for up to one year in chronic heart failure patients (New York Heart Association (NYHA) class II to IV) (Morisco et al, 1993; Mortensen, 1993a; Rengo et al, 1993b; Greenberg & Frishman, 1990b). An improvement in quality of life and a significant reduction in the number of patients requiring hospitalization for worsening of heart failure were reported with coenzyme Q10 therapy in some controlled studies (Mortensen, 1993a; Morisco et al, 1993). Beneficial effects of coenzyme Q10 in these patients have been attributed to enhanced myocardial contractility, and the drug has tended to be more effective in patients with more severe heart failure (New York Heart Association (NYHA) class III or IV) and those with DILATED CARDIOMYOPATHY and the lowest plasma levels or myocardial biopsy tissue levels of coenzyme Q10. Coenzyme Q10 was approved for use in CHF in Japan in 1974 based on a compilation survey of 31 reports (Yamamura, 1985).
b) One small, 8-month, double-blind, cross-over study DID NOT CONFIRM the efficacy of coenzyme Q10 in patients with idiopathic dilated cardiomyopathy (New York Heart Association (NYHA) class I to III) (Permanetter et al, 1992a). Compared to placebo, no significant hemodynamic or clinical improvement was seen during therapy with 100 milligrams daily as assessed by radionuclide ventriculography, echocardiography, chest X-rays, exercise testing, and impedance cardiography. Although this study suffers from a relatively small number of patients (n=25) with generally less severe heart failure than other trials (although most patients were in class II or III), it was well-controlled and failed to show any significant benefit in any group.
c) Some deficiencies of other placebo-controlled trials also warrant caution in interpretation of their findings. Many also involved small numbers of patients (n=14 to 60) (Rengo et al, 1993b; Mortensen, 1993a; Greenberg & Frishman, 1990b) and the largest study (n=600), which also employed the longest duration of treatment (one year) (Morisco et al, 1993), did not perform intensive clinical assessments or indices of myocardial function at 3-month evaluation points. Clinical benefits of coenzyme Q10, (eg, improvement in exercise capacity), although statistically significant, were not always large and at times of questionable clinical relevance. Some of these studies did not assure patient compliance with coenzyme Q10 blood level monitoring. Invasive hemodynamic techniques were not used to assess the efficacy of coenzyme Q10.
d) Additional studies addressing these problems are needed. Although there is some evidence of lower mortality rates with coenzyme Q10 therapy in severe chronic heart failure (Langsjoen et al, 1990b; Baggio et al, 1993a), this is yet to be confirmed in a well-controlled study.
e) Case reports suggest the use of oral coenzyme Q10 as a "medical bridge" to HEART TRANSPLANTATION in patients with severe heart failure, particularly dilated cardiomyopathy (Greenberg & Frishman, 1990b). Two patients with severe dilated cardiomyopathy awaiting transplantation were removed from the waiting list following addition of coenzyme Q10 to conventional treatment (captopril, digoxin, furosemide) for 5 to 9 months; left-ventricular ejection fraction increased during these periods from approximately 15% to 27%. However, improvements in these patients may have been spontaneous, and additional studies evaluating coenzyme Q10 in this role are needed.
f) Coenzyme Q10 appeared to be beneficial for congestive heart failure (CHF) patients in initial studies. Coenzyme Q10 100 milligrams (mg) was administered to 12 patients who were not well controlled with diuretics and digitalis. Subjective improvement of dyspnea and fatigue was noted in 67% of the patients examined. Myocardial improvement was reported using noninvasive procedures (Mortensen et al, 1985). In 2 placebo-controlled, double-blind, cross-over studies CHF patients received 33.3 mg of Coenzyme Q10 three times daily for 12 weeks. Increases in mean ejection fraction and stroke volume were reported; noninvasive methods were used (Langsjoen et al, 1985; Langsjoen et al, 1985a).
