EMEDZ.NET

Donnatal (Hyoscyamine, Atropine, Scopolamine, and Phenobarbital)

Hyoscyamine, atropine, scopolamine, and phenobarbital are all medications with different pharmacological properties and uses.

Hyoscyamine:
- Type: Antimuscarinic/anticholinergic alkaloid.
- Source: Found in plants such as belladonna and henbane.
- Uses: Used to treat various conditions, including gastrointestinal disorders (irritable bowel syndrome, peptic ulcers), urinary problems, and to reduce salivation before surgery.
- Mechanism of Action: Blocks the effects of acetylcholine, a neurotransmitter, at muscarinic receptors, leading to a decrease in smooth muscle contractions and other physiological responses.
Atropine:
- Type: Antimuscarinic/anticholinergic alkaloid.
- Source: Extracted from plants such as belladonna.
- Uses: Widely used in medicine to treat bradycardia (slow heart rate), organophosphate poisoning, and sometimes as a pre-anesthetic to reduce salivation.
- Mechanism of Action: Blocks the action of acetylcholine at muscarinic receptors, leading to an increase in heart rate, pupil dilation, and other effects.
Scopolamine:
- Type: Antimuscarinic/anticholinergic alkaloid.
- Source: Found in plants like belladonna and henbane.
- Uses: Often used to prevent motion sickness, nausea, and vomiting associated with certain conditions or medications.
- Mechanism of Action: Blocks acetylcholine at muscarinic receptors, affecting the vestibular system and reducing nausea and vomiting.
Phenobarbital:
- Type: Barbiturate.
- Uses: Primarily used as an anticonvulsant to treat seizures (epilepsy). It can also be used as a sedative-hypnotic in certain situations.
- Mechanism of Action: Enhances the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain, leading to a calming effect.

Donnatal (Hyoscyamine, Atropine, Scopolamine, and Phenobarbital) is a combination of drugs that provides anticholinergic, antispasmodic, and mild sedation. It has been labeled as probably effective and may be used as an adjunct to other therapies in the treatment of IBS, enterocolitis, and duodenal ulcer.

Donnatal (Hyoscyamine, atropine, scopolamine, and phenobarbital) Uses:

It is used as a suplementary treatment of irritable bowel syndrome, acute enterocolitis, and duodenal ulcer

Donnatal Dose in Adults

Donnatal Dose in the adjunct treatment of Duodenal ulcer, irritable bowel syndrome, and acute enterocolitis:

Take 1 to 2 tablets or 5 to 10 mL (measured with a spoon) of the liquid form, three to four times a day. Use it by mouth (oral).

Donnatal Dose in Childrens

Donnatal Dose in the adjunct treatment of Duodenal ulcer, irritable bowel syndrome, and acute enterocolitis:

For infants weighing 4.5 kg or more, children, and adolescents using the immediate-release form of the medicine (Donnatal elixir) to help with duodenal ulcer, irritable bowel syndrome, and acute enterocolitis, the recommended doses are as follows:

4.5 to <9.1 kg: Take 0.5 mL every 4 hours or 0.75 mL every 6 hours.
9.1 to <13.6 kg: Take 1 mL every 4 hours or 1.5 mL every 6 hours.
13.6 to <22.7 kg: Take 1.5 mL every 4 hours or 2 mL every 6 hours.
22.7 to <34 kg: Take 2.5 mL every 4 hours or 3.75 mL every 6 hours.
34 to <45.4 kg: Take 3.75 mL every 4 hours or 5 mL every 6 hours.
For those weighing 45.4 kg or more: Take 5 mL every 4 hours or 7.5 mL every 6 hours.

Donnatal Pregnancy category: C

No studies specifically examining the effects on reproduction have been conducted for this combination.
To get information about the impact on reproduction, it's recommended to refer to the individual monographs for each component of the combination.
Monographs provide detailed information about a specific drug, including its pharmacology, indications, contraindications, adverse effects, and, in this case, its effects on reproduction.

Use of hyoscyamine and atropine during breastfeeding, scopolamine and phenobarbital

The manufacturer advises caution when giving this combination to breastfeeding women. It means that there may be potential risks or uncertainties regarding the safety of the medication for both the nursing infant and the breastfeeding mother.
Also see individual agents.

Dose in Renal Disease:

No dosage adjustment recommended.

Dose in Liver disease:

No dosage adjustment recommended.

Side effects of Donnatal:

Cardiovascular:
- Palpitations
- Tachycardia
Central Nervous System:
- Dizziness
- Drowsiness
- Excitement
- Headache
- Insomnia
- Nervousness
Dermatologic:
- Hypohidrosis
- Urticaria
Gastrointestinal:
- Ageusia
- Bloating
- Constipation
- Nausea
- Vomiting
- Xerostomia
Genitourinary:
- Decreased Lactation
- Impotence
- Urinary Hesitancy
- Urinary Retention
Hypersensitivity:
- Anaphylaxis
- Hypersensitivity Reaction (May Be Severe)
Neuromuscular & Skeletal:
- Musculoskeletal Pain
- Weakness
Ophthalmic:
- Blurred Vision
- Cycloplegia
- Increased Intraocular Pressure
- Mydriasis

Contraindications to Donnatal (Hyoscyamine, atropine, scopolamine, and phenobarbital):

This medication should not be used if you are allergic to hyoscyamine, atropine, scopolamine, phenobarbital, or any part of the medicine.
It's also not suitable for people with conditions like narrow-angle glaucoma, certain gastrointestinal and genitourinary obstructions, myasthenia gravis, paralytic ileus, intestinal atony, unstable cardiovascular status during acute bleeding, severe ulcerative colitis (especially with toxic megacolon), hiatal hernia related to reflux esophagitis, acute intermittent porphyria, and if you're experiencing restlessness or excitement due to phenobarbital.

Warnings and precautions

CNS effects

This medicine might make you feel sleepy or cause blurry vision, affecting your ability to do things that need focus or alertness, like driving or using machinery.
It's important to be cautious and avoid these activities if you experience drowsiness or vision changes while taking this medication.

Diarrhea:

If you experience diarrhea while using this medication, it could be a sign of a possible incomplete blockage in your intestines.
If you have an ileostomy or colostomy, you should be especially careful.

Heat prostration:

Be careful when it's hot or you're exercising because this medication may lead to heat-related issues like heat prostration.
This means your body might struggle to cool down in warmer temperatures.
Take precautions to stay cool and hydrated, especially in hot weather or during physical activities, and be aware of how your body responds to the medication in these conditions.

Cardiovascular disease

If you have heart-related conditions such as coronary artery disease, arrhythmias, rapid heart rate (tachycardia), heart failure, or high blood pressure (hypertension), it's important to use this medication with caution.

Use of drugs:

If you have a history of drug abuse or acute alcoholism, be cautious when using this medication as there is a potential for drug dependency.
Prolonged use may lead to tolerance, meaning you might need higher doses for the same effect, and both psychological and physical dependence may develop.

Gastric ulcer treatment

In treating gastric ulcers, the use of anticholinergic medications may slow down the emptying of the stomach because of a condition called antral stasis.
This means that the movement of food through the stomach may be delayed.

Hepatic impairment

If you have liver problems or hepatic impairment, it's important to use this medication with caution.

Hyperthyroidism:

If you have hyperthyroidism (an overactive thyroid), it's important to use this medication with caution.

Neuropathy:

If you have autonomic neuropathy, which affects the nerves that control involuntary bodily functions, it's advisable to use this medication with caution.

Renal impairment

If you have renal impairment (problems with kidney function), it's important to use this medication with caution.
The kidneys play a vital role in filtering and eliminating drugs from the body, and if your kidneys are not functioning properly, adjustments in the dosage or frequency of the medication may be necessary.

Hyoscyamine, atropine, scopolamine, and phenobarbital: Drug Interaction

Risk Factor C (Monitor therapy)
Acetaminophen	Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage.
Acetylcholinesterase Inhibitors	May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.
Albendazole	PHENobarbital may decrease serum concentrations of the active metabolite(s) of Albendazole.
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amantadine	May enhance the anticholinergic effect of Anticholinergic Agents.
Amezinium	Atropine (Systemic) may enhance the stimulatory effect of Amezinium.
Amphetamines	May decrease the serum concentration of PHENobarbital.
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Bazedoxifene	PHENobarbital 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.
Benperidol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol.
Beta-Blockers	Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol.
Blood Pressure Lowering Agents	Barbiturates may enhance the hypotensive effect of Blood Pressure Lowering Agents.
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
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.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Calcifediol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol.
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.
Cannabidiol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
CarBAMazepine	CYP3A4 Inducers (Strong) may decrease the serum concentration of CarBAMazepine.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
ChlorproPAMIDE	CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE.
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.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Corticosteroids (Systemic)	CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE.
Cosyntropin	May enhance the hepatotoxic effect of PHENobarbital.
CYP2C19 Inducers (Moderate)	May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers).
CYP2C19 Inhibitors (Moderate)	May decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors).
Dabigatran Etexilate	PHENobarbital may decrease the serum concentration of Dabigatran Etexilate.
Dapsone (Topical)	May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents.
Darunavir	May decrease the serum concentration of PHENobarbital.
Dexmethylphenidate	May increase the serum concentration of PHENobarbital.
Diethylstilbestrol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Diethylstilbestrol.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Disopyramide	PHENobarbital may decrease the serum concentration of Disopyramide.
Doxercalciferol	CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol.
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.
Dronabinol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Elagolix	CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix.
EPHEDrine (Systemic)	Atropine (Systemic) may enhance the therapeutic effect of EPHEDrine (Systemic).
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Eslicarbazepine	PHENobarbital may decrease the serum concentration of Eslicarbazepine.
Estriol (Systemic)	CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Systemic).
Estriol (Topical)	CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Topical).
Etizolam	CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam.
Evogliptin	CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin.
Folic Acid	May decrease the serum concentration of PHENobarbital.
Fosphenytoin	May enhance the CNS depressant effect of PHENobarbital. Fosphenytoin may increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Fosphenytoin.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Gestrinone	PHENobarbital may decrease the serum concentration of Gestrinone.
Glecaprevir and Pibrentasvir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir.
Glucagon	Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
Griseofulvin	Barbiturates may decrease the serum concentration of Griseofulvin.
Hydrocortisone (Systemic)	CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic).
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.
Itopride	Anticholinergic Agents may diminish the therapeutic effect of Itopride.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Leucovorin Calcium-Levoleucovorin	May decrease the serum concentration of PHENobarbital.
LevETIRAcetam	PHENobarbital may decrease the serum concentration of LevETIRAcetam.
Levomefolate	May decrease the serum concentration of PHENobarbital.
Local Anesthetics	Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased.
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.
Lumacaftor	May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers).
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Methylfolate	May decrease the serum concentration of PHENobarbital.
Methylphenidate	May increase the serum concentration of PHENobarbital.
MetroNIDAZOLE (Systemic)	PHENobarbital may decrease the serum concentration of MetroNIDAZOLE (Systemic).
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirabegron	Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May decrease the serum concentration of Barbiturates.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Nalmefene	PHENobarbital may decrease the serum concentration of Nalmefene.
Nitric Oxide	May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine.
Nitroglycerin	Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption.
Orlistat	May decrease the serum concentration of Anticonvulsants.
Phenytoin	May enhance the CNS depressant effect of PHENobarbital. PHENobarbital may decrease the serum concentration of Phenytoin. Phenytoin may increase the serum concentration of PHENobarbital.
Pimavanserin	CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin.
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Pitolisant	CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
PrednisoLONE (Systemic)	CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic).
PredniSONE	CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE.
Prilocaine	Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents.
Primidone	May enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy.
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.
Propafenone	CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone.
Pyridoxine	May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day)
QuiNIDine	PHENobarbital may enhance the hepatotoxic effect of QuiNIDine. PHENobarbital may decrease the serum concentration of QuiNIDine.
Ramelteon	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ramelteon.
Ramosetron	Anticholinergic Agents may enhance the constipating effect of Ramosetron.
Reboxetine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine.
Rifamycin Derivatives	May increase the metabolism of Barbiturates.
Ritodrine	Atropine (Systemic) may enhance the adverse/toxic effect of Ritodrine.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Rufinamide.
Ruxolitinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib.
SAXagliptin	CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin.
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.
Sertraline	CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline.
Sodium Nitrite	Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
Sulthiame	May enhance the adverse/toxic effect of PHENobarbital.
Tetrahydrocannabinol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol.
Theophylline Derivatives	Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline.
Thiazide and Thiazide-Like Diuretics	Barbiturates may enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics.
Thiazide and Thiazide-Like Diuretics	Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.
Thiothixene	PHENobarbital may decrease the serum concentration of Thiothixene.
Topiramate	Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Tropisetron	CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron.
Udenafil	CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil.
Valproate Products	May increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Valproate Products.
Zonisamide	PHENobarbital may decrease the serum concentration of Zonisamide.
Zuclopenthixol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol.
Risk Factor D (Consider therapy modification)
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.
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.
Afatinib	PHENobarbital may decrease the serum concentration of Afatinib. Management: Per US labeling: if requiring chronic use of phenobarbital, increase afatinib dose by 10 mg as tolerated; reduce to original afatinib dose 2-3 days after stopping phenobarbital. Per Canadian labeling: avoid combination if possible.
Antacids	May decrease the serum concentration of Hyoscyamine. Management: Administer immediate release hyoscyamine before meals and antacids after meals when these agents are given in 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.
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.
Benzhydrocodone	PHENobarbital may enhance the CNS depressant effect of Benzhydrocodone. PHENobarbital may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Specifically, phenobarbital may decrease serum concentrations of hydrocodone. Management: Avoid use of benzhydrocodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased benzhydrocodone efficacy and withdrawal if combined.
Bictegravir	PHENobarbital may decrease the serum concentration of Bictegravir. Management: When possible consider using an alternative anticonvulsant with concurrent bictegravir, emtricitabine, and tenofovir alafenamide. If the combination must be used, monitor closely for evidence of reduced antiviral effectiveness.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
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.
Buprenorphine	PHENobarbital may enhance the CNS depressant effect of Buprenorphine. PHENobarbital may decrease the serum concentration of Buprenorphine. Management: Avoid use of buprenorphine and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased buprenorphine efficacy and withdrawal if combined.
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.
Cabozantinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers 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.
Canagliflozin	PHENobarbital may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2.
Chloramphenicol (Systemic)	May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol (Systemic).
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.
Cholestyramine Resin	May decrease the serum concentration of PHENobarbital. Management: Administer phenobarbital at least 1 hour before or 4-6 hours after administration of cholestyramine in order to minimize the risk for any significant interaction.
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 14hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy.
Codeine	PHENobarbital may enhance the CNS depressant effect of Codeine. PHENobarbital may decrease the serum concentration of Codeine. Management: Avoid use of codeine and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased codeine efficacy and withdrawal if combined.
CycloSPORINE (Systemic)	Barbiturates may increase the metabolism of CycloSPORINE (Systemic).
CYP2C19 Inducers (Strong)	May increase the metabolism of CYP2C19 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.
CYP2C19 Inhibitors (Strong)	May decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors).
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; TraMADol; Zolpidem.
Dabrafenib	May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
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.
Deferasirox	PHENobarbital may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider a 50% increase in initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical responses to guide further dosing.
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 steroid efficacy.
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.
Doxycycline	Barbiturates may decrease the serum concentration of Doxycycline.
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.
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.
Enzalutamide	May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring.
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.
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.
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.
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.
Etoposide Phosphate	CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response.
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.
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.
Felbamate	PHENobarbital may decrease the serum concentration of Felbamate. Felbamate may increase the serum concentration of PHENobarbital. Management: In patients receiving phenobarbital, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily and reduce phenobarbital dose by 20%. Monitor for increased phenobarbital concentrations/effects and decreased felbamate concentrations/effects.
FentaNYL	PHENobarbital may enhance the CNS depressant effect of FentaNYL. PHENobarbital may decrease the serum concentration of FentaNYL. Management: Avoid use of fentanyl and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased fentanyl efficacy and withdrawal if combined.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
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.
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.
HYDROcodone	PHENobarbital may enhance the CNS depressant effect of HYDROcodone. PHENobarbital may decrease the serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined.
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.
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.
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 to 60 mg/m (given as a 4-hour infusion), as tolerated, should be considered.
LamoTRIgine	Barbiturates may decrease the serum concentration of LamoTRIgine. Management: See lamotrigine prescribing information for specific age-dependent dosing guidelines regarding concurrent use with a barbiturate, as well as for adjusting lamotrigine dosing if concurrent barbiturate therapy is discontinued.
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.
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.
