Understanding Hydroxychloroquine and Drug Interactions
Hydroxychloroquine, often known by the brand name Plaquenil, is a disease-modifying antirheumatic drug (DMARD) used to treat autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus, in addition to preventing and treating malaria [1.2.3, 1.4.2]. While effective for these conditions, it can interact with a wide range of other medications. These interactions can alter the effectiveness of hydroxychloroquine or the co-administered drug, and in some cases, can lead to serious or even life-threatening adverse effects [1.4.2].
A primary concern is the risk of QT prolongation, an issue where the heart muscle takes longer than normal to recharge between beats [1.2.3]. This can lead to a dangerous and irregular heartbeat called Torsades de Pointes [1.2.7]. Other significant interactions can affect blood sugar levels, seizure thresholds, and drug absorption [1.2.3]. Therefore, it is crucial for patients to inform their healthcare provider of all prescription drugs, over-the-counter medications, and supplements they are taking.
Medications That Increase Risk of QT Prolongation
The most critical drug interaction with hydroxychloroquine involves other medications that also prolong the QT interval. Combining these drugs significantly elevates the risk of developing potentially fatal cardiac arrhythmias [1.2.3, 1.3.4]. Some medications should be avoided entirely, while others require close monitoring by a healthcare professional, which may include regular electrocardiograms (ECGs).
Drugs to Avoid or Use with Extreme Caution:
- Antiarrhythmics: Medications like amiodarone, dronedarone, quinidine, and sotalol are used to treat irregular heart rhythms, but combining them with hydroxychloroquine is highly risky [1.2.3, 1.2.4].
- Antipsychotics: Certain antipsychotics, such as thioridazine, ziprasidone, pimozide, and haloperidol, carry a risk of QT prolongation [1.2.1, 1.3.3].
- Antibiotics: Macrolide antibiotics (e.g., azithromycin, clarithromycin) and fluoroquinolone antibiotics (e.g., ciprofloxacin, levofloxacin) can interact to affect heart rhythm [1.2.3, 1.3.3]. The combination of hydroxychloroquine and azithromycin, in particular, has been associated with a greater risk of QT prolongation [1.3.2].
- Antidepressants: Tricyclic antidepressants like amitriptyline and others such as citalopram and escitalopram can also affect the QT interval [1.2.3, 1.3.3].
- Other Medications: A range of other drugs, including methadone, ondansetron (an anti-nausea medication), and certain antifungals like fluconazole, can also pose a risk [1.2.3, 1.3.3].
Interactions with Diabetes Medications
Hydroxychloroquine can lower blood sugar levels and enhance the effects of antidiabetic drugs, leading to a risk of severe hypoglycemia (low blood sugar) [1.4.3, 1.4.6]. Symptoms of hypoglycemia include dizziness, shakiness, sweating, confusion, and a fast heartbeat [1.4.1, 1.4.3]. If left untreated, severe hypoglycemia can lead to seizures or loss of consciousness [1.4.3].
Patients taking both hydroxychloroquine and diabetes medications need careful management. A healthcare provider may need to adjust the dosage of the diabetes medication and will likely recommend more frequent blood sugar monitoring [1.4.1, 1.4.6].
Commonly Interacting Diabetes Medications:
- Insulin (e.g., Lantus, Humalog, Novolog) [1.4.2, 1.4.8]
- Oral antidiabetic drugs like metformin, glipizide, and pioglitazone [1.4.2]
Interactions with Seizure Medications (Antiepileptics)
Hydroxychloroquine can lower the seizure threshold, making seizures more likely to occur [1.2.3, 1.5.2]. This can pose two problems for patients with epilepsy:
- Increased Seizure Risk: Combining hydroxychloroquine with other drugs that also lower the seizure threshold, such as bupropion (Wellbutrin) or tramadol, further increases this risk [1.2.3].
- Reduced Efficacy of Antiepileptics: Hydroxychloroquine may antagonize the action of seizure medications, making them less effective at controlling seizures [1.5.1, 1.5.3]. Some anticonvulsants like carbamazepine and phenobarbital might also reduce the concentration of hydroxychloroquine in the body [1.5.4].
Close monitoring is essential for patients with a history of seizures, and a provider might consider alternative treatments [1.5.3]. Examples of interacting seizure medications include carbamazepine, phenytoin, and phenobarbital [1.2.4].
Other Significant Drug Interactions
- Antacids and Kaolin: Over-the-counter antacids containing aluminum, magnesium, or calcium, as well as kaolin (an anti-diarrhea medication), can interfere with the absorption of hydroxychloroquine, reducing its effectiveness [1.6.1, 1.6.4, 1.6.5]. It is recommended to separate the administration of hydroxychloroquine and these products by at least 4 hours [1.6.2, 1.6.6].
- Digoxin: Hydroxychloroquine can increase the levels of digoxin, a medication for heart failure, in the body. This raises the risk of digoxin toxicity, which can manifest as nausea, vision changes, and a slow heart rate [1.7.2, 1.7.6]. Blood levels of digoxin may need to be monitored closely [1.7.2].
- Cimetidine (Tagamet): This heartburn medication can inhibit the metabolism of hydroxychloroquine, potentially doubling its concentration in the blood and increasing the risk of side effects [1.6.4, 1.7.1]. It is often recommended to avoid this combination [1.7.2].
- Cyclosporine and Methotrexate: Hydroxychloroquine can increase the levels of these immunosuppressant drugs, potentially leading to increased toxicity [1.2.3, 1.7.7].
Drug Interaction Comparison Table
| Interacting Drug Class | Example(s) | Potential Effect of Interaction | Management Recommendation |
|---|---|---|---|
| QT-Prolonging Drugs | Amiodarone, Azithromycin, Citalopram | Increased risk of life-threatening cardiac arrhythmia (Torsades de Pointes) [1.2.3] | Avoid combination or use with extreme caution and cardiac monitoring [1.2.1, 1.3.2]. |
| Antidiabetic Drugs | Insulin, Metformin, Glipizide | Increased risk of severe hypoglycemia (low blood sugar) [1.4.3, 1.4.6] | Adjust diabetes medication dose and monitor blood glucose frequently [1.4.1]. |
| Antiepileptic Drugs | Carbamazepine, Phenytoin | May lower seizure threshold and reduce the effectiveness of seizure medication [1.5.2, 1.5.3]. | Monitor for seizure activity; may require dose adjustment or alternative therapy [1.5.2]. |
| Antacids | Tums, Maalox (Calcium, Aluminum, Magnesium) | Decreased absorption and effectiveness of hydroxychloroquine [1.6.1, 1.6.4]. | Separate administration by at least 4 hours [1.6.2]. |
| Digoxin | Lanoxin | Increased digoxin levels, leading to risk of toxicity [1.7.2, 1.7.6]. | Monitor serum digoxin levels; may need to adjust dose [1.7.6]. |
| Cimetidine | Tagamet | Increased hydroxychloroquine levels, raising risk of side effects [1.7.1, 1.7.2]. | Avoid combination; consider alternatives like famotidine [1.7.2]. |
Conclusion
Managing treatment with hydroxychloroquine requires a comprehensive understanding of its potential drug interactions. The most severe risks are associated with medications that affect heart rhythm, but interactions involving antidiabetic, antiseizure, and even common over-the-counter antacids are also significant. Open and continuous communication with your doctor and pharmacist is the best way to ensure safety. Always disclose every medication and supplement you use to allow for proper risk assessment and management, which may involve dose adjustments, regular monitoring, or choosing alternative therapies.
