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UBIQUINONES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Ubiquinones, also known as lipid soluble benzoquinones, are antioxidants. They have been used in a wide variety of diseases including cardiovascular disease, liver disease, certain eye diseases, cancer and diabetes.

Specific Substances

    A) COENZYME Q10
    1) Ubidecarenone
    2) Ubidecarenonum
    3) Ubiquinone-10
    4) CAS 303-98-0
    IDEBENONE
    1) 6-(10-Hydroxydecyl)-2,3-dimethoxy-5-methyl-
    2) 1,4-benzoquinone
    3) CV 2619
    4) CAS 58186-27-9

Available Forms Sources

    A) FORMS
    1) Coenzyme Q10 is available in various multi-vitamin, multi-mineral, and multi-herbal dietary supplements.
    2) Idebenone is a synthetic product with properties (ie, antioxidant) similar to coenzyme Q10. It is bioactivated predominantly in the cytoplasm and is not dependent on mitochondrial function and has a different molecular structure than coenzyme Q10. Its suggested that the 2 agents should not be substituted for one another (Gueven et al, 2015).
    3) Ubiquinones have a basic 2,3-dimethoxy-5-methylbenzoquinone backbone which have terpenoid side chains containing 1 to 10 monosaturated trans-isoprenoid units. In humans the type containing 10 units (Q10) are found (Budavari, 1996).
    B) SOURCES
    1) These agents were isolated in 1957 and have been studied in Japan, the Soviet Union, Europe, and the United States. It is claimed that over 12 million Japanese were taking these products for management of cardiovascular disease (Anon, 1988).
    C) USES
    1) COENZYME Q10
    a) Coenzyme Q10 is alleged to be effective for treatment of arrhythmias, congestive heart failure, high blood pressure, and reduction of hypoxic injury to cardiac tissue (Greenberg & Frishman, 1987) (Solaini, 1987; Kamikawa et al, 1985; Tsutsumi et al, 1988).
    b) It is also said to be useful in the treatment of obesity, diabetes, stimulating the immune system, and countering the aging processing. It is not FDA approved in the US but is available as a food supplement (Anon, 1988).
    c) In a review, the effectiveness of coenzyme Q10 supplementation to prevent cardiovascular disease (CVD) in individuals at high risk to develop CVD was analyzed including blood pressure. It was noted that coenzyme Q10 could act directly on vascular endothelium and decrease total peripheral resistance. Its antioxidant properties may also effect free radicals that cause inactivation of endothelium-derived relaxing factor or fibrosis of arteriolar smooth muscle. It was also shown to decrease blood viscosity and improve blood flow to cardiac muscle and; therefore it may reduce blood pressure (Flowers et al, 2014).
    2) IDEBENONE
    a) Idebenone has been used in the treatment of Alzheimer's disease, liver disease, heart disease and some inherited disorders.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Ubiquinones, known as lipid soluble benzoquinones, are antioxidants that were isolated in 1957 and studied extensively in Japan, Russia, and Europe. These agents are not approved as a drug in the United States, but are available in various multi-vitamin, multi-mineral, and multi-herbal dietary supplements. Coenzyme Q10 has been used for the treatment of arrhythmias, congestive heart failure, high blood pressure, and reduction of hypoxic injury to cardiac tissue. It is also purported to be useful in the treatment of obesity, diabetes, stimulating the immune system, and countering the aging processing. Idebenone is a synthetic product with similar antioxidant properties as coenzyme Q10.
    B) PHARMACOLOGY: Not all of the functions of ubiquinones are well understood. They are involved in mitochondrial electron transport and are found in most aerobic organisms. Ubiquinones are also thought to be hydrogen carriers, which provides coupling of proton translocation to respiration via a chemiosomotic mechanism and are involved in oxidation (ie, reduction reactions in the mitochondrial respiratory chain).
    C) EPIDEMIOLOGY: It has been claimed that over 12 million Japanese people have taken these products for the management of cardiovascular disease. Overdose is unlikely with this agent.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: There are few reports of significant side effects.
    2) COMMON: The most likely adverse events reported are limited to the gastrointestinal system (ie, nausea, anorexia, gastritis, diarrhea), and have occurred in less than 1% of patients.
    3) INFREQUENT: Skin rash and pruritus are infrequent complications of oral coenzyme Q10 therapy. Mild increases in serum aminotransferases have been reported occasionally with higher oral doses of coenzyme Q10.
    4) RARE: In one study, thrombocytopenia occurred in 1 of 16 patients. Irritability, agitation, headache and/or dizziness have developed rarely during therapy; it was unclear if the events were actually drug related.
    5) ANIMAL DATA: No behavior or toxicologic effects have been reported following single or multiple doses via intraperitoneal, subQ or oral administration; however, decreased sensitivity to narcotic and convulsant agents was found.
    E) WITH POISONING/EXPOSURE
    1) OVERDOSE: There have been no reports of overdose.
    0.2.20) REPRODUCTIVE
    A) Effects have not been studied. At this time the use of ubiquinones is not recommended during pregnancy.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

