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Drug Interaction Report

2 drug interactions and 45 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

ethinyl estradiol pacritinib

Applies to: Loryna (drospirenone / ethinyl estradiol), pacritinib

Pacritinib can occasionally cause dangerous blood clots and using it together with ethinyl estradiol may increase the risk. Also, the risk is increased with age, cigarette smoking, high blood pressure, or high cholesterol. Blood clots can lead to complications such as heart attack, pulmonary embolism (blockage of an artery in the lung), and stroke.

Pacritinib may also reduce the blood levels and effects of ethinyl estradiol, which may make it less reliable as a form of birth control.

Alternative or additional methods of birth control should be used during treatment with pacritinib and for at least one week to one month after pacritinib therapy to avoid unintended pregnancy. This is particularly important because pacritinib may cause harm in the unborn child.

Talk to your doctor, gynecologist, or other healthcare professional if you have any questions or concerns and for help in selecting an effective method of birth control that is best for you. Your doctor may already be aware of the risks but has determined that this is the best course of treatment for you has taken appropriate precautions and is monitoring you closely for any potential complications.

You should seek immediate medical attention if you experience potential signs and symptoms of blood clots such as:

  • chest pain
  • shortness of breath
  • difficulty breathing
  • coughing up blood
  • sudden loss of vision
  • pain, redness, or swelling in an arm or leg
  • numbness or weakness on one side of the body

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Major:

drospirenone pacritinib

Applies to: Loryna (drospirenone / ethinyl estradiol), pacritinib

Pacritinib can occasionally cause dangerous blood clots and using it together with drospirenone may increase the risk. Also, the risk is increased with age, cigarette smoking, high blood pressure, or high cholesterol. Blood clots can lead to complications such as heart attack, pulmonary embolism (blockage of an artery in the lung), and stroke.

Pacritinib may also reduce the blood levels and effects of drospirenone, which may make it less reliable as a form of birth control.

Alternative or additional methods of birth control should be used during treatment with pacritinib and for at least one week to one month after pacritinib therapy to avoid unintended pregnancy. This is particularly important because pacritinib may cause harm in the unborn child.

Talk to your doctor, gynecologist, or other healthcare professional if you have any questions or concerns and for help in selecting an effective method of birth control that is best for you. Your doctor may already be aware of the risks but has determined that this is the best course of treatment for you has taken appropriate precautions and is monitoring you closely for any potential complications.

You should seek immediate medical attention if you experience potential signs and symptoms of blood clots such as:

  • chest pain
  • shortness of breath
  • difficulty breathing
  • coughing up blood
  • sudden loss of vision
  • pain, redness, or swelling in an arm or leg
  • numbness or weakness on one side of the body

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

Food/Lifestyle pacritinib

Applies to: pacritinib

Grapefruit juice may increase the blood levels of pacritinib.

This can increase the risk of side effects such as:

  • diarrhea
  • low blood platelet count
  • infection
  • an irregular heart rhythm that may be serious or life-threatening

You should avoid consuming grapefruit and grapefruit juice during treatment with pacritinib.

However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication.

Contact your doctor if you have any questions or concerns or if you develop dizziness, lightheadedness, fainting, shortness of breath, chest pain, or heart palpitations during treatment.

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Moderate food/lifestyle interactions

Moderate:

Caffeine ethinyl estradiol

Applies to: Loryna (drospirenone / ethinyl estradiol)

Ethinyl estradiol may increase the blood levels of caffeine. This may increase the risk and/or severity of side effects related to caffeine.

Contact your doctor if your condition changes or you experience increased side effects. You may need a dose adjustment or more frequent monitoring to safely use both medications.

It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Moderate:

Food/Lifestyle drospirenone

Applies to: Loryna (drospirenone / ethinyl estradiol)

Grapefruit juice may increase the blood levels of certain medications such as drospirenone.

You may want to limit your consumption of grapefruit and grapefruit juice during treatment with drospirenone. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication.

