Hepatic Chapter Quiz RXP PDF

There are six different HCV genotypes (l - 6) and various subtypes (e.g., la or lb). Treatment options and duration of therapy depend on the genotype, the presence of cirrhosis and whether the patient has been treated before. Preferred HCV regimens consist of 2 -3 direct-acting antivirals (PAAs) wit...

There are six different HCV genotypes (l - 6) and various subtypes (e.g., la or lb). Treatment options and duration of therapy depend on the genotype, the presence of cirrhosis and whether the patient has been treated before. Preferred HCV regimens consist of 2 -3 direct-acting antivirals (PAAs) with different mechanisms, usually for 8 - 1 2 weeks. Some combinations include ritonavir, which is not active for HCV, but is used to boost (increase) levels of HCV protease inhibitors. Ribavirin can be added to DAA therapy as an alternative treatment option. Interferon is no longer recommended in combination regimens, but could play a role when DAAs are contraindicated or too expensive. DAA Mechanisms and Regimens Preferred HCV regimen include 2-3 DAAs with different mechanisms of action (often in one tablet) Drugs for the Treatment of Secondary Hyperparathyroidism MECHANISM NAME CLUE EXAMPLES NS3/4A Protease Inhibitors -previr P for PI Glecaprevir Grazoprevir Paritaprevir Voxilaprevir NS5A Replication Complex Inhibitors -asvir Elbosvir Ledipasvir Ombitasvir Pibrentosvir Velpatasvir NS5B Polymerase Inhibitors -buvir BforNS5B Dasabuvir Sofosbuvir TIPS Dasabuvir + sofosbuvir; two DAAs with the same MOA: should not be used together in a combination regimen. What do the protease inhibitors used for HIV and HCV have in common? They are taken with food. A for NS5A, Ledipasvir Remember: Protease Inhibitors & Grub (PIG) Take With Food* *Exceptions: elbasvir/grazoprevir (Zepatier) for HCV (without regard to food) and fosamprenavir oral SUSP for HIV (without food in adults) DRUG All DAAs DOSING SAFETY/SIDE EFFECTS/MONITORING BOXED WARNING (FOR ENTIRE CLASS) Risk of reactivating HBV; test all patients for HBV before starting a DAA WARNINGS For sofosbuvir-containing regimens: do not use amiodarone with sofosbuvir as serious symptomatic bradycardia has been reported Hypoglycemia can occur when DAAs are used with insulin or other hypoglycemic drugs, unless the dose of the diabetes medication is reduced; DAAs improve glucose metabolism SIDE EFFECTS Well-tolerated; HA, fatigue, diarrhea, nausea MONITORING LFTs (including bilirubin), HCV-RNA Glecaprevir/ pibrentasvir(Mavyret) Tablet 3 tablets once daily with food Sofosbuvir/velpatasvir (Epclusa) Tablet 1 tablet daily with or without food Sofosbuvir/ledipasvir (Harvoni) Tablet 1 tablet daily with or without food Sofosbuvir/velpatasvir/ voxilaprevir (Vosevi) Tablet 1 tablet daily with food Sofosbuvir (Sovaldi) Tablet 400 mg daily with or without food Paritaprevir/ ritonavir/ombitasvir + dasabuvir (Viekira Pak') Tablets Paritaprevir/ritonavir/ombitasv ir combination tablets copackaged with dasabuvir tablets Viekira Pak: 2 tablets of paritaprevir/ritonavir/ ombitasvir once daily in the morning and 1 dasabuvir tablet twice daily with meals CONTRAINDICATIONS Mavyret: moderate-severe hepatic impairment (Child-Pugh B or C) or history of hepatic decompensation WARNINGS Potentially serious drug interactions (see DAA Drug Interactions on the following page) NOTES Sofosbuvir monotherapy is not effective and not recommended Sovaldi, Epclusa, Harvoni, Vosevi: protect from moisture; dispense in original container Epctusa, Harvoni and Vosevi: avoid or minimize acid-suppressive therapy during treatment (see DAA Drug Interactions) Mavyret, Vosevi: rare cases of liver failure or worsening liver function Pan-Genotypic (approved for all 6 HCV genotypes) for Treatment-Naive Patients Epclusa and Mavyret Approved for 8-Week Course of Therapy (select patients) Mavyret Approved for Salvage Therapy (failed previous therapy) Vosevi and Mavyret (select patients) CONTRAINDICATIONS Moderate-severe hepatic impairment (Child-Pugh B or C), history of hepatic decompensation, use with CYP3A4 substrates