Drug Summary: Antivirals & Chemotherapy PDF

ANTIVIRAL AGENTS FOR INFLUENZA a RIMANTADINE AND RESPIRATORY VIRUS THERAPEUTIC ACTIONS Inhibits viral replication by preventing the uncoating of the virus INDICATIONS Prophylaxis and treatment of illne...

ANTIVIRAL AGENTS FOR INFLUENZA a RIMANTADINE AND RESPIRATORY VIRUS THERAPEUTIC ACTIONS Inhibits viral replication by preventing the uncoating of the virus INDICATIONS Prophylaxis and treatment of illnesses caused by influenza a in adults and children PHARMACOKINETICS Oral, slow onset, peak at 6 hrs; HL of 25.4 hrs, excreted unchanged in urine CONTRAINDICATIONS & Rimantadine and Peramivir: Embryotoxic, avoid during pregnancy and lactation. CAUTION ADVERSE EFFECTS Light-headedness, dizziness, insomnia, nausea, orthostatic hypotension, depression DRUG-DRUG Amantadine/Rimantadine: Increased atropine-like effects with anticholinergics; rimantadine may reduce effectiveness of aspirin INTERACTIONS and acetaminophen. AGENTS FOR HERPES AND ACYCLOVIR CYTOMEGALOVIRUS THERAPEUTIC ACTIONS Inhibit viral DNA replication, preventing virus replication with minimal impact on human cells. INDICATIONS Effective in treating herpes simplex, herpes zoster, & CMV, particularly in immunocompromised patients. PHARMACOKINETICS Oral - onset varies, peak in 1.5-2 hrs, unknown duration IV - immediate onset, peak in 1 hr, duration unknown Topical - not generally absorbed systemically HL of 2.5-5 hrs, excreted unchanged in urine CONTRAINDICATIONS & Avoid use during pregnancy and lactation unless benefits outweigh risks. CAUTION Caution in patients with allergies, renal disease, or severe CNS disorders. ADVERSE EFFECTS Headache, vertigo, tremors, nausea, vomiting, rash DRUG-DRUG Increased risk of nephrotoxicity with other nephrotoxic drugs (e.g., aminoglycoside antibiotics).Increased drowsiness with INTERACTIONS zidovudine. NONNUCLEOSIDE REVERSE NEVIRAPINE TRANSCRIPTASE THERAPEUTIC ACTIONS Binds to HIV-1 reverse transcriptase and blocks replication of HIV by changing the structure of HIV enzyme INDICATIONS Bind to HIV-1 infected patients who have experienced clinical or immunological deterioration, in combination with other retrovirals PHARMACOKINETICS Oral, rapid onset, peak in 4 hrs HL of 45 hrs, hen 25-30 hrs, metabolized in liver, excreted in urine CONTRAINDICATIONS & Limited studies in pregnancy; use only if benefits outweigh risks. CAUTION Not recommended for breastfeeding women with HIV. Safety of delavirdine in children is not established. ADVERSE EFFECTS Headache, nausea, vomiting, diarrhea, rash, liver dysfunction, chills, fever DRUG-DRUG Nevirapine: Avoid with hormonal contraceptives, protease inhibitors. INTERACTIONS NUCLEOSIDE REVERSE ZIDOVUDINE TRANSCRIPTASE INHIBITORS THERAPEUTIC ACTIONS Thymidine analogue activated to triphosphate form, inhibits the replication of various retroviruses like HIV INDICATIONS Management of adults with symptomatic HIV infection, combined with other retrovirals, prevents maternal-fetal transmission PHARMACOKINETICS Oral - onset varies, peak in 30-90 mins IV - rapid onset, peak at the end of infusion HL of 30-60 mins, metabolized in liver, excreted via urine CONTRAINDICATIONS & Pregnancy: Zidovudine is the only proven safe agent during pregnancy. Other NRTIs should be used cautiously if benefits CAUTION outweigh risks. HIV-infected women should avoid breastfeeding. Hepatic/Renal Impairment: Use caution w/ tenofovir, zidovudine, & emtricitabine due to liver & kidney effects. Bone Marrow Suppression: Use zidovudine with caution in cases of bone marrow suppression. ADVERSE EFFECTS Headache, insomnia, dizziness, nausea, diarrhea, fever, rash, bone marrow suppression DRUG-DRUG Can cause severe drowsiness when combined with cyclosporine; patients should take safety precautions. INTERACTIONS PROTEASE INHIBITORS FOSAMPRENAVIR THERAPEUTIC ACTIONS Inhibits protease activity, leading to formation of immature, noninfectious virus particles INDICATIONS Management of adults with symptomatic HIV infection PHARMACOKINETICS Oral, onset varies, peak in 1.5-4 mins HL of 7.7 hrs, metabolized in the liver, excreted in feces and urine CONTRAINDICATIONS & Pregnancy: Saquinavir is not teratogenic but should be used cautiously. Other PIs lack adequate pregnancy studies and should CAUTION be used only when benefits outweigh risks. Breastfeeding: Women with HIV should not breastfeed, especially when taking these drugs. Hepatic Impairment: Lower doses of fosamprenavir recommended for mild/moderate dysfunction ADVERSE EFFECTS Headache, mood changes, nausea, diarrhea, fatigue, rash, steven-johnson syndrome, redistribution of body fat DRUG-DRUG Fosamprenavir: Risk of serious adverse effects if used with ritonavir in patients previously treated with PIs. INTERACTIONS FUSION INHIBITOR ENFUVIRTIDE THERAPEUTIC ACTIONS Prevents the entry of HIV-1 virus into the cells by inhibiting fusion of virus membrane with cellular membrane INDICATIONS HIV-1 patients with clinical or immunological deterioration after using other agents PHARMACOKINETICS Subcutaneous, slow onset; Peaks in 4 to 8 hours. Half-life: 3.2 to 4.4 hours; Metabolized