Riluzole is an oral glutamate antagonist approved for the treatment of amyotrophic lateral sclerosis (ALS). Riluzole does not cure the disease or improve symptoms, but it might prolong the survival of patients by approximately 3 months. Riluzole appears to be more effective in patients with bulbar-onset disease than for those with limb-onset disease. Riluzole has been used off-label for the treatment of chorea associated with Huntington's disease.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer at least 1 hour before or 2 hours after a meal.
Oral Liquid Formulations
Oral suspension
-Gently shake the bottle for at least 30 seconds until mixed well.
-Measure dosage using the provided calibrated syringe.
-Storage: After opening the riluzole suspension bottle, use within 15 days.
Other Oral Formulations
Oral dissolving film
-Do not cut or split the film.
-Do not administer with liquids.
-Administer only 1 film at a time.
-Remove film from the foil pouch.
-Apply the film to the top of the tongue where it adheres and dissolves.
-As the film dissolves, swallow saliva in a normal manner. The patient should refrain from chewing, spitting, or talking.
-Wash hands after handling.
Other Administration Route(s)
Percutaneous Endoscopic Gastronomy (PEG) Tube Administration
-Silicone and polyurethane PEG tubes can be used.
Oral suspension
-Gently shake the bottle for at least 30 seconds until mixed well.
-Measure dosage using the provided calibrated syringe.
-Flush the PEG-tube with 30 mL of water using a catheter-tip syringe.
-Administer the riluzole dose into the PEG tube immediately after flushing.
-Flush the PEG-tube a second time with 30 mL of water.
-Storage: After opening the riluzole suspension bottle, use within 15 days.
The evaluation of adverse events caused by riluzole presents some difficulty because the disease state being treated exhibits a number of manifestations often associated with adverse drug reactions. ALS affects motor neurons but does not affect sensory function. Ultimate neuronal cell death leads to muscular weakening, muscle atrophy and fasciculations, spasticity, slurred speech, dysphagia, and respiratory compromise. Decreasing lung function ultimately results in tracheostomy. In reviewing the adverse events reported most frequently for patients taking riluzole, natural disease progression must be considered.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), the following adverse gastrointestinal (GI) effects were reported more frequently in patients who received riluzole than in patients who received placebo: nausea (16% vs. 11%), vomiting (4% vs. 2%), flatulence (3% vs. 2%), xerostomia (4% vs. 3%), and abdominal pain (5% vs. 4%). Nausea, abdominal pain, and constipation were among the most frequent adverse events associated with treatment discontinuation. Adverse GI effects associated with discontinuation based upon dose included nausea and abdominal pain. Diarrhea (2.9%) and anorexia (3.2%) have also been reported. During a clinical study of 36 patients who received riluzole 100 mg/day, flatulence occurred in 8.3% of patients. Pancreatitis has been observed during postmarketing experience with riluzole. Acute pancreatitis was observed in a 79-year-old male who presented with severe upper abdominal pain and vomiting after 3 months of riluzole therapy. Abnormal labs included serum amylase 1,298 units/L, lipase 1,650 units/L, and WBC count 15.75 x 109/L. Mild swelling of the pancreas body and tail with a focal necrotic area in the distal tail was observed by CT scan. After discontinuation of riluzole and appropriate clinical management, the patient recovered and lab values returned to normal limits after 7 days. The patient was not rechallenged with riluzole.
Riluzole causes serum aminotransferase elevations in patients without a history of abnormal liver function. During clinical trials, elevated hepatic enzymes (i.e., ALT) were dose-related and were among the most frequently cited causes of study withdrawal. Some cases of hepatitis have resulted in fatalities during postmarket use. Acute hepatitis and icteric toxic hepatitis have been reported during postmarketing experience. About 50% of patients will experience at least 1 ALT concentration above the upper limit of normal (ULN), 8% will have elevations above 3 times the ULN, and about 2% will have elevations greater than 5 times the ULN. Maximum increases in ALT occurred within 3 months after starting riluzole. During clinical trials, if the ALT concentrations were less than 5 times the ULN, treatment was continued; a subsequent decline of ALT concentrations to below 2 times the ULN usually occurred within 2 to 6 months. Treatment was discontinued if ALT values exceeded 5 times the ULN. Rechallenge with the drug is not recommended in patients who experience ALT concentrations greater than 5 times the ULN. Asymptomatic elevations of hepatic transaminases have been reported and have occurred upon rechallenge with riluzole. Patients with mild or moderate hepatic disease had increases in AUC compared to patients with normal hepatic function; therefore, patients with mild or moderate hepatic disease may be at increased risk for adverse reactions. Monitor for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. Riluzole use is not recommended if patients develop hepatic transaminase concentrations more than 5 times the ULN. Discontinue therapy if there is evidence of liver dysfunction (e.g., elevated bilirubin).
