vadadustat
Vafseo
Pharmaceutical company: Akebia Therapeutics
Pharmacologic classification: Hypoxia-inducible factor prolyl hydroxylase inhibitor
Therapeutic classification: Hematopoietic
AVAILABLE FORMS
Tablets: 150 mg, 300 mg, 450 mg
INDICATIONS AND DOSAGES
Anemia due to chronic kidney disease in patients who have been on dialysis for 3 months or more
Adults not being treated with an erythropoietin stimulating agent (ESA) or switching from an ESA: Initially, 300 mg PO once daily. May increase dose in increments of 150 mg no more frequently than once every 4 weeks to achieve or maintain hemoglobin (Hb) levels between 10 g/dL to 11 g/dL. Dosage may range from 150 to 600 mg daily.
Adjust-a-dose: If Hb rises more than 1 g/dL in 2 weeks or 2 g/dL in 4 weeks, interrupt or reduce the dose. If Hb exceeds 11 g/dL, withhold the drug until Hb is 11 g/dL or less, then resume at 150 mg less than the prior dose. During transition from an ESA, RBC transfusion or temporary ESA treatment may be considered if Hb falls below 9 g/dL or the response isn't acceptable. Pause vadadustat during ESA rescue treatment. When Hb is 10 g/dL or more, vadadustat may be restarted 2 days after the last dose of epoetin, 7 days after the last dose of darbepoetin alfa, or 14 days after the last dose of methoxy polyethylene glycol-epoetin beta. Resume vadadustat at the prior dose or 150 mg more than the prior dose and titrate according to the manufacturer's instructions.
CONTRAINDICATIONS AND CAUTIONS
- Boxed Warning: This drug increases the risk of thrombotic vascular events, including venous thromboembolism, vascular access thrombosis, MI, stroke, and death. Targeting a Hb level greater than 11 g/dL may increase the risk of death, and arterial and venous thrombotic events. A target Hb level, dose of vadadustat, or dosing strategy that doesn't increase these risks hasn't been established. Use the lowest dose of the drug sufficient to reduce the need for RBC transfusion.
- Avoid use in patients with a history of MI, cerebrovascular event, or acute coronary syndrome within 3 months prior to starting treatment.
- Contraindicated for use in patients with known hypersensitivity to the drug or any of its components.
- Contraindicated for use in patients with uncontrolled hypertension. Hypertensive crisis, including hypertensive encephalopathy and seizures have been reported.
- This drug may cause liver toxicity, generally within the first 3 months of treatment. Use isn't recommended in patients with cirrhosis or active, acute liver disease.
- Use cautiously in patients with a history of GI erosion and peptic ulcer disease. This drug increases the risk of GI erosions and related GI bleeding and the need for RBC transfusions.
- This drug may have unfavorable effects on cancer growth. Use isn't recommended in patients with active malignancies.
- This drug isn't indicated as a substitute for RBC transfusions for the immediate treatment of anemia, or for anemia due to chronic kidney disease in patients not on dialysis.
- This drug should be stopped if an appropriate increase in Hb isn't achieved after 24 weeks of treatment. Evaluate for and treat alternative explanations for poor response before restarting therapy.
- Safety and effectiveness in children haven't been established.
- Dialyzable drug: Approximately 16%.
PREGNANCY-LACTATION-REPRODUCTION
- There are no adequate studies of this drug during pregnancy. Use only if benefits justify fetal risk.
- Breastfeeding isn't recommended during treatment and for 2 days after the last dose.
INTERACTIONS
Drug-drug. BCRP substrates (sulfasalazine): May increase substrate level. Monitor for adverse reactions related to BCRP substrate and refer to substrate prescribing information for dose modification, if needed.
Drugs that increase risk of GI erosion (NSAIDs, mycophenolate): May increase risk of GI erosion. Monitor patients closely.