Lopinavir	PHENobarbital may decrease the serum concentration of Lopinavir. Management: Increased doses of lopinavir may be necessary when using these agents in combination. Do not use a once daily lopinavir/ritonavir regimen together with phenobarbital. Increase monitoring of therapeutic response in all patients using this combination.
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.
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.
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.
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.
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.
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.
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.
Osimertinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib.
OXcarbazepine	PHENobarbital may decrease serum concentrations of the active metabolite(s) of OXcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. OXcarbazepine may increase the serum concentration of PHENobarbital. Management: Consider increasing the initial adult oxcarbazepine extended release tablet (Oxtellar XR) dose to 900 mg/day. No specific recommendations are available for other oxcarbazepine formulations.
OxyCODONE	PHENobarbital may enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined.
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.
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.
Pramlintide	May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.
Progestins (Contraceptive)	Barbiturates may diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended.
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.
QuiNINE	May increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of QuiNINE.
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.
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.
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.
Secretin	Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.
Sincalide	Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.
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.
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.
SUFentanil	PHENobarbital may enhance the CNS depressant effect of SUFentanil. PHENobarbital may decrease the serum concentration of SUFentanil. Management: Avoid use of sufentanil and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased sufentanil efficacy and withdrawal if combined.
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.
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.
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.
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.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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.
Temsirolimus	CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Consider increasing the dose of temsirolimus to 50 mg IV/week (from 25 mg IV/week) if a concomitant CYP3A4 strong inducer is necessary.
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.
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.
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.
Tipranavir	PHENobarbital may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of PHENobarbital.
TraMADol	PHENobarbital may enhance the CNS depressant effect of TraMADol. PHENobarbital may decrease the serum concentration of TraMADol. Management: Avoid use of tramadol and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased tramadol efficacy and withdrawal if combined.
Tricyclic Antidepressants	Barbiturates may increase the metabolism of Tricyclic Antidepressants.
Vemurafenib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with a strong CYP3A4 inducer and replace with another agent when possible. If a strong CYP3A4 inducer is indicated and unavoidable, the dose of vemurafenib may be increased by 240 mg (1 tablet) as tolerated.
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.
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.
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.
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.
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.
Risk Factor X (Avoid combination)
Abemaciclib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib.
Aclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Antihepaciviral Combination Products	CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products.
Apixaban	CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban.
Apremilast	CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast.
Aprepitant	CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant.
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.
Asunaprevir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir.
Axitinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bedaquiline	CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline.
Benznidazole	May enhance the adverse/toxic effect of Products Containing Propylene Glycol.
Bortezomib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib.
Bosutinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib.
Brigatinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Cariprazine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine.
Ceritinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib.
Cimetropium	Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.
CloZAPine	CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine.
Cobicistat	PHENobarbital may decrease the serum concentration of Cobicistat.
Cobimetinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib.
Copanlisib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib.
Crizotinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib.
Daclatasvir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir.
Dasabuvir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir.
Deflazacort	CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort.
Delamanid	CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid.
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.
Dolutegravir	PHENobarbital may decrease the serum concentration of Dolutegravir.
Doravirine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine.
Dronedarone	CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone.
Duvelisib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib.
Elbasvir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Elbasvir.
Eliglustat	CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat.
Eluxadoline	Anticholinergic Agents may enhance the constipating effect of Eluxadoline.
Elvitegravir	PHENobarbital may decrease the serum concentration of Elvitegravir.
Encorafenib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Encorafenib.
Erdafitinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Erdafitinib.
Etravirine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine.
Flibanserin	CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin.
Fosaprepitant	CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant.
Fosnetupitant	CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant.
Fostamatinib	CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib.
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.
Glasdegib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib.
Glycopyrrolate (Oral Inhalation)	Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).
Glycopyrronium (Topical)	May enhance the anticholinergic effect of Anticholinergic Agents.