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), the following centrally-mediated effects were reported more frequently in patients who received riluzole than in patients who received placebo: dizziness (4% vs. 3%), insomnia (4% vs. 3%), drowsiness (2% vs. 1%), vertigo (2% vs. 1%), and circumoral paresthesias (2% vs. 0%). Headache (44.4%), dizziness (16.7%), and drowsiness (19.4%) were observed in a study of 36 patients who received riluzole 100 mg/day. Oral hypoesthesia occurred in 29% and 38% of healthy subjects taking riluzole oral suspension or oral film, respectively, compared to 0% to 6% of subjects taking riluzole tablets. A delayed amnestic syndrome has been reported in a 53-year-old female after adjunctive use of riluzole for major depressive disorder in the setting of a clinical trial. She received riluzole 100 mg/day with sertraline 150 mg/day. After 8 weeks, riluzole was discontinued without tapering due to moderate, intermittent nausea and vomiting occurring within 10 minutes of medication ingestion. At 3 days after discontinuation, the patient developed amnesia while out for a short walk and became lost. She was found and taken to a hospital, where she continued to have memory impairment for 4 days. Notable clinical findings included mild elevation of ALT (72 units/L), AST (69 units/L), troponin I (0.15 ng/mL), and CPK (632 units/L). EKG, EEG, and CT were normal. Toxicity screens were negative, and no signs of delirium were noted; her overall evaluation was not indicative of a cardiac event. She did receive phenytoin for possible seizure and gabapentin for fibromyalgia pain. After 6 days, the patient had fully recovered and was discharged on sertraline 150 mg/day with a diagnosis of mild rhabdomyolysis. At 3-month follow-up, the patient was stable with no cognitive abnormalities. The patient may have been a slow metabolizer of the drug, leading to possible toxic concentrations at the time of discontinuation and throughout the symptomatic period. Additionally, riluzole may alter concentrations of extracellular glutamate. Changes in relative concentrations of extracellular glutamate or rapid changes in glutamate neurotransmission may have significant effects on memory.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), pruritus (4% vs. 3%) and eczema (2% vs. 1%) were reported more frequently in patients who received riluzole than in patients who received placebo. Anaphylactoid reactions have occurred.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), decreased lung function (10% vs. 9%) and increased cough (3% vs. 2%) were reported more frequently in patients who received riluzole compared to patients who received placebo. Rhinitis was observed in 13.9% of 36 patients who received riluzole 100 mg/day during a clinical study. Riluzole can cause interstitial lung disease, including hypersensitivity pneumonitis. Advise patients to report if they have respiratory symptoms (e.g., dry cough and difficult or labored breathing). Discontinue riluzole immediately if interstitial lung disease develops.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), hypertension (5% vs. 4%) and sinus tachycardia (3% vs. 1%) were reported more frequently in patients who received riluzole than in patients who received placebo.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), arthralgia was reported in 4% of patients who received riluzole and 3% of patients who received placebo.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), cystitis or urinary tract infection was reported in 3% of patients who received riluzole vs. 2% of patients who received placebo. Renal tubular impairment has been observed with riluzole use during postmarketing experience.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), asthenia was observed in 19% of patients who received riluzole vs. 12% of patients who received placebo.
During clinical trials of riluzole (100 mg/day) for amyotrophic lateral sclerosis (ALS), peripheral edema was reported in 3% of patients who received riluzole and 2% of patients who received placebo.
Riluzole can cause neutropenia. Cases of severe neutropenia, defined as an absolute neutrophil count less than 500/mm3, within the first 2 months of riluzole have been reported. Among approximately 4,000 patients who received riluzole during clinical trials, there were 3 cases of neutropenia with an absolute neutrophil count less than 500/mm3, and all were detected within the first 2 months of treatment. The neutrophil count increased on continued treatment in 1 patient, while the neutrophil count rose in another patient after therapy was discontinued. In 1 case, both neutropenia and marked anemia were observed, the etiologies of which were not established. Advise patients to report febrile illness.
