Phentermine HCl 5-HTP Complex Capsules

Phentermine

Phentermine is an oral sympathomimetic amine used as an adjunct for short-term (e.g., 8—12 weeks) treatment of exogenous obesity. The pharmacologic effects of phentermine are similar to amphetamines. Phentermine resin complex was approved by the FDA in 1959 but is no longer marketed in the US. Phentermine hydrochloride was FDA-approved in 1973.

In the mid-90s, there was renewed interest in phentermine in combination with another anorectic, fenfluramine, for the treatment of obesity and substance abuse, however, little scientific data support this practice. On July 8, 1997, the FDA issued a ‘Dear Health Care Professional’ letter warning physicians about the development of valvular heart disease and pulmonary hypertension in women receiving the combination of fenfluramine and phentermine; fenfluramine was subsequently withdrawn from the US market in fall of 1997. The use of phentermine with other anorectic agents for obesity has not been evaluated and is not recommended. In May 2011, the FDA approved a phentermine hydrochloride orally disintegrating tablet (Suprenza) for the treatment of exogenous obesity.

Dexpanthenol

Dexpanthenol is a synthetic derivative of pantothenic acid, a B complex vitamin that is widely distributed in plants and animals. Dexpanthenol is used parenterally as a gastrointestinal stimulant to treat and prevent ileus after GI surgery and in other conditions with impaired GI activity. Dexpanthenol was approved by the FDA in 1948.

Pyridoxine

Pyridoxine is a form of vitamin B6 – a water-soluble vitamin. Pyridoxine hydrochloride is the stable salt form of pyridoxine. Pyridoxine hydrochloride injection is prescribed when oral administration is not feasible, e.g., in case of gastric malabsorption syndromes, and pre-operative and post-operative conditions requiring parenteral nutrition.

Pyridoxine, or vitamin B6, is a naturally occurring vitamin found in food such as cereal grains, legumes, vegetables, liver, meat, and eggs. Pyridoxine is used to treat and prevent vitamin B6 deficiency; to prevent or treat toxicity from isoniazid, cycloserine, or hydralazine; and to treat sideroblastic anemia associated with elevated serum iron levels. It also has been used in pyridoxine-dependent neonates to treat seizures that are unresponsive to conventional therapy and in patients with metabolic disorders such as xanthurenic aciduria, primary hyperoxaluria, primary cystathioninuria, and primary homocystinuria. Pyridoxine hydrochloride has been commercially available since approval by the FDA in 1940.

Inside the body, pyridoxine is converted into its active form, the coenzyme pyridoxal 5’-phosphate. Pyridoxal 5’-phosphate is a versatile coenzyme participating in over 100 biochemical reactions mediating protein, carbohydrate, and lipid metabolism. It is crucial for the production of neurotransmitters, including dopamine, serotonin, norepinephrine, and GABA. It is also involved in regulating steroid hormone receptors and modulating the affinity of hemoglobin for oxygen.

Since humans lack the enzymes required for vitamin B6 (and pyridoxine) biosynthesis, it is an essential nutrient that needs to be procured through the diet. Dietary sources rich in vitamin B6 are fish, liver and other organ meats, potatoes and other starchy vegetables, and non-citrus fruits.3 Isolated vitamin B6 deficiency due to inadequate dietary intake is rare. Deficiency of vitamin B6 may occur in individuals with impaired renal function, genetic or autoimmune disorders, high alcohol intake, and with prolonged use of drugs including isoniazid, cycloserine, anti-epileptics, and oral contraceptives. In individuals with rheumatoid arthritis and inflammatory bowel disease, inflammatory cytokines cause low vitamin B6 levels, with greater deficiency associated with higher disease severity. People with celiac disease and other malabsorptive autoimmune disorders have vitamin B6 deficiency due to consuming a gluten-free diet low in essential vitamins. In people with alcohol dependence, the acetaldehyde produced from alcohol competes with the active form of pyridoxine for protein binding. Unbound pyridoxal 5’-phosphate – the active coenzyme form of pyridoxine – is rapidly hydrolyzed, resulting in vitamin B6 deficiency with high alcohol intake. Drugs like isoniazid and cycloserine interfere with enzymes that convert pyridoxine into pyridoxal-5-phosphate or enhance the catabolism and excretion of pyridoxine, resulting in vitamin B6 deficiency with prolonged use.

Vitamin B6 deficiency may produce symptoms such as electroencephalogram abnormalities, seizures, peripheral neuropathy, depression, confusion, dermatitis with scaling lips and cracks at the corners of the mouth, glossitis, microcytic anemia, and a weakened immune system. Low levels of vitamin B6 are associated with an increased risk of cardiovascular disorders, cognitive impairment, and certain types of cancer. However, more evidence is needed to conclusively demonstrate whether vitamin B6 supplementation reduces the risk or severity of these conditions.

Biotin

Biotin (vitamin H; coenzyme R; classified as a B vitamin) is a dietary component that is important for the metabolism of carbohydrates, fats, and amino acids. It is found primarily in the liver, kidney, and muscle. Biotin functions as an essential cofactor for five carboxylases that catalyze steps in fatty acid, glucose, and amino acid metabolism. It is also an important factor in histone modifications, gene regulation, and cell signaling. Mammals must consume biotin to replenish stores. Sources of biotin include organ meats, eggs, fish, seeds, and nuts. As a dietary supplement, biotin has been promoted to be useful in the treatment of hair and nail problems, cradle cap (seborrheic dermatitis) in phenylketonuria patients, biotinidase deficiency, diabetes, peripheral neuropathy, candida infections, and high cholesterol. It has also been used in pregnancy, hemodialysis, and peritoneal dialysis, as biotin deficiency is more likely in these situations. Biotin is found in many cosmetics products. Radiolabeled biotin is used for pretargeted radioimmunotherapy of cancerous tumors.

