Top 300 Week 9

Rifaximin brand name and class?

• Xifaxan

• Class: Antibiotic, miscellaneous

Rifaximin common FDA label indication, dosing, and titration?

• Hepatic encephalopathy, prevention: adults, 550 mg po bid

• Irritable bowel syndrome without constipation: adults, 550 mg po tid x 14 d; children > or = 8 yo, 10-30 mg/kg/d in divided doses, max 1200 mg/d

• Traveler’s diarrhea: adults and children > or = 12 yo, 200 mg po tid x 3 d continued until travel complete

Rifaximin MOA?

Rifaximin is a semisynthetic derivative of rifampin and inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase. It has clinical activity against E. coli

Rifaximin box warnings?

None

Rifaximin contraindications?

Hypersensitivity

Rifaximin drug interactions?

None known, as little drug is absorbed

Rifaximin ADR?

• Common - edema, dizziness, ascites, nausea

• Less common - headache, pruritus, anemia, increased LFTs, arthralgia

• Rare but serious - severe hypersensitivity, angioedema, urticaria

Sofosbuvir brand name and class?

• Sovaldi

• Class: Polymerase inhibitor (Anti-HCV)

Sofosbuvir common FDA label indication, dosing, and titration?

• Chronic hepatitis C (CHC) infection with genotypes 1, 2, 3, and 4 as part of combination therapy: adults, 400 mg po daily, in combination with ribavirin or ribavirin and peginterferon alfa. Children > or = 3 y of age, < 17 kg, 150 mg po daily, 17 to <35 kg, 200 mg po daily, > or = 35 kg, 400 mg po daily. Duration varies by CHC genotype. Guidelines for HCV treatment are constantly evolving. Refer to AASLD-IDSA recommendations for testing, managing, and treating hepatitis C

Sofosbuvir MOA?

A direct-acting antiviral against the hepatitis C virus. It inhibits HCV NS5B RNA-dependent RNA polymerase, essential for viral replication, and acts as a chain terminator.

Sofosbuvir box warnings?

HBV reactivation

Sofosbuvir contraindications?

Because of ribavirin risk, do not use in pregnant women, or men whose female partners are pregnant

Sofosbuvir drug interactions?

• P-glycoprotein inhibitors → decreased sofosbuvir transport increases risk of sofosbuvir toxicity → monitor carefully and consider sofosbuvir dose reduction

• P-glycoprotein inducers → increased sofosbuvir trasnport decreases sofosbuvir efficacy → avoid concurrent use or monitor carefully and consider sofosbuvir dose increases

• Amiodarone → bradycardia → avoid concurrent use or inpatient cardiac monitoring

Sofosbuvir ADR?

• Common - fatigue, headache, insomnia, chills, pruritus, rash, nausea, anemia

• Less common - diarrhea, thrombocytopenia, increased bilirubin, irritability, flu-like symptoms

• Rare but serious - pancytopenia, HBV reactivation, depression, suicidality

Sucralfate brand name and class?

• Carafate

• Class: Gastrointestinal agent, miscellaneous

Sucralfate common FDA label indication, dosing, and titration?

Duodenal ulcer: adults, 1 g po qid x 4-8 wk, then 1 g po bid if maintenance therapy is needed

Sucralfate MOA?

Forms a complex with positively charged proteins that forms a protective coating for local protection of the gastric lining against peptic acid, pepsin, and bile salts.

Sucralfate box warnings?

None

Sucralfate contraindications?

Hypersensitivity

Sucralfate drug interactions?

Orally administered medications → bind to sucralfate → separate administration by at least 2 h

Sucralfate ADR?

• Common - none known

• Less common - constipation

• Rare but serious - bezoar formation, diarrhea, GI distress, hyperglycemia

Tamsulosin brand name and class?

• Flomax

• Class: a1-Adrenergic blocker

Tamsulosin common FDA label indication, dosing, and titration?

Benign prostatic hyperplasia → 0.4 mg po daily, may titrate to 0.8 mg po daily

Tamsulosin MOA?

Tamsulosin is closely related to quinazoline derivatives that selectively block postsynaptic a1-adrenergic receptors. Total peripheral resistance is reduced through arterial and venous dilations. Reflex tachycardia that occurs with other vasodilators is infrequent because there is no presynaptic α₂-receptor blockade. The drugs also decrease total cholesterol, increase HDL cholesterol, and may improve glucose tolerance and reduce left ventricular mass during long-term therapy. They increase urine flow in BPH by relaxing smooth muscle tone in the bladder neck and prostate.

Tamsulosin box warnings?

None

Tamsulosin contraindications?

Hypersensitivity to tamsulosin

Tamsulosin drug interactions?

• a1-blockers → increases risk of hypotension → contraindicated

• CYP3A4/5 inducers → increased tamsulosin metabolism reduces tamsulosin effectiveness → monitor and consider dose increases of tamsulosin

• CYP3A4/5, CYP2D6 inhibitors → decreased tamsulosin metabolism increases risk of tamsulosin toxicity → avoid strong CYP3A4/5 CYP2D6 inhibitors. Monitor and consider dose decreases of tamsulosin with concurrent moderate CY3A4/5, CYP2D6 inhibitors

• Beta-blockers, calcium channel blockers, MAOIs → increased risk of hypotension, especially with 1st dose → monitor BP

Tamsulosin ADR?

