Amitriptyline × Solifenacin

Amitriptyline has marked anticholinergic properties (amitriptyline label). Solifenacin blocks muscarinic receptors and also causes anticholinergic adverse effects (solifenacin label). These effects add up. According to the amitriptyline label, tricyclic antidepressants can potentiate the action of anticholinergic drugs on the eye, brain, bowel and bladder, which raises the risk of paralytic ileus and hyperpyrexia. The second pathway is cardiac. QT interval prolongation is a common adverse reaction to amitriptyline (amitriptyline label). QT prolongation and torsade de pointes have occurred with solifenacin in patients with risk factors (solifenacin label). The labels describe no pharmacokinetic interaction. Solifenacin does not inhibit the cytochrome P450 (CYP) enzymes that break down amitriptyline and is unlikely to change its clearance. The labels say nothing about the effect of amitriptyline on solifenacin.

Peripheral anticholinergic effects include dry mouth, constipation, urinary retention, blurred vision, a fast heartbeat and, in people with a narrow anterior chamber angle, an attack of angle-closure glaucoma (both labels). The most serious complications are paralytic ileus and overheating with high fever, especially in hot weather, because sweating decreases (amitriptyline and solifenacin labels). Central effects include confusion, hallucinations, drowsiness and delirium (both labels). Older people have a higher risk of falls (amitriptyline label, US Food and Drug Administration, FDA). An arrhythmia due to QT interval prolongation shows as palpitations or fainting, and the electrocardiogram shows a long QT interval.

The combination is not recommended. The amitriptyline label says to avoid it with anticholinergic drugs because of the risk of paralytic ileus and hyperpyrexia (Spanish Agency of Medicines and Medical Devices, AEMPS, section 4.5). The solifenacin label of the US Food and Drug Administration (FDA) does not recommend solifenacin in patients who take drugs known to prolong the QT interval. Amitriptyline is one of these drugs (amitriptyline label, 4.4 and 4.8). For nocturnal enuresis in children, amitriptyline must not be combined with any anticholinergic drug (amitriptyline label, 4.4). Solifenacin tablets are not for children (solifenacin label, 4.2). If both drugs are still prescribed, supervise closely and adjust doses carefully. In older patients, start amitriptyline at low doses (US amitriptyline label, FDA). Before starting, rule out the solifenacin contraindications: urinary retention, severe gastrointestinal disorders, angle-closure glaucoma or a risk of these conditions (solifenacin label, 4.3). For the heart, take into account the risk factors named in both labels: marked bradycardia, decompensated heart failure, low or high potassium, low magnesium and known QT prolongation. If confusion, hallucinations or drowsiness appear, consider lowering the solifenacin dose or stopping it (US solifenacin label, FDA). Ask the patient to report constipation lasting 3 days or more or abdominal pain, and to avoid overheating in hot weather (US solifenacin label; amitriptyline label). When solifenacin is stopped to switch to another drug with anticholinergic action, wait about one week (solifenacin label, 4.5).