or inducers (increase levels can cause serious events), use with ethinyl estradiol products (avoid use during treatment and for 2 weeks after stopping) Viekira Pak: do not use with strong inducers or inhibitors of CYP2C8 WARNINGS Hepatic decompensation/failure in patients with cirrhosis. T LFTs (> 5 x ULN) within 4 wks of treatment, significant drug interaction potential, risk of HIV protease inhibitor resistance SIDE EFFECTS Insomnia, pruritus Elbasvir/grazoprevir (Zepatier) Tablet 1 tablet daily with or without food CONTRAINDICATIONS Moderate-severe hepatic impairment (Child-Pugh B or C); use with strong inducers of CYP3A4, OAYP1B l/3 inhibitors and efavirenz; all contraindications to ribavirin apply when used in combination regimens WARNINGS increase LFTs (> 5x ULN) within 4 wks of treatment, significant drug interaction potential NOTES Screening for NS5A polymorphism is recommended when treating HCV genotype 1a Zepatier: rare cases of liver failure or worsening liver function DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING All DAAs BOXED WARNING (FOR ENTIRE CLASS) Risk of reactivating HBV; test all patients for HBV before starting a DAA WARNINGS For sofosbuvir-containing regimens: do not use amiodarone with sofosbuvir as serious symptomatic bradycardia has been reported Hypoglycemia can occur when DAAs are used with insulin or other hypoglycemic drugs, unless the dose of the diabetes medication is reduced; DAAs improve glucose metabolism SIDE EFFECTS Well-tolerated; HA, fatigue, diarrhea, nausea MONITORING LFTs (including bilirubin), HCV-RNA Glecaprevir/ pibrentasvir(Mavyret) Tablet 3 tablets once daily with food Sofosbuvir/velpatasvir (Epclusa) Tablet 1 tablet daily with or without food Sofosbuvir/ledipasvir (Harvoni) Tablet 1 tablet daily with or without food Sofosbuvir/velpatasvir/ voxilaprevir (Vosevi) Tablet 1 tablet daily with food CONTRAINDICATIONS Mavyret: moderate-severe hepatic impairment (Child-Pugh B or C) or history of hepatic decompensation WARNINGS Potentially serious drug interactions (see DAA Drug Interactions on the following page) NOTES Sofosbuvir monotherapy is not effective and not recommended Sovaldi, Epclusa, Harvoni, Vosevi: protect from moisture; dispense in original container Epctusa, Harvoni and Vosevi: avoid or minimize Sofosbuvir (Sovaldi) Tablet 400 mg daily with or without food acid-suppressive therapy during treatment (see DAA Drug Interactions) Mavyret, Vosevi: rare cases of liver failure or worsening liver function Pan-Genotypic (approved for all 6 HCV genotypes) for Treatment-Naive Patients Epclusa and Mavyret Approved for 8-Week Course of Therapy (select patients) Mavyret Approved for Salvage Therapy (failed previous therapy) Vosevi and Mavyret (select patients) Paritaprevir/ ritonavir/ombitasvir + dasabuvir (Viekira Pak') Tablets Paritaprevir/ritonavir/ombitasv ir combination tablets copackaged with dasabuvir tablets Viekira Pak: 2 tablets of paritaprevir/ritonavir/ ombitasvir once daily in the morning and 1 dasabuvir tablet twice daily with meals CONTRAINDICATIONS Moderate-severe hepatic impairment (Child-Pugh B or C), history of hepatic decompensation, use with CYP3A4 substrates or inducers (increase levels can cause serious events), use with ethinyl estradiol products (avoid use during treatment and for 2 weeks after stopping) Viekira Pak: do not use with strong inducers or inhibitors of CYP2C8 WARNINGS Hepatic decompensation/failure in patients with cirrhosis. T LFTs (> 5 x ULN) within 4 wks of treatment, significant drug interaction potential, risk of HIV protease inhibitor resistance SIDE EFFECTS Insomnia, pruritus Elbasvir/grazoprevir (Zepatier) 1 tablet daily with or without food CONTRAINDICATIONS Moderate-severe hepatic Tablet impairment (Child-Pugh B or C); use with strong inducers of CYP3A4, OATP1B l/3 inhibitors and efavirenz; all contraindications to ribavirin apply when used in combination regimens WARNINGS increase LFTs (> 5x ULN) within 4 wks of treatment, significant drug interaction potential NOTES Screening for NS5A polymorphism is recommended