Riluzole is contraindicated in patients with a history of severe hypersensitivity reactions to riluzole or to any of its components.
Riluzole use is not recommended in patients with baseline elevation of serum aminotransferases more than 5 times the upper limit of normal (ULN) or evidence of liver dysfunction (e.g., elevated bilirubin). Riluzole can cause liver injury. Monitor for signs and symptoms of hepatic injury, every month for the first 3 months of treatment, and periodically thereafter. Riluzole use is not recommended if patients develop hepatic transaminase concentrations more than 5 times the ULN. Discontinue therapy if there is evidence of liver dysfunction. Patients with mild (Child-Pugh score A) or moderate hepatic disease (Child-Pugh score B) had increases in AUC compared to patients with normal hepatic function. Thus, patients with mild or moderate hepatic impairment may be at increased risk for adverse reactions. The impact of severe hepatic impairment on riluzole exposure is unknown.
Asian patients, specifically Japanese patients, are more likely to have higher riluzole concentrations. Consequently, the risk of adverse reactions may be greater in Japanese patients.
There are no adequate human data to inform the drug-associated risk with riluzole use during pregnancy. Increased mortality and other adverse developmental effects were observed during reproductive animal studies with riluzole at clinically relevant doses. When riluzole was given orally (3, 10, or 60 mg/kg/day) to pregnant rabbits during organogenesis, embryofetal mortality was increased at the high dose, and decreased fetal body weight and increased morphological variations were observed at all but the lowest dose. The no-effect dose (3 mg/kg/day) for embryofetal developmental toxicity is less than the recommended human daily dose (RHDD, 100 mg) on mg/m2 basis. Administration of oral riluzole (3, 8, or 15 mg/kg/day) to male and female rats prior to and during mating and to female rats throughout gestation and lactation increased embryofetal mortality and decreased postnatal offspring viability, growth, and functional development at the high dose; the no-effect dose (8 mg/kg/day) for embryofetal developmental toxicity was approximately equal to the RHDD on mg/m2 basis. Fertility indices were decreased at the high dose.
Riluzole is excreted in human milk. The average riluzole breast milk concentration was 94.4 mcg/L during a regimen of 50 mg twice daily in a breast-feeding woman with amyotrophic lateral sclerosis (ALS). A study predose breast milk sample was 33.8 ng/mL, suggesting steady-state riluzole concentrations; the peak riluzole concentration was 229.5 ng/mL at 2 hours after the dose. The calculated infant dose was 14.1 mcg/kg/day, and the calculated relative infant dose was 1.6% of the maternal weight-adjusted dosage with an average milk intake of 150 mL/kg/day. There are no data on the effects of riluzole on the breast-fed infant or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for riluzole and any potential adverse effects on the breast-fed infant from riluzole or the underlying maternal condition.
For the treatment of amyotrophic lateral sclerosis (ALS):
Oral dosage:
Adults: 50 mg PO twice daily.
For the treatment of chorea associated with Huntington's Disease (Huntington's Chorea)*:
Oral dosage:
Adults: 100 mg PO twice daily. A randomized, placebo-controlled dose ranging trial evaluated the change in maximal chorea scores determined by the Unified Huntington's Disease Rating Scale (UHDRS) achieved at 8 weeks with riluzole 100 mg/day PO (n = 18), riluzole 200 mg/day PO (n = 23), or placebo (n = 22). Total daily dosages were divided and given twice daily. Subjects who received 200 mg/day had significant reductions in total chorea scores (-2.2 +/- 3.3, p = 0.01) compared to placebo (+0.7 +/- 3.4); effects appear to be dose related, as no significant reductions were found with riluzole 100 mg/day. In a second randomized controlled trial, patients were randomized to riluzole 50 mg twice daily or placebo for 3 years; no significant differences in UHDRS chorea scores between riluzole and placebo were found at 3 years.
Maximum Dosage Limits:
-Adults
100 mg/day PO for ALS; 200 mg/day PO off-label for Huntington's Chorea.
-Geriatric
100mg/day PO for ALS; 200 mg/day PO off-label for Huntington's Chorea.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use is not recommended in patients with baseline elevation of serum transaminases more than 5 times the upper limit of normal (ULN) or evidence of liver dysfunction (e.g., elevated bilirubin).
