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Interactions between Option 2 and Zolmitriptan

1 drug interaction and 40 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

levonorgestrel ZOLMitriptan

Applies to: Option 2 (levonorgestrel) and zolmitriptan
Monitor

Coadministration of hormonal contraceptives may increase plasma concentrations of zolmitriptan. A retrospective pharmacokinetic analysis indicates that mean peak plasma concentration (Cmax) and systemic exposure (AUC) of zolmitriptan were 30% and 50% higher, respectively, and time to peak plasma concentration (Tmax) was delayed by one-half hour in females taking oral contraceptives. The mechanism and clinical significance are unknown, although ethinyl estradiol-mediated inhibition of CYP450 1A2 may contribute, since zolmitriptan is a substrate of this isoenzyme. Products used for hormonal replacement therapy that contain estradiol or conjugated estrogens may also have a similar effect on zolmitriptan, although clinical data is not currently available. The effect of zolmitriptan on the pharmacokinetics of oral contraceptives has not been reported.

Management

Patients should be monitored for zolmitriptan-related adverse effects and notify their doctor promptly if they experience sedation, dizziness, paresthesia, chest pain or tightness, shortness of breath, or irregular heartbeats.

References (2)
  1. (2001) "Product Information. Zomig (zolmitriptan)." Astra-Zeneca Pharmaceuticals
  2. Granfors MT, Backman JT, Laitila J, Neuvonen PJ (2005) "Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2." Clin Pharmacol Ther, 78, p. 400-11

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

levonorgestrel Food/Lifestyle

Applies to: Option 2 (levonorgestrel)
Monitor

Grapefruit or grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

Management

Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References (32)
  1. Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
Moderate:

ZOLMitriptan Food/Lifestyle

Applies to: zolmitriptan
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.

Minor food/lifestyle interactions

Minor:

levonorgestrel Alcohol (Ethanol)

Applies to: Option 2 (levonorgestrel)

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References (1)
  1. Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

Disease interactions

37 potential interactions Applies to: 31 conditions, including High Blood Pressure, High Cholesterol, Depression, Migraine, and Weight Loss.

Abnormal Uterine Bleeding

Major:

Option 2

The levonorgestrel in Option 2 has a major potential interaction with Abnormal Uterine Bleeding.

The use of contraceptives is contraindicated when there is an undiagnosed abnormal genital bleeding. Adequate diagnostic measures should be undertaken to rule out the presence of any malignancy.

Angina

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Angina.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Arrhythmia

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Arrhythmia.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue therapy is cardiac rhythm disturbances occur.

Asthma

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Asthma.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Breast Cancer

Major:

Option 2

The levonorgestrel in Option 2 has a major potential interaction with Breast Cancer.

The use of progestogens is considered by manufacturers to be contraindicated in patients with existing or suspected malignancy of the breast. Some supportive data are available for medroxyprogesterone. Specifically, medroxyprogesterone treatment may be associated with breast cancer, primarily when the drug is administered intramuscularly. A pooled analysis of two case-control studies, one from the World Health Organization and the other from New Zealand, revealed a small overall relative risk of breast cancer in women who have ever used intramuscular medroxyprogesterone acetate. The relative risk was higher in the subgroup of women who had initiated therapy within the previous 5 years. Thus, an increased risk (approximately 2-fold) is associated with intramuscular medroxyprogesterone use in the first 5 years. A more recent U.S. study also found a statistically significant increase in breast cancer risk among recent users (defined as last use within the past five years) who used depo-medroxyprogesterone acetate for 12 months or longer.

Cardiovascular Conditions and Disorders

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Cardiovascular Conditions and Disorders.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Cerebral Vascular Disorder

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Cerebral Vascular Disorder.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Cerebral Vascular Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Depression

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Depression.

The use of oral contraceptives has been associated with an increased incidence of depression. It is uncertain whether this effect is related to the estrogenic or the progestogenic component of the contraceptive, although excess progesterone activity is associated with depression. Patients with a history of depression receiving estrogen and/or progestogen therapy should be followed closely. The manufacturer of medroxyprogesterone recommends monitoring patients who have a history of depression and to not re- administer medroxyprogesterone if depression recurs.

Diabetes Mellitus

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Diabetes Mellitus.

The group of drugs known as 5-hydroxytryptamine1 receptor (5-HT1) agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Rarely, serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of coronary artery disease (CAD). Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. In general, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, tobacco use, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) should not be administered 5-HT1 agonists unless a cardiovascular evaluation provides satisfactory clinical evidence indicating the lack of CAD, ischemic heart disease, or other significant underlying cardiovascular disease. As a precaution, the manufacturers recommend that the first dose be administered under medical surveillance in such patients, and that electrocardiographic monitoring be considered during the interval immediately following administration to help detect any asymptomatic cardiac ischemia that may occur. Periodic cardiovascular evaluations should be performed during intermittent, long-term use.

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Diabetes Mellitus.

Impaired glucose tolerance has been observed in some patients administered oral contraceptives and appears to be related primarily to the estrogen dose. However, progestogens can increase insulin secretion and produce insulin resistance to varying degrees, depending on the agent. Caution and close monitoring are recommended in patients with diabetes mellitus during therapy with estrogens and/or progestogens, and adjustments made accordingly in their antidiabetic regimen.