b) One small, 8-month, double-blind, cross-over study DID NOT CONFIRM the efficacy of coenzyme Q10 in patients with idiopathic dilated cardiomyopathy (New York Heart Association (NYHA) class I to III) (Permanetter et al, 1992a). Compared to placebo, no significant hemodynamic or clinical improvement was seen during therapy with 100 milligrams daily as assessed by radionuclide ventriculography, echocardiography, chest X-rays, exercise testing, and impedance cardiography. Although this study suffers from a relatively small number of patients (n=25) with generally less severe heart failure than other trials (although most patients were in class II or III), it was well-controlled and failed to show any significant benefit in any group.
c) Some deficiencies of other placebo-controlled trials also warrant caution in interpretation of their findings. Many also involved small numbers of patients (n=14 to 60) (Rengo et al, 1993b; Mortensen, 1993a; Greenberg & Frishman, 1990b) and the largest study (n=600), which also employed the longest duration of treatment (one year) (Morisco et al, 1993), did not perform intensive clinical assessments or indices of myocardial function at 3-month evaluation points. Clinical benefits of coenzyme Q10, (eg, improvement in exercise capacity), although statistically significant, were not always large and at times of questionable clinical relevance. Some of these studies did not assure patient compliance with coenzyme Q10 blood level monitoring. Invasive hemodynamic techniques were not used to assess the efficacy of coenzyme Q10.
d) Additional studies addressing these problems are needed. Although there is some evidence of lower mortality rates with coenzyme Q10 therapy in severe chronic heart failure (Langsjoen et al, 1990b; Baggio et al, 1993a), this is yet to be confirmed in a well-controlled study.
e) Case reports suggest the use of oral coenzyme Q10 as a "medical bridge" to HEART TRANSPLANTATION in patients with severe heart failure, particularly dilated cardiomyopathy (Greenberg & Frishman, 1990b). Two patients with severe dilated cardiomyopathy awaiting transplantation were removed from the waiting list following addition of coenzyme Q10 to conventional treatment (captopril, digoxin, furosemide) for 5 to 9 months; left-ventricular ejection fraction increased during these periods from approximately 15% to 27%. However, improvements in these patients may have been spontaneous, and additional studies evaluating coenzyme Q10 in this role are needed.
f) Coenzyme Q10 appeared to be beneficial for congestive heart failure (CHF) patients in initial studies. Coenzyme Q10 100 milligrams (mg) was administered to 12 patients who were not well controlled with diuretics and digitalis. Subjective improvement of dyspnea and fatigue was noted in 67% of the patients examined. Myocardial improvement was reported using noninvasive procedures (Mortensen et al, 1985). In 2 placebo-controlled, double-blind, cross-over studies CHF patients received 33.3 mg of Coenzyme Q10 three times daily for 12 weeks. Increases in mean ejection fraction and stroke volume were reported; noninvasive methods were used (Langsjoen et al, 1985; Langsjoen et al, 1985a).