Folic Acid

Folic acid is a water-soluble, B-complex vitamin that is available orally and parenterally. This vitamin is found in a variety of foods including liver, kidneys, yeast, and leafy, green vegetables. A deficiency in folic acid can cause a variety of hematologic complications including megaloblastic and macrocytic anemias. In addition to treating megaloblastic and macrocytic anemias as well as tropical sprue, this vitamin is also used as a diagnostic aid for folate deficiency. In recent years, it has been discovered that adequate folic acid intake can substantially decrease the risk of congenital neural tube defects. Unlike the folic acid derivative leucovorin, folic acid is not clinically useful in offsetting the action of folate reductase inhibitors because it requires the enzyme dihydrofolate reductase for activation. Folic acid is also ineffective in the treatment of aplastic and normocytic anemias. Prescription forms of folic acid were approved by the FDA in 1946. In 1998, the recommended dietary allowance for all women of childbearing age who are capable of becoming pregnant was increased to 400 mcg of folic acid daily. As of 1998, the FDA has required that all food manufacturers fortify enriched grain products with folic acid to reduce the risk of congenital neural tube defects.

Methylcobalamin

Methylcobalamin, or vitamin B12, is a B vitamin. It is found in a variety of foods such as fish, shellfish, meats, and dairy products. Although methylcobalamin and vitamin B12 are terms used interchangeably, vitamin B12 is also available as hydroxocobalamin, a less commonly prescribed drug product (see Hydroxocobalamin monograph), and methylcobalamin. Methylcobalamin is used to treat pernicious anemia and vitamin B12 deficiency, as well as to determine vitamin B12 absorption in the Schilling test. Vitamin B12 is an essential vitamin found in the foods such as meat, eggs, and dairy products. Deficiency in healthy individuals is rare; the elderly, strict vegetarians (i.e., vegan), and patients with malabsorption problems are more likely to become deficient. If vitamin B12 deficiency is not treated with a vitamin B12 supplement, then anemia, intestinal problems, and irreversible nerve damage may occur.

The most chemically complex of all the vitamins, methylcobalamin is a water-soluble, organometallic compound with a trivalent cobalt ion bound inside a corrin ring which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). Methylcobalamin cannot be made by plants or by animals; the only type of organisms that have the enzymes required for the synthesis of methylcobalamin are bacteria and archaea. Higher plants do not concentrate methylcobalamin from the soil, making them a poor source of the substance as compared with animal tissues.

Ascorbic Acid

Ascorbic acid is a water-soluble vitamin found in fruits and vegetables such as citrus fruits and green peppers. It occurs as a white or slightly yellow crystal or powder with a slightly acidic taste. It is an antiscorbutic product. On exposure to air and light it gradually darkens. In the dry state, it is reasonably stable in air, but in solution, it rapidly oxidizes. Ascorbic acid is a free radical, an antioxidant scavenger, and plays a major role in oxidation-reduction reactions. Ascorbic acid is a cofactor for enzymes involved in the biosynthesis of collagen (essential for tissue maintenance and repair), carnitine, and neurotransmitters. Humans cannot synthesize ascorbic acid endogenously and a lack of dietary intake can lead to scurvy. Vitamin C is most frequently used as a nutritional supplement. It also is used as an adjunct treatment of idiopathic methemoglobinemia and with deferoxamine in the treatment of chronic iron toxicity. Ascorbic acid has been used for a variety of ailments including the common cold, gum infections, acne, depression, fertility, and cancer; however, these claims have not been substantiated and vitamin C is not recommended for these purposes (see Mechanism of Action). Ascorbic acid was approved by the FDA in 1939.

Chromium

Chromium, in its trivalent state (i.e., Cr3+), is an essential trace element that is required for proper carbohydrate, lipid, and nucleic acid metabolism in the human body. Dietary sources of chromium (Cr3+) include whole grains, egg yolks, brewer’s yeast, liver, meats, nuts, potatoes with skin, and beer. Overt signs and symptoms of chromium deficiency are usually only observed in adult patients eating diets high in refined foods or who are receiving long-term total parenteral nutrition without chromium supplementation. Clinically, overt deficiencies may be detected as the development of impaired glucose tolerance, glycosuria, and insulin resistance. Impaired protein and lipid metabolism, peripheral neuropathy, and encephalopathy secondary to chromium deficiency have also been reported. Chromium supplementation should only be expected to improve disorders that are due to chromium deficiency. Limited studies have reported that the addition of chromium picolinate supplements to the dietary regimens of patients with type 2 or steroid-induced diabetes mellitus may result in improvements in glycemic control and cholesterol in some patients, and may allow for the reduction of antidiabetic medication. However, these trials have studied few patients; the importance of chromium deficiency in the average patient with type 2 diabetes has not been established. Controversy exists concerning other claimed benefits of chromium supplementation. Among athletes, chromium is promoted as an alternative to anabolic steroids. Multiple studies have concluded that there is no evidence that chromium supplementation increases muscle mass to a level greater than that which is produced with a healthy diet and exercise alone. There also appears to be no basis for claims that chromium reduces body fat or weight. Clinical studies of chromium intake have revealed no additional changes in body-fat percentages or weight loss in either obese females or young athletes following controlled diet and exercise regimens. Other claimed uses, such as the adjunctive treatment to medical therapy for gestational diabetes after the 1st trimester or the adjunctive treatment of the dysthymic disorder, are not accepted at this time. In the US, sales of chromium picolinate supplements exceed 150 million dollars per year.