Interactions between Temsirolimus and Valacyclovir
1 drug interaction and 21 additional warnings found for the following 2 drugs:
- temsirolimus
- valacyclovir
Drug interactions
Major drug interactions
Major:
valACYclovir temsirolimus
Applies to: valacyclovir and temsirolimus
Monitor closely
Coadministration of macrolide immunosuppressants with other nephrotoxic agents may increase the risk and/or severity of renal impairment due to additive adverse effects on the kidney. No formal interaction studies have been performed. However, clinical experience in coadministration with cyclosporine indicates increased renal toxicity as evidenced by increased serum creatinine and decreased glomerular filtration rate. An interaction with ibuprofen resulting in acute renal failure was suspected in two liver transplant patients who had been stabilized on tacrolimus.
Management
Caution is advised when macrolide immunosuppressants is used in patients who have recently received or are receiving treatment with other potentially nephrotoxic drugs (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; adefovir; cidofovir; tenofovir; foscarnet; cisplatin; cyclosporine; deferasirox; gallium nitrate; lithium; mesalamine; intravenous bisphosphonates; intravenous pentamidine; high intravenous dosages of methotrexate; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents). Renal function should be closely monitored both during and after discontinuation of therapy. Patients should be advised to seek medical attention if they experience symptoms that may indicate nephrotoxicity such as decreased urine output, sudden weight gain, fluid retention, edema, or shortness of breath.
References (3)
- Sheiner PA, Mor E, Chodoff L, Glabman S, Emre S, Schwartz ME, Miller CM (1994) "Acute renal, failure associated with the use of ibuprofen in two liver transplant recipients on FK506." Transplantation, 57, p. 1132-3
- (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
- (2001) "Product Information. Rapamune (sirolimus)." Wyeth-Ayerst Laboratories
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
temsirolimus Food/Lifestyle
Applies to: temsirolimus
Generally avoid
Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.
Management
Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.
References (1)
- (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories
Disease interactions
20 potential interactions Applies to: 19 conditions, including High Cholesterol, Anaphylaxis, Diabetes Mellitus, Hemodialysis, and Liver Disease.
Anaphylaxis
Major:
temsirolimus
Temsirolimus has a major potential interaction with Anaphylaxis.
Hypersensitivity/infusion reactions, including but not limited to flushing, chest pain, dyspnea, hypotension, apnea, loss of consciousness, hypersensitivity and anaphylaxis, have been associated with the administration of temsirolimus. Caution should be exercised during the infusion and appropriate supportive care should be available. For patients who develop hypersensitivity reaction during the infusion, it is recommended to stop the infusion and close observation with the possibility of resuming therapy at a slower rate should be contemplated at the discretion of the physician. Temsirolimus infusion should be interrupted in all patients with severe infusion reactions and appropriate medical therapy administered. A benefit-risk assessment should be done prior to the continuation of therapy in patients with severe or life-threatening reactions.
Bone Marrow Transplantation
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Bone Marrow Transplantation.
Thrombotic thrombocytopenic purpura/hemolytic uremia syndrome (TTP/HUS), in some cases resulting in death, has been reported in patients with advanced HIV-1 disease, in allogeneic bone marrow transplant recipients, and in renal transplant recipients during clinical trials of valacyclovir at doses of 8 g/day. Therapy with valacyclovir should be discontinued immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS develop.
Brain Tumor
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with Brain Tumor.
Inhibition of mTOR activity results in delays of wound healing and increases the occurrence of wound-related complications, which might require surgical intervention. Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes). Caution is recommended when using these agents, particularly in the perioperative period.
Coagulation Defects and Disorders
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with Coagulation Defects and Disorders.
Inhibition of mTOR activity results in delays of wound healing and increases the occurrence of wound-related complications, which might require surgical intervention. Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes). Caution is recommended when using these agents, particularly in the perioperative period.
Dehydration
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Dehydration.
Valacyclovir is almost completely converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism; acyclovir is primarily eliminated by the kidney. Cases of acute renal failure have been reported in patients without adequate hydration. Acyclovir may precipitate in renal tubules when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Adequate hydration should be maintained for all patients. If acute renal failure and anuria occur, patients may benefit from hemodialysis until renal function is restored.
Dermatitis, Drug-Induced
Major:
temsirolimus
Temsirolimus has a major potential interaction with Dermatitis, Drug-Induced.
Hypersensitivity/infusion reactions, including but not limited to flushing, chest pain, dyspnea, hypotension, apnea, loss of consciousness, hypersensitivity and anaphylaxis, have been associated with the administration of temsirolimus. Caution should be exercised during the infusion and appropriate supportive care should be available. For patients who develop hypersensitivity reaction during the infusion, it is recommended to stop the infusion and close observation with the possibility of resuming therapy at a slower rate should be contemplated at the discretion of the physician. Temsirolimus infusion should be interrupted in all patients with severe infusion reactions and appropriate medical therapy administered. A benefit-risk assessment should be done prior to the continuation of therapy in patients with severe or life-threatening reactions.
Diabetes Mellitus
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with Diabetes Mellitus.
Elevations in serum blood glucose levels have been reported in patients taking inhibitors of mTOR (mammalian target of rapamycin). Monitoring of fasting serum glucose levels is recommended prior to the start of therapy and periodically thereafter. Clinicians should achieve control of glucose levels before initiating therapy with these agents.
Gastrointestinal Perforation
Major:
temsirolimus
Temsirolimus has a major potential interaction with Gastrointestinal Perforation.
Cases of fatal bowel perforation occurred in patients who received temsirolimus. Therapy with temsirolimus should be administered with caution in patients who may be at increased risk for gastrointestinal perforation, such as those with a history of diverticulitis. Patients presenting with new onset or worsening of abdominal symptoms or blood in the stools should be evaluated promptly for early identification of gastrointestinal perforation.
Hemodialysis
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Hemodialysis.
Valacyclovir is almost completely converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism. About one-third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session. The recommended dose of valacyclovir should be administered after hemodialysis.
High Cholesterol
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with High Cholesterol.
Elevations in cholesterol and triglyceride levels have been reported in patients taking inhibitors of mTOR (mammalian target of rapamycin). Monitoring of fasting lipid profile is recommended prior to the start of therapy and periodically thereafter. Clinicians should achieve control of lipid levels before initiating therapy with these agents.
Immunodeficiency
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Immunodeficiency.
Thrombotic thrombocytopenic purpura/hemolytic uremia syndrome (TTP/HUS), in some cases resulting in death, has been reported in patients with advanced HIV-1 disease, in allogeneic bone marrow transplant recipients, and in renal transplant recipients during clinical trials of valacyclovir at doses of 8 g/day. Therapy with valacyclovir should be discontinued immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS develop.
Infection
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with Infection.
The immunosuppressant effect of inhibitors of mTOR (mammalian target of rapamycin) may decrease host resistance to infectious agents and may predispose patients to bacterial, fungal, viral, or protozoal infections, infections with opportunistic pathogens, and reactivation of viral infections. Therapy with these agents should be administered with caution in patients with an infection, particularly active infections or any untreated systemic fungal, bacterial, parasitic, or viral infection. It is recommended to complete the treatment of preexisting invasive fungal infections prior to starting treatment and if a diagnosis of invasive systemic fungal infection is made during treatment, discontinue and treat with appropriate antifungal therapy.
Interstitial Lung Disease
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with Interstitial Lung Disease.
Cases of interstitial lung disease, some resulting in death, occurred in patients who received temsirolimus. It is recommended that patients undergo baseline radiographic assessment by lung computed tomography scan or chest radiograph prior to the initiation of therapy. Close monitoring for the occurrence of any new or worsening respiratory symptoms is advisable and if clinically significant respiratory symptoms develop, consider withholding administration until after recovery of symptoms and improvement of radiographic findings related to pneumonitis.
Liver Disease
Major:
temsirolimus
Temsirolimus has a major potential interaction with Liver Disease.
