Monograph: |
Beta-Carotene
Indications: Photosensitivity, secondary to erythropoietic protoporphyria
DESCRIPTION:
Beta-carotene, precursor of vitamin A, is a carotenoid pigment occurring naturally in green and yellow vegetables. Chemically, beta-carotene has the empirical formula C40H56 and a calculated molecular weight of 536.85. Trans-beta-carotene is a red, crystalline compound which is insoluble in water.
CLINICAL PHARMACOLOGY:
Beta-carotene, a provitamin A, belongs to the class of carotenoid pigments. In terms of its vitamin activity, 6 mcg of dietary beta-carotene is considered equivalent to 1 mcg of vitamin A (retinol). Bio-availability of beta-carotene depends on the presence of fat in the diet to act as a carrier, and bile in the intestinal tract for its absorption. Beta-carotene is metabolized, primarily in the intestine, to vitamin A at a rate of approximately 50% to 60% of normal dietary intake and falls off rapidly as intake goes up. In humans, an appreciable amount of unchanged beta-carotene is absorbed and stored in various tissues, especially the depot fat. Small amounts may be converted to vitamin A in the liver. The vitamin A derived from beta-carotene follows the same metabolic pathway as that from dietary sources. The major route of elimination is fecal excretion. Excessive ingestion of carotenes is not harmful, but it may cause yellow coloration of the skin, which disappears upon reduction or cessation of intake.
INDICATIONS AND USAGE:
Beta-carotene is used to reduce the severity of photosensitivity reactions in patients with erythropoietic protoporphyria (EPP).
CONTRAINDICATIONS:
Beta-carotene is contraindicated in patients with known hypersensitivity to the drug.
WARNINGS:
Beta-carotene has not been shown to be effective as a sunscreen.
PRECAUTIONS:
General Beta-carotene should be used with caution in patients with impaired renal or hepatic function because safe use in the presence of these conditions has not been established.
Information for the Patient Patients receiving beta-carotene should be advised against taking supplementary vitamin A since beta-carotene administration will fulfill normal vitamin A requirements. They should be cautioned to continue sun protection, and forewarned that their skin may appear slightly yellow while receiving beta-carotene.
Carcinogenesis, Mutagenesis, and Impairment of Fertility Long-term studies in animals to determine carcinogenesis have not been completed. In vitro and in vivo studies to evaluate mutagenic potential were negative. No effects on fertility in male rats were observed at doses as high as 500 mg/kg/day (100 times the recommended human dose).
Pregnancy, Teratogenic Effects, Pregnancy Category C Beta-carotene has been shown to be fetotoxic (i.e., cause an increase in resorption rate), but not teratogenic when given to rats at doses 300 to 400 times the maximum recommended human dose. No such fetotoxicity was observed at 75 times the maximum recommended human dose or less. A three-generation reproduction study in rats receiving beta-carotene at a dietary concentration of 0.1% (1000 ppm) has revealed no evidence of impaired fertility or effect on the fetus. There are no adequate and well-controlled studies in pregnant women. Beta-carotene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when beta-carotene is administered to a nursing mother.
ADVERSE REACTIONS:
Some patients may have occasional loose stools while taking beta-carotene. This reaction is sporadic and may not require discontinuance of medication. Other reactions which have been reported rarely are ecchymoses and arthralgia.
OVERDOSAGE:
There are no reported cases of overdosage. The oral LD50 of beta-carotene (suspended in 5% gum acacia solution) in mice and rats is greater than 20,000 mg/kg. No lethality was observed in mice following administration of 30-mg beadlet capsules (ground and suspended in 5% gum acacia) at a dose of 1200 mg/kg beta-carotene.
DOSAGE AND ADMINISTRATION:
Beta-carotene may be administered either as a single daily dose or in divided doses, preferably with meals.
Usage in Children: The usual dosage for children under 14 is 30 to 150 mg (1 to 5 capsules) per day. Capsules may be opened and the contents mixed in orange or tomato juice to aid administration.
Usage in Adults: The usual adult dosage is 30 to 300 mg (1 to 10 capsules) per day.
Dosage should be adjusted depending on the severity of the symptoms and the response of the patient. Several weeks of therapy are necessary to accumulate enough beta-carotene in the skin to exert its effect. Patients should be instructed not to increase exposure to sunlight until they appear carotenemic (first seen as yellowness of palms and soles). This usually occurs after two to six weeks of therapy. Exposure to the sun may then be increased gradually. The protective effect is not total and each patient should establish his or her own limits of exposure.
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