Non-iron-containing phosphate binders (calcium acetate, sevelamer carbonate): May decrease vadadustat level. Give vadadustat at least 1 hour before or 2 hours after binding agent.
OAT1 inhibitors (probenecid, rifampicin), OAT3 inhibitors (gemfibrozil, probenecid, teriflunomide): May increase vadadustat level. Monitor for too large or too rapid an increase in Hb response.
OAT3 substrates (cefaclor, ceftizoxime, famotidine, furosemide, oseltamivir carboxylate, penicillin G, sitagliptin): May increase substrate level. Monitor for adverse reactions related to OAT3 substrate and refer to substrate prescribing information for dose modification, if needed.
Oral iron supplements (ferrous sulfate, sodium ferrous citrate), iron-containing phosphate binders (ferric citrate, sucroferric oxyhydroxide): May decrease vadadustat level. Give vadadustat at least 1 hour before the supplement.
Statins (rosuvastatin, simvastatin): May increase statin level and risk for adverse reactions. Limit rosuvastatin dosage to 5 mg daily. Starting dosage of simvastatin should be 5 mg daily and maximum dosage not to exceed 20 mg daily.
Drug-lifestyle. Alcohol, tobacco: May increase risk of GI erosion. Discourage use together.
ADVERSE REACTIONS
CNS: seizures, stroke, headache, fatigue, dizziness.
CV: MI, vascular access thrombosis, hypertension.
GI: GI erosion, diarrhea, nausea, vomiting, abdominal pain.
Respiratory: dyspnea.
Other: dialysis-related complications.
Reactions in bold italics are life-threatening.
Released: September 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
resmetirom
Rezdiffra
Pharmaceutical company: Madrigal Pharmaceuticals
Pharmacologic classification: Thyroid hormone receptor-beta agonist
Therapeutic classification: Gastrointestinal drug
AVAILABLE FORMS
Tablets: 60 mg, 80 mg, 100 mg
INDICATIONS AND DOSAGES
Noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (stages F2 to F3) in conjunction with diet and exercise
Adults weighing 100 kg or more: 100 mg PO once daily.
Adults weighing less than 100 kg: 80 mg PO once daily.
Adjust-a-dose: If used with moderate CYP2C8 inhibitors in patients weighing 100 kg or more, decrease the dosage to 80 mg once daily; in patients weighing less than 100 kg, decrease dosage to 60 mg once daily.
CONTRAINDICATIONS AND CAUTIONS
- Avoid use in patients with Child-Pugh class B or C liver impairment due to increased exposure to the drug and the risk of adverse effects.
- Safety and effectiveness in patients with NASH cirrhosis haven't been established.
- Liver toxicity, cholelithiasis, acute cholecystitis, and obstructive pancreatitis have occurred in patients taking resmetirom.
- Safety and effectiveness in children or patients with a creatinine clearance less than 30 mL/minute haven't been established.
- Dialyzable drug: Unknown.
PREGNANCY-LACTATION-REPRODUCTION
- There are no adequate studies on use of this drug during pregnancy to evaluate for drug-associated risk.
- Risks to the patient and fetus related to underlying NASH with liver fibrosis include gestational diabetes, hypertensive complications, preterm birth, and postpartum hemorrhage.
- Pregnancies should be reported to Madrigal Pharmaceuticals at 1-800-905-0324 or https://www.madrigalpharma.com/contact/.
- There is no information regarding the presence of this drug in human or animal milk or how the drug affects milk production or infants who are breastfed. Weigh the benefit to the patient against the risk to the infant before use.
INTERACTIONS
Drug-drug. CYP2C8 substrates (pioglitazone): May increase substrate level. Monitor the patient closely.
Moderate CYP2C8 inhibitors (clopidogrel): May increase resmetirom level. Reduce resmetirom dose per the manufacturer's recommendations.
OATP1B1 and OATP1B3 inhibitors (cyclosporine): May increase resmetirom level. Use together isn't recommended.