Contact your doctor if your condition changes or you experience increased side effects.

Orange juice is not expected to interact.

Minor food/lifestyle interactions

Minor:

Alcohol (Ethanol) ethinyl estradiol

Applies to: Loryna (drospirenone / ethinyl estradiol)

Information for this minor interaction is available on the professional version.

Minor:

Food/Lifestyle ethinyl estradiol

Applies to: Loryna (drospirenone / ethinyl estradiol)

Information for this minor interaction is available on the professional version.

Disease interactions

40 potential interactionsApplies to: 34 conditions, including High Blood Pressure, High Cholesterol, Depression, Migraine, and Heart Failure.

Abnormal Uterine Bleeding

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Abnormal Uterine Bleeding.

The use of estrogens is contraindicated in patients with undiagnosed, abnormal vaginal bleeding. Prolonged (greater than 1 year), unopposed estrogen use (i.e. estrogen without concomitant progestin therapy) has been associated with a significant, dose-related risk of endometrial carcinoma. The risk may be offset substantially by the addition of a progestin but may not be completely abolished. Prior to initiating estrogen therapy, appropriate diagnostic tests should be performed in patients with abnormal vaginal bleeding to rule out endometrial malignancy. The same applies if recurrent or persistent bleeding develops during estrogen therapy.

Adrenal Insufficiency

Major:

Loryna

The drospirenone in Loryna has a major potential interaction with Adrenal Insufficiency.

The progestin drospirenone (DRSP) has antialdosterone activity, including the potential for hyperkalemia in high-risk patients. The use of DRSP-containing combination hormone is contraindicated in patients with conditions that predispose to hyperkalemia (renal impairment, hepatic impairment, and adrenal insufficiency). Use caution when prescribing these agents to women who regularly take other medications that can increase potassium, such as nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, heparin and aldosterone antagonists. It is recommended to monitor serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.

Angioedema

Moderate:

Loryna

The ethinyl estradiol in Loryna has a moderate potential interaction with Angioedema.

The use of exogenous estrogens may induce or exacerbate symptoms of angioedema, particularly in women with hereditary angioedema. Consider the risk versus benefits of estrogen therapy. Close monitoring is recommended when prescribing these agents to patients predisposed to angioedema.

Arrhythmia

Moderate:

pacritinib

Pacritinib has a moderate potential interaction with Arrhythmia.

Pacritinib can cause a QT prolongation of greater than 500 msec, and patients receiving this drug were more likely to develop a QT prolongation of at least 60 msec from baseline (compared to the control group) in clinical trials. This agent should be avoided in patients with QT intervals greater than 480 msec at baseline, and/or in those who are taking medications known to prolong the QTc interval. Hypokalemia should be corrected before initiating and during therapy with this agent. QT prolongation occurring during treatment should be managed with treatment interruption and electrolyte management. Periodic monitoring of ECGs and electrolytes is recommended in these patients.

Asthma

Moderate:

Loryna

The ethinyl estradiol in Loryna 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.

Bleeding Associated with Coagulation Defect

Moderate:

pacritinib

Pacritinib has a moderate potential interaction with Bleeding Associated with Coagulation Defect.

Serious episodes of bleeding, including those requiring transfusion/invasive intervention, and some leading to fatal bleeding events have been reported in patients treated with pacritinib. Platelet counts should be periodically assessed, monitoring for signs of bleeding (when indicated); hemorrhage should be managed with medical intervention, dose reductions, intermittent interruptions, and/or permanent treatment discontinuations. It is recommended to withhold pacritinib for 7 days prior to planned surgery/invasive procedure.

Bleeding Disorder

Moderate:

pacritinib

Pacritinib has a moderate potential interaction with Bleeding Disorder.

Serious episodes of bleeding, including those requiring transfusion/invasive intervention, and some leading to fatal bleeding events have been reported in patients treated with pacritinib. Platelet counts should be periodically assessed, monitoring for signs of bleeding (when indicated); hemorrhage should be managed with medical intervention, dose reductions, intermittent interruptions, and/or permanent treatment discontinuations. It is recommended to withhold pacritinib for 7 days prior to planned surgery/invasive procedure.

Breast Cancer

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Breast Cancer.

When treated with an estrogen, patients with breast cancer and bone metastases may develop severe hypercalcemia, in which case the drug should be stopped and measures be taken to reduce serum calcium levels.

Cardiovascular Conditions and Disorders

Major:

pacritinib

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

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

Cerebral Vascular Disorder

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Cerebral Vascular Disorder.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

Depression

Moderate:

Loryna

The ethinyl estradiol in Loryna 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

Moderate:

Loryna

The ethinyl estradiol in Loryna 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.

Diarrhea

Major:

pacritinib

Pacritinib has a major potential interaction with Diarrhea.

Severe diarrhea, sometimes requiring discontinuation of treatment, has occurred in patients treated with pacritinib. Preexisting diarrhea should be controlled prior to starting treatment with pacritinib. Antidiarrheal agents should be promptly used to treat diarrhea at the first onset of symptoms. Antidiarrheal agents, fluid replacement, and/or dose modification should be used to manage diarrhea. Reducing or interrupting pacritinib should be considered in patients with significant diarrhea (despite optimal supportive care).

Fluid Retention

Moderate:

Loryna

The ethinyl estradiol in Loryna 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.

Gallbladder Disease

Moderate:

Loryna

The ethinyl estradiol in Loryna has a moderate potential interaction with Gallbladder Disease.

A two- to four-fold increase in risk of gallbladder disease has been noted in women receiving postmenopausal estrogen therapy. The risk for gallbladder disease may be less for premenopausal women using oral contraceptives containing low-dose estrogens and/or progestins. Therapy with estrogens should be administered cautiously in patients with preexisting gallbladder disease or a history of pregnancy-related cholestasis.

Heart Failure

Moderate:

Loryna

The ethinyl estradiol in Loryna 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:

Loryna

The ethinyl estradiol in Loryna 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

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with High Blood Pressure.

The risk of myocardial infarction and strokes, including those associated with oral contraceptive use and some estrogen use, is increased in patients with hypertension. Moreover, estrogens (and progestogens) may elevate blood pressure and worsen the hypertension, thus compounding the risk. Clinically significant blood pressure increases have been reported during estrogen therapy, particularly in patients receiving high dosages or treated with oral contraceptive combinations having high progestational activity. These effects also increase with duration of therapy and patient age. Therapy with estrogens should be administered cautiously in patients with preexisting hypertension. Some estrogen-based therapies, such as combined hormonal contraceptives, may be contraindicated in patients with uncontrolled hypertension or hypertension with vascular disease. Patients should be monitored for changes in cardiovascular status, and their antihypertensive regimen adjusted or estrogen therapy withdrawn as necessary. In patients requiring contraception, alternative methods should be considered for those who are hypertensive, over age 35, and smoke.

High Cholesterol

Moderate:

Loryna

The ethinyl estradiol in Loryna has a moderate potential interaction with High Cholesterol.

Estrogens may cause adverse lipid changes. Use of estrogens has been associated with elevations in triglyceride levels, particularly in women with pre-existing hypertriglyceridemia. Discontinue therapy if elevated triglycerides lead to pancreatitis. Manage hypercholesterolemia appropriately as indicated.

History, Thrombotic/Thromboembolic Disorder

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

Hyperkalemia

Major:

Loryna

The drospirenone in Loryna has a major potential interaction with Hyperkalemia.

The progestin drospirenone (DRSP) has antialdosterone activity, including the potential for hyperkalemia in high-risk patients. The use of DRSP-containing combination hormone is contraindicated in patients with conditions that predispose to hyperkalemia (renal impairment, hepatic impairment, and adrenal insufficiency). Use caution when prescribing these agents to women who regularly take other medications that can increase potassium, such as nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, heparin and aldosterone antagonists. It is recommended to monitor serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.