when treating HCV genotype 1a Zepatier: rare cases of liver failure or worsening liver function DAA DRUG INTERACTIONS All DAAs have significant drug interaction potential. This summary is not all-inclusive. Consult the package labeling of each drug for additional detail. All DAAs ■ Contraindicated with strong inducers of CYP3A4 (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin. rifampin, rifabutin and St. John’s wort). ■ Most DAAs increase statin concentrations and myopathy risk. ■ Decrease BG can occur with insulin and other diabetes medications. Monitor BG and decrease diabetes medication dose as needed. Harvoni, Epclusa and Vosevi ■ Contains sofosbuvir: do not use with amiodarone due to the risk of bradycardia. ■ Antacids, H2RAs and PPIs can decrease concentrations of ledipasvir and velpatasvir. - Separate from antacids by four hours. - Take H2RAs at the same time or separated (-12 hours) and use famotidine < 40 mg BID or equivalent. - PPIs are not recommended with Epclusa. Mavyret ■ Do not use with efavirenz, HIV protease inhibitors (specifically atazanavir, darunavir, lopinavir, ritonavir), ethinyl estradiol-containing products or cyclosporine. Viekira Pak ■ Contraindicated with: strong inducers of CYP3A4, ethinyl estradiol-containing products, lovastatin, simvastatin, alfuzosin, cisapride, colchicine, ranolazine, dronedarone, lurasidone, pimozide, ergotamine derivatives, efavirenz, sildenafil (dosed for PAH), triazolam and oral midazolam. ■ Dasabuvir (component of Viekira Pak) is a substrate (major) of CYP2C8; do not use with strong inducers or inhibitors of CYP2C8 (e.g., gemfibrozil). ■ See HIV chapter for additional ritonavir drug interactions. Zepatier ■ Do not use with efavirenz, HIV protease inhibitors (specifically atazanavir, darunavir, lopinavir, saquinavir, tipranavir) or cyclosporine. ■ Not recommended with nafcillin, ketoconazole, bosentan, tacrolimus, etravirine, Stribild, Genvoya and modafinil. Drugs for the Treatment of Secondary Hyperparathyroidism DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING Ribavirin Capsule, tablet Virazole - for 400-600 mg BID. varies based on indication, patient BOXED WARNINGS Significant teratogenic RSV weight and genotype Increase tolerability if given with food Hgb< lOg/dL: decrease dose (avoid if Hgb < 8.5 g/dL) Capsule should not be crushed, chewed, opened or broken effects: not effective for monotherapy of HCV; hemolytic anemia (primary toxicity of oral therapy, mostly occurring within 1-2 wks of initiation) CONTRAINDICATIONS Pregnancy,women of childbearing age who will not use contraception reliably, male partners of pregnant women, hemoglobinopathies, CrCI < 50 mL/min (capsule), autoimmune hepatitis SIDE EFFECTS Hemolytic anemia (can worsen cardiac disease and lead to Ml; do not use in unstable cardiac disease), fatigue, HA, insomnia, N /V /D , anorexia, myalgias, hypothyroidism MONITORING CBC with differential, platelets, electrolytes, LFTs/bili, HCV-RNA, TSH, monthly pregnancy tests NOTES Avoid pregnancy in females (including in female partners of male patients) during therapy and 6 months after completion; at least 2 reliable forms of effective contraception are required during treatment and in the 6-month post-treatment follow-up period Ribavirin Drug interactions ■ Ribavirin can increase hepatotoxic effects of NRTIs; lactic acidosis can occur. ■ Zidovudine can increase risk and severity of anemia from ribavirin. - Do not use with didanosine due to cases of fatal hepatic failure, peripheral neuropathy and pancreatitis. DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING interferon-alfa-2b (IntronA) for HBV, HCV, many cancers SC dosing varies by Indication and product: BOXED WARNINGS Can cause or exacerbate neuropsychiatric, autoimmune, Ischemic or Infectious disorders; If used with ribavirin, teratogenic/anemia risk CONTRAINDICATIONS Autoimmune hepatitis, decompensated liver disease In cirrhotic patients. Infants/neonates (Pegasys) WARNINGS Neuropsychiatric events, cardiovascular events, endocrine disorders (hypo/hyperthyroidism, hypo/hyperglycemla), visual