Mifepristone and Misoprostol is a combination tablets used to terminate a pregnancy. It is indicated for medical termination of pregnancy only in females with a gestational age of two months or less.
Mifepristone and Misoprostol Uses:
Note: Not approved in the US
-
Termination of intrauterine pregnancy:
-
- Medical end of an intrauterine pregnancy with a gestational age up to 2 months as measured from the first day of the last menstrual period (assumed 28-day cycle)
-
Mifepristone and Misoprostol Dose in Adults:
Mifepristone and Misoprostol Dose in the termination of intrauterine pregnancy:
- Females: Treatment consists of 3 visits by the patient
- Day 1: Oral: Mifepristone 200 mg as a single dose
- Missed dose:
- Patient must call their health care provider without delay if the administration is delayed, or tablet is not administered at the time and date stated (listed on the completed Patient Information Card).
- Day 2 or 3: Buccal: Misoprostol 800 mcg 1 to 2 days after mifepristone administration. The dose is administered as four 200 mcg tablets as a single dose placed between cheek and gum and kept there for 30 minutes. Any remnants should be swallowed with water.
- Missed dose:
- Patient must contact their health care provider immediately if they forget to take misoprostol and it has been more than 2 days after administration of mifepristone.
- If the time is less than 48 hours since mifepristone was administered but after the time and date mentioned on the Patient Information Card, the health professional may instruct the patient to take the misoprostol tablets at once.
- Day 7 to 14 (post-treatment exam): The patient must revisit the health care provider 1 to 2 weeks after administration of mifepristone to verify that complete termination of pregnancy has happened. Termination by surgery may be needed if the treatment fails.
Use in Children:
Not indicated.
Pregnancy Risk Category: X
- This medication can be used to end a pregnancy.
- [Canadian Boxed Warn]
- It is important to warn patients that treatment can cause embryotoxicity.
- If the pregnancy is not ended, it could lead to the death of the baby.
- Both misoprostol and mifepristone are embryotoxic and have been associated with embryonic defects.
- [Canadian Boxed Warn]
- A sign of an incomplete abortion, or other complications, may be prolonged heavy bleeding.
- This may require immediate medical or surgical attention. It is important that patients seek immediate medical attention.
- [Canadian Boxed Warn]
- Patients ought to be warned of their instant return to fertility after mifepristone/misoprostol administration.
- Avoiding exposure to misoprostol and mifepristone during pregnancy is a good idea. It is important to use reliable contraceptives as soon as possible.
- Pregnancies occurred between the time of embryo removal and when menstruation returned during clinical trials.
- For more information, see individual monographs.
Use during breastfeeding:
- Breast milk contains misoprostol.
- Manufacturers do not recommend breastfeeding. Please consult individual agents.
Dose in Kidney Disease:
Use is not advised for kidney impairment (has not been studied).
Dose in Liver disease:
Use is not suggested in liver impairment (has not been studied).
Also, see individual agents (Mifepristone and Misoprostol)
Common Side Effects of Mifepristone and misoprostol:
-
Central nervous system:
- Pain
- Dizziness
- Chills
- Headache
- Fatigue
-
Gastrointestinal:
- Nausea
- Diarrhea Vomiting
- Abdominal pain
- Gastric distress
-
Genitourinary:
- Genital bleeding
- Spotting
- Uterine contractions
- Uterine cramps
-
Neuromuscular & skeletal:
- Weakness
-
Miscellaneous:
- Fever
Less Common Side Effects of Mifepristone and misoprostol:
-
Cardiovascular:
- Syncope
-
Genitourinary:
- Breast tenderness
- Endometritis
-
Hematologic & oncologic:
- Hemorrhage (including post-abortion bleeding)
Frequency of side effects not defined:
-
Cardiovascular:
- Septic shock
-
Infection:
- Bacterial infection
- Sepsis
Contraindications to Mifepristone and Misoprostol:
- Allergic reaction to misoprostol, mifepristone, or other prostaglandins or any component of the formulation
- Confirmation or suspicion of ectopic pregnancy
- Existence of an intrauterine device (IUD);
- Unconfirmed gestational birth age
- Surviving adrenal failure
- Concurrent long-term corticosteroid therapy
- Hemorrhagic conditions or simultaneous anticoagulation therapy
- Inherited porphyria;
- Asthma that isn't controlled.