Some statins (atorvastatin, pravastatin, rosuvastatin, simvastatin): May increase the level of these statins. Limit daily dosage of atorvastatin and pravastatin to 40 mg. Limit daily dosage of rosuvastatin and simvastatin to 20 mg.
Strong CYP2C8 inhibitors (gemfibrozil): May increase resmetirom level. Use together isn't recommended.
ADVERSE REACTIONS
CNS: altered sense of taste, depression, dizziness, vertigo.
CV: arrhythmia, palpitations.
GI: abdominal pain, abnormal feces, decreased appetite, constipation, diarrhea, flatulence, nausea, vomiting. GU: abnormal uterine bleeding.
Hepatic: increased AST and ALT levels, hyperbilirubinemia.
Metabolic: hypoglycemia.
Musculoskeletal: tendinopathy.
Skin: erythema, pruritus, rash, urticaria.
Reactions in bold italics are life-threatening.
Released: September 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
givinostat
Duvyzat
Pharmaceutical company: ITF Therapeutics
Pharmacologic classification: Histone deacetylase inhibitor
Therapeutic classification: Muscular dystrophy drug
AVAILABLE FORMS
Oral suspension: 8.86 mg/mL
INDICATIONS AND DOSAGES
Duchenne muscular dystrophy
Adults and children ages 6 and older weighing 60 kg or more: 53.2 mg (6 mL) PO b.i.d.
Adults and children ages 6 and older weighing 40 kg to less than 60 kg: 44.3 mg (5 mL) PO b.i.d.
Adults and children ages 6 and older weighing 20 kg to less than 40 kg: 31 mg (3.5 mL) PO b.i.d.
Adults and children ages 6 and older weighing 10 kg to less than 20 kg: 22.2 mg (2.5 mL) PO b.i.d.
Adjust-a-dose: Refer to the manufacturer's instructions for toxicity-related dosage adjustments. Dosage modification may be necessary if platelet count is less than 150 x 10
9/L verified in two assessments one week apart; for moderate or severe diarrhea; or for fasting triglycerides greater than 300 mg/dL. Withhold the drug if QTc interval is greater than 500 msec or the change from baseline is greater than 60 msec.
CONTRAINDICATIONS AND CAUTIONS
- This drug may cause GI disturbances, myelosuppression and hypertriglyceridemia.
- This drug can cause QTc interval prolongation. Avoid use in patients at increased risk for ventricular arrythmias, including those with congenital long QT syndrome, coronary artery disease, electrolyte disturbance, or use with other medications that cause QT prolongation.
- Safety and effectiveness in children less than 6 years haven't been established.
- Dialyzable drug: Unknown.
PREGNANCY-LACTATION-REPRODUCTION
- There are no data available on use during pregnancy or breastfeeding as Duchenne muscular dystrophy predominately affects young males.
INTERACTIONS
- Drug-drug. CYP3A4 substrates (midazolam, codeine, cyclosporine), OCT2 substrates (procainamide, cisplatin, gentamicin): May increase risk of adverse effects. Closely monitor patients when the drug is used in combination with orally administered substrates in which a slight change in substrate level may lead to toxicity.
- Drugs that prolong QTc interval (amiodarone, erythromycin, sertraline, haloperidol, methadone): May increase QTc prolongation. Avoid use together. If concomitant use can't be avoided, monitor ECG.
- Drug-herb. Herbs that prolong QTc interval (echinacea, ginseng, St. John's wort): May increase QTc prolongation. Discourage use together.
ADVERSE REACTIONS
CNS: fever, fatigue.
CV: QTc prolongation.
GI: diarrhea, abdominal pain, nausea, vomiting, constipation, decreased appetite.
Hematologic: thrombocytopenia, neutropenia, anemia.
Metabolic: hypertriglyceridemia, hypothyroidism.
Musculoskeletal: myalgia, arthralgia.
Skin: rash.
Reactions in bold italics are life-threatening.
Released: September 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer