Chronic HBV Treatment Linked to Increased Rates of Colorectal and Cervical Cancer
A potential link between long-term oral treatment with nucleos(t)ide analogues for chronic hepatitis B virus (HBV) and an increased risk of colorectal (P = .029) and cervical (P = .049) cancers was demonstrated in a presentation at The International Liver Congress.1
Selected patients with chronic HBV receive prolonged treatment with nucleos(t)ide analogues, which are used to prevent the virus from reproducing. Notably, questions have been raised about the long-term safety of such treatments.
"Although our analysis showed that nucleos(t)ide analogue treatment does not increase overall incidence of liver, lung, breast, and urinary/renal malignancies, it did reveal that patients with hepatitis B virus on this treatment had a higher risk of developing colorectal and cervical cancers," said Professor Grace Wong, MD, Department of Medicine & Therapeutics Academic at the Chinese University of Hong Kong and lead study author. "In light of these findings we strongly urge regular screening of these cancers to help prevent them from developing in patients taking nucleos(t)ide analogue treatment."
The research team analyzed data on 45 299 patients with chronic HBV, including 7323 (16.16%) who had undergone nucleos(t)ide analogue treatment. Follow-up continued for up to 7 years.
At the median follow-up of 4.4 years, malignancies occurred in 538 (2.1%) of the untreated patients and 274 (5.7%) patients who had received nucleos(t)ide analogue therapy. Nucleos(t)ide analogue-treated patients had higher risks of developing colorectal cancer(adjusted hazard ratio (aHR) 2.17; 95% confidence interval (Cl) 1.08-4.36; P = .029) and cervical cancer (aHR 4.41; 95% Cl 1.01-19.34; P = .049).
The risk across patients treated versus untreated with nucleos(t)ide analogues was similar for developing other malignancies, including lung and pleural cancers, breast cancer, and renal conditions.
This large-scale study links treatment with nucleos(t)ide analogues and the development of cervical and colorectal cancer, which may change cancer surveillance and management of patients treated for HBV.
Source : Oncology Nurse Advisor (May 2016)
Hep C Drug Linked to Fatal Skin Reactions
The oral hepatitis C drug telaprevir (Incivek) will now carry a boxed warning about potentially fatal skin reactions in the wake of multiple deaths, its manufacturer said Wednesday.
According to a statement from Vertex Pharmaceuticals, "Fatal cases of serious skin reactions have been reported in patients with progressive rash and systemic symptoms who continued to receive Incivek combination treatment after a serious skin reaction was identified."
The new warning stresses that combination treatment with telaprevir should be stopped immediately in patients with serious skin reactions, such as rashes with systemic symptoms or progressive severe rashes. Discontinuation of other drugs with the potential for skin reactions also should be considered.
Serious skin reactions were seen during the drug's clinical trials prior to approval, including some requiring hospitalization and considered life-threatening. The risk was noted on telaprevir's original label.
But these events were rare -- affecting less than 1% of patients -- and all patients eventually recovered, Vertex said.
The reports of deaths associated with skin reactions emerged during postmarketing surveillance. The company did not indicate how many fatalities were reported.
"Given the severity of the events reported in the postmarketing setting, and the importance of discontinuing Incivek combination treatment in the event of one of these reactions, the information has been given greater prominence through a boxed warning," Vertex said.
It also said the telaprevir label had been modified with new information on the time to onset of anemia and on its management.
The drug, a hepatitis C virus protease inhibitor, was approved in May 2011.
Source : MedPage Today
FDA Drug Safety Communication: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury
Facts about statins and protease inhibitors
- Statins are a class of prescription drugs used together with diet and exercise to reduce blood levels of low-density lipoprotein (LDL) cholesterol (“bad cholesterol”).
- HIV protease inhibitors are a class of prescription anti-viral drugs used to treat HIV.
- HCV protease inhibitors are a class of prescription anti-viral drugs used to treat hepatitis C infection.