Warnings and precautions
-
Bacterial infections:
- Clostridium sordellii, a bacterium, has been reported to have occurred after the product was used.
- These infections can be fatal or even deadly in rare cases. Septic shock is a possible complication.
- Patients may not experience fever, abdominal pain, or other symptoms.
- However, leukocytosis may be present with marked left shift, tachycardia and hemoconcentration, and general malaise.
- Patients with symptoms such as nausea, vomiting, diarrhea, or faintness that last more than 24 hours after misoprostol administration should be evaluated immediately for serious bacterial infection/sepsis.
- You should quickly evaluate a constant fever of >=38degC (100.4degF) or pelvic tenderness.
-
Bleeding: [Canadian Boxed Warn]
- Long-term heavy bleeding could indicate an incomplete abortion or other complications. It is important to seek immediate medical or surgical attention.
- Patients should seek immediate medical attention.
- As an example of excessive bleeding, the manufacturer suggests that you soak 2 thick sanitary napkins each hour for 2 consecutive hours.
- Patients with anemia, especially severe, should be careful.
-
CNS effects
- Possible lightheadedness that may lead to mental or physical impairments. Patients should be aware of tasks that require mental attention (e.g. driving, operating machinery).
-
Embryotoxicity: [Canadian Boxed Warn]
- Patients are advised to be aware that embryotoxicity can occur if treatment is not stopped.
- Both misoprostol and mifepristone are embryotoxic, and have been associated with fetal anomalies.
-
Hypersensitivity reactions
- Allergic reactions (e.g., angioedema, anaphylaxis, skin rash) have been seen with mifepristone/misoprostol; in some cases, angioedema occurred within 1 hour of misoprostol administration.
- Treat hypersensitive patients who present with symptoms or signs of hypersensitivity.
-
Insufficiency of the adrenals:
- Use with caution in the event of acute adrenal failure. This has not been tested.
- Mifepristone inhibits glucocorticoid activities; adjustments in adrenal substitute therapy may need to be made.
-
Asthma
- Bronchospasm may occur with prostaglandins or prostaglandin analogues. Patients with asthma should be restrained.
- Uncontrolled asthma is a reason to avoid this medication.
-
Cardiovascular disease
- After prostaglandin administration (including misoprostol), severe cardiovascular events were reported.
- Avoid use in women suffering from cardiovascular disease.
- Women with diabetes or high blood pressure should be cautious.
-
Diabetes:
- Avoid use in diabetic women (has not been tested).
-
Hepatic impairment
- Patients with hepatic impairment should not be given this medication (no studies have been done).
-
Malnutrition:
- If the patient is not well-nourished, (has not been studied), do not use.
-
Renal impairment
- Patients with impaired renal function should not be used (has not been tested).
-
Seizure disorder:
- Patients with seizure disorders should be closely monitored for any similarities or prostaglandins.
Mifepristone and misoprostol (United States: Not available): Drug Interaction
|
Alosetron |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron. |
|
Androgens |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. |
|
Antidiabetic Agents |
May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. |
|
Benperidol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Benperidol. |
|
Betamethasone (Ophthalmic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Betamethasone (Ophthalmic). |
|
Bictegravir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bictegravir. |
|
Bortezomib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Bosentan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. |
|
Bosentan |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. |
|
Brentuximab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. |
|
Brinzolamide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide. |
|
Budesonide (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Nasal). |
|
Budesonide (Oral Inhalation) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Oral Inhalation). |
|
Calcifediol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Calcifediol. |
|
Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabidiol. |
|
Cannabis |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. |
|
Cannabis |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. |
|
Carvedilol |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. |
|
Cinacalcet |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cinacalcet. |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CloZAPine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Codeine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Codeine. |
|
Corticosteroids (Orally Inhaled) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Exceptions: Beclomethasone (Oral Inhalation); Triamcinolone (Systemic). |
|
CYP2B6 Substrates (High risk with Inhibitors) |
MiFEPRIStone may increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Moderate) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
DexAMETHasone (Ophthalmic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of DexAMETHasone (Ophthalmic). |
|
Dexketoprofen |
May diminish the therapeutic effect of MiFEPRIStone. |
|
Digoxin |
MiFEPRIStone may increase the serum concentration of Digoxin. Management: Measure serum digoxin concentration 1-2 weeks following mifepristone initiation, and in accordance with normal clinical practice thereafter, adjusting dose as needed. |
|
Dofetilide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dofetilide. |
|
Doxercalciferol |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Doxercalciferol. |
|
Dronabinol |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. |
|
Dronabinol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol. |
|
Dutasteride |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride. |