disorders (retinopathy, decrease In vision), pancreatitis, myelosuppression, skin reactions SIDE EFFECTS CNS effects (fatigue, depression, anxiety, weakness), Gl upset, T LFTs (5-10 X ULN during treatment), myelosuppression, mild alopecia Pegylated interferon-alfa-2a Intron A: 3 times weekly (Pegasys) - for HBV and HCV Pegasys and Peglntron: weekly Pegylated interferon-alfa-2b (Peglntron, Sylatron) - for HCV Flu-llke syndrome (fever, chills, HA, malaise); pre-treat with acetaminophen and an antihistamine MONITORING CBC w ith differential, platelets, LFTs, uric acid, SCr, electrolytes, TGs, thyroid function tests, serum HBV-DNA or HCV-RNA levels ■ Alfa: HBV, HCV and some cancers ■ Beta: Multiple sclerosis (MS) Interferons do not provide a cure and are hard to take, A flu-like syndrome after the injection is common. The list of boxed warnings and warnings Is long. DRUG DOSING All HBV NRTIs CrCI < 50 mL/min: decrease dose or frequency Exception: Vemlidy (see below) Tenofovir disoproxil fumarate. TDF (Viread) SAFETY/SIDE EFFECTS/MONITORING Lactic acidosis and severe hepatomegaly with steatosis,which can be fatal (downgraded from boxed warning to warning for both tenofovir formulations and lamivudine) Exacerbations of HBV can occur upon discontinuation, monitor closely Can cause HIV resistance in HBV patients with unrecognized or untreated HIV infection (downgraded from boxed warning to warning for both tenofovir formulations) See HIV chapter for further information 300 mg daily WARNINGS Tablet, powder (oral) Preferred therapy Tenofovir alafenamide TAF (Vemlidy) Tablet Preferred therapy 25 mg daily with food CrCI < 15 mL/min: not recommended Renal toxicity including acute renal failure and/or Fanconi syndrome, osteomalacia and i bone mineral density SIDE EFFECTS TDF: renal impairment, j bone mineral density, N/V/D, increase LFTs, increase CPK, headache, depression TAF: nausea, headache, abdominal pain, fatigue, cough, decrease bone mineral density, increase LFTs NOTES Viread tablets and Vemlidy: protect from moisture; dispense only in original container TAF is associated with decrease renal and bone toxicity compared to TDF Vemlidy is approved only for treating HBV; see HIV chapter for tenofovir alafenamide combination products used for HIV Entecavir (Baraclude) Tablet, oral solution Preferred therapy Nucleoside-treatment naive: 0.5 mg daily Lamivudine-resistant: 1 mg daily Take on empty stomach SIDE EFFECTS Peripheral edema, pyrexia, ascites. Increase LFTs, hematuria, nephrotoxicity. Increase SCr NOTES Food reduces AUC by 18-20%; take on an empty stomach (2 hours before or after a meal) Lamivudine (Epivir HBV) Tablet, oral solution 100 mg daily 150 mg BID or 300 mg daily if co-infected with HIV BOXED WARNING Do not use Epivir HBV for treatment of HIV (contains lower dose of lamivudine); can result in HIV resistance SIDE EFFECTS Headache, N /V /D , fatigue, insomnia, myalgias, increase LFTs, pancreatitis (rare) Adefovir (Hepsera) Tablet 10 mg daily BOXED WARNING Caution in patients with renal impairment or those at risk of renal toxicity (including concurrent nephrotoxic drugs or NSAIDs) SIDE EFFECTS HA, weakness, abdominal pain, hematuria, rash, nephrotoxicity NRTI Drug Interactions ■ Ribavirin can increase hepatotoxic effects of all NRTIs; lactic acidosis can occur. ■ Tenofovir formulations: do not use with risk of virologic failure and potential for increase side effect - Tenofovir alafenamide is a P-gp substrate; do not use with oxcarbazepine, phenytoin, phenobarbital, rifampin and St. John's wort. - SMX/TMP can increase lamivudine levels due to decrease excretion. Vasoconstricting Medications for Bleeding Varices DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING Octreotide (Sandostatin, Sandostatin LAR Depot, others) Analog of somatostatin with greater potency and longer duration of action Bolus: 25-100 mcg IV (usual 50 mcg), can repeat in 1 hr if hemorrhage not controlled Continuous infusion: 25-50 mcg/hr X 2-5 days SIDE EFFECTS Bradycardia, cholelithiasis, biliary sludge, chest