CDC warns: extreme heat can make common medications dangerous

The Centers for Disease Control and Prevention (CDC), the principal federal public health agency in the United States, has issued guidance for physicians and patients regarding the risks that excessive heat can pose when it interacts with certain medications. The agency warns that people on long-term treatments should discuss with their doctor well in advance of heatwaves about hydration, symptoms to watch for, and the possible need for closer monitoring.

Which medications are affected

Amongst the prescribed treatments that may increase the risk of side effects during heatwaves are diuretics, anticholinergic agents (which block acetylcholine, involved in sweating, salivation, digestion, bladder contraction, and heart rate) and certain psychotropic medications.

The CDC warns that some combinations are particularly hazardous: "Certain medication combinations, such as an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) with a diuretic, can significantly increase the risk of bodily harm caused by heat exposure."

ACE inhibitors (e.g. Enalapril, Ramipril) and ARBs (e.g. Losartan, Valsartan) are used for hypertension and heart failure. A similar risk is posed by angiotensin receptor-neprilysin inhibitors (ARNIs), newer medications used primarily for heart failure.

For children and adolescents, the CDC identifies the following as potentially hazardous: non-selective antihistamines (e.g. diphenhydramine), stimulants such as methylphenidate used for ADHD, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and diuretics.

How heat affects the action of medications

According to the CDC, these substances may promote dehydration, alter blood pressure regulation, reduce the body's ability to dissipate heat, or impair thermoregulatory mechanisms. The risk increases when multiple classes of medication are combined. Amongst the possible effects listed by the agency:

• Reduced sensation of thirst – with diuretics, ACE inhibitors, ARBs, and ARNIs;
• Interference with central thermoregulation – with antipsychotics, anticholinergics, and stimulants;
• Impaired sweating and cooling – increased with SSRIs and SNRIs, decreased with tricyclic antidepressants, typical/atypical antipsychotics, and anticholinergics;
• Volume depletion, hypotension, or reduced cardiac output, which may lead to dizziness, fainting, and falls; combined with dehydration, these may promote acute kidney injury when taking non-steroidal anti-inflammatory drugs (Ibuprofen, Naproxen, Diclofenac), diuretics, beta-blockers (Metoprolol, Bisoprolol), tricyclic antidepressants, or laxatives;
• Insufficient dilation of superficial blood vessels in the skin, preventing the body from dissipating heat effectively – with aspirin, beta-blockers, and clopidogrel;
• Drug toxicity due to reduced clearance in dehydrated individuals, particularly for medications with a narrow therapeutic index such as carbamazepine and lithium;
• Electrolyte imbalance – caused, for example, by diuretics, antacids, laxatives, lithium, and trimethoprim-sulfamethoxazole;
• Drowsiness, dizziness, or difficulty concentrating that may mask the sensation of thirst – with opioids, benzodiazepines, typical/atypical antipsychotics, antidepressants, and anticonvulsants.

The CDC further notes: "Heat exposure can damage drug delivery devices or degrade medications. Inhalers, for example, can explode in hot environments, such as car boots on hot days. EpiPens may malfunction or deliver less epinephrine when exposed to heat. Insulin, which must be kept refrigerated, may become less effective if left in the heat for extended periods of time."

Sensitivity to sunlight

Some medications increase the skin's sensitivity to sunlight: the antifungals flucytosine, griseofulvin, and voriconazole, as well as the antibiotics metronidazole, tetracyclines, and fluoroquinolones. These can cause a rash resembling sunburn. Those using them are advised to avoid sun exposure, wear protective clothing and hats, and apply a broad-spectrum sunscreen (with both UVA and UVB filters) with a minimum SPF of 30.

Recommended precautions

People taking medications from the classes mentioned above should pay particular attention to heat exposure and avoid it as much as possible. It is important to speak with their treating physician, who can determine whether closer monitoring is necessary or whether, in certain circumstances, the treatment should be adjusted. Treatment must never be altered or discontinued on one's own initiative, without a doctor's guidance.

Any change to the dose or dosing regimen must be individualised, based on the class of medication and the risk-benefit balance, as determined by the physician. Patients should ask their doctor which signs and symptoms might indicate an interaction between heat and their treatment, when to seek medical assistance, and what to do in an emergency.

With regard to storage, insulin must be kept in accordance with the package leaflet: unopened reserves are generally stored in the refrigerator (2–8°C), whilst the pen or vial in use should be kept at room temperature for the period specified by the manufacturer. Prolonged exposure to heat reduces its efficacy. Medications must never be left in a car or in places that may become excessively warm, and the storage conditions stated in the package leaflet must always be observed – most medications are kept at room temperature, away from heat, direct light, and moisture, though some, such as insulin or certain biological products, require refrigeration. Pressurised devices such as inhalers may be affected by very high temperatures and, in rare cases, may explode.