Midone

Midone Medicine

Contraindications

See also:
What is the most important information I should know about Midone?

You should not use this medication if you are allergic to Midone or phenobarbital (Luminal, Solfoton), or if you have porphyria.

Before taking this medication, tell your doctor if you are allergic to any drugs, or if you are pregnant or breast-feeding.

You may have thoughts about suicide while taking this medication. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

If you are taking Midone to prevent seizures, keep taking the medication even if you feel fine. You may have an increase in seizures if you stop taking Midone. Follow your doctor's instructions.

To be sure this medication is helping your condition, your blood may need to be tested on a regular basis. Do not miss any scheduled appointments.

Do not change your dose of Midone without your doctor's advice. Tell your doctor if the medication does not seem to work as well in treating your condition.

Carry an ID card or wear a medical alert bracelet stating that you are taking Midone, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are taking a seizure medication.



Undesirable effects

See also:
What are the possible side effects of Midone?

Applies to Midone: oral suspension, oral tablet

In addition to its needed effects, some unwanted effects may be caused by Midone (the active ingredient contained in Midone). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking Midone:

More common:

  • Shakiness and unsteady walk
  • unsteadiness, trembling, or other problems with muscle control or coordination
Less common:
  • Unusual excitement or restlessness (especially in children and in the elderly)
Rare
  • Chills
  • cough or hoarseness
  • fainting spells
  • fever and sore throat
  • fever with or without chills
  • general feeling of tiredness or weakness
  • irregular heartbeat
  • lower back or side pain
  • painful or difficult urination
  • pale skin
  • shortness of breath
  • skin rash
  • sores, ulcers, or white spots on the lips or in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness

If any of the following symptoms of overdose occur while taking Midone, get emergency help immediately:

Symptoms of overdose:

  • Confusion
  • continuous, uncontrolled rolling eye movements
  • double vision
  • troubled breathing
Minor Side Effects

Some of the side effects that can occur with Midone may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

  • Clumsiness or unsteadiness
  • dizziness or lightheadedness
  • feeling of constant movement of self or surroundings
  • sensation of spinning
Less common:
  • Decreased sexual ability
  • drowsiness
  • loss of appetite
  • mood or mental changes
  • nausea or vomiting

Therapeutic indications

An indication is a term used for the list of condition or symptom or illness for which the medicine is prescribed or used by the patient. For example, acetaminophen or paracetamol is used for fever by the patient, or the doctor prescribes it for a headache or body pains. Now fever, headache and body pains are the indications of paracetamol. A patient should be aware of the indications of medications used for common conditions because they can be taken over the counter in the pharmacy meaning without prescription by the Physician.

Midone, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.

Midone is used alone or in combination with other medicines, to control seizures (convulsions) in the treatment of epilepsy. Midone is an anticonvulsant that works in the brain tissue to stop seizures.

Midone is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, Midone is used in certain patients with the following medical conditions:

  • Essential tremor.

Name of the medicinal product

Midone

Qualitative and quantitative composition

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Midone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of Midone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)

Special warnings and precautions for use

Use Midone as directed by your doctor. Check the label on the medicine for exact dosing instructions.

  • Take Midone by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
  • Take Midone on a regular schedule to get the most benefit from it.
  • Taking Midone at the same time each day will help you remember to take it.
  • Do not suddenly stop taking Midone. You may have an increased risk of side effects (eg, seizures). If you need to stop Midone or add a new medicine, your doctor will gradually lower your dose.
  • Continue to take Midone even if you feel well. Do not miss any doses.
  • If you miss a dose of Midone, take it as soon as possible. If it is within 1 hour of your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Midone.

There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.Use: Labeled Indications

Management of grand mal, psychomotor, and focal seizures

Off Label UsesEssential tremor

Data from a systematic review including 14 studies (3 randomized controlled trials, 9 crossover studies, and 2 case series) support the use of Midone for the treatment of essential tremor in some populations.

Dosage (Posology) and method of administration

Adult Dosage

Patients 8 years of age and older who have received no previous treatment may be started on Midone according to the following regimen using either 50 mg or scored 250 mg Midone tablets:

Days 1 to 3: 100 to 125 mg at bedtime.

