Drug Interaction Report
1 drug interaction and 39 additional warnings found for the following 2 drugs:
- Amen (medroxyprogesterone)
- valproic acid
Drug interactions
Moderate drug interactions
Moderate:valproic acid medroxyPROGESTERone
Applies to: valproic acid, Amen (medroxyprogesterone)
Using medroxyPROGESTERone together with valproic acid can cause loss of seizure control or symptoms such as:
- tremors
- poor muscle coordination
- increased seizures
- changes in behavior
Talk with your doctor before using these medications together, and report any side effects promptly. You may need a dose adjustment or special tests to safely take 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.
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:Food/Lifestyle valproic acid
Applies to: valproic acid
Alcohol can increase the nervous system side effects of valproic acid such as:
- dizziness
- drowsiness
- difficulty concentrating
Some people may also experience impairment in thinking and judgment.
You should avoid or limit the use of alcohol while being treated with valproic acid.
Do not use more than the recommended dose of valproic acid, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you.
Talk to your doctor or pharmacist if you have any questions or concerns.
Disease interactions
38 potential interactionsApplies to: 30 conditions, including High Blood Pressure, High Cholesterol, Depression, Migraine, and Weight Loss.
Abnormal Uterine Bleeding
Major:Amen
The medroxyPROGESTERone in Amen 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.
Major:Amen
The medroxyPROGESTERone in Amen has a major potential interaction with Abnormal Uterine Bleeding.
The use of medroxyprogesterone in women with undiagnosed vaginal bleeding is contraindicated. Most women using medroxyprogesterone experience disruption of menstrual bleeding patterns. Altered menstrual bleeding patterns include amenorrhea, irregular or unpredictable bleeding or spotting, prolonged spotting or bleeding, and heavy bleeding. Rule out the possibility of organic pathology if abnormal bleeding persists or is severe, and institute appropriate treatment.
Asthma
Moderate:Amen
The medroxyPROGESTERone in Amen 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 Disorder
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Bleeding Disorder.
The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.
Brain Anomalies incl Congenital
Major:valproic acid
Valproic acid has a major potential interaction with Brain Anomalies incl Congenital.
The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.
Breast Cancer
Major:Amen
The medroxyPROGESTERone in Amen 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.
Cerebral Vascular Disorder
Major:Amen
The medroxyPROGESTERone in Amen has a major potential interaction with Cerebral Vascular Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Coagulation Defects and Disorders
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Coagulation Defects and Disorders.
The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.
Depression
Major:valproic acid
Valproic acid has a major potential interaction with Depression.
Antiepileptic drugs can increase depression and suicidal thoughts or behaviors in patients receiving these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts and unusual changes in mood or behavior. Caregivers and family should be alert for the emergence or worsening of symptoms. Behaviors of concern should be reported immediately to the healthcare providers.
Moderate:Amen
The medroxyPROGESTERone in Amen 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.
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Depression.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Diabetes Mellitus
Moderate:Amen
The medroxyPROGESTERone in Amen 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.
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Diabetes Mellitus.
Valproate is partially eliminated in the urine as a ketone-containing metabolite, which may lead to a false interpretation of the urine ketone test. Clinicians should be cognizant of this interaction when prescribing or administering valproate products to patients with diabetes.
Fluid Retention
Moderate:Amen
The medroxyPROGESTERone in Amen 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 Failure
Moderate:Amen
The medroxyPROGESTERone in Amen 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.
High Blood Pressure
Moderate:Amen
The medroxyPROGESTERone in Amen 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
Moderate:Amen
The medroxyPROGESTERone in Amen 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, Thrombotic/Thromboembolic Disorder
Major:Amen
The medroxyPROGESTERone in Amen has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
HIV-1 Infection
Moderate:valproic acid
Valproic acid has a moderate potential interaction with HIV-1 Infection.
Some in vitro studies suggest that valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequences are unknown, and the relevance of these findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. However, this should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.
Hypoparathyroidism
Moderate:Amen
The medroxyPROGESTERone in Amen has a moderate potential interaction with Hypoparathyroidism.
Estrogens should be used with caution in individuals with severe hypocalcemia or hypoparathyroidism. Estrogen-induced hypocalcemia may occur in patients with hypoparathyroidism; consider whether the benefits of estrogen therapy outweigh the risks.
Intellectual Disability
Major:valproic acid
Valproic acid has a major potential interaction with Intellectual Disability.
Valproic acid and derivative products are contraindicated in patients with known urea cycle disorders (UCD), as hyperammonemic encephalopathy, sometimes fatal, has been reported on these patients following the initiation of treatment. Prior to the initiation of therapy, the evaluation for UCD should be considered in patients with history of unexplained encephalopathy or comma, encephalopathy associated with a protein load, pregnancy- related or postpartum encephalopathy, unexplained intellectual disability, or history of elevated plasma ammonia or glutamine. Also, those with family history of UCD or family history of unexplained infant deaths. Patients who develop symptoms of hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment including treatment discontinuation and be evaluated for underlying urea cycle disorders.
Major:valproic acid
Valproic acid has a major potential interaction with Intellectual Disability.
The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.
Liver Disease
Major:Amen
The medroxyPROGESTERone in Amen 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:valproic acid
Valproic acid has a major potential interaction with Liver Disease.
The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.