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Riluzole has not been studied in patients undergoing hemodialysis.
*non-FDA-approved indication
Acetaminophen; Ibuprofen: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Allopurinol: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and allopurinol. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Amlodipine; Atorvastatin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and atorvastatin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Amobarbital: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Aspirin, ASA; Omeprazole: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.
Atorvastatin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and atorvastatin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Auranofin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and auranofin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Azathioprine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and azathioprine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Barbiturates: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Busulfan: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and busulfan. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Butalbital; Acetaminophen: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Capmatinib: (Moderate) Coadministration of riluzole with capmatinib may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely. Riluzole is a CYP1A2 substrate and capmatinib is a moderate CYP1A2 inhibitor.
Carbamazepine: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and carbamazepine. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and carbamazepine is a CYP1A2 inducer.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Chlorpromazine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and chlorpromazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ciprofloxacin: (Moderate) Coadministration of riluzole with ciprofloxacin may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and ciprofloxacin is a CYP1A2 inhibitor.
Dantrolene: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and dantrolene. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Deferasirox: (Moderate) Coadministration of riluzole with deferasirox may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and deferasirox is a CYP1A2 inhibitor.
Desogestrel; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Dextromethorphan; Quinidine: (Major) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and quinidine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Diclofenac: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and diclofenac. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Diclofenac; Misoprostol: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and diclofenac. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Didanosine, ddI: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and didanosine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Dienogest; Estradiol valerate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Disulfiram: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and disulfarim. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Drospirenone: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Drospirenone; Estetrol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Drospirenone; Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Drospirenone; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Efavirenz: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and efavirenz. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and efavirenz. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and efavirenz. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Enasidenib: (Moderate) Coadministration of riluzole with enasidenib may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely. Riluzole is a CYP1A2 substrate and enasidenib is a strong CYP1A2 inhibitor.
Erythromycin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and erythromycin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Estradiol; Levonorgestrel: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Estradiol; Norethindrone: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Estradiol; Norgestimate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Ethinyl Estradiol; Norelgestromin: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Ethinyl Estradiol; Norgestrel: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Etonogestrel; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Ezetimibe; Simvastatin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and simvastatin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Fexinidazole: (Moderate) Coadministration of riluzole with fexinidazole may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely. Riluzole is a CYP1A2 substrate and fexinidazole is a moderate CYP1A2 inhibitor.
Floxuridine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and floxuridine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Flutamide: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and flutamide. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Fluvoxamine: (Moderate) Coadministration of riluzole with fluvoxamine may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and fluvoxamine is a CYP1A2 inhibitor.
Food: (Major) Advise patients to avoid cannabis use during riluzole treatment due to decreased exposure of riluzole which may alter its efficacy. Cannabis use induces CYP1A2 and riluzole is a CYP1A2 substrate. The induction potential of cannabis is greatest with chronic inhalation. Other routes of administration or sporadic use may have less of an effect.
Fosphenytoin: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and fosphenytoin. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and fosphenytoin is a CYP1A2 inducer.
Green Tea: (Minor) Some green tea products contain caffeine, which may inhibit the CYP1A2-mediated metabolism of riluzole. Also, as a substrate for CYP1A2, riluzole might affect the clearance of other drugs that depend on CYP1A2 for hepatic oxidative metabolism, including caffeine. Clinical documentation is lacking.
Hydralazine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and hydralazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and hydralazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Hydrocodone; Ibuprofen: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ibuprofen: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ibuprofen; Famotidine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ibuprofen; Oxycodone: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ibuprofen. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Infliximab: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and infliximab. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Interferon Alfa-2b: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and interferon alfa. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Interferon Alfa-n3: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and interferon alfa. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Interferon Beta-1a: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and interferon beta. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Interferon Beta-1b: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and interferon beta. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Isoniazid, INH: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and isoniazid. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and rifampin. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and rifampin is a CYP1A2 inducer. (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and isoniazid. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present. (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and pyrazinamide. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Isoniazid, INH; Rifampin: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and rifampin. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and rifampin is a CYP1A2 inducer. (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and isoniazid. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ketoconazole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ketoconazole. Concomitant use may increase the risk for hepatotoxicity. Discontinue therapy if clinical signs of liver dysfunction are present.
Leflunomide: (Moderate) Coadministration of riluzole with leflunomide may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and leflunomide is a CYP1A2 inducer.