Infection

Major:

pacritinib

Pacritinib has a major potential interaction with Infection.

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving pacritinib. It is recommended to avoid the use of pacritinib in patients with an active, serious infection, including localized infections and to consider the risks and benefits before starting treatment. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment. Treatment should be interrupted if a patient develops a serious infection, an opportunistic infection, or sepsis and appropriate therapy should be instituted according to clinical guidelines. Close monitoring is recommended.

Ischemic Heart Disease

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Ischemic Heart Disease.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

Liver Disease

Major:

Loryna

The drospirenone in Loryna has a major potential interaction with Liver Disease.

The progestin drospirenone (DRSP) has antialdosterone activity, including the potential for hyperkalemia in high-risk patients. The use of DRSP-containing combination hormone is contraindicated in patients with conditions that predispose to hyperkalemia (renal impairment, hepatic impairment, and adrenal insufficiency). Use caution when prescribing these agents to women who regularly take other medications that can increase potassium, such as nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, heparin and aldosterone antagonists. It is recommended to monitor serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.

Moderate:

Loryna

The ethinyl estradiol in Loryna has a moderate potential interaction with Liver Disease.

Estrogens are primarily metabolized by the liver. Use of estrogen therapy is contraindicated in patients with liver dysfunction or disease. Patients with impaired hepatic function may be at increased risk for adverse effects associated with estrogen administration due to decreased drug clearance. Patients with hepatic hemangiomas are at increased risk of exacerbation with use of estrogens. Therapy with estrogens should be administered cautiously in patients with cholestatic jaundice associated with past estrogen use or with pregnancy. In addition, clinicians should be aware that estrogen therapy may affect liver function tests.

Melasma

Moderate:

Loryna

The ethinyl estradiol in Loryna has a moderate potential interaction with Melasma.

The use of exogenous estrogens may occasionally cause chloasma, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking combination oral contraceptives.

Migraine

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Migraine.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

Moderate:

Loryna

The ethinyl estradiol in Loryna 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.

Neoplasia, Estrogen Dependent

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Neoplasia, Estrogen Dependent.

The use of estrogens is generally contraindicated in patients with known or suspected estrogen-dependent neoplasia such as breast and endometrial cancer, since it may stimulate tumor proliferation. High dosages of estrogens may be used for the palliative treatment of inoperable, metastatic breast cancer, but only in appropriately selected men and postmenopausal women.

Pancreatitis

Moderate:

Loryna

The ethinyl estradiol in Loryna has a moderate potential interaction with Pancreatitis.

Estrogens may cause adverse lipid changes. Use of estrogens has been associated with elevations in triglyceride levels, particularly in women with pre-existing hypertriglyceridemia. Discontinue therapy if elevated triglycerides lead to pancreatitis. Manage hypercholesterolemia appropriately as indicated.

Renal Dysfunction

Major:

Loryna

The drospirenone in Loryna has a major potential interaction with Renal Dysfunction.

The progestin drospirenone (DRSP) has antialdosterone activity, including the potential for hyperkalemia in high-risk patients. The use of DRSP-containing combination hormone is contraindicated in patients with conditions that predispose to hyperkalemia (renal impairment, hepatic impairment, and adrenal insufficiency). Use caution when prescribing these agents to women who regularly take other medications that can increase potassium, such as nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, heparin and aldosterone antagonists. It is recommended to monitor serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.

Moderate:

Loryna

The ethinyl estradiol in Loryna 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.

Seizures

Moderate:

Loryna

The ethinyl estradiol in Loryna 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:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Smoking.

Cigarette smoking increases the risk of serious cardiovascular events from estrogen-containing combination oral contraceptives (COC). This risk increases with age, particularly in females over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in females who are over 35 years of age and smoke.

Major:

pacritinib

Pacritinib has a major potential interaction with Smoking.

