Administer hydroxychloroquine with caution in patients with glucosephosphate dehydrogenase deficiency G6PD deficiency due to the risk of hemolysis. Hydroxychloroquine should be used with caution in patients with neurological disease and myopathy. Skeletal muscle myopathy or neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction have been reported. Assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with hydroxychloroquine. The safety and efficacy of the chronic use of hydroxychloroquine for systemic lupus erythematosus and juvenile idiopathic arthritis in children and infants have not been established.
Children are especially sensitive to the 4-aminoquinoline compounds. Fatalities have been reported after accidental exposure of chloroquine; some cases involved relatively small doses e. Strongly warn patients to keep hydroxychloroquine out of the reach of pediatric patients, including neonates, infants, children, and adolescents. Cases of human pregnancy resulting in live birth to women exposed to hydroxychloroquine have been reported in the literature; no increase in the rate of birth defects has been demonstrated.
Embryonic deaths and malformations of anophthalmia and microphthalmia in the offspring have been reported when pregnant rats received large doses of chloroquine. Guidelines recommend hydroxychloroquine as an alternative to chloroquine as a treatment option for acute malaria and for prophylaxis in pregnant women during all trimesters.
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Hydroxychloroquine may also be appropriate for pregnancies complicated by lupus. Use caution when administering hydroxychloroquine to breast-feeding women.
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Hydroxychloroquine is excreted in the breast milk, and it is known that infants are extremely sensitive to the toxic effects of 4-aminoquinolines. Breast milk concentrations ranged from In infants monitored for up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision, or hearing. Previous American Academy of Pediatrics AAP recommendations considered hydroxychloroquine as usually compatible with breast-feeding.
Use hydroxychloroquine with caution in patients with hypoglycemia or diabetes mellitus. Hydroxychloroquine can cause severe, life-threatening hypoglycemia in patients treated with or without antidiabetic medications. Warn patients about the risk of hypoglycemia and the associated clinical signs and symptoms.
Monitor blood glucose and adjust treatment as necessary in patients presenting with clinical symptoms of hypoglycemia during hydroxychloroquine treatment. Hydroxychloroquine prolongs the QT interval. Use hydroxychloroquine with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances.
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Females, geriatric patients, patients with diabetes, thyroid disease, malnutrition, liver impairment, or those who drink alcohol to excess may also be at increased risk for QT prolongation. Chronic toxicity should be considered when conduction disorders bundle-branch block, AV block or biventricular hypertrophy are diagnosed. If cardiotoxicity is suspected, prompt discontinuation of hydroxychloroquine may prevent life-threatening cardiac complications.
Because renal clearance of hydroxychloroquine does not correlate with creatinine clearance, dosage adjustments are not required in patients with renal impairment. However, a dosage reduction may be necessary in patients with renal disease or in patients with concomitant medications known to affect the kidney.
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Acarbose: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
Acetaminophen; Butalbital; Caffeine; Codeine: Moderate Concomitant use of codeine with hydroxychloroquine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved.
Discontinuation of hydroxychloroquine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If hydroxychloroquine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate.
Hydroxychloroquine is a moderate inhibitor of CYP2D6. Acetaminophen; Caffeine; Dihydrocodeine: Moderate Concomitant use of dihydrocodeine with hydroxychloroquine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved.
Discontinuation of hydroxychloroquine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Acetaminophen; Codeine: Moderate Concomitant use of codeine with hydroxychloroquine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal.
Acetaminophen; Hydrocodone: Moderate Concomitant use of hydrocodone with hydroxychloroquine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.
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It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of hydroxychloroquine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If hydroxychloroquine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate.
Hydrocodone is a substrate for CYP2D6. Acetazolamide: Moderate Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as acetazolamide. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Acetohexamide: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including sulfonylureas, are coadministered. Aclidinium; Formoterol: Moderate Use caution with coadministration of hydroxychloroquine and long-acting beta-agonists.
Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval.
This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Albiglutide: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the incretin mimetics, are coadministered. Albuterol: Minor Use caution with coadministration of hydroxychloroquine and short-acting beta-agonists.
Albuterol; Ipratropium: Minor Use caution with coadministration of hydroxychloroquine and short-acting beta-agonists. Alfuzosin: Major Avoid coadministration of hydroxychloroquine and alfuzosin. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. Alogliptin: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the dipeptidyl peptidase-4 inhibitors, are coadministered.
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Alogliptin; Metformin: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including metformin, are coadministered. Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the dipeptidyl peptidase-4 inhibitors, are coadministered. Alogliptin; Pioglitazone: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the dipeptidyl peptidase-4 inhibitors, are coadministered.
Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the thiazolidinediones, are coadministered. Alpha-glucosidase Inhibitors: Moderate Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the alpha-glucosidase inhibitors, are coadministered.
Amiodarone: Major Avoid coadministration of hydroxychloroquine and amiodarone. Ventricular arrhythmias and torsade de pointes TdP have been reported with the use of hydroxychloroquine. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Amitriptyline: Major Avoid coadministration of hydroxychloroquine and tricyclic antidepressants. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy elevated serum concentrations.
Amitriptyline; Chlordiazepoxide: Major Avoid coadministration of hydroxychloroquine and tricyclic antidepressants. Amobarbital: Moderate Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as amobarbital. Amoxicillin; Clarithromycin; Lansoprazole: Major Avoid coadministration of hydroxychloroquine and clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Amoxicillin; Clarithromycin; Omeprazole: Major Avoid coadministration of hydroxychloroquine and clarithromycin.
Ampicillin: Moderate Administer oral ampicillin 2 hours before or 2 hours after hydroxychloroquine. Ampicillin bioavailability may be decreased with coadministration of hydroxychloroquine as a significant reduction in ampicillin bioavailability was observed with the structurally similar chloroquine in a study of healthy volunteers. The reduction of ampicillin bioavailability could be attributed to slower gastric emptying and enhancement of gut motility produced by chloroquine.