Days 4 to 6: 100 to 125 mg b.i.d.

Days 7 to 9: 100 to 125 mg t.i.d.

Day 10 to

Maintenance: 250 mg t.i.d.

For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg Midone tablets in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.

INITIAL: ADULTS AND CHILDREN OVER 8

KEY:•=50 mg tablet; ••=250 mgtablet
DAY 1 2 3 4 5 6
AM •• •• ••
NOON
PM •• ••
DAY 7 8 9 10 11 12
AM • • •• •• Adjust to Maintenance
NOON • • •• ••
PM • • •• ••

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of Midone may be necessary for optimal dosage adjustment. The clinically effective serum level for Midone is between 5 to 12 μg/mL.

In Patients Already Receiving Other Anticonvulsants

Midone should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with Midone alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.

Pediatric Dosage

For children under 8 years of age, the following regimen may be used:

Days 1 to 3: 50 mg at bedtime.

Days 4 to 6: 50 mg b.i.d.

Days 7 to 9: 100 mg b.i.d.

Day 10 to

Maintenance: 125 mg t.i.d. to 250 mg t.i.d.

For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or, 10 to 25 mg/kg/day in divided doses.

How suppliedMidone Tablets

Each square-shaped, scored, yellow tablet, identified by “Midone 250” and an embossed M, contains 250 mg of Midone, in bottles of 100 (NDC 66490-691-10)

Each square-shaped, scored, white tablet, identified by “Midone 50” and an embossed M, contains 50 mg of Midone, in bottles of 100 (NDC 66490-690-10)

Store at 20°C-25°C (68°F-77°F).

.

Dispense in a tight, light-resistant container with a child-resistant closure.

Manufactured by: Piramal Enterprises Limited, Plot No. 67-70, Sector - 2, Pithampur, 454775, Dist. Dhar, Madhya Pradesh, INDIA. Distributed by: Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA. Revised: Sep 2012.

Interaction with other medicinal products and other forms of interaction

See also:
What other drugs will affect Midone?

Abemaciclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. Consider therapy modification

Acalabrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Consider therapy modification

Acetaminophen: Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Monitor therapy

Afatinib: Midone may decrease the serum concentration of Afatinib. Management: Per US labeling: if requiring chronic use of Midone, increase afatinib dose by 10 mg as tolerated; reduce to original afatinib dose 2-3 days after stopping primidonel. Per Canadian labeling: avoid combination if possible. Consider therapy modification

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Alpelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alpelisib. Avoid combination

Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Apalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apalutamide. Monitor therapy

Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Consider therapy modification

Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Avoid combination

Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Avoid combination

ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification

ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Consider therapy modification

Artemether: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether. Avoid combination

Asunaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir. Avoid combination

Avapritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avapritinib. Avoid combination

Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Avoid combination

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: Midone may enhance the adverse/toxic effect of Barbiturates. Midone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy. Monitor therapy

Bazedoxifene: Midone may decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Monitor therapy

Bedaquiline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Avoid combination

Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Monitor therapy

Benzhydrocodone: Midone may enhance the CNS depressant effect of Benzhydrocodone. Midone may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Specifically, serum concentrations of hydrocodone may be decreased. Management: Avoid use of benzhydrocodone and primidonel when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased benzhydrocodone efficacy and withdrawal if combined. Consider therapy modification

Beta-Blockers: Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Monitor therapy

Bictegravir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bictegravir. Management: Rifampin is specifically contraindicated, and the use of carbamazepine, phenytoin, or phenobarbital is not recommended when alternatives are acceptable Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: Barbiturates may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Avoid combination

Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Consider therapy modification

Brigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib. Avoid combination

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: Midone may enhance the CNS depressant effect of Buprenorphine. Midone may decrease the serum concentration of Buprenorphine. Management: Avoid use of buprenorphine and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased buprenorphine efficacy and withdrawal if combined. Consider therapy modification

BuPROPion: CYP2B6 Inducers (Weak) may decrease the serum concentration of BuPROPion. Monitor therapy

