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Drug Interactions between Aristospan Intralesional and saquinavir

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

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Interactions between your drugs

Major

triamcinolone saquinavir

Applies to: Aristospan Intralesional (triamcinolone) and saquinavir

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of triamcinolone. No pharmacokinetic data are available. However, there have been numerous published case reports of Cushing's syndrome and adrenal suppression associated with concomitant use of triamcinolone with various ritonavir-containing antiretroviral regimens and one case report with nefazodone.

MANAGEMENT: The possibility of increased corticosteroid effects should be considered when triamcinolone is used with potent CYP450 3A4 inhibitors. Some authorities advise against concomitant use unless the potential benefit outweighs the risk. If coadministration is necessary, a lower dosage of triamcinolone may be appropriate. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if triamcinolone is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma).

References

  1. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  2. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
  3. Hagan JB, Erickson D, Singh RJ "Triamcinolone Acetonide Induced Secondary Adrenal Insufficiency Related to Impaired CYP3A4 Metabolism by Coadministration of Nefazodone." Pain Med (2010):
  4. Dort K, Padia S, Wispelwey B, Moore CC "Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report." AIDS Res Ther 6 (2009): 10
  5. Levine D, Ananthakrishnan S, Garg A "Iatrogenic Cushing syndrome after a single intramuscular corticosteroid injection and concomitant protease inhibitor therapy." J Am Acad Dermatol 65 (2011): 877-8
  6. Grierson MJ, Harrast MA "Iatrogenic Cushing Syndrome After Epidural Steroid Injections for Lumbar Radiculopathy in an HIV-Infected Patient Treated With Ritonavir: A Case Report Highlighting Drug Interactions for Spine Interventionalists." PM R 4 (2012): 234-7
  7. Albert NE, Kazi S, Santoro J, Dougherty R "Ritonavir and Epidural Triamcinolone as a Cause of Iatrogenic Cushing's Syndrome." Am J Med Sci (2012):
  8. Fessler D, Beach J, Keel J, Stead W "Iatrogenic hypercortisolism complicating triamcinolone acetonide injections in patients with HIV on ritonavir-boosted protease inhibitors." Pain Physician 15 (2012): 489-93
  9. Schwarze-Zander C, Klingmuller D, Klumper J, Strassburg CP, Rockstroh JK "Triamcinolone and ritonavir leading to drug-induced Cushing syndrome and adrenal suppression: description of a new case and review of the literature." Infection (2013):
  10. Hall JJ, Hughes CA, Foisy MM, Houston S, Shafran S "Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient receiving ritonavir boosted darunavir." Int J STD AIDS (2013):
  11. McConkey HZ, Williams H, Kulasegaram R, Graham E "Orbital floor triamcinolone causing Cushing's syndrome in a patient treated with Kaletra for HIV 1." BMJ Case Rep 2013 (2013):
  12. Sadarangani S, Berg ML, Mauck W, Rizza S "Iatrogenic Cushing Syndrome Secondary to Ritonavir-Epidural Triamcinolone Interaction: An Illustrative Case and Review." Interdiscip Perspect Infect Dis 2014 (2014): 849432
View all 12 references

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Drug and food interactions

Moderate

saquinavir food

Applies to: saquinavir

ADJUST DOSING INTERVAL: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant. A high degree of intersubject variability in the grapefruit juice effect was also observed. The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown. However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability. Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.

References

  1. "Product Information. Invirase (saquinavir)." Roche Laboratories PROD (2001):
  2. Kupferschmidt HHT, Fattinger KE, Ha HR, Follath F, Krahenbuhl S "Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man." Br J Clin Pharmacol 45 (1998): 355-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Eagling VA, Profit L, Back DJ "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol 48 (1999): 543-52
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
View all 6 references

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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.

Further information

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