Leuprolide; Norethindrone: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Levoketoconazole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and ketoconazole. Concomitant use may increase the risk for hepatotoxicity. Discontinue therapy if clinical signs of liver dysfunction are present.
Levonorgestrel: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Lopinavir; Ritonavir: (Moderate) Coadministration of riluzole with ritonavir may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
Mercaptopurine, 6-MP: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and mercaptopurine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Meropenem: (Moderate) Coadministration of riluzole with meropenem may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Meropenem; Vaborbactam: (Moderate) Coadministration of riluzole with meropenem may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and meropenem is a CYP1A2 inducer.
Methohexital: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Methotrexate: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and methotrexate. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Methoxsalen: (Moderate) Coadministration of riluzole with methoxsalen may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and methoxsalen is a CYP1A2 inhibitor.
Methyldopa: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and methyldopa. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Mexiletine: (Moderate) Coadministration of riluzole with mexiletine may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and mexiletine is a CYP1A2 inhibitor.
Minocycline: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and minocycline. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Modafinil: (Moderate) Coadministration of riluzole with modafinil may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and modafinil is a CYP1A2 inducer.
Nevirapine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and nevirapine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Nirmatrelvir; Ritonavir: (Moderate) Coadministration of riluzole with ritonavir may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
Nitrofurantoin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and nitrofurantoin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Norethindrone: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Norethindrone; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Norgestimate; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Norgestrel: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Omeprazole: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.
Omeprazole; Sodium Bicarbonate: (Moderate) Coadministration of riluzole with omeprazole may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and omeprazole is a CYP1A2 inducer.
Oral Contraceptives: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Peginterferon Alfa-2a: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and peginterferon alfa-2a. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Peginterferon Alfa-2b: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and peginterferon alfa-2b. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Peginterferon beta-1a: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and peginterferon beta-1a. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Pentobarbital: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Pexidartinib: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and pexidartinib. Discontinue riluzole if clinical signs of liver dysfunction are present. Concomitant use may increase the risk for hepatotoxicity.
Phenobarbital: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Phenytoin: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and phenytoin. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and phenytoin is a CYP1A2 inducer.
Pretomanid: (Major) Avoid coadministration of pretomanid with riluzole, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Primidone: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Propylthiouracil, PTU: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and propylthiouracil. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Pyrazinamide, PZA: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and pyrazinamide. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Quinidine: (Major) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and quinidine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Quinine: (Moderate) Coadministration of riluzole with quinine may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and quinine is a CYP1A2 inducer.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Rifampin: (Moderate) Monitor for signs and symptoms of hepatic injury and decreased riluzole efficacy during coadministration of riluzole and rifampin. Concomitant use may increase the risk for hepatotoxicity and may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and rifampin is a CYP1A2 inducer.
Ritlecitinib: (Moderate) Coadministration of riluzole with ritlecitinib may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely. Riluzole is a CYP1A2 substrate and ritlecitinib is a moderate CYP1A2 inhibitor.
Ritonavir: (Moderate) Coadministration of riluzole with ritonavir may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and ritonavir is a CYP1A2 inducer.
Rucaparib: (Moderate) Coadministration of riluzole with rucaparib may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and rucaparib is a CYP1A2 inhibitor.
Secobarbital: (Moderate) Coadministration of riluzole with barbiturates may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and barbiturates are CYP1A2 inducers.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Monitor patients for increased riluzole-related adverse events, such as gastrointestinal symptoms and elevated hepatic enzymes, when hormonal contraceptives are prescribed concurrently. Serum concentrations of riluzole, a CYP1A2 substrate, may increase when oral contraceptives, moderate CYP1A2 inhibitors, are used concurrently. In vitro findings suggest an increase in riluzole exposure is likely when a CYP1A2 inhibitor is given.
Simvastatin: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and simvastatin. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Coadministration of riluzole with taurursodiol may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and taurursodiol is a CYP1A2 inducer.
St. John's Wort, Hypericum perforatum: (Moderate) Coadministration of riluzole with St. John's Wort may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and St. John's Wort is a CYP1A2 inducer.
Sulfadiazine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and sulfadiazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and sulfamethoxazole. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Sulfasalazine: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and sulfasalazine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Sulindac: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and sulindac. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Teriflunomide: (Moderate) Coadministration of riluzole with teriflunomide may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and teriflunomide is a CYP1A2 inducer.