    A) No specific laboratory measures are indicated.
    B) Monitor vital signs including blood pressure.
    C) In patients with a history of congestive heart failure, cardia disease or arrhythmias obtain a baseline ECG as indicated. Institute continuous cardiac monitoring as necessary.
    D) Although bleeding has not been reported with coenzyme Q10, its reported antiplatelet effect may increase the risk of bleeding. Obtain a baseline CBC and platelet count after a significant exposure or in patients that may be at risk (ie, coadministration anticoagulants) for bleeding.
    E) Plasma blood levels are not anticipated to be helpful to guide therapy. Normal (endogenous) blood levels for coenzyme Q10 are 0.7 to 1 mcg/mL.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) There is no specific antidote or treatment. Treatment is symptomatic and supportive. For ongoing vomiting and/or diarrhea, monitor fluid status and electrolytes. Administer IV fluids and correct electrolyte abnormalities as necessary.
    B) DECONTAMINATION
    1) PREHOSPITAL: Gastrointestinal decontamination is unlikely to be necessary in patients with a minor exposure. Consider prehospital administration of activated charcoal in patients with a potentially toxic ingestion who are awake and able to protect their airway.
    2) HOSPITAL: Consider activated charcoal in patients following a recent large ingestion or if coingestants are suspected and the patient is alert and the airway is protected.
    C) AIRWAY MANAGEMENT
    1) Airway management is unlikely to be necessary following exposure to these agents. Assess airway and ensure adequate ventilation in patients as necessary.
    D) ANTIDOTE
    1) There is no specific antidote.
    E) ENHANCED ELIMINATION
    1) Extracorporeal methods have not been evaluated. However, it is not anticipated that enhanced elimination methods would be necessary following exposure to these agents.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic child with a minor exposure (1 to 2 tablets) can be monitored at home with appropriate adult supervision. A child with an episode of vomiting can still be monitored at home if the ingestion was minor. An asymptomatic adult with an inadvertent ingestion of several tablets (2 to 3 tablets) can remain at home and should be instructed to call if anything more than minor gastrointestinal symptoms develop.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear
    G) PHARMACOKINETICS
    1) COENZYME Q10: Coenzyme Q10 is absorbed slowly from the small intestine likely due to its high molecular weight. It is absorbed faster with food.
    2) IDEBENONE: Rapidly absorbed. Tmax: 1 to 3 hours. Half-life: 10 to 13 hours. In animal models, a wide biodistribution of intact, unmetabolized idebenone with the highest levels found in the liver and kidney; lowest levels were found in the heart and brain. The differences between idebenone and coenzyme Q10 are likely due to the major difference in solubility of both molecules.
    H) PITFALLS
    1) Failure to obtain an adequate history of exposure.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

Range Of Toxicity

    A) TOXIC DOSE: A toxic dose has not been established for these agents. COENZYME Q10: Up to 60 mg/kg/day or 45 mg/kg/day have been taken without significant symptoms.
    B) THERAPEUTIC DOSE: There is no standardized dosing for these products. COENZYME Q10: ESTIMATED DAILY INTAKE FROM FOOD: 3 to 5 mg daily. GENERAL DOSAGE GUIDELINES: ADULT: Up to 1200 mg/day; CHILD: Up to 10 mg/kg/day; higher doses have been suggested in some pathological conditions. These doses are considered to be safe and well tolerated. SPECIFIC CONDITIONS: ADULT: 30 to 45 mg/kg/day for 2 to 16 weeks was effective in reducing blood pressure in 4 of 17 patients. Fourteen of 16 patients given 60 mg/day for 16 weeks showed significant blood pressure reduction. IDEBENONE: ORAL: 90 mg daily in divided doses has been given for the treatment of mental impairment associated with cerebrovascular disorders.