in the liver, recycled in tissues, not excreted. CONTRAINDICATIONS & Contraindicated in patients with hypersensitivity to any component of the drug and in nursing mothers. CAUTION Use with caution in patients with lung disease or pregnancy. ADVERSE EFFECTS Insomnia, depression, peripheral neuropathy, nausea, diarrhea, pneumonia, injection site reactions. DRUG-DRUG No reported drug interactions, but caution is advised when combined with other drugs. INTERACTIONS CCR5 CORECEPTOR MARAVIROC ANTAGONIST THERAPEUTIC ACTIONS Binds to human chemokine receptor CCR5 on cell membrane, prevents interaction of HIV-1 and CCR5; HIV cannot enter the cell, cannot multiply INDICATIONS Combination antiretroviral treatment for adults with CCR5 tropic HIV-1 PHARMACOKINETICS Oral, slow onset, peak in 0.5-4 hrs HL of 14-28 hrs, metabolized in liver, excreted in feces and urine CONTRAINDICATIONS & Contraindicated in patients with hypersensitivity to any component and in nursing mothers. CAUTION Not established for use in children. Caution in liver disease, hepatitis B co-infection, cardiovascular risk, and hypotension. Use in pregnancy only if benefits outweigh risks. ADVERSE EFFECTS Severe hepatotoxicity (black box warning) often preceded by allergic reactions. Dizziness, paresthesias, nausea, vomiting, diarrhea, cough, upper respiratory infection, fever, musculoskeletal symptoms, hepatoxicity DRUG-DRUG Increased toxicity with CYP3A inhibitors (e.g., ketoconazole, ritonavir). INTERACTIONS Decreased effectiveness with CYP3A inducers (e.g., nevirapine, rifampin). Avoid use with St. John’s wort due to loss of antiviral effects. INTEGRASE INHIBITORS RALTEGAVIR THERAPEUTIC ACTIONS Inhibits activity of virus-specific enzyme integrase; prevents formation of HIV-1 provirus INDICATIONS Patients with evidence of viral replication PHARMACOKINETICS Oral, rapid onset, peak in 3 hrs HL of 9 hrs, metabolized in liver, excreted in feces and urine CONTRAINDICATIONS & Contraindicated in cases of hypersensitivity, as initial treatment in adults, for use in children, & for nursing mothers. Caution in CAUTION patients at risk for rhabdomyolysis or myopathy, and during pregnancy. Strict adherence to drug regimen is necessary to prevent resistance. ADVERSE EFFECTS Common: Headache, dizziness. Increased risk of rhabdomyolysis and myopathy. DRUG-DRUG Risk of decreased serum levels with rifampin; monitor and adjust dose if necessary. INTERACTIONS Avoid use of St. John’s wort, which can reduce drug effectiveness. ANTI-HEPATITIS B AGENTS ADEFOVIR THERAPEUTIC ACTIONS Inhibit reverse transcriptase in hepatitis B virus, causing DNA chain termination, blocking viral replication, and decreasing viral load. INDICATIONS Indicated for treatment of chronic hepatitis B in adults with active viral replication and elevated serum aminotransferases or histologically active disease. PHARMACOKINETICS Oral, rapid onset, peak in 0.6-4 hrs, unknown duration HL of 7.5 hrs, excreted in urine CONTRAINDICATIONS & Contraindicated with known allergy to the drugs and during lactation due to potential toxicity. CAUTION Use caution in patients with renal impairment, severe liver disease, and during pregnancy (effects on the fetus are unknown). ADVERSE EFFECTS Headache, asthenia, nausea, severe to fatal hepatomegaly with steatosis, nephrotoxicity, lactic acid acidosis, exacerbation of hep.b when discontinued DRUG-DRUG Increased risk of renal toxicity when combined with other nephrotoxic drugs. INTERACTIONS Close monitoring needed if such combinations are used; evaluate risks vs. benefits if renal function deteriorates. ANTI-HEPATITIS C AGENTS SIMEPREVIR THERAPEUTIC ACTIONS Inhibits hepatitis c protease formation preventing replication INDICATIONS For chronic hepatitis in adults with compensated liver dysfunction PHARMACOKINETICS Oral, rapid onset, peak in 4-6 hrs, unknown duration HL of 10-12 hrs, excreted in feces CONTRAINDICATIONS & Contraindicated with known allergy, lactation, and pregnancy (due to ribavirin toxicity). CAUTION Caution in patients with severe liver disease due to increased toxicity.  Safety not established for patients with hepatitis B and/or HIV (risk of disease exacerbation). High financial burden associated with these drugs. ADVERSE EFFECTS Common: Fatigue, nausea, diarrhea, and rash. DRUG-DRUG Risk of toxic effects or loss of therapeutic effect if combined with other protease inhibitors or antivirals. INTERACTIONS Dosage adjustments may be needed when combining with other drugs. Avoid St. John’s wort as it reduces effectiveness. LOCALLY ACTIVE ANTIVIRAL AGENTS THERAPEUTIC ACTIONS Antiviral agents interfere with viral replication and metabolic processes. INDICATIONS Indicated for specific, local viral infections PHARMACOKINETICS No mention in the book. CONTRAINDICATIONS & Not absorbed systemically. CAUTION Caution required for patients with known allergic reactions to topical drugs. ADVERSE EFFECTS Common adverse effects include local burning, stinging, and discomfort. These effects are temporary and usually occur at the time of administration. DRUG-DRUG No mention in the book INTERACTIONS