|
Enfortumab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. |
|
Estrogen Derivatives |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Estrogen Derivatives. |
|
Evogliptin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Evogliptin. |
|
Fosnetupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fostamatinib |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fostamatinib. |
|
Galantamine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Galantamine. |
|
Grapefruit Juice |
May increase the serum concentration of MiFEPRIStone. |
|
Herbs (Hypoglycemic Properties) |
May enhance the hypoglycemic effect of HypoglycemiaAssociated Agents. |
|
Hypoglycemia-Associated Agents |
May enhance the hypoglycemic effect of other HypoglycemiaAssociated Agents. |
|
Ifosfamide |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. |
|
Imatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib. |
|
Imidafenacin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Imidafenacin. |
|
Lacosamide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide. |
|
Levamlodipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levamlodipine. |
|
Levobupivacaine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. |
|
Lornoxicam |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Lornoxicam. |
|
Lumefantrine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumefantrine. |
|
Maitake |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Meperidine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Meperidine. |
|
Monoamine Oxidase Inhibitors |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Naldemedine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naldemedine. |
|
Nalfurafine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nalfurafine. |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Ospemifene |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene. |
|
Oxybutynin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin. |
|
Parecoxib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Parecoxib. |
|
Paricalcitol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol. |
|
Pegvisomant |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Pimecrolimus |
CYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus. |
|
Polatuzumab Vedotin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be increased. |
|
Pranlukast |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast. |
|
Propafenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Prothionamide |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
QT-prolonging Agents (Highest Risk) |
QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Quinolones |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. |
|
Ramelteon |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ramelteon. |
|
Repaglinide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. |
|
Retapamulin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin. Management: Avoid this combination in patients less than 2 years old. No action is required in other populations. |
|
Rilpivirine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine. |
|
RomiDEPsin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of RomiDEPsin. |
|
Salicylates |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Selective Serotonin Reuptake Inhibitors |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Sibutramine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sibutramine. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
SORAfenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SORAfenib. |
|
Tasimelteon |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. |
|
Tenoxicam |
May diminish the therapeutic effect of MiFEPRIStone. |
|
Tetrahydrocannabinol |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. |
|
Tetrahydrocannabinol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol. |
|
Tetrahydrocannabinol and Cannabidiol |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Specifically, concentrations of tetrahydrocannabinol may be increased. |
|
Tetrahydrocannabinol and Cannabidiol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
TraMADol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraMADol. |
|
Upadacitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Upadacitinib. |
|
Vilanterol |
May increase the serum concentration of CYP3A4 Inhibitors (Strong). |
|
Vindesine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vindesine. |
|
Zolpidem |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zolpidem. |
|
Risk Factor D (Consider therapy modification) |
|
|
Abemaciclib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Abemaciclib. Management: In patients taking abemaciclib at a dose of 200 mg or 150 mg twice daily, reduce the dose to 100 mg twice daily when combined with strong CYP3A4 inhibitors. In patients taking abemaciclib 100 mg twice daily, decrease the dose to 50 mg twice daily. |
|
Alitretinoin (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alitretinoin (Systemic). Management: Consider reducing the alitretinoin dose to 10 mg when used together with strong CYP3A4 inhibitors. Monitor for increased alitretinoin effects/toxicities if combined with a strong CYP3A4 inhibitor. |
|
Almotriptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor. Avoid concurrent use in patients with impaired hepatic or renal function. |
|
ALPRAZolam |
|
|
ARIPiprazole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. |
|
ARIPiprazole Lauroxil |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. |
|
Avatrombopag |
MiFEPRIStone may increase the serum concentration of Avatrombopag. Management: Management of this interaction varies based on avatrombopag indication. Dose adjustments are required for patients using avatrombopag for chronic immune thrombocytopenia. See monograph for details. |
|
Bedaquiline |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline. Management: Limit duration of concurrent use of bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of continued use outweighs the possible risks. Monitor for toxic effects of bedaquiline. Exceptions discussed in separate monographs. |
|
Brexpiprazole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose 50% with strong CYP3A4 inhibitors; reduce to 25% of usual if used with both a moderate CYP3A4 inhibitor and a CYP2D6 inhibitor in patients not being treated for MDD, or strong CYP3A4 inhibitor used in a CYP2D6 poor metabolizer. |
|
Brigatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with strong CYP3A4 inhibitors when possible. If combination cannot be avoided, reduce the brigatinib dose by approximately 50%, rounding to the nearest tablet strength (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). |
|
Budesonide (Topical) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. |
|
BusPIRone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of BusPIRone. Management: Limit the buspirone dose to 2.5 mg daily and monitor patients for increased buspirone effects/toxicities if combined with strong CYP3A4 inhibitors. |
|
Cabazitaxel |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel. Management: Concurrent use of cabazitaxel with strong inhibitors of CYP3A4 should be avoided when possible. If such a combination must be used, consider a 25% reduction in the cabazitaxel dose. |
|
Cabozantinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib. Management: Avoid use of a strong CYP3A4 inhibitor with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. |
|
Cariprazine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cariprazine. Management: Cariprazine dose reductions of 50% are required; specific recommended management varies slightly for those stable on cariprazine versus those just starting cariprazine. See prescribing information or full interaction monograph for details. |
|
Ceritinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ceritinib. Management: If such combinations cannot be avoided, the ceritinib dose should be reduced by approximately one-third (to the nearest 150 mg). Resume the prior ceritinib dose after cessation of the strong CYP3A4 inhibitor. Exceptions discussed in separate monographs. |
|
Cilostazol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving strong inhibitors of CYP3A4. |
|
Colchicine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. |
|
Conivaptan |
May increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 600 mg/day when combined with conivaptan. Monitor for increased mifepristone toxicity regardless of dose or indication. |
|
Copanlisib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Copanlisib. Management: If concomitant use of copanlisib and strong CYP3A4 inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. Monitor patients for increased copanlisib effects/toxicities. |
|
Crizotinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib. Management: Avoid concomitant use of crizotinib and strong CYP3A4 inhibitors whenever possible. If combined use cannot be avoided, decrease the crizotinib dose to 250 mg daily. Exceptions are discussed in separate monographs. |
|
CYP2C9 Substrates (High risk with Inhibitors) |
MiFEPRIStone may increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 900 mg/day when combined with a strong CYP3A4 inhibitor. Monitor for increased mifepristone toxicity regardless of dose or indication. |
|
CYP3A4 Substrates (High risk with Inhibitors) |
MiFEPRIStone may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
Daclatasvir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Daclatasvir. Management: Decrease the daclatasvir dose to 30 mg once daily if combined with a strong CYP3A4 inhibitor. No dose adjustment is needed when daclatasvir is used with darunavir/cobicistat. |
|
Dasatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib. Management: This combination should be avoided if possible. If combined, dasatinib dose reductions are recommended. See full monograph for details. Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Delamanid |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Delamanid. Management: Increase ECG monitoring frequency if delamanid is combined with strong CYP3A4 inhibitors due to the risk for QTc interval prolongation. Continue frequent ECG assessments throughout full delamanid treatment period. Exceptions discussed separately. |
|
Diclofenac (Systemic) |
CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Diclofenac (Systemic). Management: Consider using a reduced dose of diclofenac when used together with moderate CYP2C9 inhibitors. Arthrotec (diclofenac and misoprostol) prescribing information recommends a maximum dose of 50 mg twice daily. |
|
DOCEtaxel |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOCEtaxel. Management: Avoid the concomitant use of docetaxel and strong CYP3A4 inhibitors when possible. If combined use is unavoidable, consider a 50% docetaxel dose reduction and monitor for increased docetaxel toxicities. |
|
DOXOrubicin (Conventional) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. |
|
Drospirenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Drospirenone. Management: Drospirenone use is contraindicated specifically when the strong CYP3A4 inhibitors atazanavir and cobicistat are administered concurrently. Caution should be used when drospirenone is coadministered with other strong CYP3A4 inhibitors. |
|
Duvelisib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor. |
|
Elagolix |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Elagolix. Management: Use of the elagolix 200 mg twice daily dose with a strong CYP3A4 inhibitor for longer than 1 month is not recommended. Limit combined use of the elagolix 150 mg once daily dose with a strong CYP3A4 inhibitor to a maximum of 6 months. |
|
Eliglustat |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. |
|
Encorafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and strong CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose. See monograph for details. |
|
Entrectinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Entrectinib. Management: Avoid strong CYP3A4 inhibitors during treatment with entrectinib. Reduce dose to 100 mg/day if combination cannot be avoided in adults and those 12 yrs of age or older with a BSA of at least 1.5 square meters. No alternative dosing provided for others. |
|
Erdafitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. |
|
Erlotinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). |
|
Estrogen Derivatives (Contraceptive) |
MiFEPRIStone may diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). MiFEPRIStone may increase the serum concentration of Estrogen Derivatives (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. |
|
Eszopiclone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). |
|
Etizolam |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Etizolam. Management: Consider use of lower etizolam doses when using this combination; specific recommendations concerning dose adjustment are not available. Monitor clinical response to the combination closely. |
|
Fedratinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fedratinib. Management: Consider alternatives when possible. If used together, decrease fedratinib dose to 200 mg/day. After the inhibitor is stopped, increase fedratinib to 300 mg/day for the first 2 weeks and then to 400 mg/day as tolerated. |
|
Fesoterodine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses greater than 4 mg daily in adult patients who are also receiving strong CYP3A4 inhibitors. |
|
Fluticasone (Oral Inhalation) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Monitor patients using such a combination more closely. |
|
Fluvastatin |
MiFEPRIStone may increase the serum concentration of Fluvastatin. Management: Use fluvastatin at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment. |
|
Fosamprenavir |
May increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 600 mg/day when combined with fosamprenavir. Monitor for increased mifepristone toxicity regardless of dose or indication. |
|
Gilteritinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Gilteritinib. Management: Consider alternatives to the use of a strong CYP3A4 inhibitor with gilteritinib. If the combination cannot be avoided, monitor more closely for evidence of gilteritinib toxicities. |
|
Glasdegib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Glasdegib. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor closely for evidence of QT interval prolongation and other adverse reactions to glasdegib. |
|
GuanFACINE |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination. |
|
Iloperidone |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor. |
|
Istradefylline |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Istradefylline. Management: Limit the maximum istradefylline dose to 20 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased istradefylline effects/toxicities. |
|
Ivacaftor |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for productspecific recommendations. |
|
Ivosidenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivosidenib. Management: Avoid use of a strong CYP3A4 inhibitor with ivosidenib whenever possible. When combined use is required, reduce the ivosidenib dose to 250 mg once daily. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs. |
|
Ixabepilone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. |
|
Larotrectinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inhibitors with larotrectinib. If this combination cannot be avoided, reduce the larotrectinib dose by 50%. Increase to previous dose after stopping the inhibitor after a period of 3 to 5 times the inhibitor half-life. |
|
Levomilnacipran |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran. Management: Do not exceed a maximum adult levomilnacipran dose of 80 mg/day in patients also receiving strong CYP3A4 inhibitors. |
|
Lorlatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with strong CYP3A4 inhibitors. If the combination cannot be avoided, reduce the lorlatinib dose from 100 mg once daily to 75 mg once daily, or from 75 mg once daily to 50 mg once daily. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Manidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inhibitors. If combined, monitor closely for increased manidipine effects and toxicities. Manidipine dose reductions may be required. |
|
Maraviroc |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4 inhibitors in patients with Clcr less than 30 mL/min. |
|
Midostaurin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and strong CYP3A4 inhibitors if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Exceptions are discussed in separate monographs. |
|
Mirodenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Mirodenafil. Management: Consider using a lower dose of mirodenafil when used with strong CYP3A4 inhibitors. Monitor for increased mirodenafil effects/toxicities with the use of this combination. |
|
Nilotinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Management: Avoid if possible. If combination needed, decrease nilotinib to 300 mg once/day for patients with resistant or intolerant Ph+ CML or to 200 mg once/day for patients with newly diagnosed Ph+ CML in chronic phase. Exceptions discussed in separate monograph. |
|
Olaparib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Olaparib. Management: Avoid use of strong CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 100 mg twice daily. |
|
OxyCODONE |
CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. |
|
Oxytocin |
MiSOPROStol may enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: The manufacturer of misoprostol recommends avoiding concomitant use with oxytocin. Misoprostol may augment effects of oxytocin, particularly when given within 4 hours of oxytocin initiation. |
