Eletriptan

Mechanism

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and clarithromycin strongly inhibits this enzyme. According to its own prescribing information, clarithromycin can raise the levels of drugs broken down by CYP3A enzymes and increase or prolong their adverse effects. The labels give no study of this exact pair. The closest guide is erythromycin, another macrolide antibiotic. At 1000 mg, it raised the eletriptan area under the curve (AUC) 3.6-fold and lengthened its half-life from 4.6 to 7.1 hours. Ketoconazole 400 mg raised the AUC 5.9-fold. Like other triptans, eletriptan can cause coronary artery spasm. In clinical trials, doses of 60 mg or more caused short-lived rises in blood pressure.

Symptoms

Tightness, pain or pressure in the chest, throat, neck and jaw is common after eletriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, sometimes in people without known heart disease. Rarely, blood pressure rises sharply, even to a hypertensive crisis. Spasm of other arteries can cause Raynaud's syndrome or bowel ischaemia with abdominal pain and bloody diarrhoea. Stroke and brain haemorrhage have occurred after triptans.

Management

The combination is contraindicated (eletriptan label, US Food and Drug Administration, FDA). The eletriptan summary of product characteristics (SmPC) says not to use eletriptan with clarithromycin or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). Wait at least 72 hours after the last dose of clarithromycin before giving eletriptan (eletriptan label, FDA). If eletriptan has been taken during clarithromycin treatment and chest pain or tightness suggesting cardiac ischaemia appears, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop eletriptan if arrhythmias occur and monitor blood pressure during treatment (eletriptan label, FDA). If signs of spasm in other arteries appear, such as abdominal pain with blood in the stool or white, cold fingers, rule out vasospasm before the next dose (eletriptan label, FDA).

Mechanism

Both drugs constrict arteries. Eletriptan stimulates serotonin receptors in the vessel wall, and drugs of this group can cause coronary artery spasm. Ergotamine constricts blood vessels and can cause myocardial ischaemia, or rarely infarction, even in people with no known heart disease. Vasospasm after ergot drugs can be prolonged. In clinical trials, oral ergotamine with caffeine given 1 and 2 hours after eletriptan raised blood pressure only slightly. Still, the effects of the two drugs added up, as their pharmacology predicts.

Symptoms

Coronary artery spasm causes chest pain, pressure or tightness, sometimes severe and spreading to the throat, neck or jaw, and can lead to myocardial infarction. Serious arrhythmias such as ventricular tachycardia and ventricular fibrillation have been reported within a few hours of taking drugs of this group. Vasospasm from ergotamine causes numbness and tingling in the fingers and toes, headache and pain over the heart. With severe spasm, the limbs turn blue and their pulses disappear. Spasm of the intestinal arteries causes abdominal pain with bloody diarrhoea, and spasm of the finger arteries causes Raynaud's syndrome. In rare cases, blood pressure rises to a hypertensive crisis.

Management

The eletriptan documents of the Spanish Agency of Medicines and Medical Devices (AEMPS) and the US Food and Drug Administration (FDA) contraindicate the combination. The Spanish summary of product characteristics (SmPC) for ergotamine with caffeine contraindicates all triptans (AEMPS). Keep at least 24 hours between the two drugs, in either order (eletriptan SmPC, AEMPS, and label, FDA). If ergotamine has not stopped the attack, do not add a triptan for the same attack (ergotamine with caffeine SmPC, AEMPS). If chest pain or tightness suggesting cardiac ischaemia appears after an eletriptan dose, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop ergotamine at once if numbness or tingling in the fingers, pain over the heart or other signs of vasospasm appear (ergotamine with caffeine SmPC, AEMPS). Stop eletriptan if arrhythmias occur, and monitor blood pressure during treatment (eletriptan label, FDA). If abdominal pain with blood in the stool or white fingers appear, rule out vasospasm before the next eletriptan dose (eletriptan label, FDA). Taking ergotamine, triptans or both on 10 or more days a month can cause medication overuse headache, with more frequent attacks (eletriptan label, FDA).

Mechanism

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and itraconazole strongly inhibits this enzyme. No study has looked at this pair directly, but according to the itraconazole label, itraconazole is likely to raise eletriptan concentrations. The closest guide is data on other strong CYP3A4 inhibitors. Ketoconazole 400 mg raised the eletriptan area under the curve (AUC) 5.9-fold and lengthened its half-life from 4.8 to 8.3 hours. Erythromycin 1000 mg raised the AUC 3.6-fold. After itraconazole is stopped, its plasma levels take 7–14 days to become almost undetectable. Like other triptans, eletriptan can cause coronary artery spasm. In clinical trials, doses of 60 mg or more caused short-lived rises in blood pressure.

Symptoms

Tightness, pain or pressure in the chest, throat, neck and jaw is common after eletriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, sometimes in people without known heart disease. Rarely, blood pressure rises sharply, even to a hypertensive crisis. Spasm of other arteries can cause Raynaud's syndrome or bowel ischaemia with abdominal pain and bloody diarrhoea. Stroke and brain haemorrhage have occurred after triptans.

Management

The combination is contraindicated (eletriptan label, US Food and Drug Administration, FDA). The eletriptan summary of product characteristics (SmPC) says not to use eletriptan with itraconazole or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). The itraconazole SmPC also lists eletriptan as not recommended: avoid it during itraconazole treatment and for 2 weeks after stopping itraconazole (itraconazole SmPC, AEMPS). The FDA eletriptan label requires a gap of at least 72 hours after a strong inhibitor. Yet after itraconazole is stopped, its plasma levels take 7–14 days to become almost undetectable, and even longer in liver cirrhosis or with other CYP3A4 inhibitors (itraconazole SmPC, AEMPS). If eletriptan has been taken during itraconazole treatment and chest pain or tightness suggesting cardiac ischaemia appears, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop eletriptan if arrhythmias occur and monitor blood pressure during treatment (eletriptan label, FDA). If signs of spasm in other arteries appear, such as abdominal pain with blood in the stool or white, cold fingers, rule out vasospasm before the next dose (eletriptan label, FDA).

Mechanism

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and ketoconazole strongly inhibits this enzyme. In a clinical study, ketoconazole 400 mg raised the peak eletriptan concentration (Cmax) 2.7-fold and the area under the curve (AUC) 5.9-fold. It also lengthened the eletriptan half-life from 4.8 to 8.3 hours. According to the ketoconazole summary of product characteristics of the European Medicines Agency (EMA), ketoconazole interactions can be stronger with a higher dose or a shorter dosing interval. Like other triptans, eletriptan can cause coronary artery spasm. In clinical trials, doses of 60 mg or more caused short-lived rises in blood pressure. At clinical doses, eletriptan neither inhibits nor induces cytochrome P450 enzymes, so it does not affect ketoconazole.

Symptoms

Tightness, pain or pressure in the chest, throat, neck and jaw is common after eletriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, sometimes in people without known heart disease. Rarely, blood pressure rises sharply, even to a hypertensive crisis. Spasm of other arteries can cause Raynaud's syndrome or bowel ischaemia with abdominal pain and bloody diarrhoea. Stroke and brain haemorrhage have occurred after triptans.

Management

The combination is contraindicated (eletriptan label, US Food and Drug Administration, FDA). The eletriptan summary of product characteristics (SmPC) says not to use eletriptan with ketoconazole or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). The ketoconazole SmPC also lists the combination as not recommended (European Medicines Agency, EMA). Wait at least 72 hours after the last dose of ketoconazole before giving eletriptan (eletriptan and ketoconazole tablet labels, FDA). This concerns oral ketoconazole. In the European Union, its tablets are indicated for endogenous Cushing's syndrome (ketoconazole SmPC, EMA). After a cream is applied to the skin, ketoconazole is not measurable in plasma and no systemic effects are expected (ketoconazole cream SmPC, AEMPS). If eletriptan has been taken during ketoconazole treatment and chest pain or tightness suggesting cardiac ischaemia appears, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop eletriptan if arrhythmias occur and monitor blood pressure during treatment (eletriptan label, FDA). If signs of spasm in other arteries appear, such as abdominal pain with blood in the stool or white, cold fingers, rule out vasospasm before the next dose (eletriptan label, FDA).

Mechanism

Eletriptan is a serotonin agonist, CYP3A4 substrate. With phenelzine – fatal serotonin syndrome.

Symptoms

Agitation, tachycardia, hyperthermia, myoclonus, hyperreflexia within hours.

Management

Combination contraindicated. 14 days after MAOI withdrawal before starting triptan.

Mechanism

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and ritonavir strongly inhibits this enzyme. The labels give no study of this exact pair. The closest guide is data on other strong CYP3A4 inhibitors. Ketoconazole 400 mg raised the eletriptan area under the curve (AUC) 5.9-fold and lengthened its half-life from 4.8 to 8.3 hours. Erythromycin 1000 mg raised the AUC 3.6-fold. Like other triptans, eletriptan can cause coronary artery spasm. The Paxlovid (nirmatrelvir with ritonavir) labels explain the contraindication by the risk of serious adverse reactions, including cardiovascular and cerebrovascular events.

Symptoms

Tightness, pain or pressure in the chest, throat, neck and jaw is common after eletriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, sometimes in people without known heart disease. Rarely, blood pressure rises sharply, even to a hypertensive crisis. Spasm of other arteries can cause Raynaud's syndrome or bowel ischaemia with abdominal pain and bloody diarrhoea. Stroke and brain haemorrhage have occurred after triptans.

Management

The combination is contraindicated (eletriptan label, US Food and Drug Administration, FDA). The Paxlovid labels, where ritonavir is combined with nirmatrelvir, also contraindicate it (European Medicines Agency, EMA, and FDA). The eletriptan summary of product characteristics (SmPC) says not to use eletriptan with ritonavir or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). Wait at least 72 hours after the last dose of ritonavir before giving eletriptan (eletriptan label, FDA; Paxlovid labels, EMA and FDA). The documents set no dose condition, so the contraindication also covers the low ritonavir doses used to boost other antiviral drugs, including in Paxlovid. If eletriptan has been taken during ritonavir treatment and chest pain or tightness suggesting cardiac ischaemia appears, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop eletriptan if arrhythmias occur and monitor blood pressure during treatment (eletriptan label, FDA). If signs of spasm in other arteries appear, such as abdominal pain with blood in the stool or white, cold fingers, rule out vasospasm before the next dose (eletriptan label, FDA).