Alpha Lipoic Acid Injection

Overview of Alpha Lipoic Acid Injection

Dosage Strength of Alpha Lipoic Acid Injection

25 mg/mL 30 mL Vial

General Information

Alpha lipoic acid (ALA, thioctic acid) is an endogenous, potent antioxidant that is purported to be useful in the treatment of diabetes mellitus, diabetic neuropathy, dementia secondary to Alzheimer's disease or human immunodeficiency virus (HIV) infection, glaucoma, amanita mushroom poisoning, and alcoholic liver disease. Studies supporting the use of ALA in the treatment of diabetes and diabetic neuropathy are available. The majority of studies are short in duration (e.g., 3—5 weeks) and were completed with a small number of study participants; however, small studies of both 6 months and 24 months duration have been completed in patients with diabetic neuropathy. ALA has been used extensively in the treatment of diabetic neuropathy in Germany since 1959. Studies supporting the effectiveness of ALA in other purported indications in humans are lacking or inconclusive. Further investigations of ALA in the treatment of Alzheimer's disease, HIV-related dementia, or liver diseases are needed before it can be recommended for use for those conditions.

Mechanism of Action

Endogenous alpha lipoic acid is available as both an R- and S- enantiomer; the R-enantiomer is the biologically active component, although most human clinical trials have used a racemic mixture of ALA. After oral or intraperitoneal administration, ALA is rapidly absorbed and distributed into various tissues including the heart, liver, and skeletal muscle. ALA is readily reduced to dihydrolipoic acid (DHLA) in body tissues. ALA is extensively metabolized, and very little is excreted as unchanged drug; ALA and DHLA are both water and fat soluble. ALA and DHLA are potent antioxidants that can scavenge reactive oxygen species and chelate metals (iron and copper for ALA and cadmium for DHLA), and ALA is natural cofactor of mitochondrial dehydrogenase complexes. In addition, DHLA may be able to regenerate oxidized vitamins E and C and glutathione.

Diabetes mellitus type 2: Several preliminary, short-term studies indicate that ALA may be effective in improving insulin sensitivity in patients with type 2 diabetes mellitus; administration of ALA has been shown to increase skeletal muscle glucose uptake and glucose disposal thereby improving insulin sensitivity and glucose utilization in patients with type 2 diabetes mellitus.

Diabetic neuropathy: Evidence indicates that oxidative stress and lipid peroxidation are major causes of neuropathic pain and dysfunction. Because of its antioxidant properties, ALA has been shown to improve the symptoms of neuropathy in patients with diabetes; a meta-analysis of 4 trials using intravenous ALA daily for 3 weeks reports that ALA is associated with a significant improvement in total symptoms scores including pain, burning, and numbness and neuropathic impairment scores including pin-prick sensation, touch-pressure sensation, and ankle reflexes.

Uses/Documentation

Current evidence indicates that alpha lipoic acid may have a role in improving insulin sensitivity in patients with type 2 diabetes mellitus as well as improving symptoms in patients with diabetic neuropathy. Data regarding use for other indications are either inconclusive or lacking.

For diabetes mellitus type 2: In 74 well-controlled patients with type 2 diabetes, ALA at a dosage of 600—1800 mg/day PO for 4 weeks (19 patients receiving 600 mg/day, 18 patients receiving 1200 mg/day, and 18 patients receiving 1800 mg/day) increased the metabolic clearance rate of glucose, a measure of insulin sensitivity, by 27% (p <0.01) as compared to placebo (n=19) (Jacob et al., 1999). In a second study, 600 mg PO twice daily of ALA for 4 weeks significantly increased insulin sensitivity in patients with type 2 diabetes mellitus; the glucose disposal rate increased from 3.2 +/- 1.9 at baseline to 6 +/- 2.7 mg/kg/min (p <0.01) at 4 weeks. The insulin sensitivity index increased from 4.7 +/- 2.7 to 7.7 +/- 3.6 mg/kg/min per mIU (p <0.05) (Kamenova, 2006). Adults: Other small, clinical studies utilizing IV ALA at doses of 1000 mg/day for 1 day or 500 mg/day for 10 days have demonstrated improvements in insulin sensitivity.