Clinical Effects

Summary Of Exposure

    A) USES: Ubiquinones, known as lipid soluble benzoquinones, are antioxidants that were isolated in 1957 and studied extensively in Japan, Russia, and Europe. These agents are not approved as a drug in the United States, but are available in various multi-vitamin, multi-mineral, and multi-herbal dietary supplements. Coenzyme Q10 has been used for the treatment of arrhythmias, congestive heart failure, high blood pressure, and reduction of hypoxic injury to cardiac tissue. It is also purported to be useful in the treatment of obesity, diabetes, stimulating the immune system, and countering the aging processing. Idebenone is a synthetic product with similar antioxidant properties as coenzyme Q10.
    B) PHARMACOLOGY: Not all of the functions of ubiquinones are well understood. They are involved in mitochondrial electron transport and are found in most aerobic organisms. Ubiquinones are also thought to be hydrogen carriers, which provides coupling of proton translocation to respiration via a chemiosomotic mechanism and are involved in oxidation (ie, reduction reactions in the mitochondrial respiratory chain).
    C) EPIDEMIOLOGY: It has been claimed that over 12 million Japanese people have taken these products for the management of cardiovascular disease. Overdose is unlikely with this agent.
    D) WITH THERAPEUTIC USE
    1) ADVERSE EFFECTS: There are few reports of significant side effects.
    2) COMMON: The most likely adverse events reported are limited to the gastrointestinal system (ie, nausea, anorexia, gastritis, diarrhea), and have occurred in less than 1% of patients.
    3) INFREQUENT: Skin rash and pruritus are infrequent complications of oral coenzyme Q10 therapy. Mild increases in serum aminotransferases have been reported occasionally with higher oral doses of coenzyme Q10.
    4) RARE: In one study, thrombocytopenia occurred in 1 of 16 patients. Irritability, agitation, headache and/or dizziness have developed rarely during therapy; it was unclear if the events were actually drug related.
    5) ANIMAL DATA: No behavior or toxicologic effects have been reported following single or multiple doses via intraperitoneal, subQ or oral administration; however, decreased sensitivity to narcotic and convulsant agents was found.
    E) WITH POISONING/EXPOSURE
    1) OVERDOSE: There have been no reports of overdose.

Heent

    3.4.3) EYES
    A) PHOTOPHOBIA has been reported rarely during oral therapy with coenzyme Q10 (Baggio et al, 1993), although a causal relationship is doubtful.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) WITH THERAPEUTIC USE
    a) No cardiac toxicity has yet been identified.
    b) Several studies have shown a positive effect in treatment of myocardial disorders (Kamikawa et al, 1985; Ishiyama et al, 1976; Greenberg & Frishman, 1988).
    c) Ubiquinones were found to increase the cardiac ejection fraction in a series of patients (Langsjoen et al, 1988).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH THERAPEUTIC USE
    a) IRRITABILITY or AGITATION, HEADACHE, and DIZZINESS have occurred rarely during oral coenzyme Q10 therapy (Garrido-Maraver et al, 2014; Baggio et al, 1993; Wilkinson et al, 1976; Lampertico & Comis, 1993). It is unclear if any of these effects are definitely drug-related.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) When ubiquinones were injected into animals intraperitoneally and subcutaneously and given intragastrically, single and multiple doses produced no behavioral or toxicologic changes. They did produce regulatory activities in the CNS in that sensitivity to various narcotic and convulsant agents was reduced (Shadurskii et al, 1982).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Gastritis, nausea, anorexia, abdominal pain, vomiting, and diarrhea are rare side effects during therapeutic use. These symptoms affected less than 1% of the 5,000 individuals in one study (Anon, 1988; Kamikawa et al, 1985).
    2) Other adverse gastrointestinal effects of oral coenzyme Q10 can include: epigastric pain/discomfort, heartburn, and appetite suppression (Rengo et al, 1993; Baggio et al, 1993; Lampertico & Comis, 1993; Greenberg & Frishman, 1990; Matthews et al, 1993; Kamikawa et al, 1985a). However, their incidence has been less than 1% in large studies (Greenberg & Frishman, 1990; Lampertico & Comis, 1993; Baggio et al, 1993).
    3) Gastrointestinal effects of oral coenzyme Q10 have responded to dose reduction, and have tended to subside with continued therapy (Lampertico & Comis, 1993; Matthews et al, 1993); withdrawal of therapy has been required only rarely (Baggio et al, 1993).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TOXIC LIVER DISEASE
    1) WITH THERAPEUTIC USE
    a) Mild increases in serum aminotransferases have been reported occasionally with higher oral doses of coenzyme Q10 (300 mg daily) (Greenberg & Frishman, 1990). However, there are no reports of overt hepatotoxicity with the drug.