Temsirolimus is contraindicated in patients with bilirubin >1.5×ULN. Caution is recommended when treating patients with mild hepatic impairment and a dose reduction may be needed depending on AST and bilirubin levels. Dosage adjustment is needed based on hepatic function; therefore, assessment of AST and bilirubin levels is recommended before initiation of therapy and periodically thereafter.
Neutropenia
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Neutropenia.
Thrombotic thrombocytopenic purpura/hemolytic uremia syndrome (TTP/HUS), in some cases resulting in death, has been reported in patients with advanced HIV-1 disease, in allogeneic bone marrow transplant recipients, and in renal transplant recipients during clinical trials of valacyclovir at doses of 8 g/day. Therapy with valacyclovir should be discontinued immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS develop.
Organ Transplant
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Organ Transplant.
Thrombotic thrombocytopenic purpura/hemolytic uremia syndrome (TTP/HUS), in some cases resulting in death, has been reported in patients with advanced HIV-1 disease, in allogeneic bone marrow transplant recipients, and in renal transplant recipients during clinical trials of valacyclovir at doses of 8 g/day. Therapy with valacyclovir should be discontinued immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS develop.
Pulmonary Impairment
Moderate:
temsirolimus
Temsirolimus has a moderate potential interaction with Pulmonary Impairment.
Cases of interstitial lung disease, some resulting in death, occurred in patients who received temsirolimus. It is recommended that patients undergo baseline radiographic assessment by lung computed tomography scan or chest radiograph prior to the initiation of therapy. Close monitoring for the occurrence of any new or worsening respiratory symptoms is advisable and if clinically significant respiratory symptoms develop, consider withholding administration until after recovery of symptoms and improvement of radiographic findings related to pneumonitis.
Renal Dysfunction
Major:
temsirolimus
Temsirolimus has a major potential interaction with Renal Dysfunction.
Cases of renal failure, including acute renal failure and elevations of serum creatinine and proteinuria, some with a fatal outcome, have been observed in patients treated with inhibitors of mTOR (mammalian target of rapamycin). Therapy with these agents should be administered cautiously in patients with renal dysfunction, in particularly where patients have additional risk factors that may further impair renal function. Renal impairment is not expected to influence drug exposure, and no dosage adjustment is recommended in patients with renal impairment. Monitoring of renal function, including measurement of blood urea nitrogen (BUN), urinary protein, or serum creatinine, is recommended prior to the start of therapy and periodically thereafter.
Moderate:
valacyclovir
valACYclovir has a moderate potential interaction with Renal Dysfunction.
Valacyclovir is almost completely converted to acyclovir and L-valine by first-pass intestinal and/or hepatic metabolism; acyclovir is primarily eliminated by the kidney. Cases of acute renal failure and CNS side effects (including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy) have been reported in patients with preexisting renal disease who received higher-than-recommended doses of valacyclovir for their level of renal function. Cases of acute renal failure have also been reported in patients receiving other nephrotoxic agents. Therapy with valacyclovir should be administered cautiously in elderly patients (with or without renal dysfunction) and patients receiving other nephrotoxic agents. Dosage reductions are recommended in patients with renal dysfunction. If acute renal failure and anuria occur, patients may benefit from hemodialysis until renal function is restored; valacyclovir should be discontinued if CNS side effects develop.
Vaccination
Major:
temsirolimus
Temsirolimus has a major potential interaction with Vaccination.
The administration of live vaccines should be avoided during therapy with inhibitor of mTOR (mammalian target of rapamycin). It is recommended that close contact with individuals who have received live vaccines should be avoided because of the potential risk for shedding from the household contact and transmission to patient. It is recommended to be up-to-date with all required immunizations, as recommended by current immunization guidelines, before initiating therapy with these agents.
More resources
temsirolimus
A total of 733 drugs are known to interact with temsirolimus.
- Temsirolimus is in the drug class mTOR inhibitors.
- Temsirolimus is used to treat Renal Cell Carcinoma (RCC).
valacyclovir
A total of 94 drugs are known to interact with valacyclovir.
- Valacyclovir is in the drug class purine nucleosides.
- Valacyclovir is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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