|
Panobinostat |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat. Management: Reduce the panobinostat dose to 10 mg when it must be used with a strong CYP3A4 inhibitor. |
|
PAZOPanib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PAZOPanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib adult dose to 400 mg. Further dose reductions may also be required. |
|
Pexidartinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pexidartinib. Management: Avoid use of pexidartinib with strong CYP3A4 inhibitors if possible. If combined use cannot be avoided, the pexidartinib dose should be reduced. Decrease 800 mg or 600 mg daily doses to 200 mg twice daily. Decrease doses of 400 mg/day to 200 mg/day. |
|
Pimavanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. |
|
Piperaquine |
CYP3A4 Inhibitors (Strong) may enhance the QTc-prolonging effect of Piperaquine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Piperaquine. Management: Avoid concomitant use of piperaquine and strong CYP3A4 inhibitors when possible. If the combination cannot be avoided, frequent ECG monitoring is recommended due to the risk for QTc prolongation. Exceptions are discussed separately. |
|
PONATinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib. Management: Per ponatinib U.S. prescribing information, the adult starting dose of ponatinib should be reduced to 30 mg daily during treatment with any strong CYP3A4 inhibitor. |
|
Progestins (Contraceptive) |
MiFEPRIStone may diminish the therapeutic effect of Progestins (Contraceptive). MiFEPRIStone may increase the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. |
|
QUEtiapine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of regular dose after starting strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Exceptions discussed separately. |
|
Reboxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Reboxetine. |
|
Ribociclib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ribociclib. Management: Avoid use of ribociclib with strong CYP3A4 inhibitors when possible; if combined use cannot be avoided, reduce ribociclib dose to 400 mg once daily. Exceptions are discussed in separate monographs. |
|
Ruxolitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib. Management: This combination should be avoided under some circumstances. See monograph for details. |
|
SAXagliptin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SAXagliptin. Management: Limit the saxagliptin dose to 2.5 mg daily when combined with strong CYP3A4 inhibitors. When using the saxagliptin combination products saxagliptin/dapagliflozin or saxagliptin/dapagliflozin/metformin, avoid use with strong CYP3A4 inhibitors. |
|
Sildenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sildenafil. Management: Use of sildenafil for pulmonary hypertension should be avoided with strong CYP3A4 inhibitors. When used for erectile dysfunction, starting adult dose should be reduced to 25 mg. Maximum adult dose with ritonavir or cobicistat is 25 mg per 48 hours. |
|
Solifenacin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Solifenacin. Management: Limit solifenacin doses to 5 mg daily when combined with strong CYP3A4 inhibitors. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
SUFentanil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUFentanil. Management: If a strong CYP3A4 inhibitor is initiated in a patient on sufentanil, consider a sufentanil dose reduction and monitor for increased sufentanil effects and toxicities (eg, respiratory depression). |
|
SUNItinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, sunitinib dose decreases are recommended, and vary by indication. See full monograph for details. |
|
Tadalafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil. Management: Recommendations regarding use of tadalafil in patients also receiving strong CYP3A4 inhibitors may vary based on indication and/or international labeling. Consult appropriate product labeling. |
|
Temsirolimus |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inhibitors whenever possible. If combined, decrease temsirolimus dose to 12.5 mg per week and monitor patients for increased temsirolimus effects and toxicities. |
|
Tezacaftor |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tezacaftor. Management: When combined with strong CYP3A4 inhibitors, tezacaftor/ivacaftor should be administered in the morning, twice a week, approximately 3 to 4 days apart. No evening doses of ivacaftor alone should be administered. |
|
Thiotepa |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inhibitors. If concomitant use is unavoidable, monitor for adverse effects and decreased efficacy. |
|
Tofacitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib. Management: Tofacitinib dose reductions are recommended when combined with strong CYP3A4 inhibitors. Recommended dose adjustments vary by tofacitinib formulation and therapeutic indication. See full monograph for details. |
|
Tolterodine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. |
|
Toremifene |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Management: Use of toremifene with strong CYP3A4 inhibitors should be avoided if possible. If coadministration is necessary, monitor for increased toremifene toxicities, including QTc interval prolongation. Exceptions are discussed in separate monograph. |
|
TraZODone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. |
|
Valbenazine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. |
|
Vardenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. See full drug interaction monograph for details. |
|
Vemurafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with strong CYP3A4 inhibitors when possible. Consider use of an alternative that is not a strong inhibitor of CYP3A4 as clinically appropriate. |
|