BusPIRone: CYP3A4 Inducers (Strong) may decrease the serum concentration of BusPIRone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed. Consider therapy modification

Cabazitaxel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabazitaxel. Monitor therapy

Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Consider therapy modification

Calcifediol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. Monitor therapy

Calcium Channel Blockers: Barbiturates may increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Exceptions: Clevidipine. Monitor therapy

Canagliflozin: Midone may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 200 mg/day in patients tolerating 100 mg/day. A further increase to 300 mg/day can be considered in patients with an estimated glomerular filtration rate (GFR) of 60 mL/min/1.73 m2 or greater. Consider therapy modification

Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Monitor therapy

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CarBAMazepine. Monitor therapy

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of Midone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Midone. Exceptions: Brinzolamide; Dorzolamide. Monitor therapy

Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Avoid combination

Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Avoid combination

Chloramphenicol (Systemic): May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol (Systemic). Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE. Monitor therapy

Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Consider therapy modification

Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Clindamycin (Systemic). Refer to the specific clindamycin (systemic) - rifampin drug interaction monograph for information concerning that combination. Monitor therapy

CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Management: Avoid use with strong CYP3A4 inducers when possible. If combined, monitor patients closely and consider clozapine dose increases. Clozapine dose reduction and further monitoring may be required when strong CYP3A4 inducers are discontinued. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Cobicistat: Midone may decrease the serum concentration of Cobicistat. Avoid combination

Cobimetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. Avoid combination

Codeine: Midone may enhance the CNS depressant effect of Codeine. Midone may decrease the serum concentration of Codeine. Management: Avoid use of codeine and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased codeine efficacy and withdrawal if combined. Consider therapy modification

Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Avoid combination

Corticosteroids (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE. Monitor therapy

Cosyntropin: May enhance the hepatotoxic effect of Midone. Monitor therapy

Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Avoid combination

CycloSPORINE (Systemic): Barbiturates may increase the metabolism of CycloSPORINE (Systemic). Consider therapy modification

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Exceptions: Benzhydrocodone; Buprenorphine; CarBAMazepine; Etizolam; HYDROcodone; Mirtazapine; TraMADol; Zolpidem. Consider therapy modification

Dabigatran Etexilate: Midone may decrease the serum concentration of Dabigatran Etexilate. Monitor therapy

Dabrafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dabrafenib. Monitor therapy

Daclatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. Avoid combination

Dasabuvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir. Avoid combination

Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Consider therapy modification

Deflazacort: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

Delamanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. Avoid combination

DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of DexAMETHasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Consider therapy modification

Dexmethylphenidate: May increase serum concentrations of the active metabolite(s) of Midone. Specifically, phenobarbital concentrations could become elevated. Dexmethylphenidate may increase the serum concentration of Midone. Monitor therapy

Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. Avoid combination

Diethylstilbestrol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Diethylstilbestrol. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dolutegravir: Midone may decrease the serum concentration of Dolutegravir. Specifically, the Midone metabolite phenobarbital may decrease Dolutegravir serum concentrations. Avoid combination

Doravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine. Avoid combination

Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inducers in patients treated with doxorubicin. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Avoid combination

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Duvelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib. Avoid combination

Elagolix: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix. Monitor therapy

Elbasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elbasvir. Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Avoid combination

Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Avoid combination

Encorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Encorafenib. Avoid combination

Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy

Entrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Entrectinib. Avoid combination

Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Consider therapy modification

Eravacycline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Consider therapy modification

Erdafitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erdafitinib. Avoid combination

Erlotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib. Management: Avoid combination if possible. If combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Eslicarbazepine: Midone may decrease the serum concentration of Eslicarbazepine. (based on studies with phenobarbital) Monitor therapy

Estriol (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Estrogen Derivatives (Contraceptive): Barbiturates may diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Consider therapy modification

Etizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. Monitor therapy

Etoposide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Consider therapy modification

Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Consider therapy modification

Etravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine. Avoid combination

Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers if possible. If coadministration cannot be avoided, double the daily dose of everolimus using increments of 5 mg or less. Monitor everolimus serum concentrations closely when indicated. Consider therapy modification

Evogliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin. Monitor therapy

Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. Consider therapy modification

Fedratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fedratinib. Avoid combination

Felbamate: May increase serum concentrations of the active metabolite(s) of Midone. Specifically, phenobarbital concentrations may increase. Midone may decrease the serum concentration of Felbamate. Management: In patients receiving Midone, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily and reduce Midone dose by 20%. Monitor for increased phenobarbital concentrations/effects and decreased felbamate concentrations/effects. Consider therapy modification

FentaNYL: Midone may enhance the CNS depressant effect of FentaNYL. Midone may decrease the serum concentration of FentaNYL. Management: Avoid use of fentanyl and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased fentanyl efficacy and withdrawal if combined. Consider therapy modification

Flibanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Folic Acid: May decrease the serum concentration of Midone. Additionally, folic acid may decrease concentrations of active metabolites of Midone (e.g., phenobarbital). Monitor therapy

Fosaprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Avoid combination

Fosnetupitant: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Avoid combination

Fosphenytoin: May increase the metabolism of Midone. The ratio of Midone:phenobarbital is thus changed. Monitor therapy

Fostamatinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Avoid combination

Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Consider therapy modification

Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Avoid combination

Gestrinone: Midone may decrease the serum concentration of Gestrinone. Monitor therapy

Glasdegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib. Avoid combination

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grazoprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Grazoprevir. Avoid combination

Griseofulvin: Barbiturates may decrease the serum concentration of Griseofulvin. Monitor therapy

GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a strong CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating strong CYP3A4 inducer therapy in a patient already taking guanfacine. Consider therapy modification

Hemin: Barbiturates may diminish the therapeutic effect of Hemin. Avoid combination

HYDROcodone: Midone may enhance the CNS depressant effect of HYDROcodone. Midone may decrease the serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined. Consider therapy modification

Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of Barbiturates. Management: Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination. Consider therapy modification

Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Avoid combination

Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Avoid combination

Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Consider therapy modification

Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Avoid combination

Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Avoid combination

Istradefylline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Istradefylline. Avoid combination

Itraconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Avoid combination

Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Avoid combination

Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Avoid combination

Ivosidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivosidenib. Avoid combination

Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m (given as a 4-hour infusion), as tolerated, should be considered. Consider therapy modification

Ixazomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

LamoTRIgine: May enhance the adverse/toxic effect of Midone. Specifically, the risk for hematologic toxicities may be increased. Midone may decrease the serum concentration of LamoTRIgine. Management: For patients taking Midone without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. Consider therapy modification

Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Consider therapy modification

Larotrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inducers with larotrectinib. If this combination cannot be avoided, double the larotrectinib dose. Reduced to previous dose after stopping the inducer after a period of 3 to 5 times the inducer half-life. Consider therapy modification

Ledipasvir: Midone may decrease the serum concentration of Ledipasvir. Avoid combination

Lefamulin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with strong CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lemborexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lemborexant. Avoid combination

Letermovir: May increase the serum concentration of UGT1A1 Inducers. Avoid combination

Leucovorin Calcium-Levoleucovorin: May decrease the serum concentration of Midone. Additionally, leucovorin/levoleucovorin may decrease concentrations of active metabolites of Midone (e.g., phenobarbital). Monitor therapy

LevETIRAcetam: Midone may decrease the serum concentration of LevETIRAcetam. Monitor therapy

Levomefolate: May decrease serum concentrations of the active metabolite(s) of Midone. Levomefolate may decrease the serum concentration of Midone. Monitor therapy

Levomethadone: Midone may decrease the serum concentration of Levomethadone. Monitor therapy

LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Lorlatinib: CYP3A4 Inducers (Strong) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. Avoid combination

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Avoid combination

Lumateperone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumateperone. Avoid combination

Lumefantrine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine. Avoid combination

Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Avoid combination

Macimorelin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macimorelin. Avoid combination

Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Avoid combination

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Manidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Consider therapy modification

Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. Consider therapy modification

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Midone: Midone may decrease the serum concentration of Midone. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methoxyflurane: Barbiturates may enhance the nephrotoxic effect of Methoxyflurane. Barbiturates may increase the metabolism of Methoxyflurane. Avoid combination

