Side Effects of Loratadine-Pseudoephedrine Combination Products
The combination of loratadine and pseudoephedrine is generally well tolerated, but pseudoephedrine can cause insomnia, irritability, palpitations, loss of appetite, and tremor, while loratadine (a second-generation antihistamine) causes minimal sedation at recommended doses. 1
Common Side Effects
Pseudoephedrine-Related Effects
- Insomnia is one of the most frequently reported side effects, occurring significantly more often than with placebo 1, 2
- Nervousness and irritability are common stimulant-related effects 1, 2
- Palpitations and increased heart rate occur due to α-adrenergic stimulation, with meta-analyses showing pseudoephedrine increases heart rate by approximately 2.83 beats/min 1
- Loss of appetite may occur with oral decongestant use 1
- Tremor can develop, particularly with higher doses or frequent administration 1, 3
- Sleep disturbance is a recognized adverse effect that may be additive with caffeine consumption 1
Loratadine-Related Effects
- Minimal sedation - loratadine is classified as a second-generation antihistamine without sedation at recommended doses 1
- No performance impairment at standard 10 mg doses 1
- Side effects are generally minimal compared to first-generation antihistamines 1
Cardiovascular Effects
Blood Pressure Changes
- Small increase in systolic blood pressure (0.99 mmHg; 95% CI, 0.08-1.90) with pseudoephedrine 1
- No significant effect on diastolic blood pressure (0.63 mmHg; 95% CI, -0.10 to 1.35) 1
- Blood pressure elevation is generally observed in hypertensive patients, not normotensive individuals 1
- Patients with controlled hypertension should be monitored due to interindividual variation in response 1
High-Risk Populations and Contraindications
Use with Extreme Caution or Avoid In:
- Cardiac conditions: arrhythmias, angina pectoris, coronary artery disease, cerebrovascular disease 1
- Hypertension: particularly uncontrolled hypertension 1, 4
- Hyperthyroidism 1
- Bladder neck obstruction 1
- Closed-angle glaucoma 1
- Older adults and young children require special caution 1
Pediatric Considerations
- Well tolerated in children over 6 years when used in appropriate doses 1
- Dangerous in infants and young children - associated with agitated psychosis, ataxia, hallucinations, and even death 1
- Risks and benefits must be carefully weighed before use in children below age 6 years 1
Drug Interactions and Additive Effects
- Caffeine consumption may produce additive adverse effects with pseudoephedrine 1
- Stimulant medications (e.g., ADHD medications) may increase risk of tachyarrhythmias, insomnia, and hyperactivity 1
- MAO inhibitors: Do not use if currently taking MAOIs or within 2 weeks of stopping MAOI therapy 5
Comparative Safety Data
- In a head-to-head Thai study, extended-release loratadine-pseudoephedrine had significantly fewer tremor cases (10.7%) compared to immediate-release formulations (39%) at day 14 3
- One patient discontinued immediate-release therapy due to insomnia, while extended-release formulations were better tolerated 3
- Clinical trials show insomnia and nervousness occur in significantly more patients treated with loratadine-pseudoephedrine combinations compared to loratadine alone or placebo 2
When to Stop and Seek Medical Attention
Per FDA labeling, stop use and consult a physician if 5:
- Nervousness, dizziness, or sleeplessness occur
- Symptoms do not improve within 7 days or occur with fever
- Do not exceed recommended dosage 5
Clinical Pearls
- The combination is more effective than either component alone for seasonal allergic rhinitis, but this comes with the pseudoephedrine side effect profile 2
- Monitor blood pressure in hypertensive patients, even those with controlled hypertension 1
- Consider limiting use to no more than twice weekly to avoid medication-overuse complications 4
- For patients with cardiovascular concerns, topical decongestants may be safer alternatives for short-term use 4