Voriconazole
Tretinoin, ATRA Interactions
Keratolytic agents or products that contain keratolytic agents, such as benzoyl peroxide, resorcinol, sulfur, salicylic acid, lactic acid, and medicated or abrasive soaps or cleansers, can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided. Similarly, products that contain ethanol, lime, menthol, spices, or perfumes can further dry and irritate the skin and should not be used with tretinoin; it is advisable to allow the effects of such preparations to subside before initiating topical tretinoin treatment.
Concurrent oral tretinoin therapy with drugs that inhibit the hepatic cytochrome (CYP) P450 enzyme system can result in significant increases in serum tretinoin levels. In 13 patients who had received oral tretinoin daily for 4 consecutive weeks, a 72% increase in mean tretinoin plasma AUC was observed when ketoconazole (400 mg to 1200 mg PO) was given 1 hour before the tretinoin dose. This interaction may be due to inhibition of tretinoin metabolism by the azole antifungal; the precise CYP enzymes involved have not been identified, but CYP3A, 2C8 and 2E have been implicated in preliminary data. Similar interactions may occur with other systemic azole antifungals, such as voriconazole. No specific studies have been done with oral tretinoin and other inhibitors of CYP450 isoenzymes (such as cimetidine, cyclosporine, diltiazem, erythromycin, and verapamil), however, patients should be closely monitored for tretinoin toxicity while receiving concomitant therapy.
Concurrent oral tretinoin therapy with drugs that are inducers of the hepatic cytochrome (CYP) P450 enzyme system can result in significant decreases in serum tretinoin levels (CYP450 substrate). Inducers of the hepatic cytochrome (CYP) P450 enzyme system include barbiturates, carbamazepine, griseofulvin, felbamate, phenytoin or fosphenytoin (and possibly ethotoin), rifampin, rifabutin, rifapentine, topiramate, and troglitazone. Patients should be closely monitored for decreased clinical effects while receiving concomitant therapy.
Patients should avoid supplementation with vitamin A or treatment with other retinoids during treatment with systemic or topical tretinoin therapy to avoid potential additive toxic effects.
The bile-acid sequestrants cholestyramine and colestipol are well-known to cause drug interactions by binding and decreasing the oral administration of many drugs, which may include interaction with oral tretinoin; to minimize drug interactions, administer other drugs at least 1 hour before or at least 4 - 6 hours after the administration of cholestyramine or colestipol.
The concomitant use of systemic tretinoin and systemic tetracyclines should generally be avoided, due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances. Amiodarone, danazol, gentamicin, ibuprofen, lithium, and thyroid hormones are also associated with an increased risk of pseudotumor cerebri and should be used cautiously in combination with systemic tretinoin. Retinoids as a class have also been associated with photosensitivity. Known photosensitizers such as tetracyclines may have additive effects. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Retinoids may cause photosensitivity. Retinoids may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment. Administer with caution to patients who are also taking drugs known to be photosensitizers such as quinolones (particularly sparfloxacin), phenothiazines, sulfonamides, sulfonylureas, and thiazide diuretics. Patients should take care and use proper techniques to limit sunlight and UV exposure.
Due to orlistat’s mechanism of action, the potential exists for the malabsorption of drugs and dietary supplements. The effect on absorption of the vitamin A supplements (or retinoids, vitamin A analogues) is not known at this time. However, patients who received orlistat without vitamin supplementation during clinical studies developed significantly lower levels of vitamin A over a 1 to 2 year period when compared with the placebo group. The manufacturer recommends that fat-soluble vitamin supplements (and analogues) be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption. Due the effect of orlistat on fat absorption and lower levels of fat-soluble vitamins during clinical trials, the bioavailability of orally administered tretinoin may be decreased during concurrent therapy. Close monitoring of patients receiving oral tretinoin therapy with orlistat is recommended.
Patients receiving other agents that may cause hepatotoxicity, including systemic retinoids, could be at increased risk of liver-related side effects of methotrexate and should be monitored closely during methotrexate therapy. Although no longer available commercially in the United States, etretinate has been shown to increase methotrexate serum concentrations and cases of hepatotoxicity (e.g., hepatitis) have also been reported in patients receiving etretinate and methotrexate concomitantly; concurrent use is contraindicated. Acitretin is the principal active component of etretinate; consequently, the combination of methotrexate and acitretin is also contraindicated. Topical retinoid products do not appear to pose this increased risk for liver problems. Concurrent use of any retinoids (topical or systemic), which are photosensitizers, with methotrexate may result in additive photosensitivity.
Rare cases of fatal thrombotic complications have been reported in patients treated with systemic tretinoin, ATRA and antifibrinolytic agents. This is thought to be due to the persistent procoagulant tendency often associated with systemic tretinoin, ATRA therapy. Examples of antifibrinolytic agents include aminocaproic acid, aprotinin, and tranexamic acid. Close monitoring of patients receiving systemic tretinoin therapy with antifibrinolytic agents is strongly recommended and should be avoided if possible.
[ Last revised: 10/28/2005 2:56:00 PM ]
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