• Common - dizziness, headache, abnormal ejaculation, rhinitis, positional hypotension

• Less common - asthenia, edema, fatigue, nausea, somnolence, vertigo, sexual dysfunction, blurred vision

• Rare but serious - angioedema, retinal detachment, priapism

Tizanidine brand name and class?

• Zanaflex

• Class: Centrally acting skeletal muscle relaxant, a2-agonist

Tizanidine common FDA label indication, dosing, and titration?

Muscle spascity: 2 mg po up to tid, may titrate to 8 mg po q6-8h with max dose of 36 mg/d

Tizanidine MOA?

Tizanidine is a centrally acting muscle relaxant. The drug is an imidazole derivative, structurally unrelated to other muscle relaxants. Tizanidine is an agonist of a2-adrenergic receptors, which decreases spasticity by increasing presynaptic inhibition; however, it does not have antihypertensive properties

Tizanidine box warnings?

None

Tizanidine contraindications?

Hypersensitivity to tizanidine; concurrent use with CYP1A2 inhibitors

Tizanidine drug interactions?

• CYP1A2 inhibitors → inhibition of tizanidine metabolism and increased risk of tizanidine toxicity → do not coadminister; select alternative antispasmodic

• Phenytoin, fosphenytoin → unknown mechanism; results in increased serum concentrations of phenytoin and resulting phenytoin toxicity → monitor for signs of phenytoin toxicity and adjust dose accordingly

• CNS depressants → additive CNS depression → avoid concurrent use

Tizanidine ADR?

• Common - hypotension, xerostomia, asthenia, dizziness, somnolence, muscle weakness

• Less common - constipation, vomiting, dyskinesia, amblyopia, feeling nervous, syncope, depression

• Rare but serious - AMI, thrombocytopenia, hepatitis, PE, hypersensitivity, death, slowed or difficult breathing when used in combination with opioids

Trimethoprim (TMP) /Sulfamethoxazole (SMZ) brand name and class?

• Bactrim, Septra

• Class: Sulfonamide antibiotic

TMP/SMZ common FDA label indication, dosing, and titration?

• Acute infective exacerbation of COPD: 800 mg SMZ and 160 mg TMP po q12h x 5-7 d

• HIV infection, Pneumocystis pneumonia: 1600 mg SMZ and 320 mg TMP po tid x 21 d

• HIV infection or immunocompromised, Pneumocystis pneumonia, prophylaxis: adults, 800 mg SMZ and 160 mg TMP po 3 times weekly (e.g. MWF); children > or = 1 mo of age, 750 mg/m²/d SMZ and 150 mg/m²/d TMP in 2 divided doses po 3 times/wk on consecutive days, max 160 mg TMP/dose

• Travler’s diarrhea: 800 mg SMZ and 160 mg TMP po bid x 5 d

• Urinary tract infection: adult, 800 mg SMZ and 160 mg TMP po bid x 3-7 d for uncomplicated or 14 d for complicated; children > or = 2 mo of age, 8 mg/kg TMP component/d po bid x 10 d, max 160 mg TMP/dose

TMP/SMZ MOA?

SMZ competitively inhibits the synthesis of dihydropteroic acid (an inactive folic acid precursor) in microorganisms. TMP inhibits the enzymatic reduction of dihydrofolic acid to tetrahydrofolic acid. The combination is active against many bacteria and P. carinii. TMP/SMZ has in vitro activity against MRSA, but clinical success has been variable and unpredictable.

TMP/SMZ box warnings?

None

TMP/SMZ contraindications?

Hypersensitivity to sulfonamides, children <2 mo, pregnant patients at term, megaloblastic anemia due to folate deficiency, history of drug-induced thrombocytopenia with use of sulfonamides or trimethoprim, marked hepatic damage or severe renal disease, concomitant administration with dofetilide

TMP/SMZ drug interactions?

• Antiarrhythmic agents, agents that prolong the QTc interval → increased risk of QTc prolongation and other cardiac events → avoid concurrent use or monitor carefully and consider dose reductions

• CYP2C8, CYP2C9 substrates → TMP is a CYP2C8 and CYP2C9 inhibitor, decreased metabolism of substrates, increases risk of substrate toxicity → consider decreased dose of CYP2C8 and CYP2C9 substrates

• CYP3A4/5 and CYP2C9 inducers → increased TMP metabolism reduces TMP efficacy → monitor and consider dose increases of TMP

• CYP3A4/5 and CYP2C9 inhibitors → decreased TMP metabolism increases risk of TMP toxicity → monitor and consider dose decreases of TMP

• Typhoid vaccine, BCG (intravesical), cholera vaccine → antibiotics may diminish therapeutic effect of vaccines → avoid concurrent use

• Sodium picosulfate → antibiotics may decreased therapeutic effect → use alternative agent for bowel prep prior to colonoscopy

• Methotrexate → increased toxicity of methotrexate through synergistic antifolate effects of TMP → avoid concurrent use or consider methotrexate dose reduction or monitoring methotrexate levels

TMP/SMZ ADR?

• Common - diarrhea, nausea

• Less common - skin rash, urticaria

• Rare but serious - severe hypersensitivity, renal failure, hepatic failure, pancytopenia, arrhythmias, Stevens-Johnson syndrome, hyperkalemia, hypoglycemia, hemolytic anemia