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) THROMBOCYTOPENIA was described in one of 16 patients treated with oral coenzyme Q10 for mitochondrial disease in one study (Matthews et al, 1993). However, other factors were more likely responsible (eg, viral infection, other medications). No other adverse hematologic effects have been reported in clinical trials.
    B) BLEEDING
    1) WITH POISONING/EXPOSURE
    a) Although bleeding has not been reported with coenzyme Q10, its reported antiplatelet effect may increase the risk of bleeding (Garrido-Maraver et al, 2014).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) ALLERGIC RASH and PRURITUS are infrequent complications of oral coenzyme Q10 therapy (less than 0.5% of patients) (Garrido-Maraver et al, 2014; Lampertico & Comis, 1993; Langsjoen et al, 1990; Baggio et al, 1993). Oral coenzyme Q10 was discontinued due to the appearance of a rash in one patient in one study (Baggio et al, 1993).
    b) An itching EXANTHEMA was described in 2 of 21 heart failure patients treated with intravenous coenzyme Q10 (50 to 100 mg) (Ishiyama et al, 1976a).
    B) VITILIGO
    1) WITH THERAPEUTIC USE
    a) Facial vitiligo was reported in some individuals following daily use of over-the-counter topical anti-ageing agents containing coenzyme Q10. In all cases, the patients were fair skinned with no prior history of depigmentation. The cream was discontinued and the areas of facial depigmentation were successfully treated using narrowband ultraviolet B-activated propseudocatalase PC-KUS (Schallreuter, 2013).

Reproductive

    3.20.1) SUMMARY
    A) Effects have not been studied. At this time the use of ubiquinones is not recommended during pregnancy.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no human data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    2) Teratogenic effects are unlikely based on studies in rats and mice, and epidemiological studies of women treated with ubiquinones during pregnancy (TERIS , 1991).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory measures are indicated.
    B) Monitor vital signs including blood pressure.
    C) In patients with a history of congestive heart failure, cardia disease or arrhythmias obtain a baseline ECG as indicated. Institute continuous cardiac monitoring as necessary.
    D) Although bleeding has not been reported with coenzyme Q10, its reported antiplatelet effect may increase the risk of bleeding. Obtain a baseline CBC and platelet count after a significant exposure or in patients that may be at risk (ie, coadministration anticoagulants) for bleeding.
    E) Plasma blood levels are not anticipated to be helpful to guide therapy. Normal (endogenous) blood levels for coenzyme Q10 are 0.7 to 1 mcg/mL.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) No specific laboratory abnormalities have been identified.
    2) Although bleeding has not been reported with coenzyme Q10, its reported antiplatelet effect may increase the risk of bleeding (Garrido-Maraver et al, 2014). Obtain a baseline CBC and platelet count after a significant exposure or in patients that may be at risk (ie, coadministration anticoagulants) for bleeding.

Methods

    A) CHROMATOGRAPHY
    1) One method using reversed phase high performance liquid chromatography claims a lower detection limit of 0.1 ng for ubiquinone and dolichol (Elmberger et al, 1989).
    B) OTHER
    1) 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.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic child with a minor exposure (1 to 2 tablets) can be monitored at home with appropriate adult supervision. A child with an episode of vomiting can still be monitored at home if the ingestion was minor. An asymptomatic adult with an inadvertent ingestion of several tablets (2 to 3 tablets) can remain at home and should be instructed to call if anything more than minor gastrointestinal symptoms develop.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) No specific laboratory measures are indicated.
    B) Monitor vital signs including blood pressure.
    C) In patients with a history of congestive heart failure, cardia disease or arrhythmias obtain a baseline ECG as indicated. Institute continuous cardiac monitoring as necessary.
    D) Although bleeding has not been reported with coenzyme Q10, its reported antiplatelet effect may increase the risk of bleeding. Obtain a baseline CBC and platelet count after a significant exposure or in patients that may be at risk (ie, coadministration anticoagulants) for bleeding.
    E) Plasma blood levels are not anticipated to be helpful to guide therapy. Normal (endogenous) blood levels for coenzyme Q10 are 0.7 to 1 mcg/mL.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) Gastrointestinal decontamination is unlikely to be necessary in patients with a minor exposure.
    2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF TOXICITY
    a) There is no specific antidote or treatment. Treatment is symptomatic and supportive. For ongoing vomiting and/or diarrhea, monitor fluid status and electrolytes. Administer IV fluids and correct electrolyte abnormalities as necessary.
    B) MONITORING OF PATIENT
    1) No specific laboratory measures are indicated.
    2) Monitor vital signs including blood pressure. In patients with a history of congestive heart failure, cardia disease or arrhythmias obtain a baseline ECG as indicated. Institute continuous cardiac monitoring as necessary.
    3) Although bleeding has not been reported with coenzyme Q10, its reported antiplatelet effect may increase the risk of bleeding. Obtain a baseline CBC and platelet count after a significant exposure or in patients that may be at risk (ie, coadministration anticoagulants) for bleeding.
    4) Plasma blood levels are not anticipated to be helpful to guide therapy.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Enhanced Elimination

    A) SUMMARY
    1) Extracorporeal methods have not been evaluated. However, it is not anticipated that enhanced elimination methods would be necessary following exposure to these agents.