Venetoclax |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Venetoclax. Management: This combination is contraindicated during venetoclax initiation and ramp-up in patients with CLL/SLL. Reduced venetoclax doses are required during ramp-up for patients with AML, and reduced doses are required for all patients during maintenance therapy. |
|
Vilazodone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg daily in patients receiving strong CYP3A4 inhibitors. The original vilazodone dose can be resumed following discontinuation of the strong CYP3A4 inhibitor. |
|
Voxelotor |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inhibitors. If concomitant use is unavoidable, reduce the voxelotor dose to 1,000 mg once daily. |
|
Zanubrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. |
|
Zopiclone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. |
|
Zuclopenthixol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor for increased zuclopenthixol levels/toxicity. |
|
Risk Factor X (Avoid combination) |
|
|
Acalabrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Acalabrutinib. |
|
Ado-Trastuzumab Emtansine |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component. |
|
Alfuzosin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. |
|
Antacids |
May enhance the adverse/toxic effect of MiSOPROStol. More specifically, concomitant use with magnesium-containing antacids may increase the risk of diarrhea. Management: Avoid concomitant use of misoprostol and magnesium-containing antacids. In patients requiring antacid therapy, employ magnesium-free preparations. Monitor for increased adverse effects (e.g., diarrhea, dehydration). Exceptions: Aluminum Hydroxide; Calcium Carbonate; Potassium Bicarbonate; Sodium Bicarbonate. |
|
Anticoagulants |
MiFEPRIStone may enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. |
|
Aprepitant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Aprepitant. |
|
Astemizole |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Asunaprevir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Asunaprevir. |
|
Avanafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil. |
|
Avapritinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Avapritinib. |
|
Axitinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A inhibitor whenever possible. If a strong CYP3A inhibitor must be used with axitinib, a 50% axitinib dose reduction is recommended. |
|
Barnidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Barnidipine. |
|
Blonanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Blonanserin. |
|
Bosutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib. |
|
Bromocriptine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Bromocriptine. |
|
Budesonide (Systemic) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic). |
|
Carbetocin |
MiSOPROStol may enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. |
|
Cobimetinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Cobimetinib. |
|
Corticosteroids (Systemic) |
MiFEPRIStone may diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. |
|
CycloSPORINE (Systemic) |
MiFEPRIStone may increase the serum concentration of CycloSPORINE (Systemic). Management: Avoid cyclosporine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
CYP3A4 Inducers (Strong) |
May decrease the serum concentration of MiFEPRIStone. |
|
Dabrafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dabrafenib. |
|
Dapoxetine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine. |
|
Dihydroergotamine |
MiFEPRIStone may increase the serum concentration of Dihydroergotamine. Management: Avoid dihydroergotamine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Domperidone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Dronedarone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Eletriptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eletriptan. |
|
Eplerenone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. |
|
Ergotamine |
MiFEPRIStone may increase the serum concentration of Ergotamine. Management: Avoid ergotamine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Everolimus |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. |
|
FentaNYL |
MiFEPRIStone may increase the serum concentration of FentaNYL. Management: Avoid fentanyl during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Flibanserin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Flibanserin. |
|
Fluticasone (Nasal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Nasal). |
|
Fosaprepitant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fosaprepitant. |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Halofantrine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Ibrutinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ibrutinib. Management: Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for 7 days or less), interrupt ibrutinib therapy until the strong CYP3A4 inhibitor is discontinued. |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Irinotecan Products |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. |
|
Isavuconazonium Sulfate |
CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inhibitors (Strong) may increase isavuconazole serum concentrations. Management: Combined use is considered contraindicated per US labeling. Lopinavir/ritonavir (and possibly other uses of ritonavir doses less than 400 mg every 12 hours) is treated as a possible exception to this contraindication despite strongly inhibiting CYP3A4. |
|
Ivabradine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivabradine. |
|
Lapatinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib. Management: If an overlap in therapy cannot be avoided, consider reducing lapatinib adult dose to 500 mg/day during, and within 1 week of completing, treatment with the strong CYP3A4 inhibitor. |
|
Lefamulin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets and strong inhibitors of CYP3A4. |
|
Lemborexant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lemborexant. |
|
Lercanidipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine. |