Grazoprevir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Grazoprevir.
Hemin	Barbiturates may diminish the therapeutic effect of Hemin.
Ibrutinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib.
Idelalisib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib.
Ipratropium (Oral Inhalation)	May enhance the anticholinergic effect of Anticholinergic Agents.
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.
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.
Itraconazole	CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole.
Ivabradine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine.
Ivacaftor	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor.
Ivosidenib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivosidenib.
Ixazomib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib.
Lapatinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating 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.
Ledipasvir	PHENobarbital may decrease the serum concentration of Ledipasvir.
Levosulpiride	Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
Lorlatinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib.
Lumefantrine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine.
Lurasidone	CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone.
Macimorelin	Atropine (Systemic) may diminish the diagnostic effect of Macimorelin.
Macitentan	CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan.
Methoxyflurane	Barbiturates may enhance the nephrotoxic effect of Methoxyflurane. Barbiturates may increase the metabolism of Methoxyflurane.
Methoxyflurane	CYP2A6 Inducers may enhance the nephrotoxic effect of Methoxyflurane. CYP2A6 Inducers may increase the metabolism of Methoxyflurane.
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.
Midostaurin	CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin.
MiFEPRIStone	CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone.
Naldemedine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine.
Naloxegol	CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol.
Neratinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib.
Netupitant	CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant.
NIFEdipine	CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine.
Nilotinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
NiMODipine	CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine.
Nisoldipine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine.
Olaparib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxatomide	May enhance the anticholinergic effect of Anticholinergic Agents.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Palbociclib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib.
Panobinostat	CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
PAZOPanib	CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib.
Piperaquine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Piperaquine.
PONATinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib.
Potassium Chloride	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.
Potassium Citrate	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.
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.
Ranolazine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine.
Regorafenib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib.
Revefenacin	Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.
Ribociclib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib.
Rilpivirine	PHENobarbital may decrease the serum concentration of Rilpivirine.
Rivaroxaban	CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban.
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.
RomiDEPsin	CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin.
Simeprevir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
Sofosbuvir	PHENobarbital may decrease the serum concentration of Sofosbuvir.
Somatostatin Acetate	May enhance the adverse/toxic effect of Barbiturates. Specifically, Somatostatin Acetate may enhance or prolong Barbiturate effects, including sedative effects.
Sonidegib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib.
SORAfenib	CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib.
Stiripentol	PHENobarbital may decrease the serum concentration of Stiripentol.
Tasimelteon	CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon.
Tenofovir Alafenamide	PHENobarbital may decrease the serum concentration of Tenofovir Alafenamide.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
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.
Tiotropium	Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
Tofacitinib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib.
Tolvaptan	CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed.
Toremifene	CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene.
Toremifene	Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin.
Ulipristal	CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal.
Ulipristal	Barbiturates may decrease the serum concentration of Ulipristal.
Umeclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Valbenazine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine.
Vandetanib	CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib.
Velpatasvir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir.
Venetoclax	CYP3A4 Inducers (Strong) may decrease the serum concentration of Venetoclax.
VinCRIStine (Liposomal)	CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal).
Vinflunine	CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine.
Vorapaxar	CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar.
Voriconazole	Barbiturates may decrease the serum concentration of Voriconazole.
Voxilaprevir	CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxilaprevir.

Monitoring parameters:

None mentioned.

How to administer Donnatal?

It is administered in two to four divided doses about 30 minutes before meals.

Mechanism of action of Donnatal (Hyoscyamine, atropine, scopolamine, and phenobarbital):

Anticholinergic agents, such as hyoscyamine, atropine, and scopolamine, work by blocking the effects of acetylcholine at certain nerve endings.
Acetylcholine is a neurotransmitter that plays a role in transmitting signals in the nervous system.
These anticholinergic medications inhibit the muscarinic actions of acetylcholine specifically at postganglionic parasympathetic neuroeffector sites.
These sites include smooth muscles, secretory glands, and certain areas in the central nervous system (CNS).
The effects of these medications are related to the dose administered, meaning that the specific responses to the anticholinergic properties vary depending on the amount of the medication taken.

Absorption:

These anticholinergic agents, including hyoscyamine, atropine, and scopolamine, are effectively taken up by the body when ingested, showing good absorption from the gastrointestinal (GI) tract.
This means that when these medications are taken orally, they are efficiently absorbed into the bloodstream from the digestive system.
The absorption process is an important factor in determining how the drugs will be distributed and exert their effects throughout the body.

International Brands of Hyoscyamine, atropine, scopolamine, and phenobarbital: