Understanding Hydroxychloroquine (Plaquenil)
Hydroxychloroquine, commonly known by the brand name Plaquenil, is a medication used to treat autoimmune diseases like rheumatoid arthritis and lupus, as well as to prevent and treat malaria [1.2.5]. It works by modifying the immune system's response and has anti-inflammatory properties [1.6.4]. While effective for its approved indications, its use requires caution due to a narrow therapeutic window and the potential for significant drug-drug interactions (DDIs) [1.2.1]. These interactions can alter the effectiveness of hydroxychloroquine or the co-administered drug, and more importantly, can lead to severe adverse effects [1.2.4].
The Primary Risks: QT Prolongation and Other Dangers
A major concern with hydroxychloroquine is its potential to prolong the QT interval of the heart [1.2.4]. The QT interval is the time it takes for your heart muscle to contract and then recover. A prolonged QT interval can lead to a dangerous type of irregular heartbeat called Torsades de Pointes, which can be life-threatening [1.4.1]. This risk is significantly amplified when hydroxychloroquine is taken with other medications that also affect the heart's rhythm [1.2.5]. Other risks include hypoglycemia (low blood sugar), a lowered seizure threshold, and vision damage [1.2.4, 1.2.5]. Therefore, a thorough review of all current medications with a healthcare provider is essential before starting treatment.
Medications That Affect Heart Rhythm (QT-Prolonging Drugs)
Combining hydroxychloroquine with other drugs that prolong the QT interval is one of the most dangerous interactions. The additive effect significantly increases the risk of ventricular arrhythmias [1.10.4]. Patients should not take hydroxychloroquine with certain medications, and close monitoring is required for others [1.2.1].
Absolutely avoid or use with extreme caution:
- Antiarrhythmics: Amiodarone, dronedarone, sotalol, quinidine, flecainide [1.2.1, 1.2.4, 1.3.1]. Co-administration with amiodarone, for instance, has been linked to long QT syndrome [1.2.1].
- Antipsychotics: Pimozide, thioridazine, ziprasidone, haloperidol, quetiapine [1.2.3, 1.2.4, 1.3.1].
- Antibiotics: Macrolides (azithromycin, clarithromycin) and fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) [1.2.2, 1.2.4, 1.3.1]. The combination of hydroxychloroquine and azithromycin, in particular, has been shown to cause greater QT prolongation than hydroxychloroquine alone [1.4.2].
- Antidepressants: Citalopram, escitalopram, and tricyclic antidepressants like amitriptyline [1.2.4, 1.3.1].
- Other Drugs: Methadone, ondansetron, and certain antifungals like ketoconazole [1.2.4, 1.3.1, 1.4.3].
Diabetes Medications
Hydroxychloroquine can lower blood sugar levels and enhance the effects of hypoglycemic treatments [1.10.4]. When taken with diabetes medications, there is an increased risk of severe hypoglycemia (dangerously low blood sugar) [1.2.5]. Symptoms include sweating, dizziness, shakiness, and in severe cases, seizures or coma [1.2.5].
Requires close monitoring and potential dose adjustment:
- Insulin (all types, e.g., Lantus, Humalog) [1.2.2, 1.6.2].
- Oral antidiabetic drugs: Metformin, glipizide, glyburide, sitagliptin (Januvia) [1.2.2, 1.2.3, 1.2.4].
Your healthcare provider may need to lower the dose of your diabetes medication and will likely recommend more frequent blood sugar monitoring [1.6.2].
Seizure Medications (Anticonvulsants)
Hydroxychloroquine can lower the seizure threshold, making seizures more likely to occur [1.2.4, 1.7.1]. This effect can be twofold: it increases the risk of seizures in susceptible individuals and may also reduce the effectiveness of anti-seizure medications [1.7.2, 1.10.4].
Drugs that interact include:
- Carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin) [1.2.3, 1.7.1]. These drugs may also reduce the effectiveness of hydroxychloroquine [1.2.1].