In a major safety study of a Janus kinase (JAK) inhibitor, tofacitinib, in rheumatoid arthritis patients 50 years and older with at least 1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden cardiovascular death) and major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) were observed with the JAK inhibitor when compared with tumor necrosis factor (TNF) blockers. Patients who were current or past smokers had an additional increased risk. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including baricitinib, upadacitinib, ruxolitinib, fedratinib, ritlecitinib, deuruxolitinib, and pacritinib. Consider the benefits and risks for each individual patient prior and during treatment with JAK inhibitors, especially in patients with other cardiovascular risk factors, history of cardiovascular events, and patients who are current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and what to do if they occur.

Major:

pacritinib

Pacritinib has a major potential interaction with Smoking.

Malignancies (including lymphomas and solid tumors) have been reported in patients treated with tofacitinib, baricitinib, upadacitinib, deuruxolitinib and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions. Patients who are current or past smokers are at additional increased risk of malignancies. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, pacritinib, and fedratinib. Before starting or continuing therapy, the benefits and risks for the individual patient should be considered, especially in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer), patients who develop a malignancy during therapy, and patients who are current or past smokers. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Thrombotic/Thromboembolic Disorder

Major:

Loryna

The ethinyl estradiol in Loryna has a major potential interaction with Thrombotic/Thromboembolic Disorder.

The use of estrogens is considered by manufacturers and some authorities to be contraindicated in patients with active thrombotic, thromboembolic, or thrombophilic disorders. The use of estrogen-containing oral contraceptives is additionally deemed contraindicated in patients with a history of such disorders and/or current cerebrovascular or coronary artery disease. Females with a history of migraines with aura are at an increased risk for stroke and this stroke risk may be further increased in females who have migraines with aura with use of combination oral contraceptives. Hypercoagulability and changes in various clotting factors and blood components have been observed in women receiving estrogen therapy. Known preexisting risk factors for increased thromboembolic or cardiovascular events include smoking, especially over age of 35; hypertension; hyperlipidemia; obesity; diabetes; age over 40; and lupus. Therapy with estrogens should be administered cautiously in the lowest effective dosage and only after careful consideration of risks and benefits. Estrogens should be avoided in patients with a history of thrombotic and thromboembolic disorders associated with estrogen use, except when used in the treatment of metastatic breast or prostatic malignancy.

Major:

pacritinib

Pacritinib has a major potential interaction with Thrombotic/Thromboembolic Disorder.

Thrombosis (including deep venous thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, and arterial thrombosis) has occurred in patients treated for inflammatory conditions with Janus kinase (JAK) inhibitors, including baricitinib, tofacitinib, deuruxolitinib and upadacitinib. Many of these adverse events were serious and some resulted in death. Based on a shared mechanism of action, this risk should be considered for other JAK inhibitors, including ruxolitinib, fedratinib, and pacritinib. In general, JAK inhibitors should be avoided in patients who may be at increased risk of thrombosis. Tofacitinib should be used at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response when treating ulcerative colitis. If symptoms of thrombosis occur in any patients receiving JAK inhibitors, treatment should be discontinued and patients should be evaluated promptly and treated appropriately.

Thyroid Disease

Moderate:

Loryna

The ethinyl estradiol in Loryna 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

Moderate:

pacritinib

Pacritinib has a moderate potential interaction with Ventricular Arrhythmia.

Pacritinib can cause a QT prolongation of greater than 500 msec, and patients receiving this drug were more likely to develop a QT prolongation of at least 60 msec from baseline (compared to the control group) in clinical trials. This agent should be avoided in patients with QT intervals greater than 480 msec at baseline, and/or in those who are taking medications known to prolong the QTc interval. Hypokalemia should be corrected before initiating and during therapy with this agent. QT prolongation occurring during treatment should be managed with treatment interruption and electrolyte management. Periodic monitoring of ECGs and electrolytes is recommended in these patients.

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.

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Further information

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