Drug Interactions between dexamethasone / ketorolac / moxifloxacin and vadadustat

Moxifloxacin and other medications in its class can cause tendinitis and tendon rupture, and the risk may be increased when combined with a steroid such as dexAMETHasone. Older adults over 60 years of age and those who have received a kidney, heart, and/or lung transplant may be particularly susceptible. Tendon rupture can occur during or up to several months after finishing moxifloxacin treatment and may require surgery or result in prolonged disability. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Stop taking moxifloxacin and call your doctor immediately if you experience pain, swelling, or inflammation of a tendon area such as the back of the ankle, shoulder, biceps, hand, or thumb. You should also avoid exercise or use of the affected area until further instruction from your doctor. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Using dexAMETHasone together with ketorolac may increase the risk of side effects in the gastrointestinal tract such as inflammation, bleeding, ulceration, and rarely, perforation. Gastrointestinal perforation is a potentially fatal condition and medical emergency where a hole forms all the way through the stomach or intestine. You should take these medications with food to lessen the risk. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Your doctor may also be able to recommend medications to help protect the stomach and intestine if you are at high risk for developing serious gastrointestinal complications. You should seek immediate medical attention if you experience any unusual bleeding or bruising, or have other signs and symptoms of bleeding such as dizziness; lightheadedness; red or black, tarry stools; coughing up or vomiting fresh or dried blood that looks like coffee grounds; severe headache; and weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with vadadustat may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4, CYP450 2C8 and CYP450 2C9 isoenzymes as well as substrates of the organic anion transporter 3 (OAT3). Vadadustat is an inhibitor of CYP450 3A4 and CYP450 2C8 in vitro and an inhibitor of CYP450 2C9 and OAT3 in vivo. A drug interaction study evaluating the effect of vadadustat (600 mg) on the pharmacokinetics of celecoxib, a CYP450 2C9 substrate, showed an increase in peak plasma concentration (Cmax) and systemic exposure (AUC) by 60% and 11%, respectively. In another drug interaction study evaluating the effect of repeat doses of vadadustat (600 mg once daily) on the pharmacokinetics of furosemide, an OAT1/OAT3 substrate, a 2-fold increase in furosemide systemic exposure (AUC) was observed. However, clinical data are not available for vadadustat with CYP450 3A4 or CYP450 2C8 substrates.

MONITOR: Coadministration of vadadustat with drugs that are known to increase the risk of gastrointestinal erosion may increase the risk of gastric or esophageal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, were reported during vadadustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat is coadministered with drugs that are substrates of CYP450 3A4, CYP450 2C8, CYP450 2C9 and/or OAT3 and that also carry a known risk of gastrointestinal erosion including certain NSAIDs (e.g., naproxen, ibuprofen, diclofenac), corticosteroids (e.g., methylprednisolone, prednisolone, prednisone), and certain chemotherapeutic agents (e.g., kinase inhibitors, paclitaxel, docetaxel). Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools. Monitoring for other signs and symptoms of increased exposure to the affected substrate should be considered whenever vadadustat is added to or withdrawn from therapy. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 3A4, CYP450 2C8, CYP450 2C9 and/or OAT3 inhibitor.

Moxifloxacin may rarely cause central nervous system side effects such as tremors, involuntary muscle movements, anxiety, confusion, depression, hallucinations or seizures, and combining it with other medications that can also affect the central nervous system such as ketorolac may increase that risk. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Coadministration of hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitors, such as vadadustat or daprodustat, with drugs that are known to increase the risk of gastrointestinal erosion may increase the risk of gastric or esophageal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, were reported during vadadustat and daprodustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat or daprodustat are coadministered with drugs that have a known risk of gastrointestinal erosion, including but not limited to NSAIDs, corticosteroids, oral bisphosphonates, oral potassium formulations, anticoagulants as well as certain chemotherapeutic agents (e.g., kinase inhibitors) and antibiotics. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.