Fluid Retention

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Fluid Retention.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Heart Disease

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Heart Disease.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Heart Failure

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Heart Failure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Hepatic Tumor

Major:

Option 2

The levonorgestrel in Option 2 has a major potential interaction with Hepatic Tumor.

The use of oral contraceptives is contraindicated in patients with liver tumors. An increased risk of benign hepatic adenomas and hepatocellular carcinomas has been associated with long-term, oral estrogen- progestin contraceptive use of at least 4 years and 8 years, respectively. Although these tumors are rare and have not been reported with other types of estrogen or progestogen therapies, any preparation containing estrogens and/or progestogens should probably be avoided in patients with existing tumors of the liver. Hepatic hemangiomas and nodular hyperplasia of the liver have been reported with isolated estrogen therapy.

High Blood Pressure

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with High Blood Pressure.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

High Cholesterol

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with High Cholesterol.

The group of drugs known as 5-hydroxytryptamine1 receptor (5-HT1) agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Rarely, serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of coronary artery disease (CAD). Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. In general, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, tobacco use, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) should not be administered 5-HT1 agonists unless a cardiovascular evaluation provides satisfactory clinical evidence indicating the lack of CAD, ischemic heart disease, or other significant underlying cardiovascular disease. As a precaution, the manufacturers recommend that the first dose be administered under medical surveillance in such patients, and that electrocardiographic monitoring be considered during the interval immediately following administration to help detect any asymptomatic cardiac ischemia that may occur. Periodic cardiovascular evaluations should be performed during intermittent, long-term use.

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with High Cholesterol.

Some progestogenic agents may elevate plasma LDL levels and/or lower HDL levels, although data have been inconsistent. Patients with preexisting hyperlipidemia may require closer monitoring during progestogen therapy, and adjustments made accordingly in their lipid-lowering regimen.

History (Familial) - Ischemic Heart Disease

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with History (Familial) - Ischemic Heart Disease.

The group of drugs known as 5-hydroxytryptamine1 receptor (5-HT1) agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Rarely, serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of coronary artery disease (CAD). Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. In general, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, tobacco use, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) should not be administered 5-HT1 agonists unless a cardiovascular evaluation provides satisfactory clinical evidence indicating the lack of CAD, ischemic heart disease, or other significant underlying cardiovascular disease. As a precaution, the manufacturers recommend that the first dose be administered under medical surveillance in such patients, and that electrocardiographic monitoring be considered during the interval immediately following administration to help detect any asymptomatic cardiac ischemia that may occur. Periodic cardiovascular evaluations should be performed during intermittent, long-term use.

History, Thrombotic/Thromboembolic Disorder

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

History - Cerebrovascular Disease

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with History - Cerebrovascular Disease.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

History - Myocardial Infarction

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with History - Myocardial Infarction.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Ischemic Heart Disease

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Ischemic Heart Disease.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Liver Disease

Major:

Option 2

The levonorgestrel in Option 2 has a major potential interaction with Liver Disease.

The use of progestogens, in general, is contraindicated in patients with impaired hepatic function or liver disease. There are little or no data concerning the pharmacokinetic disposition of the different progestogens in patients with hepatic disease. However, most hormones, including progestational hormones, are known to be extensively metabolized by the liver. Medroxyprogesterone should not be used by women with significant liver disease and should be discontinued if jaundice or disturbances of liver function occur.

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Liver Disease.

Zolmitriptan is primarily metabolized by the liver. Following oral administration in patients with severe hepatic impairment, plasma concentrations of zolmitriptan were significantly increased (up to several-fold) compared to healthy controls. Some patients experienced 20 to 80 mm Hg elevations in systolic and/or diastolic blood pressure after a 10 mg dose, presumably due to drug accumulation. Therapy with zolmitriptan should be administered cautiously in patients with impaired hepatic function. Lower dosages, no more than 2.5 mg, as well as blood pressure monitoring should be considered in patients with moderate or severe hepatic impairment.

Menopause

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Menopause.

The group of drugs known as 5-hydroxytryptamine1 receptor (5-HT1) agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Rarely, serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of coronary artery disease (CAD). Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. In general, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, tobacco use, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) should not be administered 5-HT1 agonists unless a cardiovascular evaluation provides satisfactory clinical evidence indicating the lack of CAD, ischemic heart disease, or other significant underlying cardiovascular disease. As a precaution, the manufacturers recommend that the first dose be administered under medical surveillance in such patients, and that electrocardiographic monitoring be considered during the interval immediately following administration to help detect any asymptomatic cardiac ischemia that may occur. Periodic cardiovascular evaluations should be performed during intermittent, long-term use.

Migraine

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Migraine.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Prinzmetal's Angina

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Prinzmetal's Angina.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with a history or current symptoms or signs of ischemic coronary artery disease (CAD), coronary artery vasospasm (including Prinzmetal's angina), cerebrovascular syndromes (stroke or TIA), peripheral vascular disease (including ischemic bowel disease), uncontrolled hypertension, and any other significant underlying cardiovascular disease. 5-HT1 agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Some serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of CAD. Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. Cerebrovascular events have included cerebral hemorrhage, subarachnoid hemorrhage, and stroke, some resulting in fatalities. However, the relationship to 5-HT1 agonists is uncertain and, in a number of cases, the cerebrovascular events may have been primary where symptoms were mistaken to be migraine.