- A side effect of taking HIV protease inhibitors is increased cholesterol and triglyceride (fat) levels. Therefore, some patients taking HIV protease inhibitors may need to take cholesterol-lowering medicines such as statins.
The U.S. Food and Drug Administration (FDA) is issuing updated recommendations concerning drug-drug interactions between drugs for human immunodeficiency virus (HIV) or hepatitis C virus (HCV) known as protease inhibitors and certain cholesterol-lowering drugs known as statins. Protease inhibitors and statins taken together may raise the blood levels of statins and increase the risk for muscle injury (myopathy). The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal. The labels for both the HIV protease inhibitors and the affected statins have been updated to contain consistent information about the drug-drug interactions. These labels also have been updated to include dosing recommendations for those statins that may safely be co-administered with HIV or HCV protease inhibitors (see Statin Dose Limitations below).
Healthcare professionals should refer to the current drug labels for protease inhibitors and statins for the latest recommendations on prescribing these drugs.
Patients should contact their healthcare professional if they have any questions or concerns about taking protease inhibitors and statins.
- Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) protease inhibitors can interact with cholesterol-lowering statins to increase the risk of muscle injury.
- Patients should inform their healthcare professional about all medicines that they are taking or plan to take prior to starting an HIV or HCV protease inhibitor or statin.
- HIV and HCV protease inhibitors should never be taken (are contraindicated) with lovastatin (Mevacor) and simvastatin (Zocor) (see Statin Dose Limitations below).
- Patients should contact their healthcare professional if they have any questions or concerns about HIV or HCV protease inhibitors or statins.
- Patients should report side effects from the use of HIV or HCV protease inhibitors and/or statins to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.
- Co-administration of human immunodeficiency virus (HIV) or hepatitis C virus (HCV) protease inhibitors with certain statins can increase the risk of myopathy/rhabdomyolysis.
- Healthcare professionals should follow the recommendations in the drug labels when prescribing HIV or HCV protease inhibitors with statins (also see Statin Dose Limitations below).
- Healthcare professionals should report adverse events involving HIV or HCV protease inhibitors and/or statins to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
The results from a drug-drug interaction study with atorvastatin and lopinavir/ritonavir that were previously in the atorvastatin label have not yet been validated. Therefore, these results have been removed from the label and the dose cap of atorvastatin 20 mg when co-administered with lopinavir/ritonavir has also been removed. Pending validation of the study, healthcare professionals should use caution when co-administering atorvastatin with lopinavir/ritonavir and use the lowest necessary dose of atorvastatin.
Lovastatin and simvastatin
Lovastatin and simvastatin are sensitive in vivo cytochrome P450 3A4 (CYP3A4) substrates. Therefore, strong CYP3A4 inhibitors are predicted to significantly increase lovastatin and simvastatin exposures. A literature review indicates that itraconazole, a strong CYP3A4 inhibitor, increases lovastatin exposure up to 20-fold, and the drug interaction appears to result in rhabdomyolysis.1 Itraconazole increases simvastatin exposure up to 13-fold. Hence, other CYP3A4 inhibitors, including ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, nefazodone, human immunodeficiency virus (HIV) protease inhibitors, and the hepatitis C virus (HCV) protease inhibitors boceprevir and telaprevir, are also expected to significantly increase lovastatin and simvastatin exposures. Therefore, concomitant administration of lovastatin and simvastatin with HIV protease inhibitors or HCV protease inhibitors (boceprevir and telaprevir) is contraindicated.
The HIV protease inhibitor combinations lopinavir/ritonavir and atazanavir/ritonavir increase rosuvastatin exposure up to 3-fold. For these combinations, the dose of rosuvastatin should be limited to 10 mg.
Statin Dose Limitations
Table Press Source
- Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med. 1995;333:664-5.
Source : FDA
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FDA Drug Safety Communication: Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs
The U.S. Food and Drug Administration (FDA) is notifying healthcare professionals and patients that drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together.