- Co-administration with another antimalarial, mefloquine, which also lowers the seizure threshold, drastically increases the risk of seizures and should be avoided [1.7.2, 1.9.1].
Other Significant Drug Interactions
Several other common medications can have clinically significant interactions with hydroxychloroquine.
- Antacids and Kaolin: Products containing magnesium, aluminum, or calcium (like Tums or Rolaids) can interfere with the absorption of hydroxychloroquine, reducing its effectiveness [1.5.1, 1.5.4]. It is recommended to separate the administration of antacids and hydroxychloroquine by at least 4 hours [1.2.2, 1.5.5].
- Cimetidine (Tagamet): This heartburn medication can inhibit the metabolism of hydroxychloroquine, potentially doubling its concentration in the bloodstream [1.8.2, 1.8.3]. This increases the risk of toxicity, and the combination should be avoided [1.8.2]. Alternative H2-blockers like famotidine may be safer [1.2.5].
- Digoxin: Used for heart failure and atrial fibrillation, digoxin has a narrow therapeutic index [1.10.3]. Hydroxychloroquine can increase digoxin levels in the blood, raising the risk of digoxin toxicity [1.10.1, 1.10.2]. Close monitoring of digoxin levels is required if these drugs must be used together [1.10.3].
- Cyclosporine: Hydroxychloroquine can increase the levels of this immunosuppressant, leading to a higher risk of side effects like kidney problems [1.2.4, 1.2.5].
- Methotrexate: While sometimes used together to treat rheumatoid arthritis, the combination can increase the risk of methotrexate side effects [1.2.5].
Comparison of Key Hydroxychloroquine Interactions
| Interacting Drug Class | Specific Examples | Primary Risk | Management Recommendation |
|---|---|---|---|
| QT-Prolonging Drugs | Amiodarone, Azithromycin, Citalopram, Pimozide | Severe cardiac arrhythmia (Torsades de Pointes) [1.2.4, 1.4.1] | Avoid co-administration whenever possible; requires intensive cardiac monitoring if unavoidable [1.2.1, 1.2.3]. |
| Diabetes Medications | Insulin, Metformin, Glipizide | Severe hypoglycemia (low blood sugar) [1.2.5, 1.6.2] | Adjust dose of diabetes medication and monitor blood glucose frequently [1.6.2]. |
| Seizure Medications | Carbamazepine, Phenytoin, Mefloquine | Increased risk of seizures; reduced efficacy of anticonvulsants [1.7.1, 1.7.2] | Avoid combination, especially with mefloquine. Monitor seizure activity and consider alternative medications [1.7.2, 1.9.1]. |
| Antacids | Tums, Rolaids, Kaolin | Decreased absorption and effectiveness of hydroxychloroquine [1.5.4] | Separate administration by at least 4 hours [1.5.5]. |
| Cimetidine (Tagamet) | Cimetidine | Increased hydroxychloroquine levels and toxicity [1.8.2] | Avoid combination. Use an alternative like famotidine [1.2.5, 1.8.3]. |
| Digoxin | Digoxin (Lanoxin) | Increased digoxin levels and risk of toxicity [1.10.3] | Monitor serum digoxin levels closely and adjust dose as needed [1.10.2]. |
Conclusion
Managing treatment with hydroxychloroquine requires a comprehensive understanding of its potential drug interactions. The most critical interactions are with medications that also prolong the QT interval, which can lead to life-threatening heart rhythm problems. Additionally, patients taking medications for diabetes, seizures, heartburn, and other heart conditions must exercise extreme caution. Always provide your healthcare provider with a complete list of all medications you are taking, including over-the-counter drugs and supplements, to create a safe and effective treatment plan. Never start or stop any medication without first consulting your doctor.
For more detailed information, consult authoritative sources such as the U.S. National Library of Medicine's page on Hydroxychloroquine.