|
Lomitapide |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide. |
|
Lovastatin |
MiFEPRIStone may increase the serum concentration of Lovastatin. Management: Avoid lovastatin during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Lumateperone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lumateperone. |
|
Lurasidone |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. |
|
Macitentan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan. |
|
Naloxegol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Naloxegol. |
|
Neratinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Neratinib. |
|
NiMODipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of NiMODipine. |
|
Nisoldipine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. |
|
Palbociclib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Palbociclib. |
|
Phenylbutazone |
May diminish the therapeutic effect of MiFEPRIStone. Management: Phenylbutazone should not be used for 8-12 days following mifepristone administration. |
|
Pimozide |
MiFEPRIStone may enhance the QTc-prolonging effect of Pimozide. MiFEPRIStone may increase the serum concentration of Pimozide. Management: Avoid pimozide during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
QuiNIDine |
MiFEPRIStone may enhance the QTc-prolonging effect of QuiNIDine. MiFEPRIStone may increase the serum concentration of QuiNIDine. Management: Avoid quinidine during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Radotinib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Radotinib. |
|
Ranolazine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. |
|
Red Yeast Rice |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. |
|
Regorafenib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib. |
|
Rupatadine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rupatadine. |
|
Salmeterol |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. |
|
Silodosin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin. |
|
Simeprevir |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir. |
|
Simvastatin |
MiFEPRIStone may increase the serum concentration of Simvastatin. Management: Avoid simvastatin during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Siponimod |
MiFEPRIStone may increase the serum concentration of Siponimod. Management: Coadministration of siponimod with miferpristone, a moderate inhibitor of CYP2C9 and a strong inhibitor of CYP3A4 is not recommended. |
|
Sirolimus |
MiFEPRIStone may increase the serum concentration of Sirolimus. Management: Avoid sirolimus during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Sonidegib |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Sonidegib. |
|
St John's Wort |
May decrease the serum concentration of MiFEPRIStone. |
|
Suvorexant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant. |
|
Tacrolimus (Systemic) |
MiFEPRIStone may enhance the QTc-prolonging effect of Tacrolimus (Systemic). MiFEPRIStone may increase the serum concentration of Tacrolimus (Systemic). Management: Avoid tacrolimus during and 2 weeks following mifepristone for treatment of hyperglycemia in Cushing's syndrome. The interaction magnitude could be lower with single doses used to terminate pregnancy, but neither effect has been studied clinically. |
|
Tamsulosin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. |
|
Terfenadine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Ticagrelor |
CYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. |
|
Tolvaptan |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan. |
|
Trabectedin |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin. |
|
Triazolam |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Triazolam. |
|
Ubrogepant |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ubrogepant. |
|
Udenafil |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Udenafil. |
|
Ulipristal |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combo should be monitored for ulipristal toxicity. |
|
VinCRIStine (Liposomal) |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of VinCRIStine (Liposomal). |
|
Vinflunine |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vinflunine. |
|
Vorapaxar |
CYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar. |
Monitoring parameters:
- Before starting the procedure, confirm pregnancy and Rh status;
- Evaluate hemoglobin and hematocrit if anemia is suspected.
- After the procedure:
- Clinical examination, human chorionic gonadotropin (HCG) testing, and/or ultrasound 7 to 14 days after administration of mifepristone/misoprostol to validate complete abortion of pregnancy;
- Hemoglobin, hematocrit, and red blood cell count in cases of heavy bleeding.
- Consider CBC in any patient who reports revulsion, vomiting, or diarrhea and weakness with or without abdominal pain, and without fever or other signs of infection more than 24 hours after administration.
How to administer Mifepristone and Misoprostol?
Oral: To be administered under the supervision of a certified prescriber. Provide the patient with a phone number and the name of the provider to contact in case of queries or emergencies.
Mechanism of action of Mifepristone and Misoprostol:
Mifepristone, an artificial steroid, competitively binds with the intracellular progesterone-receptor. This blocks the effects of progesterone.
This causes contraction-inducing activity within the myometrium when it is used for abortion.
Mifepristone can also cause cervical ripening. Misoprostol, a synthetic prostaglandin E1 substitute that causes contractions in myometrium and relaxation in the cervix, is known as Misoprostol.
See individual agents (Mifepristone and Misoprostol)
International Brands of Mifepristone and misoprostol:
- Mifegymiso
- Abortom
- Medabon
- MS-2 Step
- Mtprost
- Sunmedabon
Mifepristone and Misoprostol Brand Names in Pakistan:
No Brands Available in Pakistan.
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