4.5.E Diabetes mellitus
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
In combination with fenofibrate, may enhance circulation and reduce levels of glycosylated hemoglobin in diabetic patients; may also improve EPITHELIAL DYSFUNCTION
More study is required to validate efficacy
More study is required to validate efficacy
3) Adult:
a) In a group of dyslipidemic type 2 diabetics, a 12-week course of combined FENOFIBRATE with COENZYME Q10 significantly enhanced brachial artery flow and vasodilation of forearm micro-circulation, although neither fenofibrate nor coenzyme Q10 given as monotherapy improved vascular flow. Fenofibrate alone reduced low-density lipoprotein cholesterol (LDL-C) and triglycerides, while raising high-density lipoprotein cholesterol (HDL-C); and coenzyme Q10 (CoQ) alone significantly lowered blood pressure. Glycosylated hemoglobin levels were decreased by the combination therapy. These findings emanated from a small randomized, double-blind trial (n=80). Enrollees received daily doses of micronized fenofibrate 200 milligrams (mg) (n=20), CoQ 200 mg (n=20), fenofibrate 200 mg plus CoQ 200 mg (n=20), or placebo (n=20). Forearm blood flow was measured by venous occlusion plethysmography using solutions of acetylcholine, bradykinin, sodium nitroprusside, and N(G)-monomethyl-L-arginine. After 12 weeks, significant reductions had occurred in LDL-C (3.3 to 2.9 millimoles/liter (mmol/L) (128 to 112 mg/dL); p=0.014) and triglycerides (2.4 to 1.3 mmol/L (212 to 115 mg/dL); p less than 0.001) among those receiving fenofibrate monotherapy; also HDL-C had increased from 0.94 to 1.1 mmol/L (36 to 42 mg/dL) (p less than 0.001). In the CoQ monotherapy group, systolic blood pressure decreased from 128.1 to 124.8 (p=0.033). In patients receiving fenofibrate and CoQ, glycosylated hemoglobin (HbA1c) concentrations decreased from 7.5% to 7.2%. Also in the combination group, forearm arterial flow significantly increased with acetylcholine (31% to 43%; p=0.001), bradykinin (19% to 41%; p=0.016), and sodium nitroprusside (50% to 60%; p=0.006). Vasodilator function associated with combination therapy was shown to normalize when compared to flow measurements in a non-diabetic control group. All trial participants were allowed to take aspirin concomitantly. Further investigation is needed of combination fenofibrate/CoQ in diabetic patients at risk for cardiovascular events (Playford et al, 2003).
b) Coenzyme Q10 improved endothelial dysfunction in diabetic patients but not in non-diabetic subjects. In a randomized, double-blind, placebo-controlled trial, 40 normotensive patients with type 2 diabetes, in good glycemic control (HbA1c 6.2% to 6.9%) but with dyslipidemia, were given coenzyme Q10 200 milligrams (mg) per day or placebo for 12 weeks after a 6-week run-in during which they were instructed to consume a fat-modified diet of constant antioxidant composition. Flow-mediated dilation (FMD) of the brachial artery increased by 1.6% after coenzyme Q10 treatment and decreased by 0.4% after placebo treatment (p=0.005). Nitrate- mediated dilation was not affected by coenzyme Q10 treatment. Although improved relative to baseline, post-treatment FMD remained lower than the mean value from 18 non-diabetic, normolipidemic patients ((Watts et al, 2002).
b) Coenzyme Q10 improved endothelial dysfunction in diabetic patients but not in non-diabetic subjects. In a randomized, double-blind, placebo-controlled trial, 40 normotensive patients with type 2 diabetes, in good glycemic control (HbA1c 6.2% to 6.9%) but with dyslipidemia, were given coenzyme Q10 200 milligrams (mg) per day or placebo for 12 weeks after a 6-week run-in during which they were instructed to consume a fat-modified diet of constant antioxidant composition. Flow-mediated dilation (FMD) of the brachial artery increased by 1.6% after coenzyme Q10 treatment and decreased by 0.4% after placebo treatment (p=0.005). Nitrate- mediated dilation was not affected by coenzyme Q10 treatment. Although improved relative to baseline, post-treatment FMD remained lower than the mean value from 18 non-diabetic, normolipidemic patients ((Watts et al, 2002).
4.5.F Drug-related alopecia - Warfarin adverse reaction
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category C
See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Case reports suggest usefulness in treatment of ALOPECIA induced by warfarin therapy
3) Adult:
a) Two case reports suggested that oral coenzyme Q10 is effective in the treatment of warfarin-induced alopecia. Two patients developed hair loss 2 months after starting warfarin therapy (2 to 4 milligrams (mg) per day). Each patient began receiving coenzyme Q10 (30 mg/day); 1 month later hair loss had stopped in both patients. In 1 patient coenzyme Q10 was discontinued for 2 months and hair loss recurred. Coenzyme Q10 was restarted and hair loss stopped. It has been suggested that coenzyme Q10 may improve mitochondrial respiration in hair roots (Nagao et al, 1995).
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