For diabetic neuropathy (neuropathic pain of diabetic origin): In 12 patients treated with ALA 600 mg PO three times daily for 3 weeks, total symptom score (TSS) and the neuropathy disability score (NDS) improved at week 3 compared to patients taking placebo; the TSS decreased by 47% in the ALA group compared to only 24% in the placebo group (p=0.021), and the NDS decreased by 0.27 points in the ALA group compared to an increase in 0.18 points in the placebo group (p=0.025) (Ruhnaut et al., 1999). Similarly, in 181 patients with diabetes, the use of ALA 600 mg/day PO (n=45), 1200 mg/day PO (n=47) or 1800 mg/day PO (n=46) for 5 weeks significantly decreased TSS of the feet by 4.5—4.9 points compared to a decrease of 2.9 points in patients taking placebo (n=43, p <0.05 for all groups of ALA vs. placebo). However, the incidence of side effects increased in a dose-dependent manner in patients taking ALA (Ziegler et al, 2006). In a trial of 26 patients with diabetic neuropathy, 600 mg of ALA once daily (route of administration not specified) for 3 months improved not only symptom scores, but also nerve conduction velocity of motor fibers (Negrisanu et al., 1999). Similarly, 600 mg/day IV of ALA for up to 3 weeks has been shown to be of benefit in improving TSS (Ametov et al, 2003). However, in a study comparing 1200 mg IV/day, 600 mg IV/day, 100 mg IV/day, and placebo for 3 weeks, TSS improved significantly in patients receiving 1200 mg IV or 600 mg IV as compared to placebo, but side effects occurred in 33% of patients taking 1200 mg/day, 18% in patients taking 600 mg/day, and 21% of patient receiving placebo (Ziegler et al., 1995). Several studies have also investigated the use of ALA 600 or 1200 mg/day IV for 1—3 weeks followed by either 600 or 1200 mg/day PO of ALA for 6—24 months; the study lasting only 6 months in duration did not find a significant difference between active treatment or placebo, but the study lasting 24 months did find a significant improvement in nerve conduction velocity without significant adverse effects. In addition to peripheral neuropathy, preliminary evidence indicates that ALA may be beneficial in patients with cardiac autonomic neuropathy. Patients with cardiac autonomic neuropathy received either 800 mg of ALA PO once daily (n=39) or placebo (n=34) for 4 months; heart rate variation improved significantly in patients taking ALA compared to placebo, although changes in cardiovascular autonomic symptoms did not differ between the 2 groups (Ziegler et al., 1997).

Contraindications/Precautions

Diabetes mellitus: Alpha lipoic acid may decrease blood glucose concentrations; patients with diabetes mellitus should use ALA with caution and monitor their blood glucose concentrations. Patients should also be instructed on the signs and symptoms of hypoglycemia.

Pregnancy and lactation: Evidence supporting the use of ALA in pregnancy and lactation is lacking. Women who are pregnant or breast-feeding their infants should avoid its use until information regarding safety and efficacy are available.

Interactions

Antidiabetic agents: Alpha lipoic acid has been shown to increase glucose utilization and decrease insulin resistance. Patients receiving antidiabetic agents in combination with ALA may be at increased risk for hypoglycemia; dosage adjustments of antidiabetic agents may be necessary. Furthermore, patients should be instructed to monitor their blood glucose concentrations while taking ALA. In one study, some patients with type 2 diabetes mellitus receiving both ALA and sulfonylureas required a dose reduction in the sulfonylurea due to mild symptoms of hypoglycemia (Jacob et al, 1999)

Drugs that decrease the effects of antidiabetic agents: Alpha lipoic acid has been shown to increase glucose utilization and decrease insulin resistance. Patients receiving other drugs that may increase blood glucose concentrations or insulin resistance may counteract the beneficial effects of ALA. Such drugs include anti-retroviral protease inhibitors, atypical antipsychotics, beta-blockers, corticosteroids, cyclosporine, dextrothyroxine, diuretics, glucagon, isoniazid, INH, niacin, phenothiazines, somatropin, rh-GH, sympathomimetics, tacrolimus, triamterene, and thyroid hormones. NOTE: This list is not inclusive of all drugs that can decrease the effects of antidiabetic agents.

Drugs that increase the effects of antidiabetic agents: Alpha lipoic acid has been shown to increase glucose utilization and decrease insulin resistance. Patients receiving other drugs that may decrease blood glucose concentrations or insulin resistance may enhance the beneficial effects of ALA, possibly causing hypoglycemia. Such drugs include ACE inhibitors, androgens, bortezomib, chromium, disopyramide, fibric acid derivatives, garlic, Allium sativum, green tea, guanethidine, horse chestnut, Aesculus hippocastanum, MAOIs, octreotide, and orlistat. Patients with diabetes taking ALA plus any of these other drugs should be advised to monitor their blood glucose concentrations. NOTE: This list is not inclusive of all drugs that increase the effects of antidiabetic agents.

Drugs that increase or decrease the effects of antidiabetic agents: Alpha lipoic acid has been shown to increase glucose utilization and decrease insulin resistance. Patients receiving other drugs that may increase or decrease blood glucose concentrations or insulin resistance may counteract the beneficial effects of ALA or enhance its effects and increase the risk of hypoglycemia. Such drugs include clonidine, cisapride, ethanol, lithium, metoclopramide, pentamidine, and quinolones. Patients with diabetes taking any of these drugs in combination with ALA should be advised to monitor their blood glucose concentrations. NOTE: This list is not inclusive of all drugs that may increase or decrease the effects of antidiabetic agents.

Drugs that mask the signs and symptoms of hypoglycemia: Alpha lipoic acid has been shown to increase glucose utilization and decrease insulin resistance; hypoglycemia may be possible. Patients receiving other drugs that mask the signs and symptoms of hypoglycemia such as beta-blockers, clonidine, reserpine, guanethidine in combination with ALA should be advised to monitor their blood glucose concentrations. NOTE: This list is not inclusive of all drugs that may mask the signs and symptoms of hypoglycemia.

Adverse Reactions/Side Effects

Alpha lipoic acid appears to be well-tolerated. In clinical trials of patients with diabetes, a few patients reported symptoms consistent with mild hypoglycemia. In addition, allergic skin conditions have been reported in patients taking oral ALA. In a study in patients with peripheral neuropathy, a dose-dependent increase in the incidence of nausea, vomiting and vertigo was reported with the highest incidence in those patients taking 1200 mg and 1800 mg/day PO of ALA (Ziegler et al., 2006).

Storage

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

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