Renal Dysfunction

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Renal Dysfunction.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Moderate:

zolmitriptan

ZOLMitriptan has a moderate potential interaction with Renal Dysfunction.

Zolmitriptan is excreted in the urine primarily as metabolites but also as unchanged drug. Following oral administration in patients with renal impairment, the clearance of zolmitriptan was not significantly altered in patients with moderate impairment (CrCl = 26 to 50 mL/min) but was reduced by 25% in patients with severe impairment (CrCl = 5 to 25 mL/min) compared to healthy controls. Therapy with rizatriptan should be administered cautiously in patients with significantly impaired renal function. A lower initial dosage may be appropriate.

Seizures

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Seizures.

Estrogens and progestogens may cause fluid retention, particularly when given in high dosages or for prolonged periods. Therapy with these agents should be administered cautiously in patients who have preexisting problems with excess fluid. In addition, patients with conditions that may be adversely affected by fluid accumulation, such as asthma, epilepsy, migraine, and cardiovascular or renal dysfunction, should be observed for exacerbation of their condition during estrogen and/or progestogen therapy.

Smoking

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Smoking.

The group of drugs known as 5-hydroxytryptamine1 receptor (5-HT1) agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Rarely, serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of coronary artery disease (CAD). Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. In general, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, tobacco use, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) should not be administered 5-HT1 agonists unless a cardiovascular evaluation provides satisfactory clinical evidence indicating the lack of CAD, ischemic heart disease, or other significant underlying cardiovascular disease. As a precaution, the manufacturers recommend that the first dose be administered under medical surveillance in such patients, and that electrocardiographic monitoring be considered during the interval immediately following administration to help detect any asymptomatic cardiac ischemia that may occur. Periodic cardiovascular evaluations should be performed during intermittent, long-term use.

Thrombotic/Thromboembolic Disorder

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

The use of levonorgestrel requires careful assessment and caution in conditions of arterial disease, including stroke and myocardial infarction, and also, in patients with increased blood pressure and coagulopathies.

Thyroid Disease

Moderate:

Option 2

The levonorgestrel in Option 2 has a moderate potential interaction with Thyroid Disease.

When administering estrogen and/or progestogen therapy in patients with thyroid disorders, clinicians should be aware that these hormones may affect thyroid function tests. Patients on thyroid replacement therapy may require higher doses of thyroid hormone and appropriate monitoring. Changes have mostly been reported with the use of combination oral contraceptives. Specifically, thyroid-binding globulin (TBG) may be increased, resulting in elevated circulating total thyroid hormone, as measured by PBI (protein-bound iodine), T4 by column or radioimmunoassay, or T3 by radioimmunoassay. Free T3 resin uptake may be decreased. On the contrary, a decrease in TBG and, consequently, thyroxine concentration, has been reported by the manufacturers of the progestin-only (norethindrone) oral contraceptives.

Ventricular Arrhythmia

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Ventricular Arrhythmia.

The use of 5-hydroxytryptamine receptor (5-HT1) agonists is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT1 agonists. Discontinue therapy is cardiac rhythm disturbances occur.

Weight Loss

Major:

zolmitriptan

ZOLMitriptan has a major potential interaction with Weight Loss.

The group of drugs known as 5-hydroxytryptamine1 receptor (5-HT1) agonists can cause vasospastic reactions, including coronary vasospasm, peripheral vascular ischemia, and colonic ischemia. Rarely, serious adverse cardiac events including acute myocardial infarction, arrhythmia, cardiac arrest, and death have been reported within a few hours following the administration of 5-HT1 agonists, in some cases even in patients with no prior history or findings of coronary artery disease (CAD). Significant elevation in blood pressure, including hypertensive crisis, has also been reported on rare occasions in patients with and without a history of hypertension, as have transient increases in blood pressure and peripheral vascular resistance. In general, patients with potentially unrecognized CAD as predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, tobacco use, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) should not be administered 5-HT1 agonists unless a cardiovascular evaluation provides satisfactory clinical evidence indicating the lack of CAD, ischemic heart disease, or other significant underlying cardiovascular disease. As a precaution, the manufacturers recommend that the first dose be administered under medical surveillance in such patients, and that electrocardiographic monitoring be considered during the interval immediately following administration to help detect any asymptomatic cardiac ischemia that may occur. Periodic cardiovascular evaluations should be performed during intermittent, long-term use.

Minor:

Option 2

The levonorgestrel in Option 2 has a minor potential interaction with Weight Loss.

Progestogens can cause weight gain, which may be significant (as is the case with parenteral medroxyprogesterone) and undesirable in obese patients attempting to lose weight.

More resources

Option 2

A total of 277 drugs are known to interact with Option 2.

zolmitriptan

A total of 166 drugs are known to interact with zolmitriptan.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.