pain, fatigue, HA, pruritus, hyperglycemia, hypoglycemia (highest risk in type 1 diabetes), N/V/D, hypothyroidism, abdominal pain, malaise, fever, dizziness, flatulence, constipation, injection site pain, arthropathy, myalgias, URTIs MONITORING Blood glucose, HR, ECG Vasopressin (Vasostrict) Antidiuretic hormone analog Not first line (usually used with nitroglycerin IV to prevent myocardial ischemia) Infusion: 0.2-0.4 units/min IV (max 0.8 units/min), max duration 24 hours SIDE EFFECTS Arrhythmias, chest pain. Ml, decrease cardiac output, increase BP, N/V MONITORING BP, HR, ECG, fluid balance Non-Selective Beta-Blockers for Portal Hypertension DRUG DOSING Nadolol (Corgard) Initial: 40 mg PO daily Propranolol (Inderal LA, InderalXL, InnoPran XL, Hemangeol) Initial: 20 mg PO BID SAFETY/SIDE EFFECTS/MONITORING Refer to the Hypertension chapter for a complete review of beta-blockers. BOXED W ARNING Do not withdraw beta-blockers abruptly (particularly in patients with CAD), gradually taper over 1-2 wks to avoid acute tachycardia, HTN and/or ischemia CONTRAINDICATIONS Sinus bradycardia, 2nd or 3rd degree heart block, sick sinus syndrome (unless patient has a functioning artificial pacemaker) or cardiogenic shock; do not initiate in patients with an active asthma exacerbation WARNING Non-selective drugs are used for portal hypertension; use extreme caution with asthma, severe COPD, peripheral vascular disease or Raynaud’s disease (a condition with vasospasms in the extremities) Can mask signs of hyperthyroidism and aggravate psychiatric conditions; use caution in patients with diabetes (particularly with recurrent hypoglycemia) MONITORING HR, BP Hepatic encepalopaty DRUG Lactulose (Enulose, Constulose. Generlac, Kristalose) Oral solution and packet DOSING SAFETY/SIDE EFFECTS/MONITORING Treatment: 30-45 mL (or 20-30 grams) PO every hour until stool evacuation; then 30-45 mL (20-30 grams) PO 3-4 times/day, titrated to produce 2-3 soft bowel movements daily CONTRAINDICATIONS Low galactose diet SIDE EFFECTS Flatulence, diarrhea, dyspepsia, abdominal discomfort, dehydration, hypernatremia, hypokalemia MONITORING Mental status, bowel movements, ammonia, fluid status, electrolytes Enema: Q4-6H PRN Prevention: 30-45 mL (or 20-30 grams) PO 3-4 times/day. titrated to produce 2-3 soft bowel movements daily Rifaximin (Xifaxan) Tablet Treatment (off-label): 400 mg PO Q8H x 5-10 days Prevention: 550 mg PO BID SIDE EFFECTS Peripheral edema, dizziness, fatigue, nausea, ascites, flatulence, headache MONITORING Mental status, ammonia Neomycin 4-12 grams daily divided Q4-6H x 5-6 days BOXED WARNINGS Neurotoxicity (hearing loss, vertigo, ataxia); nephrotoxicity (particularly in renal impairment or with concurrent use of other nephrotoxic drugs): can cause neuromuscular blockade and respiratory paralysis especially when given soon after anesthesia or with muscle relaxants SIDE EFFECTS Gl upset, ototoxicity, nephrotoxicity, irritation/soreness of mouth/rectal area MONITORING Mental status, renal function, hearing, ammonia Metronidazole (Flagyl) 250mg POQ6-12H NOTES Do not use long term due to peripheral neuropathies See Infectious Diseases 1 chapter for additional information ALL DIRECT-ACTING ANTIVIRALS ■ Many drug interactions. Mavyret ■ Take with food. Viekira Pak ■ Can cause liver damage. ■ Viekira Pak contains two different types of tablets. You m ust take both types o f tablets exactly as prescribed to treat your chronic hepatitis C virus (HCV) infection. - One tablet contains the medicines ombitasvir, paritaprevir and ritonavir (take two tablets once daily). - The other tablet contains the medicine dasabuvir (take one tablet tw ice daily). RIBAVIRIN ■ Avoid in pregnancy (teratogenic), including in male partners of pregnant women. ■ Can cause hemolytic anemia. NRTIs ■ Can cause lactic acidosis. ■ EpivirHBV tablets and oral solution are not interchangeable with the Epivir tablets and solution used in HIV (which have higher doses). ■ Take entecavir on an empty stomach. BETA-BLOCKERS ■ Do not abruptly discontinue without consulting your healthcare provider.