Testosterone: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and testosterone. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Thioguanine, 6-TG: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and thioguanine. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Tipranavir: (Moderate) Coadministration of riluzole with tipranavir may result in decreased riluzole efficacy. In vitro findings suggest decreased riluzole exposure is likely. Riluzole is a CYP1A2 substrate and tipranavir is a CYP1A2 inducer.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking riluzole. Smoking tobacco has been observed to enhance riluzole clearance by greater than 20% which may decrease riluzole exposure and result in loss of efficacy. Riluzole is a CYP1A2 substrate and smoking tobacco induces CYP1A2.
Valproic Acid, Divalproex Sodium: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and valproic acid. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Vemurafenib: (Moderate) Coadministration of riluzole with vemurafenib may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and vemurafenib is a CYP1A2 inhibitor.
Viloxazine: (Moderate) Coadministration of riluzole with viloxazine may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely. Riluzole is a CYP1A2 substrate and viloxazine is a strong CYP1A2 inhibitor.
Zafirlukast: (Moderate) Coadministration of riluzole with zafirlukast may increase the risk for riluzole-related adverse reactions, such as gastrointestinal symptoms and elevated hepatic enzymes. In vitro findings suggest an increase in riluzole exposure is likely; riluzole is a CYP1A2 substrate and zafirlukast is a CYP1A2 inhibitor.
Riluzole modulates the actions of glutamate. The mechanism by which this happens is not clearly known but may include direct effects on the neurotransmitter itself and target receptors, the inhibition of glutamate release, blockade or inactivation of voltage-dependent sodium channels that are important for glutamate release, interference with intracellular events that result from binding of glutamate to receptors, and/or inhibition of arachidonic acid metabolism. Animal studies have shown that riluzole has a neuroprotective effect that delays neuronal injury or death.
Riluzole is administered orally. Riluzole is highly bound to plasma protein (about 96%), mainly to albumin and lipoproteins. Hepatic metabolism is extensive, producing 6 major and a number of minor metabolites. The primary metabolic pathways are oxidation by CYP1A2 and direct and sequential glucoronidation by UGT-HP4. Approximately 90% of a dose is excreted in the urine; however, only 2% is excreted as unchanged drug. Elimination in the feces accounts for 5% of a dose. Riluzole is largely excreted as its glucuronide metabolites (85%). The elimination half-life is 12 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, UGT-HP4
Riluzole is primarily metabolized by CYP1A2 and UGT-HP4.
-Route-Specific Pharmacokinetics
Oral Route
Riluzole is well absorbed from the GI tract (90%) and has absolute bioavailability of about 60%. Absorption is affected by high-fat meals, which reduce the AUC by about 20% and peak blood concentrations by about 45%. Riluzole exhibits linear pharmacokinetics. Steady-state plasma concentrations are achieved within 5 days of multiple-dose administration. Riluzole has similar pharmacokinetic properties after intragastric administration via feeding tubes and oral administration.
-Special Populations
Hepatic Impairment
The AUC of riluzole was approximately 1.7- and 3-fold greater in patients with mild (Child Pugh score A) and moderate (Child Pugh score B) hepatic impairment, respectively. The pharmacokinetics of riluzole in severe hepatic impairment (Child Pugh score C) have not been studied.
Renal Impairment
According to a single dose study, there is no significant difference in pharmacokinetic parameters between patients with moderate or severe renal insufficiency and healthy volunteers. The pharmacokinetics of riluzole have not been studied in patients undergoing hemodialysis.
Geriatric
The pharmacokinetics of riluzole were compared in 18 healthy geriatric volunteers (70 years or older) and 18 healthy gender- and weight-matched young volunteers (18 to 35 years). After receipt of a 5-day regimen of riluzole 50 mg twice daily, there were no statistically significant differences in Cmax, AUC, or clearance between the populations. The half-life of riluzole was significantly greater in young subjects (49.03 hours vs. 40.3 hours; p = 0.0149).
Gender Differences
The mean AUC of riluzole is approximately 45% higher in females compared to males.
Ethnic Differences
The clearance of riluzole was 50% lower in male Japanese subjects than in White subjects, after normalizing for body weight.
Other
Tobacco Smoking
The clearance of riluzole in tobacco smokers is 20% greater than in nonsmokers.