Metabolic Disorders
Major:valproic acid
Valproic acid has a major potential interaction with Metabolic Disorders.
The use of valproate derivatives is contraindicated in patients with hepatic disease or significant hepatic dysfunction. Serious and potentially fatal hepatotoxicity has been reported in patients treated with these agents. The risk appears to be greatest in children less than 2 years of age--particularly those on multiple anticonvulsants and those with congenital metabolic disorders, severe seizure disorders accompanied by intellectual disability, or organic brain disease--and decreases considerably in progressively older patient groups. Therapy with valproate products should be administered with extreme caution and as a sole agent in patients with risk factors for valproate-related hepatotoxicity. In reported cases, the onset has generally been within the first 6 months of treatment and may be preceded by nonspecific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, nausea, vomiting, and a loss of seizure control. Patients should be monitored closely for appearance of these symptoms, and therapy withdrawn immediately if significant hepatic dysfunction occurs. Liver function tests should be performed prior to initiating therapy and at frequent intervals thereafter, especially during the first 6 months. However, clinicians should bear in mind that transient, dose-related, asymptomatic elevations in serum transaminase, amylase and ammonia levels may commonly occur and often return to normal with or without dosage adjustment.
Major:valproic acid
Valproic acid has a major potential interaction with Metabolic Disorders.
Valproic acid and derivative products are contraindicated in patients with known urea cycle disorders (UCD), as hyperammonemic encephalopathy, sometimes fatal, has been reported on these patients following the initiation of treatment. Prior to the initiation of therapy, the evaluation for UCD should be considered in patients with history of unexplained encephalopathy or comma, encephalopathy associated with a protein load, pregnancy- related or postpartum encephalopathy, unexplained intellectual disability, or history of elevated plasma ammonia or glutamine. Also, those with family history of UCD or family history of unexplained infant deaths. Patients who develop symptoms of hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment including treatment discontinuation and be evaluated for underlying urea cycle disorders.
Migraine
Moderate:Amen
The medroxyPROGESTERone in Amen 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.
Osteoporosis
Major:Amen
The medroxyPROGESTERone in Amen has a major potential interaction with Osteoporosis.
The use of intramuscular medroxyprogesterone for contraception has been shown to induce bone loss, particularly during the early years of therapy. With continued use, the decline in bone density subsequently approaches the normal rate of age-related loss. Therapy with parenteral medroxyprogesterone should be administered cautiously in patients with osteoporosis or chronic use of drugs that can reduce bone mass, such as anticonvulsants or corticosteroids.
Psychosis
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Psychosis.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Renal Dysfunction
Moderate:Amen
The medroxyPROGESTERone in Amen 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:Amen
The medroxyPROGESTERone in Amen 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.
Thrombocytopathy
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Thrombocytopathy.
The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.
Thrombocytopenia
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Thrombocytopenia.
The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.
Thrombotic/Thromboembolic Disorder
Major:Amen
The medroxyPROGESTERone in Amen has a major potential interaction with Thrombotic/Thromboembolic Disorder.
The use of progestogens, in general, is considered by manufacturers to be contraindicated in patients with active thrombophlebitis, cerebrovascular disease, or a current or past history of thromboembolic disorders. While the role of progestogens in the development of thromboembolic events associated with hormonal therapy is often unclear and thought to be secondary to that of estrogens, it may not be insignificant. Medroxyprogesterone, a common progestational agent, has been shown to produce a hypercoagulable state in high dosages. Whether or not this effect contributes to the development of thrombotic events is unknown. However, thrombophlebitis and pulmonary embolism have been reported with megestrol, an antineoplastic and progestational agent. In addition, an increased risk of nonfatal venous thrombosis has been associated with oral contraceptive combinations containing desogestrel or gestodene relative to those that contain other progestins (e.g., levonorgestrel, norethindrone), suggesting some degree of hemostatic effect by progestogens.
Thyroid Disease
Moderate:Amen
The medroxyPROGESTERone in Amen 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.
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Thyroid Disease.
The manufacturers state that there have been reports of altered thyroid function tests associated with the use of valproate. However, no specific information is given. Clinicians should be cognizant of this potential effect when prescribing or administering valproate products to patients with thyroid disease.
Vitamin K Deficiency
Moderate:valproic acid
Valproic acid has a moderate potential interaction with Vitamin K Deficiency.
The use of valproate derivatives may be associated with dose-related thrombocytopenia, the incidence of which is generally low but has been reported at up to 27% in one study using high dosages (approximately 50 mg/kg/day of valproic acid). In that study, platelet counts returned to normal in all patients, some despite continued treatment. Valproate may also inhibit the secondary phase of platelet aggregation, although this effect is unlikely to be of clinical significance except during the concomitant use of other drugs that affect coagulation. However, altered bleeding time, ecchymosis, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage have been reported rarely. Hypofibrinogenemia has also been observed. Therapy with valproate products, particularly at high dosages, should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. The manufacturers recommend platelet counts and coagulation tests prior to initiating therapy and at periodic intervals thereafter, as well as before planned surgery. The dosage should be reduced or the drug withdrawn if clinical evidence of hemorrhage, bruising, or a disorder of hemostasis or coagulation occurs.
Weight Loss
Minor:Amen
The medroxyPROGESTERone in Amen 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.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
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