Range Of Toxicity

Summary

    A) TOXIC DOSE: A toxic dose has not been established for these agents. COENZYME Q10: Up to 60 mg/kg/day or 45 mg/kg/day have been taken without significant symptoms.
    B) THERAPEUTIC DOSE: There is no standardized dosing for these products. COENZYME Q10: ESTIMATED DAILY INTAKE FROM FOOD: 3 to 5 mg daily. GENERAL DOSAGE GUIDELINES: ADULT: Up to 1200 mg/day; CHILD: Up to 10 mg/kg/day; higher doses have been suggested in some pathological conditions. These doses are considered to be safe and well tolerated. SPECIFIC CONDITIONS: ADULT: 30 to 45 mg/kg/day for 2 to 16 weeks was effective in reducing blood pressure in 4 of 17 patients. Fourteen of 16 patients given 60 mg/day for 16 weeks showed significant blood pressure reduction. IDEBENONE: ORAL: 90 mg daily in divided doses has been given for the treatment of mental impairment associated with cerebrovascular disorders.

Therapeutic Dose

    7.2.1) ADULT
    A) SUMMARY
    1) There is no standardized dosing for these products.
    2) COENZYME Q-10
    a) ESTIMATED DAILY INTAKE FROM FOOD: 3 to 5 mg daily (Garrido-Maraver et al, 2014).
    b) GENERAL DOSAGE GUIDELINES: ADULT: Up to 1200 mg/day orally; higher doses have been suggested in some pathological conditions. This dose is considered to be safe and well tolerated (Garrido-Maraver et al, 2014).
    c) 30 to 45 milligrams/kilogram/day for 2 to 16 weeks was effective in reducing blood pressure in 4 of 17 patients (Yamagami, 1975; Yamagami, 1976).
    d) 14 of 16 patients given 60 milligrams/day for 16 weeks showed significant blood pressure reduction (Folkers, 1981).
    3) IDEBENONE
    a) An oral dose of 90 mg daily in divided doses after meals has been given for treatment of mental impairment associated with cerebrovascular disorders (S Sweetman , 2002).
    7.2.2) PEDIATRIC
    A) SUMMARY
    1) There is no standardized dosing for these products.
    B) COENZYME Q10
    1) ESTIMATED DAILY INTAKE FROM FOOD: 3 to 5 mg daily (Garrido-Maraver et al, 2014).
    2) GENERAL DOSAGE GUIDELINES: CHILD: Up to 10 mg/kg/day; higher doses have been suggested in some pathological conditions. This dose is considered to be safe and well tolerated (Garrido-Maraver et al, 2014).

Minimum Lethal Exposure

    A) SUMMARY
    1) A minimum lethal dose has not been established.

Maximum Tolerated Exposure

    A) SUMMARY
    1) Up to 60 mg/kg/day or 45 mg/kg/day have been taken without significant symptoms (Folkers, 1981; Yamagami, 1976).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) COENZYME Q-10
    B) IDEBENONE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 757 mg/kg (RTECS, 2002)
    2) LD50- (ORAL)MOUSE:
    a) >10 g/kg (RTECS, 2002)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) >10 g/kg (RTECS, 2002)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 830 mg/kg (RTECS, 2002)
    5) LD50- (ORAL)RAT:
    a) >10 g/kg (RTECS, 2002)
    6) LD50- (SUBCUTANEOUS)RAT:
    a) 10 g/kg (RTECS, 2002)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Ubiquinones are involved in mitochondrial electron transport and are found in most aerobic organisms. Both cyctochrome C reductase and ubiquinone levels increased in red muscle in rats given exercise training (Gohil, 1987).
    B) Ubiquinones are also thought to be hydrogen carriers, which provides coupling of proton translocation to respiration via a chemiosomotic mechanism (Trumbower, 1981).
    C) Ubiquinones are involved in oxidation - reduction reactions in the mitochondrial respiratory chain (Anon, 1988).
    D) Experiments done on animals suggest that ubiquinones retard ATP breakdown metabolites, allowing ATP to be reconstructed by salvage process during reoxygenation (Takeo, 1987) (Yoshikawa et al, 1987).
    E) Not all of the functions of ubiquinones are well understood. Studies have shown that Q 10 occurs in a mobile environment within the cell and may have many activities besides that of electron transport (Anon, 1988; Cornell, 1987).

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