Patients should not stop taking any of their medicines without talking to their healthcare professional. Patients should contact their healthcare professional if they have any questions or concerns.
Healthcare professionals who have started patients infected with both chronic HCV and HIV on Victrelis and antiretroviral therapy containing a ritonavir-boosted protease inhibitor should closely monitor patients for HCV treatment response and for potential HCV and HIV virologic rebound.
A drug interaction study showed that taking boceprevir (Victrelis) with ritonavir (Norvir) in combination with atazanavir (Reyataz) or darunavir (Prezista), or with Kaletra (lopinavir/ritonavir) reduced the blood levels of the HIV medicines and boceprevir in the body (see Data Summary below). FDA will be updating the Victrelis drug label to include information about these drug interactions.
Merck and Company has issued a Dear Healthcare Professional letter (PDF - 67KB) with information about this drug interaction study.
Additional Information for Patients
- Drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and ritonavir used in combination with other human immunodeficiency virus (HIV) protease inhibitors can potentially reduce the effectiveness of these medicines when they are used together.
- Patients should not stop taking any of their medicines without talking to their healthcare professional.
- Patients should contact their healthcare professional if they have any questions or concerns about Victrelis or HIV protease inhibitors.
- Patients should report side effects from the use of Victrelis or HIV protease inhibitors to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of this page.
Additional Information for Healthcare Professionals
- Drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and ritonavir-boosted atazanavir, lopinavir, and darunavir can potentially reduce the effectiveness of these medicines when co-administered.
- Healthcare professionals who have initiated Victrelis in combination with peginterferon alfa and ribavirin in HIV-HCV co-infected patients on fully suppressive antiretroviral therapy containing a ritonavir-boosted protease inhibitor should discuss these findings with those patients, and closely monitor those patients for HCV treatment response and for potential HCV and HIV virologic rebound.
- Victrelis (boceprevir) and Incivek (telaprevir) were approved in May, 2011, each in combination with peginterferon alfa and ribavirin for treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease. Neither NS3/4A protease inhibitor is approved for treatment of patients co-infected with HIV. Drug interaction data with telaprevir and ritonavir-boosted HIV protease inhibitors can be found in the Incivek drug label (PDF - 314KB). Information about clinical trials in HIV-HCV co-infected patients can be found at ClinicalTrials.gov.
- Healthcare professionals should report adverse events involving Victrelis or HIV protease inhibitors to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
A pharmacokinetic study evaluated drug interactions between boceprevir (Victrelis) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors in healthy volunteers (n=39). In the study, concomitant administration of Victrelis (boceprevir) with ritonavir (Norvir) in combination with atazanavir (Reyataz), darunavir (Prezista), or with lopinavir/ritonavir (Kaletra) resulted in reduced exposures of the HIV medicines and boceprevir. Victrelis reduced mean trough concentrations of ritonavir-boosted atazanavir, lopinavir, and darunavir by 49, 43 and 59 percent, respectively. Mean reductions of 34 to 44 percent and 25 to 36 percent were observed in area under the curve (AUC) and peak concentration (Cmax) of atazanavir, lopinavir, and darunavir. Co-administration of ritonavir-boosted atazanavir with Victrelis did not alter the exposure (AUC) of boceprevir, but co-administration of Victrelis with lopinavir/ritonavir or ritonavir-boosted darunavir decreased the AUC of boceprevir by 45 and 32 percent, respectively.
.Facts about Victrelis (boceprevir) and HIV protease inhibitors
- Victrelis is a hepatitis C virus (HCV) protease inhibitor used with the medicines peginterferon alfa and ribavirin to treat chronic (long-lasting) hepatitis C infection in adults who have not been treated before or who have failed previous treatment.
- HIV protease inhibitors are a class of anti-viral drugs used to treat HIV infection.
- Ritonavir is an HIV protease inhibitor used to “boost” other HIV protease inhibitors, increasing their levels in the blood and making them more effective.
Source : FDA (Feb 2012)
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