Methylfolate: May decrease the serum concentration of Midone. Monitor therapy

Methylphenidate: May increase serum concentrations of the active metabolite(s) of Midone. Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the serum concentration of Midone. Monitor therapy

MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification

MetroNIDAZOLE (Systemic): Midone may decrease the serum concentration of MetroNIDAZOLE (Systemic). Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May enhance the CNS depressant effect of Barbiturates. Mianserin may diminish the therapeutic effect of Barbiturates. Barbiturates may decrease the serum concentration of Mianserin. Avoid combination

Midostaurin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. Avoid combination

MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. Avoid combination

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Consider therapy modification

Mirtazapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirtazapine. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Barbiturates. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naldemedine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. Avoid combination

Nalmefene: Midone may decrease the serum concentration of Nalmefene. Monitor therapy

Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Avoid combination

Neratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib. Avoid combination

Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Avoid combination

NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Avoid combination

Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Avoid combination

NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Avoid combination

Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Avoid combination

OLANZapine: CYP1A2 Inducers (Weak) may decrease the serum concentration of OLANZapine. Monitor therapy

Olaparib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Osilodrostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osilodrostat. Monitor therapy

Osimertinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. Consider therapy modification

OXcarbazepine: CYP3A4 Inducers (Strong) may decrease the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Monitor therapy

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: Midone may enhance the CNS depressant effect of OxyCODONE. Midone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Consider therapy modification

Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Avoid combination

Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Avoid combination

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

PAZOPanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. Avoid combination

Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Pexidartinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pexidartinib. Avoid combination

Phenytoin: May increase the metabolism of Midone. The ratio of Midone:phenobarbital is thus changed. Monitor therapy

Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Avoid combination

Piperaquine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Piperaquine. Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pitolisant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant. Management: For patients who are stable on pitolisant doses of 8.9 mg or 17.8 mg/day and who are also taking a strong CYP3A4 inducer, increase the pitolisant dose over 7 days to double the original dose (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Consider therapy modification

Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Monitor therapy

PONATinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Use of praziquantel with strong CYP3A4 inducers is contraindicated. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Avoid combination

PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). Monitor therapy

PredniSONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. Monitor therapy

Pretomanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pretomanid. Avoid combination

Progestins (Contraceptive): Midone may diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification

Propacetamol: Barbiturates may increase the metabolism of Propacetamol. This may 1) diminish the desired effects of propacetamol; and 2) increase the risk of liver damage. Monitor therapy

Propafenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. Monitor therapy

Pyridoxine: May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) Monitor therapy

QUEtiapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. Consider therapy modification

QuiNIDine: Midone may decrease the serum concentration of QuiNIDine. Monitor therapy

Radotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Consider therapy modification

Ramelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ramelteon. Monitor therapy

Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Avoid combination

Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Monitor therapy

Regorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Avoid combination

Ribociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib. Avoid combination

Rifamycin Derivatives: May increase the metabolism of Barbiturates. Monitor therapy

Rilpivirine: Midone may decrease the serum concentration of Rilpivirine. Avoid combination

Rimegepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rimegepant. Avoid combination

RisperiDONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of RisperiDONE. Management: Consider increasing the dose of oral risperidone (to no more than double the original dose) if a strong CYP3A4 inducer is initiated. For patients on IM risperidone, consider an increased IM dose or supplemental doses of oral risperidone. Consider therapy modification

Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Avoid combination

Roflumilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Avoid combination

Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Management: Avoid rolapitant use in patients requiring chronic administration of strong CYP3A4 inducers. Monitor for reduced rolapitant response and the need for alternative or additional antiemetic therapy even with shorter-term use of such inducers. Consider therapy modification

RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Avoid combination

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: Midone may decrease the serum concentration of Rufinamide. Monitor therapy

Ruxolitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib. Monitor therapy

SAXagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sertraline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline. Monitor therapy

Simeprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. Avoid combination

Sirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus. Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sofosbuvir: Midone may decrease the serum concentration of Sofosbuvir. Avoid combination

Somatostatin Acetate: May enhance the adverse/toxic effect of Barbiturates. Specifically, Somatostatin Acetate may enhance or prolong Barbiturate effects, including sedative effects. Avoid combination

Sonidegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. Avoid combination

SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Avoid combination

SUFentanil: Midone may enhance the CNS depressant effect of SUFentanil. Midone may decrease the serum concentration of SUFentanil. Management: Avoid use of sufentanil and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased sufentanil efficacy and withdrawal if combined. Consider therapy modification

Sulthiame: Midone may enhance the adverse/toxic effect of Sulthiame. Monitor therapy

SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, sunitinib dose increases are recommended, and vary by indication. See full monograph for details. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Consider therapy modification

Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Strong) may decrease the serum concentration of Tamoxifen. Management: Consider alternatives to concomitant use of strong CYP3A4 inducers and tamoxifen. If the combination cannot be avoided, monitor for reduced therapeutic effects of tamoxifen. Consider therapy modification

Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Avoid combination

Tazemetostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tazemetostat. Avoid combination

Telithromycin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Telithromycin. Avoid combination

Temsirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Consider therapy modification

Teniposide: Barbiturates may decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

Tenofovir Alafenamide: Midone may decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tezacaftor and Ivacaftor. Avoid combination

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Theophylline Derivatives: Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

Thiotepa: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Strong) may decrease the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Consider therapy modification

Thiothixene: Midone may decrease the serum concentration of Thiothixene. Monitor therapy

TiaGABine: CYP3A4 Inducers (Strong) may decrease the serum concentration of TiaGABine. Management: Approximately 2-fold higher tiagabine doses and a more rapid dose titration will likely be required in patients concomitantly taking a strong CYP3A4 inducer. Consider therapy modification

Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Avoid combination

Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Avoid combination

Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: Avoid concurrent use of strong CYP3A4 inducers with the Jynarque brand of tolvaptan. For patients receiving the Samsca brand of tolvaptan, monitor patient response to tolvaptan and adjust tolvaptan dose if required. Consider therapy modification

Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Avoid combination

Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Avoid combination

TraMADol: Midone may enhance the CNS depressant effect of TraMADol. Midone may decrease the serum concentration of TraMADol. Management: Avoid use of tramadol and Midone when possible. Monitor for respiratory depression/sedation. Because Midone is also a strong CYP3A4 inducer, monitor for decreased tramadol efficacy and withdrawal if combined. Consider therapy modification

Tricyclic Antidepressants: Barbiturates may increase the metabolism of Tricyclic Antidepressants. Management: Monitor for decreased efficacy of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. Tricyclic antidepressant dose adjustments are likely required. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tropisetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. Monitor therapy

Ubrogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ubrogepant. Avoid combination

Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Monitor therapy

Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Avoid combination

Ulipristal: Barbiturates may decrease the serum concentration of Ulipristal. Avoid combination

Upadacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Upadacitinib. Avoid combination

Valbenazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Avoid combination

Valproate Products: May decrease the metabolism of Midone. More specifically, the metabolism of phenobarbital, Midone's primary active metabolite, may be decreased. Midone may increase the serum concentration of Valproate Products. Monitor therapy

Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Avoid combination

Velpatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Avoid combination

Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid coadministartion of vemurafenib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after discontinuation of strong CYP3A4 inducer. Consider therapy modification

Venetoclax: CYP3A4 Inducers (Strong) may decrease the serum concentration of Venetoclax. Avoid combination

Vilazodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1-2 weeks after inducer discontinuation. Consider therapy modification

VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Avoid combination

Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the metabolism of Vitamin K Antagonists. Management: Monitor INR more closely. An anticoagulant dose increase may be needed after a barbiturate is initiated or given at an increased dose. Anticoagulant dose decreases may be needed following barbiturate discontinuation or dose reduction. Consider therapy modification

Vorapaxar: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. Avoid combination

Voriconazole: Barbiturates may decrease the serum concentration of Voriconazole. Avoid combination

Vortioxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Consider therapy modification

Voxelotor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

Voxilaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxilaprevir. Avoid combination

Zaleplon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zalephon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Consider therapy modification

Zanubrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zanubrutinib. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Monitor therapy