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Drug Interactions between levamlodipine and posaconazole

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

posaconazole levamlodipine

Applies to: posaconazole and levamlodipine

MONITOR: Coadministration with azole agents may increase the plasma concentrations of calcium channel blockers (CCBs), especially the dihydropyridines (e.g., amlodipine, felodipine, nicardipine, nifedipine, nisoldipine). The mechanism involves inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of most CCBs. In a pharmacokinetic study, nisoldipine mean peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 11- and 24-fold, respectively, during concomitant treatment with ketoconazole. Significant increases of severalfold in felodipine and nifedipine plasma concentrations have also been observed during coadministration with itraconazole. Theoretically, the interaction may potentiate the risk of ventricular dysfunction, congestive heart failure, and peripheral and pulmonary edema, particularly in patients with preexisting risk factors (e.g., a history of congestive heart failure; cardiac disease such as ischemic and valvular disease; significant pulmonary disease such as chronic obstructive pulmonary disorder; edematous disorders such as renal failure). There have been case reports of leg and ankle edema in patients treated with various itraconazole-dihydropyridine combinations.

MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if calcium channel blockers are used in combination with azole agents. Dosage reduction may be required for the calcium channel blocker, particularly if it is a dihydropyridine. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

References (8)
  1. Rosen T (1994) "Debilitating edema associated with itraconazole therapy." Arch Dermatol, 130, p. 260-1
  2. Neuvonen PJ, Suhonen R (1995) "Itraconazole interacts with felodipine." J Am Acad Dermatol, 33, p. 134-5
  3. Tailor SAN, Gupta AK, Walker SE, Shear NH (1996) "Peripheral edema due to nifedipine-itraconazole interaction: a case report." Arch Dermatol, 132, p. 350-2
  4. Tailor SAN (1996) "Peripheral edema due to nifedipine-itraconazole interaction: a case report." Arch Dermatol, 132, p. 1374
  5. Jalava KM, Olkkola KT, Neuvonen PJ (1997) "Itraconazole greatly increases plasma concentrations and effects of felodipine." Clin Pharmacol Ther, 61, p. 410-5
  6. Heinig R, Adelmann HG, Ahr G (1999) "The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine." Eur J Clin Pharmacol, 55, p. 57-60
  7. Sandstrom R, Knutson TW, Knutson L, Jansson B, Lennernas H (1999) "The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans." Br J Clin Pharmacol, 48, p. 180-9
  8. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation

Drug and food interactions

Moderate

posaconazole food

Applies to: posaconazole

ADJUST DOSING INTERVAL: Food significantly increases the absorption of posaconazole from the oral suspension but only modestly from the delayed-release tablet. Following single-dose administration, posaconazole mean peak plasma concentration (Cmax) and systemic exposure (AUC) are approximately 2.5 to 3 times higher when the oral suspension is given with a nonfat meal or a nutritional supplement (14 grams of fat) than when given under fasting conditions, and approximately 3.5 to 4 times higher when given during or 20 minutes after a high-fat meal (50 grams of fat) than under fasting conditions. Acidic beverages may also increase posaconazole absorption. In 12 healthy volunteers, administration of a single 400 mg dose of posaconazole suspension with 12 ounces of ginger ale increased posaconazole Cmax by 92% and AUC by 70% compared to administration after fasting. In contrast, the Cmax and AUC of posaconazole increased by just 16% and 51%, respectively, when posaconazole tablets were given as a single 300 mg dose to healthy volunteers after a high-fat meal relative to a fasted state.

GENERALLY AVOID Concomitant use of alcohol and posaconazole administered in the form of delayed-release oral suspension may lead to a faster release of posaconazole. An in vitro dissolution study determined a potential for alcohol-induced dose-dumping with the delayed-release oral suspension of posaconazole.

MONITOR: In 5 study subjects, posaconazole Cmax decreased by 27% to 53% and AUC decreased by 33% to 51% when the oral suspension was administered via a nasogastric tube as opposed to orally.

MANAGEMENT: Posaconazole tablets should be taken with food, whereas posaconazole oral suspension should be administered during or immediately (i.e., within 20 minutes) following a full meal to enhance bioavailability. Patients who cannot eat a full meal should take the suspension with a liquid nutritional supplement or an acidic carbonated beverage such as ginger ale. In patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking another formulation of posaconazole, alternative antifungal therapy should be considered; otherwise, monitor patients closely for breakthrough fungal infections. Patients receiving posaconazole via a nasogastric tube should also be closely monitored due to increased risk of treatment failure associated with lower plasma exposure. Administration of alcohol with posaconazole from the delayed-release oral suspension formulation is not recommended.

References (4)
  1. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  2. Sansone-Parsons A, Krishna G, Calzetta A, et al. (2006) "Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers." Antimicrob Agents Chemother, 50, p. 1881-3
  3. Krishna G, Moton A, Ma L, Malavade D, Medlock M, McLeod J (2008) "Effect of gastric pH, dosing regimen and prandial state, food and meal timing relative to dose, and gastro-intestinal motility on absorption and pharmacokinetics of the antifungal posaconazole." 18th European Congress of Clinical Microbiology and Infectious Diseases, April, p. 20
  4. Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P (2011) "Effect of pH and Comedication on Gastrointestinal Absorption of Posaconazole: Monitoring of Intraluminal and Plasma Drug Concentrations." Clin Pharmacokinet, 50, p. 725-34

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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